Conference Coverage

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

A version of this article first appeared on Medscape.com.

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

A version of this article first appeared on Medscape.com.

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

A version of this article first appeared on Medscape.com.

LIVERPOOL — “Healthy doctors make healthy patients”, stated a GP during a workshop at the Royal College of General Practitioners (RCGP) annual meeting. The session aimed to encourage GPs to embed lifestyle medicine into primary care through collaborative action.

Callum Leese from Aberfeldy Medical Practice in Scotland, who is also a lecturer at the University of Dundee for the Scottish Clinical Research Excellence Development Scheme (SCREDS), discussed the benefits of lifestyle medicine services in addressing lifestyle-related diseases, reducing their contribution towards the prevalence of chronic conditions, and helping prevent premature mortality. 

Leese is leading a project to make Aberfeldy the healthiest town in Scotland by promoting physical activities, such as the 2-km, 5-km, and 7-km Santa Stride walking group in November, and a recent food festival to encourage healthy cooking and eating. “There’s loads of things that can be done to try and inspire change,” he said. “The research is fairly unequivocal in that healthy doctors make healthy patients,” Leese asserted. “The most important thing we can do is target our doctors and our nurses and make them advocates for what we want to see with our patients.”

Speaking to this news organization, he emphasized that, “if the doctors are moving, they’re much more likely to promote it, and if they’re eating well, they’re much more likely to be able to be evangelistic.” 
 

Physical Activity Advice Shows High Return

About one-third of the population in the United Kingdom are physically inactive, which costs the economy £7.2 billion, with £1 billion attributed directly to the NHS, he informed the workshop.

As an honorary support fellow in physical activity and lifestyle medicine at the RCGP, Leese specializes in integrating physical activity into primary care settings. “We know it’s cost effective. If we compare it to smoking cessation advice, we know that we need to give advice to one person about 50 times for one person to stop smoking in primary care. But for physical activity, you need to give advice to 12 people for one person to increase their physical activity levels to meet the guidance,” he noted.

Leese stressed the importance of short but effective discussions between GPs and patients. He gave examples of online resources to recommend to patients, such as Moving Medicine, which aims to help healthcare professionals integrate physical activity into routine clinical conversations, or the RCGP toolkit (the Physical Activity Hub). “It really takes 1 minute of asking if the patient has ever considered being more active, and briefly explaining that being more active might have really significant outcomes for their condition,” he said.

In primary care, most patients who need to be more physically activity are directed toward 12-week exercise referral schemes, and sometimes we use social prescribing, for example, inviting patients to walk in groups, Leese explained. “However, despite the best intentions, about 78% of GPs aren’t doing it [advising on physical activity] regularly,” he noted. He cited four main challenges: lack of time, knowledge, resources, and financial support.
 

Geographical Variation in Social Prescribing

Social prescribing, which links patients with non–medical community support, also varies widely across the United Kingdom. “Social prescribing is a real example of that because it’s really well established in some places and not in others,” Leese remarked. He noted that inner-city and rural areas often have different needs. Contrary to some expectations, city dwellers are sometimes more active than those living in rural areas because despite having lots of green space for physical activity, “they tend to park the car outside the front door and park again right outside their place of work, whereas in London, for example, you can persuade people to get off a stop early on the Tube or a stop early in the bus.”

MAN v FAT 5-a-side Football

Leese also emphasized the importance of innovation in implementing lifestyle medicine, pointing out that nonmedical personnel, social prescribers, and health coaches can alleviate time pressures on GPs.

Citing an example of a physical activity-related intervention, he described a UK-wide organization developed for men in the 40s-50s age group, called MAN v FAT, which involves a novel weight-related way of playing five-a-side football. Players have a weigh-in before each game and teams are rewarded with points on the pitch for every pound lost as a team since their last match.

However, Leese acknowledged the need to tailor physical activity advice to different age groups. For example, “in an 80-year-old, physical activity might improve their balance and they’re less likely to fall and break something.” 
 

Lifestyle Clinics

Leese cited the PCN Lifestyle Clinics, originating from the Leamington Primary Care Network (PCN), as an example of successful lifestyle medicine integration to help address the needs of people living with chronic conditions. “We don’t want to prescribe a model, but we can draw on a program run by the Leamington Spa PCN, that involves four group sessions of 6-10 people focused on lifestyle,” he said. 

The weekly group-based sessions are run by a GP, a health and wellbeing coach, a dietitian, and a psychiatrist. Together, they cover four aspects of lifestyle and health comprising individual challenges, how community influences behavior and vice versa, food and nutrition, and physical activity for health and wellbeing.

“We try to debunk some of those myths around nutrition, compared with diet, and physical activity, compared with exercise. So, for example, the idea that exercise is usually considered to be using an elliptical cross-trainer whereas physical activity, which might be just dancing in your kitchen while you’re making dinner, is something that can be done more easily,” explained Leese.

Physical activities include running and swimming in collaboration with a leisure center. “It’s an amazing program,” he remarked. 

Outcomes from 142 patients who attended the Lifestyle Clinic at a North Leamington GP practice over 14 months showed that 53% gained confidence in making lifestyle changes, 60% noticed a positive impact on their physical health, and 77% reported positive impacts on their mental health.
 

GP Embraces Lifestyle Medicine

Rachel Burnett, a GP from Park Medical Practice in Derby, a delegate who attended the session, commented on the central idea of incorporating lifestyle medicine into primary care practice. She told this news organization that, “I think it could prevent a lot of ill health and therefore a lot of health inequalities just by embedding lifestyle medicine into our work. To hear about the Leamington Spa project and how it›s been a success was really inspiring.”

Referring to her own practice, Burnett said: “My patients are familiar with the way I go on and on about lifestyle measures, but I believe the way forward is with group sessions because we need to give the same advice to a large number of patients, for example, with prediabetes. This could save time and resource, and I think patients who are more likely to make the changes will actually attend the sessions so we’re not wasting our breath.” 

Neither Leese nor Burnett declared any relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

LIVERPOOL — “Healthy doctors make healthy patients”, stated a GP during a workshop at the Royal College of General Practitioners (RCGP) annual meeting. The session aimed to encourage GPs to embed lifestyle medicine into primary care through collaborative action.

Callum Leese from Aberfeldy Medical Practice in Scotland, who is also a lecturer at the University of Dundee for the Scottish Clinical Research Excellence Development Scheme (SCREDS), discussed the benefits of lifestyle medicine services in addressing lifestyle-related diseases, reducing their contribution towards the prevalence of chronic conditions, and helping prevent premature mortality. 

Leese is leading a project to make Aberfeldy the healthiest town in Scotland by promoting physical activities, such as the 2-km, 5-km, and 7-km Santa Stride walking group in November, and a recent food festival to encourage healthy cooking and eating. “There’s loads of things that can be done to try and inspire change,” he said. “The research is fairly unequivocal in that healthy doctors make healthy patients,” Leese asserted. “The most important thing we can do is target our doctors and our nurses and make them advocates for what we want to see with our patients.”

Speaking to this news organization, he emphasized that, “if the doctors are moving, they’re much more likely to promote it, and if they’re eating well, they’re much more likely to be able to be evangelistic.” 
 

Physical Activity Advice Shows High Return

About one-third of the population in the United Kingdom are physically inactive, which costs the economy £7.2 billion, with £1 billion attributed directly to the NHS, he informed the workshop.

As an honorary support fellow in physical activity and lifestyle medicine at the RCGP, Leese specializes in integrating physical activity into primary care settings. “We know it’s cost effective. If we compare it to smoking cessation advice, we know that we need to give advice to one person about 50 times for one person to stop smoking in primary care. But for physical activity, you need to give advice to 12 people for one person to increase their physical activity levels to meet the guidance,” he noted.

Leese stressed the importance of short but effective discussions between GPs and patients. He gave examples of online resources to recommend to patients, such as Moving Medicine, which aims to help healthcare professionals integrate physical activity into routine clinical conversations, or the RCGP toolkit (the Physical Activity Hub). “It really takes 1 minute of asking if the patient has ever considered being more active, and briefly explaining that being more active might have really significant outcomes for their condition,” he said.

In primary care, most patients who need to be more physically activity are directed toward 12-week exercise referral schemes, and sometimes we use social prescribing, for example, inviting patients to walk in groups, Leese explained. “However, despite the best intentions, about 78% of GPs aren’t doing it [advising on physical activity] regularly,” he noted. He cited four main challenges: lack of time, knowledge, resources, and financial support.
 

Geographical Variation in Social Prescribing

Social prescribing, which links patients with non–medical community support, also varies widely across the United Kingdom. “Social prescribing is a real example of that because it’s really well established in some places and not in others,” Leese remarked. He noted that inner-city and rural areas often have different needs. Contrary to some expectations, city dwellers are sometimes more active than those living in rural areas because despite having lots of green space for physical activity, “they tend to park the car outside the front door and park again right outside their place of work, whereas in London, for example, you can persuade people to get off a stop early on the Tube or a stop early in the bus.”

MAN v FAT 5-a-side Football

Leese also emphasized the importance of innovation in implementing lifestyle medicine, pointing out that nonmedical personnel, social prescribers, and health coaches can alleviate time pressures on GPs.

Citing an example of a physical activity-related intervention, he described a UK-wide organization developed for men in the 40s-50s age group, called MAN v FAT, which involves a novel weight-related way of playing five-a-side football. Players have a weigh-in before each game and teams are rewarded with points on the pitch for every pound lost as a team since their last match.

However, Leese acknowledged the need to tailor physical activity advice to different age groups. For example, “in an 80-year-old, physical activity might improve their balance and they’re less likely to fall and break something.” 
 

Lifestyle Clinics

Leese cited the PCN Lifestyle Clinics, originating from the Leamington Primary Care Network (PCN), as an example of successful lifestyle medicine integration to help address the needs of people living with chronic conditions. “We don’t want to prescribe a model, but we can draw on a program run by the Leamington Spa PCN, that involves four group sessions of 6-10 people focused on lifestyle,” he said. 

The weekly group-based sessions are run by a GP, a health and wellbeing coach, a dietitian, and a psychiatrist. Together, they cover four aspects of lifestyle and health comprising individual challenges, how community influences behavior and vice versa, food and nutrition, and physical activity for health and wellbeing.

“We try to debunk some of those myths around nutrition, compared with diet, and physical activity, compared with exercise. So, for example, the idea that exercise is usually considered to be using an elliptical cross-trainer whereas physical activity, which might be just dancing in your kitchen while you’re making dinner, is something that can be done more easily,” explained Leese.

Physical activities include running and swimming in collaboration with a leisure center. “It’s an amazing program,” he remarked. 

Outcomes from 142 patients who attended the Lifestyle Clinic at a North Leamington GP practice over 14 months showed that 53% gained confidence in making lifestyle changes, 60% noticed a positive impact on their physical health, and 77% reported positive impacts on their mental health.
 

GP Embraces Lifestyle Medicine

Rachel Burnett, a GP from Park Medical Practice in Derby, a delegate who attended the session, commented on the central idea of incorporating lifestyle medicine into primary care practice. She told this news organization that, “I think it could prevent a lot of ill health and therefore a lot of health inequalities just by embedding lifestyle medicine into our work. To hear about the Leamington Spa project and how it›s been a success was really inspiring.”

Referring to her own practice, Burnett said: “My patients are familiar with the way I go on and on about lifestyle measures, but I believe the way forward is with group sessions because we need to give the same advice to a large number of patients, for example, with prediabetes. This could save time and resource, and I think patients who are more likely to make the changes will actually attend the sessions so we’re not wasting our breath.” 

Neither Leese nor Burnett declared any relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

LIVERPOOL — “Healthy doctors make healthy patients”, stated a GP during a workshop at the Royal College of General Practitioners (RCGP) annual meeting. The session aimed to encourage GPs to embed lifestyle medicine into primary care through collaborative action.

Callum Leese from Aberfeldy Medical Practice in Scotland, who is also a lecturer at the University of Dundee for the Scottish Clinical Research Excellence Development Scheme (SCREDS), discussed the benefits of lifestyle medicine services in addressing lifestyle-related diseases, reducing their contribution towards the prevalence of chronic conditions, and helping prevent premature mortality. 

Leese is leading a project to make Aberfeldy the healthiest town in Scotland by promoting physical activities, such as the 2-km, 5-km, and 7-km Santa Stride walking group in November, and a recent food festival to encourage healthy cooking and eating. “There’s loads of things that can be done to try and inspire change,” he said. “The research is fairly unequivocal in that healthy doctors make healthy patients,” Leese asserted. “The most important thing we can do is target our doctors and our nurses and make them advocates for what we want to see with our patients.”

Speaking to this news organization, he emphasized that, “if the doctors are moving, they’re much more likely to promote it, and if they’re eating well, they’re much more likely to be able to be evangelistic.” 
 

Physical Activity Advice Shows High Return

About one-third of the population in the United Kingdom are physically inactive, which costs the economy £7.2 billion, with £1 billion attributed directly to the NHS, he informed the workshop.

As an honorary support fellow in physical activity and lifestyle medicine at the RCGP, Leese specializes in integrating physical activity into primary care settings. “We know it’s cost effective. If we compare it to smoking cessation advice, we know that we need to give advice to one person about 50 times for one person to stop smoking in primary care. But for physical activity, you need to give advice to 12 people for one person to increase their physical activity levels to meet the guidance,” he noted.

Leese stressed the importance of short but effective discussions between GPs and patients. He gave examples of online resources to recommend to patients, such as Moving Medicine, which aims to help healthcare professionals integrate physical activity into routine clinical conversations, or the RCGP toolkit (the Physical Activity Hub). “It really takes 1 minute of asking if the patient has ever considered being more active, and briefly explaining that being more active might have really significant outcomes for their condition,” he said.

In primary care, most patients who need to be more physically activity are directed toward 12-week exercise referral schemes, and sometimes we use social prescribing, for example, inviting patients to walk in groups, Leese explained. “However, despite the best intentions, about 78% of GPs aren’t doing it [advising on physical activity] regularly,” he noted. He cited four main challenges: lack of time, knowledge, resources, and financial support.
 

Geographical Variation in Social Prescribing

Social prescribing, which links patients with non–medical community support, also varies widely across the United Kingdom. “Social prescribing is a real example of that because it’s really well established in some places and not in others,” Leese remarked. He noted that inner-city and rural areas often have different needs. Contrary to some expectations, city dwellers are sometimes more active than those living in rural areas because despite having lots of green space for physical activity, “they tend to park the car outside the front door and park again right outside their place of work, whereas in London, for example, you can persuade people to get off a stop early on the Tube or a stop early in the bus.”

MAN v FAT 5-a-side Football

Leese also emphasized the importance of innovation in implementing lifestyle medicine, pointing out that nonmedical personnel, social prescribers, and health coaches can alleviate time pressures on GPs.

Citing an example of a physical activity-related intervention, he described a UK-wide organization developed for men in the 40s-50s age group, called MAN v FAT, which involves a novel weight-related way of playing five-a-side football. Players have a weigh-in before each game and teams are rewarded with points on the pitch for every pound lost as a team since their last match.

However, Leese acknowledged the need to tailor physical activity advice to different age groups. For example, “in an 80-year-old, physical activity might improve their balance and they’re less likely to fall and break something.” 
 

Lifestyle Clinics

Leese cited the PCN Lifestyle Clinics, originating from the Leamington Primary Care Network (PCN), as an example of successful lifestyle medicine integration to help address the needs of people living with chronic conditions. “We don’t want to prescribe a model, but we can draw on a program run by the Leamington Spa PCN, that involves four group sessions of 6-10 people focused on lifestyle,” he said. 

The weekly group-based sessions are run by a GP, a health and wellbeing coach, a dietitian, and a psychiatrist. Together, they cover four aspects of lifestyle and health comprising individual challenges, how community influences behavior and vice versa, food and nutrition, and physical activity for health and wellbeing.

“We try to debunk some of those myths around nutrition, compared with diet, and physical activity, compared with exercise. So, for example, the idea that exercise is usually considered to be using an elliptical cross-trainer whereas physical activity, which might be just dancing in your kitchen while you’re making dinner, is something that can be done more easily,” explained Leese.

Physical activities include running and swimming in collaboration with a leisure center. “It’s an amazing program,” he remarked. 

Outcomes from 142 patients who attended the Lifestyle Clinic at a North Leamington GP practice over 14 months showed that 53% gained confidence in making lifestyle changes, 60% noticed a positive impact on their physical health, and 77% reported positive impacts on their mental health.
 

GP Embraces Lifestyle Medicine

Rachel Burnett, a GP from Park Medical Practice in Derby, a delegate who attended the session, commented on the central idea of incorporating lifestyle medicine into primary care practice. She told this news organization that, “I think it could prevent a lot of ill health and therefore a lot of health inequalities just by embedding lifestyle medicine into our work. To hear about the Leamington Spa project and how it›s been a success was really inspiring.”

Referring to her own practice, Burnett said: “My patients are familiar with the way I go on and on about lifestyle measures, but I believe the way forward is with group sessions because we need to give the same advice to a large number of patients, for example, with prediabetes. This could save time and resource, and I think patients who are more likely to make the changes will actually attend the sessions so we’re not wasting our breath.” 

Neither Leese nor Burnett declared any relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

CARLSBAD, CALIF. — Lasers and energy-based treatments alone or in combination with medical therapy may improve outcomes for patients with moderate to severe acne, according to Arielle Kauvar, MD.

At the Controversies and Conversations in Laser and Cosmetic Surgery annual symposium, Kauvar, director of New York Laser & Skin Care, New York City, highlighted several reasons why using lasers for acne is beneficial. “First, we know that topical therapy alone is often ineffective, and antibiotic treatment does not address the cause of acne and can alter the skin and gut microbiome,” she said. “Isotretinoin is highly effective, but there’s an increasing reluctance to use it. Lasers and energy devices are effective in treating acne and may also treat the post-inflammatory hyperpigmentation and scarring associated with it.”

The pathogenesis of acne is multifactorial, she continued, including a disruption of sebaceous gland activity, with overproduction and alteration of sebum and abnormal follicular keratinization. Acne also causes an imbalance of the skin microbiome, local inflammation, and activation of both innate and adaptive immunity.

“Many studies point to the fact that inflammation and immune system activation may actually be the primary event” of acne formation, said Kauvar, who is also a clinical professor of dermatology at New York University, New York City. “This persistent immune activation is also associated with scarring,” she noted. “So, are we off the mark in terms of trying to kill sebaceous glands? Should we be concentrating on anti-inflammatory approaches?” 

AviClear became the first 1726-nm laser cleared by the US Food and Drug Administration (FDA) for the treatment of mild to severe acne vulgaris in 2022, followed a few months later with the FDA clearance of another 1726-nm laser, the Accure Acne Laser System in November 2022. These lasers cause selective photothermolysis of sebaceous glands, but according to Kauvar, “access to these devices is somewhat limited at this time.”

What is available includes her go-to device, the pulsed dye laser (PDL), which has been widely studied and shown in a systematic review and meta-analysis of studies to be effective for acne. The PDL “targets dermal blood vessels facilitating inflammation, upregulates TGF-beta, and inhibits CD4+ T cell-mediated inflammation,” she said. “It can also treat PIH [post-inflammatory hyperpigmentation] and may be helpful in scar prevention.”

In an abstract presented at The American Society for Laser Medicine and Surgery (ASLMS) 2024 annual meeting, Kauvar and colleagues conducted a real-world study of PDL therapy in 15 adult women with recalcitrant acne who were maintained on their medical treatment regimen. Their mean age was 27 years, and they had skin types II-IV; they underwent four monthly PDL treatments with follow-up at 1 and 3 months. At each visit, the researchers took digital photographs and counted inflammatory acne lesions, non-inflammatory acne lesions, and post-inflammatory pigment alteration (PIPA) lesions.

The main outcomes of interest were the investigator global assessment (IGA) scores at the 1- and 3-month follow-up visits. Kauvar and colleagues observed a significant improvement in IGA scores at the 1- and 3-month follow-up visits (P < .05), with an average decrease of 1.8 and 1.6 points in the acne severity scale, respectively, from a baseline score of 3.4. By the 3-month follow-up visits, counts of inflammatory and non-inflammatory lesions decreased significantly (P < .05), and 61% of study participants showed a decrease in the PIPA count. No adverse events occurred. 

Kauvar disclosed that she has conducted research for Candela, Lumenis, and Sofwave, and is an adviser to Acclaro.

A version of this article first appeared on Medscape.com.

CARLSBAD, CALIF. — Lasers and energy-based treatments alone or in combination with medical therapy may improve outcomes for patients with moderate to severe acne, according to Arielle Kauvar, MD.

At the Controversies and Conversations in Laser and Cosmetic Surgery annual symposium, Kauvar, director of New York Laser & Skin Care, New York City, highlighted several reasons why using lasers for acne is beneficial. “First, we know that topical therapy alone is often ineffective, and antibiotic treatment does not address the cause of acne and can alter the skin and gut microbiome,” she said. “Isotretinoin is highly effective, but there’s an increasing reluctance to use it. Lasers and energy devices are effective in treating acne and may also treat the post-inflammatory hyperpigmentation and scarring associated with it.”

The pathogenesis of acne is multifactorial, she continued, including a disruption of sebaceous gland activity, with overproduction and alteration of sebum and abnormal follicular keratinization. Acne also causes an imbalance of the skin microbiome, local inflammation, and activation of both innate and adaptive immunity.

“Many studies point to the fact that inflammation and immune system activation may actually be the primary event” of acne formation, said Kauvar, who is also a clinical professor of dermatology at New York University, New York City. “This persistent immune activation is also associated with scarring,” she noted. “So, are we off the mark in terms of trying to kill sebaceous glands? Should we be concentrating on anti-inflammatory approaches?” 

AviClear became the first 1726-nm laser cleared by the US Food and Drug Administration (FDA) for the treatment of mild to severe acne vulgaris in 2022, followed a few months later with the FDA clearance of another 1726-nm laser, the Accure Acne Laser System in November 2022. These lasers cause selective photothermolysis of sebaceous glands, but according to Kauvar, “access to these devices is somewhat limited at this time.”

What is available includes her go-to device, the pulsed dye laser (PDL), which has been widely studied and shown in a systematic review and meta-analysis of studies to be effective for acne. The PDL “targets dermal blood vessels facilitating inflammation, upregulates TGF-beta, and inhibits CD4+ T cell-mediated inflammation,” she said. “It can also treat PIH [post-inflammatory hyperpigmentation] and may be helpful in scar prevention.”

In an abstract presented at The American Society for Laser Medicine and Surgery (ASLMS) 2024 annual meeting, Kauvar and colleagues conducted a real-world study of PDL therapy in 15 adult women with recalcitrant acne who were maintained on their medical treatment regimen. Their mean age was 27 years, and they had skin types II-IV; they underwent four monthly PDL treatments with follow-up at 1 and 3 months. At each visit, the researchers took digital photographs and counted inflammatory acne lesions, non-inflammatory acne lesions, and post-inflammatory pigment alteration (PIPA) lesions.

The main outcomes of interest were the investigator global assessment (IGA) scores at the 1- and 3-month follow-up visits. Kauvar and colleagues observed a significant improvement in IGA scores at the 1- and 3-month follow-up visits (P < .05), with an average decrease of 1.8 and 1.6 points in the acne severity scale, respectively, from a baseline score of 3.4. By the 3-month follow-up visits, counts of inflammatory and non-inflammatory lesions decreased significantly (P < .05), and 61% of study participants showed a decrease in the PIPA count. No adverse events occurred. 

Kauvar disclosed that she has conducted research for Candela, Lumenis, and Sofwave, and is an adviser to Acclaro.

A version of this article first appeared on Medscape.com.

CARLSBAD, CALIF. — Lasers and energy-based treatments alone or in combination with medical therapy may improve outcomes for patients with moderate to severe acne, according to Arielle Kauvar, MD.

At the Controversies and Conversations in Laser and Cosmetic Surgery annual symposium, Kauvar, director of New York Laser & Skin Care, New York City, highlighted several reasons why using lasers for acne is beneficial. “First, we know that topical therapy alone is often ineffective, and antibiotic treatment does not address the cause of acne and can alter the skin and gut microbiome,” she said. “Isotretinoin is highly effective, but there’s an increasing reluctance to use it. Lasers and energy devices are effective in treating acne and may also treat the post-inflammatory hyperpigmentation and scarring associated with it.”

The pathogenesis of acne is multifactorial, she continued, including a disruption of sebaceous gland activity, with overproduction and alteration of sebum and abnormal follicular keratinization. Acne also causes an imbalance of the skin microbiome, local inflammation, and activation of both innate and adaptive immunity.

“Many studies point to the fact that inflammation and immune system activation may actually be the primary event” of acne formation, said Kauvar, who is also a clinical professor of dermatology at New York University, New York City. “This persistent immune activation is also associated with scarring,” she noted. “So, are we off the mark in terms of trying to kill sebaceous glands? Should we be concentrating on anti-inflammatory approaches?” 

AviClear became the first 1726-nm laser cleared by the US Food and Drug Administration (FDA) for the treatment of mild to severe acne vulgaris in 2022, followed a few months later with the FDA clearance of another 1726-nm laser, the Accure Acne Laser System in November 2022. These lasers cause selective photothermolysis of sebaceous glands, but according to Kauvar, “access to these devices is somewhat limited at this time.”

What is available includes her go-to device, the pulsed dye laser (PDL), which has been widely studied and shown in a systematic review and meta-analysis of studies to be effective for acne. The PDL “targets dermal blood vessels facilitating inflammation, upregulates TGF-beta, and inhibits CD4+ T cell-mediated inflammation,” she said. “It can also treat PIH [post-inflammatory hyperpigmentation] and may be helpful in scar prevention.”

In an abstract presented at The American Society for Laser Medicine and Surgery (ASLMS) 2024 annual meeting, Kauvar and colleagues conducted a real-world study of PDL therapy in 15 adult women with recalcitrant acne who were maintained on their medical treatment regimen. Their mean age was 27 years, and they had skin types II-IV; they underwent four monthly PDL treatments with follow-up at 1 and 3 months. At each visit, the researchers took digital photographs and counted inflammatory acne lesions, non-inflammatory acne lesions, and post-inflammatory pigment alteration (PIPA) lesions.

The main outcomes of interest were the investigator global assessment (IGA) scores at the 1- and 3-month follow-up visits. Kauvar and colleagues observed a significant improvement in IGA scores at the 1- and 3-month follow-up visits (P < .05), with an average decrease of 1.8 and 1.6 points in the acne severity scale, respectively, from a baseline score of 3.4. By the 3-month follow-up visits, counts of inflammatory and non-inflammatory lesions decreased significantly (P < .05), and 61% of study participants showed a decrease in the PIPA count. No adverse events occurred. 

Kauvar disclosed that she has conducted research for Candela, Lumenis, and Sofwave, and is an adviser to Acclaro.

A version of this article first appeared on Medscape.com.

Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.

And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.

However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.

“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.

This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
 

How Did They Do It?

“Smuggle” may be a flip term, but it’s not inaccurate.

Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.

They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.

Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.

A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
 

Why Insulin?

Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.

“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.

In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.

“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.

There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.

There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.

“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.

While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
 

A version of this article first appeared on Medscape.com.

Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.

And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.

However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.

“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.

This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
 

How Did They Do It?

“Smuggle” may be a flip term, but it’s not inaccurate.

Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.

They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.

Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.

A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
 

Why Insulin?

Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.

“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.

In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.

“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.

There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.

There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.

“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.

While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
 

A version of this article first appeared on Medscape.com.

Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.

And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.

However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.

“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.

This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
 

How Did They Do It?

“Smuggle” may be a flip term, but it’s not inaccurate.

Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.

They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.

Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.

A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
 

Why Insulin?

Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.

“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.

In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.

“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.

There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.

There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.

“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.

While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
 

A version of this article first appeared on Medscape.com.

PHILADELPHIA — Pimavanserin (Nuplazid, Acadia) is noninferior to quetiapine in patients with Parkinson’s disease psychosis at 56 days, results from a phase 3 trial showed.

In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.

Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.

Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.

Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.

“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.

The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
 

Primary Outcome at 56 Days

The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.

Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.

The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).

The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
 

Secondary Endpoints and Safety

Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:

• SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
• SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
• Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
• Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)

Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.

Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
 

Delayed Onset of Action?

During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.

“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.

Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.

Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.

“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.

Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.

“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”

Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.

Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Pimavanserin (Nuplazid, Acadia) is noninferior to quetiapine in patients with Parkinson’s disease psychosis at 56 days, results from a phase 3 trial showed.

In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.

Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.

Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.

Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.

“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.

The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
 

Primary Outcome at 56 Days

The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.

Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.

The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).

The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
 

Secondary Endpoints and Safety

Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:

• SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
• SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
• Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
• Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)

Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.

Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
 

Delayed Onset of Action?

During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.

“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.

Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.

Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.

“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.

Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.

“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”

Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.

Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Pimavanserin (Nuplazid, Acadia) is noninferior to quetiapine in patients with Parkinson’s disease psychosis at 56 days, results from a phase 3 trial showed.

In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.

Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.

Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.

Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.

“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.

The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
 

Primary Outcome at 56 Days

The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.

Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.

The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).

The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
 

Secondary Endpoints and Safety

Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:

• SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
• SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
• Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
• Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)

Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.

Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
 

Delayed Onset of Action?

During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.

“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.

Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.

Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.

“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.

Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.

“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”

Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.

Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — It’s important for pediatricians not only to understand the causes and effects of climate change but also to know how to discuss this issue with families and make risk-based adjustments to their clinical practice based on the individual health and circumstances of each patient. That’s one of the key messages delivered at the annual meeting of the American Academy of Pediatrics (AAP) by Elizabeth C. Matsui, MD, MHS, professor of population health and pediatrics and director of the Center for Health and Environment Education and Research at the University of Texas at Austin Dell Medical School. 

“Even though climate change has been here and has been affecting health already for a while, it’s just really impossible to ignore right now,” she told attendees in a session focused on climate change impacts on allergies and asthma. “The challenge is connecting the dots between something that is much larger, or feels much larger, than the patient and the family that’s in front of you.” 

The reality, however, is that climate change is now impacting patients’ health on an individual level, and pediatricians have a responsibility to understand how that’s happening and to help their families prepare for it. 

“From the perspective of someone who went into medicine to practice and take care of the individual patient, I think it has been more difficult to connect those dots, and for the people in this room, it’s our job to connect those dots,” Matsui said. She also acknowledged that many of the solutions are frustratingly limited to the policy level and challenging to implement, “but it doesn’t mean that we can’t make a difference for the patients who are in front of us.” 

Charles Moon, MD, a pediatrician and Pediatric Environmental Health Fellow at the Children’s Environmental Health Center, Icahn School of Medicine at Mount Sinai, New York City, found the talk particularly helpful in providing information about both the broader issue and what it means on a local practice level. 

“The biggest takeaway is that more people and more pediatricians are tuning in to this issue and realizing the dangers,” Moon said. “It’s clear that a larger community is forming around this, and I think we are at the cusp where more and more people will be coming in. We are really focusing on taking all the data and trying to figure out solutions. I think the solutions orientation is the most important part.” 
 

Understanding the Big Picture

Matsui opened with a general discussion of the human causes of climate change and the effects on a global scale presently and in the future. For example, over the past 800,000 years, carbon dioxide levels have never been above 300 ppm, but they surpassed that threshold in 1911 and have reached 420 ppm today. The trapping of heat in Earth’s atmosphere caused by the increase in carbon dioxide and other greenhouse gases is leading to multiple phenomena that impact health, such as longer growing seasons; increased droughts, heat waves, and wildfire seasons; and higher temperatures. These changes, in turn, affect allergens and asthma.

Children are particularly vulnerable to climate change impacts because they have a higher risk for developing asthma, allergic disease, and infections, Matsui said. Childhood is a critical period for lung and immune development, and the Environmental Protection Agency’s 2023 Climate Change and Children’s Health and Well-Being report projects that an increase of 2° C in global warming will result in an additional 34,500 pediatric asthma cases and 228,000 allergic rhinitis cases per year, driven largely by predicted increases in ozone and 2.5-µm particulate matter. The report also forecasts an increase in 6240 asthma emergency department visits and 332 additional respiratory hospitalizations per year. 

“We know that these associations that we see between climate change exposures and poor respiratory health outcomes in kids are biologically plausible,” Matsui said. “They’re not just correlation without causation. A lot of the mechanisms for how air pollution, allergies, and other factors directly affect the lungs of the airway epithelium have been worked out.” 
 

An Increase in Allergens and Viral Infections

Pediatricians should prepare for anticipated growth in allergens and viral infections. The longer growing seasons mean that pollen seasons will also lengthen. Meanwhile, higher concentrations of carbon dioxide cause individual plants to produce more pollen. 

“As the winters get warmer, mice that might not be able to survive during the winter are surviving, and mice reproduce at a very rapid rate,” she said. “The increase in moisture means that dust mites, which absorb their water — they drink by absorbing humidity that’s in the air — will be present in higher concentrations, and their range will expand.”

Fungal and mold exposures are also increasing, not just outdoors but also indoors, “and there are all sorts of allergic and respiratory health consequences of fungal exposure,” Matsui said. As hurricanes and flooding increase, storm damage can also make indoor environments more conducive to fungal and mold growth. 

Extreme weather from climate change also affects infrastructure. “When there’s healthcare infrastructure disruption and other infrastructure disruption, it adds to the challenge,” she said. “It compounds all the other threat to health from climate change, so this overall problem of climate change and health is multidimensional and very complicated.”

Then there’s the impact of climate change on respiratory viruses, which are a major driver of asthma exacerbations, Matsui said. The greater variability in daytime temperatures affects environmental reservoirs, transmission patterns, geographical ranges, and seasonality of various respiratory pathogens. The prevalence of respiratory syncytial virus infections, for example, increases during humid periods. 

“This is coupled with the fact that the projected increases in air pollution increase susceptibility to respiratory virus infections,” Matsui said. “In fact, climate change and air pollution are inextricably linked.” 
 

Climate Change and Air Pollution

Climate disruption creates extreme weather patterns that then lead to worsening air quality due to high temperatures; heavier precipitation; and more forest fires, droughts, dust storms, thunderstorms, hurricanes, stagnation events, and other extreme weather. Matsui shared a map showing the substantial increase in days with stagnant air since 1973. During stagnation events, air pollution builds up in the atmosphere because of a stable air mass that remains over a region for several days, with low-level winds and no precipitation. 

The pollutants can then contribute to rising temperatures. Black carbon particulate matter released from the burning of forests and other biomass absorbs more solar radiation, further contributing to temperature increases. Data from the National Bureau of Economic Research has shown that the US made big strides in reducing air pollution from 2009 through 2016, but it began to reverse in 2016 as severe weather events picked up. 

Pediatricians need to be cognizant of the synergistic effect of these different impacts as well. “We oftentimes talk about these problems in a silo, so we may talk about air pollution and health effects, or allergens and health effects, or heat and health effects, but all of these interact with each other and further compound the health effects,” compared to just one of them in isolation, Matsui said.

For example, air pollution increases sensitivity to allergen exposure and increases reaction severity, which disrupts the immune tolerance to allergens. “Heat and air pollution also interact, and the combination of the two is more deadly than either one alone,” she said. 

Air pollution from wildfire smoke is also more toxic to the lungs than air pollution from other sources, so if there’s wildfire-based air pollution, the impact on respiratory hospitalizations is significantly greater. Even in places that would not otherwise be at risk for wildfires, the threat remains of air pollution from more distant fires, as New York City experienced from Canadian wildfires last year. 

“This is a problem that is not just isolated to the parts of the world where the wildfires are located,” Matsui said.

Moon, who practices in New York City, said he really appreciated Matsui’s perspectives and nuanced advice as a subspecialist “because it’s obvious that the way we deliver healthcare is going to have to change based on climate change.” He hopes to see more subspecialists from other pediatric areas getting involved in looking at climate impacts and providing nuanced advice about changing clinical care similar to the examples Matsui provided. 

Air pollution can also be deadly, as a landmark case in the United Kingdom revealed a few years ago when the court ruled that a child’s death from an asthma attack was directly due to air pollution. In addition to causing worse asthma symptoms and exacerbations, air pollution also adds to the risk of developing asthma and impedes lung growth, all of which disproportionately affects disadvantaged and minoritized communities, she said. 
 

Greater Impact on Disadvantaged Populations

Matsui called attention to the equity implications of climate change impacts on health. 

“If you have a community that does not have the infrastructure and access to resources, and that same community has a prevalence of asthma that is double that of their more advantaged and white counterparts, then the impacts of climate change are going to be amplified even more,” she said.

For example, a 2019 study found that the biggest predictor of the location of ragweed plants has to do with vacant lots and demolition of housing. Ragweed plants being more common in neighborhoods with vacant lots will disproportionately affect disadvantaged neighborhoods, she said. Another study found in Baltimore that mouse allergens — specifically urine — were a bigger cause of asthma in low-income children than were cockroach allergens. 

“It’s important to consider context,” including age, gender and social and behavioral context, she said. “We as pediatricians know that children are particularly vulnerable, and what happens to them has an effect across the lifespan.” 

Furthermore, pediatricians are aware that disadvantaged and minoritized communities lack infrastructure; often live in areas with greater air pollution; often have heat islands in their communities without protection, such as tree canopy; and may be at greater flooding risk. “Poverty is also associated with increased vulnerability” because of poorer housing and infrastructure, less education, less access to care, more preexisting health conditions and greater discrimination, she said.
 

Three Cornerstone Interventions

Interventions fall into three main buckets, Matsui said: mitigation, adaption, and resilience. 

“Mitigation means reducing greenhouse gas and air pollution production and trying to enhance sinks for greenhouse gases,” she said. Mitigation strategies primarily occur at the policy level, with improved regulation, treaties, and market-based approaches, such as carbon tax and cap and trade. 

Adaptation includes actions that lessen the impact on health and environment, such as infrastructure changes and implementation of air conditioning. Examples of climate change adaptation strategies also mostly come from policy but largely at state and local levels, where individual pediatricians have a greater voice and influence. These can include changes in urban planning to address heat islands, flooding risk, and public transportation’s contribution to air pollution and climate change. It can also include changes in housing regulation and policy and investments in healthcare, such as expanded Medicaid and health insurance and investing in disaster planning and readiness. 

“Resilience is a more holistic concept,” Matsui said, “which advocates for system-wide, multilevel changes and involves a range of strategies to enhance social, human, natural, physical, and financial capacities.”
 

What Pediatricians Can Do

Pediatricians have an important role to play when it comes to climate change and health impacts. 

“The first step is sort of understanding the complexity of climate change in terms of its potential health effects, but also being prepared to talk with our patients and their families about it,” Matsui said. “The second step is advocacy.” She drew attention to the February policy statement in Pediatrics that discusses precisely the ways in which pediatricians can leverage their expertise and credibility. 

“Pediatricians are ideal advocates with whom to partner and uplift youth and community voices working to advance zero-carbon energy policy and climate justice,” she said. “There are many opportunities to advocate for climate solution policies at the local, state, national, and even international level.” 

These roles can include educating elected officials and health insurance entities about the risks that climate change poses to allergies, asthma, and child health more broadly, as well as the benefits of local solutions, including improved air quality, tree canopy, and green space. “There are lots of opportunities to engage with the community, including speaking at public hearings, serving as an expert testimony, and writing letters to the editor,” she said. 

The impact of these efforts can be further maximized by working with other healthcare professionals. Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program, noted during Q&A that every AAP chapter in the country has climate advocates. She added that the AAP is the first medical board to have climate modules in their maintenance of certification specifically designed to incorporate climate change education into well visits.
 

Adjusting Clinical Care

Meanwhile, in patient care, Matsui acknowledged it can be frustrating to think about what a massive impact climate has and simultaneously challenging to engage families in discussions about it. However, a wide range of resources are available that can be provided to patients. 

“For a patient in front of you, being informed and prepared to talk about it is the first step to being able to assess their climate change risk and provide tailored guidance,” she said. Tailored guidance takes into account the child’s specific health situation and the risks they’re most likely to encounter, such as wildfire smoke, air pollution, longer pollen seasons, environmental allergens, or disruption of infrastructure. 

“If I am seeing a patient with asthma who is allergic to a particular pollen, I can anticipate that pollen may be present in higher levels of the future, and that the season for that pollen may be longer,” Matsui said. “So if I’m thinking about allergen immunotherapy for that patient, future risk may be something that would push the conversation and the shared decision-making” from possible consideration to more serious consideration, depending on the child’s age. 

“Another example is a patient with asthma, thinking about wildfire risk and having them prepared, because we know from data that wildfire air pollution is going to be worse for that child than pollution from other sources, and there are ways for them to be prepared,” Matsui said. For instance, having an HVAC system with a high-grade air filter (at least a MERV 13) will filter the air better if a wildfire causes smoke to descend over an area. Portable, less expensive HEPA filters are also an option if a family cannot upgrade their system, and wearing an N95 or N95-equivalent mask can also reduce the impact of high air pollution levels. 

An example of thinking about the impact of potential infrastructure disruption could be ensuring patients have enough of all their medications if they’re close to running out. “It’s important for them to always have think about their medications and get those refills ahead of a storm,” she said.
 

Additional Resources 

Understanding that pediatricians may not have time to discuss all these issues or have broader conversations about climate change during visits, Matsui highlighted the AAP website of resources on climate change. In addition to resources for pediatricians, such as a basic fact sheet about climate change impacts on children’s health and the technical report that informed the policy statement, the site has multiple resources for families:

• Climate Change Impact: Safeguarding Your Family’s Health and Well-being (video), How to Talk With Children About Climate Change, Climate Change & Children’s Health: AAP Policy Explained, Climate Checkup for Children’s Health: Little Changes With Big Impact, How Climate Change Can Make Children Sick: What Parents Need to Know, Climate Change & Wildfires: Why Kids Are Most at Risk, Climate Change, Extreme Weather & Children: What Families Need to Know, Extreme Heat & Air Pollution: Health Effects on Babies & Pregnant People, and

The following resources can also be helpful to pediatricians and/or families:

• Ready.gov, AirNow, Patient Exposure and the Air Quality Index, Protecting Vulnerable Patient Populations from Climate Hazards: A Referral Guide for Health Professionals from the US Department of Health and Human Services, Low Income Home Energy Assistance Program (LIHEAP), Weatherization Assistance Program, and the Disaster Supplemental Nutrition Assistance Program (D-SNAP)

In some states, Medicaid will provide or cover the cost of air conditioning and/or air filters.

The presentation did not involve external funding. Drs. Matsui and Moon had no disclosures. 
 

A version of this article first appeared on Medscape.com.

ORLANDO — It’s important for pediatricians not only to understand the causes and effects of climate change but also to know how to discuss this issue with families and make risk-based adjustments to their clinical practice based on the individual health and circumstances of each patient. That’s one of the key messages delivered at the annual meeting of the American Academy of Pediatrics (AAP) by Elizabeth C. Matsui, MD, MHS, professor of population health and pediatrics and director of the Center for Health and Environment Education and Research at the University of Texas at Austin Dell Medical School. 

“Even though climate change has been here and has been affecting health already for a while, it’s just really impossible to ignore right now,” she told attendees in a session focused on climate change impacts on allergies and asthma. “The challenge is connecting the dots between something that is much larger, or feels much larger, than the patient and the family that’s in front of you.” 

The reality, however, is that climate change is now impacting patients’ health on an individual level, and pediatricians have a responsibility to understand how that’s happening and to help their families prepare for it. 

“From the perspective of someone who went into medicine to practice and take care of the individual patient, I think it has been more difficult to connect those dots, and for the people in this room, it’s our job to connect those dots,” Matsui said. She also acknowledged that many of the solutions are frustratingly limited to the policy level and challenging to implement, “but it doesn’t mean that we can’t make a difference for the patients who are in front of us.” 

Charles Moon, MD, a pediatrician and Pediatric Environmental Health Fellow at the Children’s Environmental Health Center, Icahn School of Medicine at Mount Sinai, New York City, found the talk particularly helpful in providing information about both the broader issue and what it means on a local practice level. 

“The biggest takeaway is that more people and more pediatricians are tuning in to this issue and realizing the dangers,” Moon said. “It’s clear that a larger community is forming around this, and I think we are at the cusp where more and more people will be coming in. We are really focusing on taking all the data and trying to figure out solutions. I think the solutions orientation is the most important part.” 
 

Understanding the Big Picture

Matsui opened with a general discussion of the human causes of climate change and the effects on a global scale presently and in the future. For example, over the past 800,000 years, carbon dioxide levels have never been above 300 ppm, but they surpassed that threshold in 1911 and have reached 420 ppm today. The trapping of heat in Earth’s atmosphere caused by the increase in carbon dioxide and other greenhouse gases is leading to multiple phenomena that impact health, such as longer growing seasons; increased droughts, heat waves, and wildfire seasons; and higher temperatures. These changes, in turn, affect allergens and asthma.

Children are particularly vulnerable to climate change impacts because they have a higher risk for developing asthma, allergic disease, and infections, Matsui said. Childhood is a critical period for lung and immune development, and the Environmental Protection Agency’s 2023 Climate Change and Children’s Health and Well-Being report projects that an increase of 2° C in global warming will result in an additional 34,500 pediatric asthma cases and 228,000 allergic rhinitis cases per year, driven largely by predicted increases in ozone and 2.5-µm particulate matter. The report also forecasts an increase in 6240 asthma emergency department visits and 332 additional respiratory hospitalizations per year. 

“We know that these associations that we see between climate change exposures and poor respiratory health outcomes in kids are biologically plausible,” Matsui said. “They’re not just correlation without causation. A lot of the mechanisms for how air pollution, allergies, and other factors directly affect the lungs of the airway epithelium have been worked out.” 
 

An Increase in Allergens and Viral Infections

Pediatricians should prepare for anticipated growth in allergens and viral infections. The longer growing seasons mean that pollen seasons will also lengthen. Meanwhile, higher concentrations of carbon dioxide cause individual plants to produce more pollen. 

“As the winters get warmer, mice that might not be able to survive during the winter are surviving, and mice reproduce at a very rapid rate,” she said. “The increase in moisture means that dust mites, which absorb their water — they drink by absorbing humidity that’s in the air — will be present in higher concentrations, and their range will expand.”

Fungal and mold exposures are also increasing, not just outdoors but also indoors, “and there are all sorts of allergic and respiratory health consequences of fungal exposure,” Matsui said. As hurricanes and flooding increase, storm damage can also make indoor environments more conducive to fungal and mold growth. 

Extreme weather from climate change also affects infrastructure. “When there’s healthcare infrastructure disruption and other infrastructure disruption, it adds to the challenge,” she said. “It compounds all the other threat to health from climate change, so this overall problem of climate change and health is multidimensional and very complicated.”

Then there’s the impact of climate change on respiratory viruses, which are a major driver of asthma exacerbations, Matsui said. The greater variability in daytime temperatures affects environmental reservoirs, transmission patterns, geographical ranges, and seasonality of various respiratory pathogens. The prevalence of respiratory syncytial virus infections, for example, increases during humid periods. 

“This is coupled with the fact that the projected increases in air pollution increase susceptibility to respiratory virus infections,” Matsui said. “In fact, climate change and air pollution are inextricably linked.” 
 

Climate Change and Air Pollution

Climate disruption creates extreme weather patterns that then lead to worsening air quality due to high temperatures; heavier precipitation; and more forest fires, droughts, dust storms, thunderstorms, hurricanes, stagnation events, and other extreme weather. Matsui shared a map showing the substantial increase in days with stagnant air since 1973. During stagnation events, air pollution builds up in the atmosphere because of a stable air mass that remains over a region for several days, with low-level winds and no precipitation. 

The pollutants can then contribute to rising temperatures. Black carbon particulate matter released from the burning of forests and other biomass absorbs more solar radiation, further contributing to temperature increases. Data from the National Bureau of Economic Research has shown that the US made big strides in reducing air pollution from 2009 through 2016, but it began to reverse in 2016 as severe weather events picked up. 

Pediatricians need to be cognizant of the synergistic effect of these different impacts as well. “We oftentimes talk about these problems in a silo, so we may talk about air pollution and health effects, or allergens and health effects, or heat and health effects, but all of these interact with each other and further compound the health effects,” compared to just one of them in isolation, Matsui said.

For example, air pollution increases sensitivity to allergen exposure and increases reaction severity, which disrupts the immune tolerance to allergens. “Heat and air pollution also interact, and the combination of the two is more deadly than either one alone,” she said. 

Air pollution from wildfire smoke is also more toxic to the lungs than air pollution from other sources, so if there’s wildfire-based air pollution, the impact on respiratory hospitalizations is significantly greater. Even in places that would not otherwise be at risk for wildfires, the threat remains of air pollution from more distant fires, as New York City experienced from Canadian wildfires last year. 

“This is a problem that is not just isolated to the parts of the world where the wildfires are located,” Matsui said.

Moon, who practices in New York City, said he really appreciated Matsui’s perspectives and nuanced advice as a subspecialist “because it’s obvious that the way we deliver healthcare is going to have to change based on climate change.” He hopes to see more subspecialists from other pediatric areas getting involved in looking at climate impacts and providing nuanced advice about changing clinical care similar to the examples Matsui provided. 

Air pollution can also be deadly, as a landmark case in the United Kingdom revealed a few years ago when the court ruled that a child’s death from an asthma attack was directly due to air pollution. In addition to causing worse asthma symptoms and exacerbations, air pollution also adds to the risk of developing asthma and impedes lung growth, all of which disproportionately affects disadvantaged and minoritized communities, she said. 
 

Greater Impact on Disadvantaged Populations

Matsui called attention to the equity implications of climate change impacts on health. 

“If you have a community that does not have the infrastructure and access to resources, and that same community has a prevalence of asthma that is double that of their more advantaged and white counterparts, then the impacts of climate change are going to be amplified even more,” she said.

For example, a 2019 study found that the biggest predictor of the location of ragweed plants has to do with vacant lots and demolition of housing. Ragweed plants being more common in neighborhoods with vacant lots will disproportionately affect disadvantaged neighborhoods, she said. Another study found in Baltimore that mouse allergens — specifically urine — were a bigger cause of asthma in low-income children than were cockroach allergens. 

“It’s important to consider context,” including age, gender and social and behavioral context, she said. “We as pediatricians know that children are particularly vulnerable, and what happens to them has an effect across the lifespan.” 

Furthermore, pediatricians are aware that disadvantaged and minoritized communities lack infrastructure; often live in areas with greater air pollution; often have heat islands in their communities without protection, such as tree canopy; and may be at greater flooding risk. “Poverty is also associated with increased vulnerability” because of poorer housing and infrastructure, less education, less access to care, more preexisting health conditions and greater discrimination, she said.
 

Three Cornerstone Interventions

Interventions fall into three main buckets, Matsui said: mitigation, adaption, and resilience. 

“Mitigation means reducing greenhouse gas and air pollution production and trying to enhance sinks for greenhouse gases,” she said. Mitigation strategies primarily occur at the policy level, with improved regulation, treaties, and market-based approaches, such as carbon tax and cap and trade. 

Adaptation includes actions that lessen the impact on health and environment, such as infrastructure changes and implementation of air conditioning. Examples of climate change adaptation strategies also mostly come from policy but largely at state and local levels, where individual pediatricians have a greater voice and influence. These can include changes in urban planning to address heat islands, flooding risk, and public transportation’s contribution to air pollution and climate change. It can also include changes in housing regulation and policy and investments in healthcare, such as expanded Medicaid and health insurance and investing in disaster planning and readiness. 

“Resilience is a more holistic concept,” Matsui said, “which advocates for system-wide, multilevel changes and involves a range of strategies to enhance social, human, natural, physical, and financial capacities.”
 

What Pediatricians Can Do

Pediatricians have an important role to play when it comes to climate change and health impacts. 

“The first step is sort of understanding the complexity of climate change in terms of its potential health effects, but also being prepared to talk with our patients and their families about it,” Matsui said. “The second step is advocacy.” She drew attention to the February policy statement in Pediatrics that discusses precisely the ways in which pediatricians can leverage their expertise and credibility. 

“Pediatricians are ideal advocates with whom to partner and uplift youth and community voices working to advance zero-carbon energy policy and climate justice,” she said. “There are many opportunities to advocate for climate solution policies at the local, state, national, and even international level.” 

These roles can include educating elected officials and health insurance entities about the risks that climate change poses to allergies, asthma, and child health more broadly, as well as the benefits of local solutions, including improved air quality, tree canopy, and green space. “There are lots of opportunities to engage with the community, including speaking at public hearings, serving as an expert testimony, and writing letters to the editor,” she said. 

The impact of these efforts can be further maximized by working with other healthcare professionals. Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program, noted during Q&A that every AAP chapter in the country has climate advocates. She added that the AAP is the first medical board to have climate modules in their maintenance of certification specifically designed to incorporate climate change education into well visits.
 

Adjusting Clinical Care

Meanwhile, in patient care, Matsui acknowledged it can be frustrating to think about what a massive impact climate has and simultaneously challenging to engage families in discussions about it. However, a wide range of resources are available that can be provided to patients. 

“For a patient in front of you, being informed and prepared to talk about it is the first step to being able to assess their climate change risk and provide tailored guidance,” she said. Tailored guidance takes into account the child’s specific health situation and the risks they’re most likely to encounter, such as wildfire smoke, air pollution, longer pollen seasons, environmental allergens, or disruption of infrastructure. 

“If I am seeing a patient with asthma who is allergic to a particular pollen, I can anticipate that pollen may be present in higher levels of the future, and that the season for that pollen may be longer,” Matsui said. “So if I’m thinking about allergen immunotherapy for that patient, future risk may be something that would push the conversation and the shared decision-making” from possible consideration to more serious consideration, depending on the child’s age. 

“Another example is a patient with asthma, thinking about wildfire risk and having them prepared, because we know from data that wildfire air pollution is going to be worse for that child than pollution from other sources, and there are ways for them to be prepared,” Matsui said. For instance, having an HVAC system with a high-grade air filter (at least a MERV 13) will filter the air better if a wildfire causes smoke to descend over an area. Portable, less expensive HEPA filters are also an option if a family cannot upgrade their system, and wearing an N95 or N95-equivalent mask can also reduce the impact of high air pollution levels. 

An example of thinking about the impact of potential infrastructure disruption could be ensuring patients have enough of all their medications if they’re close to running out. “It’s important for them to always have think about their medications and get those refills ahead of a storm,” she said.
 

Additional Resources 

Understanding that pediatricians may not have time to discuss all these issues or have broader conversations about climate change during visits, Matsui highlighted the AAP website of resources on climate change. In addition to resources for pediatricians, such as a basic fact sheet about climate change impacts on children’s health and the technical report that informed the policy statement, the site has multiple resources for families:

• Climate Change Impact: Safeguarding Your Family’s Health and Well-being (video), How to Talk With Children About Climate Change, Climate Change & Children’s Health: AAP Policy Explained, Climate Checkup for Children’s Health: Little Changes With Big Impact, How Climate Change Can Make Children Sick: What Parents Need to Know, Climate Change & Wildfires: Why Kids Are Most at Risk, Climate Change, Extreme Weather & Children: What Families Need to Know, Extreme Heat & Air Pollution: Health Effects on Babies & Pregnant People, and

The following resources can also be helpful to pediatricians and/or families:

• Ready.gov, AirNow, Patient Exposure and the Air Quality Index, Protecting Vulnerable Patient Populations from Climate Hazards: A Referral Guide for Health Professionals from the US Department of Health and Human Services, Low Income Home Energy Assistance Program (LIHEAP), Weatherization Assistance Program, and the Disaster Supplemental Nutrition Assistance Program (D-SNAP)

In some states, Medicaid will provide or cover the cost of air conditioning and/or air filters.

The presentation did not involve external funding. Drs. Matsui and Moon had no disclosures. 
 

A version of this article first appeared on Medscape.com.

ORLANDO — It’s important for pediatricians not only to understand the causes and effects of climate change but also to know how to discuss this issue with families and make risk-based adjustments to their clinical practice based on the individual health and circumstances of each patient. That’s one of the key messages delivered at the annual meeting of the American Academy of Pediatrics (AAP) by Elizabeth C. Matsui, MD, MHS, professor of population health and pediatrics and director of the Center for Health and Environment Education and Research at the University of Texas at Austin Dell Medical School. 

“Even though climate change has been here and has been affecting health already for a while, it’s just really impossible to ignore right now,” she told attendees in a session focused on climate change impacts on allergies and asthma. “The challenge is connecting the dots between something that is much larger, or feels much larger, than the patient and the family that’s in front of you.” 

The reality, however, is that climate change is now impacting patients’ health on an individual level, and pediatricians have a responsibility to understand how that’s happening and to help their families prepare for it. 

“From the perspective of someone who went into medicine to practice and take care of the individual patient, I think it has been more difficult to connect those dots, and for the people in this room, it’s our job to connect those dots,” Matsui said. She also acknowledged that many of the solutions are frustratingly limited to the policy level and challenging to implement, “but it doesn’t mean that we can’t make a difference for the patients who are in front of us.” 

Charles Moon, MD, a pediatrician and Pediatric Environmental Health Fellow at the Children’s Environmental Health Center, Icahn School of Medicine at Mount Sinai, New York City, found the talk particularly helpful in providing information about both the broader issue and what it means on a local practice level. 

“The biggest takeaway is that more people and more pediatricians are tuning in to this issue and realizing the dangers,” Moon said. “It’s clear that a larger community is forming around this, and I think we are at the cusp where more and more people will be coming in. We are really focusing on taking all the data and trying to figure out solutions. I think the solutions orientation is the most important part.” 
 

Understanding the Big Picture

Matsui opened with a general discussion of the human causes of climate change and the effects on a global scale presently and in the future. For example, over the past 800,000 years, carbon dioxide levels have never been above 300 ppm, but they surpassed that threshold in 1911 and have reached 420 ppm today. The trapping of heat in Earth’s atmosphere caused by the increase in carbon dioxide and other greenhouse gases is leading to multiple phenomena that impact health, such as longer growing seasons; increased droughts, heat waves, and wildfire seasons; and higher temperatures. These changes, in turn, affect allergens and asthma.

Children are particularly vulnerable to climate change impacts because they have a higher risk for developing asthma, allergic disease, and infections, Matsui said. Childhood is a critical period for lung and immune development, and the Environmental Protection Agency’s 2023 Climate Change and Children’s Health and Well-Being report projects that an increase of 2° C in global warming will result in an additional 34,500 pediatric asthma cases and 228,000 allergic rhinitis cases per year, driven largely by predicted increases in ozone and 2.5-µm particulate matter. The report also forecasts an increase in 6240 asthma emergency department visits and 332 additional respiratory hospitalizations per year. 

“We know that these associations that we see between climate change exposures and poor respiratory health outcomes in kids are biologically plausible,” Matsui said. “They’re not just correlation without causation. A lot of the mechanisms for how air pollution, allergies, and other factors directly affect the lungs of the airway epithelium have been worked out.” 
 

An Increase in Allergens and Viral Infections

Pediatricians should prepare for anticipated growth in allergens and viral infections. The longer growing seasons mean that pollen seasons will also lengthen. Meanwhile, higher concentrations of carbon dioxide cause individual plants to produce more pollen. 

“As the winters get warmer, mice that might not be able to survive during the winter are surviving, and mice reproduce at a very rapid rate,” she said. “The increase in moisture means that dust mites, which absorb their water — they drink by absorbing humidity that’s in the air — will be present in higher concentrations, and their range will expand.”

Fungal and mold exposures are also increasing, not just outdoors but also indoors, “and there are all sorts of allergic and respiratory health consequences of fungal exposure,” Matsui said. As hurricanes and flooding increase, storm damage can also make indoor environments more conducive to fungal and mold growth. 

Extreme weather from climate change also affects infrastructure. “When there’s healthcare infrastructure disruption and other infrastructure disruption, it adds to the challenge,” she said. “It compounds all the other threat to health from climate change, so this overall problem of climate change and health is multidimensional and very complicated.”

Then there’s the impact of climate change on respiratory viruses, which are a major driver of asthma exacerbations, Matsui said. The greater variability in daytime temperatures affects environmental reservoirs, transmission patterns, geographical ranges, and seasonality of various respiratory pathogens. The prevalence of respiratory syncytial virus infections, for example, increases during humid periods. 

“This is coupled with the fact that the projected increases in air pollution increase susceptibility to respiratory virus infections,” Matsui said. “In fact, climate change and air pollution are inextricably linked.” 
 

Climate Change and Air Pollution

Climate disruption creates extreme weather patterns that then lead to worsening air quality due to high temperatures; heavier precipitation; and more forest fires, droughts, dust storms, thunderstorms, hurricanes, stagnation events, and other extreme weather. Matsui shared a map showing the substantial increase in days with stagnant air since 1973. During stagnation events, air pollution builds up in the atmosphere because of a stable air mass that remains over a region for several days, with low-level winds and no precipitation. 

The pollutants can then contribute to rising temperatures. Black carbon particulate matter released from the burning of forests and other biomass absorbs more solar radiation, further contributing to temperature increases. Data from the National Bureau of Economic Research has shown that the US made big strides in reducing air pollution from 2009 through 2016, but it began to reverse in 2016 as severe weather events picked up. 

Pediatricians need to be cognizant of the synergistic effect of these different impacts as well. “We oftentimes talk about these problems in a silo, so we may talk about air pollution and health effects, or allergens and health effects, or heat and health effects, but all of these interact with each other and further compound the health effects,” compared to just one of them in isolation, Matsui said.

For example, air pollution increases sensitivity to allergen exposure and increases reaction severity, which disrupts the immune tolerance to allergens. “Heat and air pollution also interact, and the combination of the two is more deadly than either one alone,” she said. 

Air pollution from wildfire smoke is also more toxic to the lungs than air pollution from other sources, so if there’s wildfire-based air pollution, the impact on respiratory hospitalizations is significantly greater. Even in places that would not otherwise be at risk for wildfires, the threat remains of air pollution from more distant fires, as New York City experienced from Canadian wildfires last year. 

“This is a problem that is not just isolated to the parts of the world where the wildfires are located,” Matsui said.

Moon, who practices in New York City, said he really appreciated Matsui’s perspectives and nuanced advice as a subspecialist “because it’s obvious that the way we deliver healthcare is going to have to change based on climate change.” He hopes to see more subspecialists from other pediatric areas getting involved in looking at climate impacts and providing nuanced advice about changing clinical care similar to the examples Matsui provided. 

Air pollution can also be deadly, as a landmark case in the United Kingdom revealed a few years ago when the court ruled that a child’s death from an asthma attack was directly due to air pollution. In addition to causing worse asthma symptoms and exacerbations, air pollution also adds to the risk of developing asthma and impedes lung growth, all of which disproportionately affects disadvantaged and minoritized communities, she said. 
 

Greater Impact on Disadvantaged Populations

Matsui called attention to the equity implications of climate change impacts on health. 

“If you have a community that does not have the infrastructure and access to resources, and that same community has a prevalence of asthma that is double that of their more advantaged and white counterparts, then the impacts of climate change are going to be amplified even more,” she said.

For example, a 2019 study found that the biggest predictor of the location of ragweed plants has to do with vacant lots and demolition of housing. Ragweed plants being more common in neighborhoods with vacant lots will disproportionately affect disadvantaged neighborhoods, she said. Another study found in Baltimore that mouse allergens — specifically urine — were a bigger cause of asthma in low-income children than were cockroach allergens. 

“It’s important to consider context,” including age, gender and social and behavioral context, she said. “We as pediatricians know that children are particularly vulnerable, and what happens to them has an effect across the lifespan.” 

Furthermore, pediatricians are aware that disadvantaged and minoritized communities lack infrastructure; often live in areas with greater air pollution; often have heat islands in their communities without protection, such as tree canopy; and may be at greater flooding risk. “Poverty is also associated with increased vulnerability” because of poorer housing and infrastructure, less education, less access to care, more preexisting health conditions and greater discrimination, she said.
 

Three Cornerstone Interventions

Interventions fall into three main buckets, Matsui said: mitigation, adaption, and resilience. 

“Mitigation means reducing greenhouse gas and air pollution production and trying to enhance sinks for greenhouse gases,” she said. Mitigation strategies primarily occur at the policy level, with improved regulation, treaties, and market-based approaches, such as carbon tax and cap and trade. 

Adaptation includes actions that lessen the impact on health and environment, such as infrastructure changes and implementation of air conditioning. Examples of climate change adaptation strategies also mostly come from policy but largely at state and local levels, where individual pediatricians have a greater voice and influence. These can include changes in urban planning to address heat islands, flooding risk, and public transportation’s contribution to air pollution and climate change. It can also include changes in housing regulation and policy and investments in healthcare, such as expanded Medicaid and health insurance and investing in disaster planning and readiness. 

“Resilience is a more holistic concept,” Matsui said, “which advocates for system-wide, multilevel changes and involves a range of strategies to enhance social, human, natural, physical, and financial capacities.”
 

What Pediatricians Can Do

Pediatricians have an important role to play when it comes to climate change and health impacts. 

“The first step is sort of understanding the complexity of climate change in terms of its potential health effects, but also being prepared to talk with our patients and their families about it,” Matsui said. “The second step is advocacy.” She drew attention to the February policy statement in Pediatrics that discusses precisely the ways in which pediatricians can leverage their expertise and credibility. 

“Pediatricians are ideal advocates with whom to partner and uplift youth and community voices working to advance zero-carbon energy policy and climate justice,” she said. “There are many opportunities to advocate for climate solution policies at the local, state, national, and even international level.” 

These roles can include educating elected officials and health insurance entities about the risks that climate change poses to allergies, asthma, and child health more broadly, as well as the benefits of local solutions, including improved air quality, tree canopy, and green space. “There are lots of opportunities to engage with the community, including speaking at public hearings, serving as an expert testimony, and writing letters to the editor,” she said. 

The impact of these efforts can be further maximized by working with other healthcare professionals. Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program, noted during Q&A that every AAP chapter in the country has climate advocates. She added that the AAP is the first medical board to have climate modules in their maintenance of certification specifically designed to incorporate climate change education into well visits.
 

Adjusting Clinical Care

Meanwhile, in patient care, Matsui acknowledged it can be frustrating to think about what a massive impact climate has and simultaneously challenging to engage families in discussions about it. However, a wide range of resources are available that can be provided to patients. 

“For a patient in front of you, being informed and prepared to talk about it is the first step to being able to assess their climate change risk and provide tailored guidance,” she said. Tailored guidance takes into account the child’s specific health situation and the risks they’re most likely to encounter, such as wildfire smoke, air pollution, longer pollen seasons, environmental allergens, or disruption of infrastructure. 

“If I am seeing a patient with asthma who is allergic to a particular pollen, I can anticipate that pollen may be present in higher levels of the future, and that the season for that pollen may be longer,” Matsui said. “So if I’m thinking about allergen immunotherapy for that patient, future risk may be something that would push the conversation and the shared decision-making” from possible consideration to more serious consideration, depending on the child’s age. 

“Another example is a patient with asthma, thinking about wildfire risk and having them prepared, because we know from data that wildfire air pollution is going to be worse for that child than pollution from other sources, and there are ways for them to be prepared,” Matsui said. For instance, having an HVAC system with a high-grade air filter (at least a MERV 13) will filter the air better if a wildfire causes smoke to descend over an area. Portable, less expensive HEPA filters are also an option if a family cannot upgrade their system, and wearing an N95 or N95-equivalent mask can also reduce the impact of high air pollution levels. 

An example of thinking about the impact of potential infrastructure disruption could be ensuring patients have enough of all their medications if they’re close to running out. “It’s important for them to always have think about their medications and get those refills ahead of a storm,” she said.
 

Additional Resources 

Understanding that pediatricians may not have time to discuss all these issues or have broader conversations about climate change during visits, Matsui highlighted the AAP website of resources on climate change. In addition to resources for pediatricians, such as a basic fact sheet about climate change impacts on children’s health and the technical report that informed the policy statement, the site has multiple resources for families:

• Climate Change Impact: Safeguarding Your Family’s Health and Well-being (video), How to Talk With Children About Climate Change, Climate Change & Children’s Health: AAP Policy Explained, Climate Checkup for Children’s Health: Little Changes With Big Impact, How Climate Change Can Make Children Sick: What Parents Need to Know, Climate Change & Wildfires: Why Kids Are Most at Risk, Climate Change, Extreme Weather & Children: What Families Need to Know, Extreme Heat & Air Pollution: Health Effects on Babies & Pregnant People, and

The following resources can also be helpful to pediatricians and/or families:

• Ready.gov, AirNow, Patient Exposure and the Air Quality Index, Protecting Vulnerable Patient Populations from Climate Hazards: A Referral Guide for Health Professionals from the US Department of Health and Human Services, Low Income Home Energy Assistance Program (LIHEAP), Weatherization Assistance Program, and the Disaster Supplemental Nutrition Assistance Program (D-SNAP)

In some states, Medicaid will provide or cover the cost of air conditioning and/or air filters.

The presentation did not involve external funding. Drs. Matsui and Moon had no disclosures. 
 

A version of this article first appeared on Medscape.com.

ORLANDO — More than half of youth improved after receiving a dose of naloxone by emergency medical services (EMS) after an emergency dispatch call, according to research presented at the American Academy of Pediatrics 2024 National Conference.

“Emergency responders or EMS are often the first to arrive to an opioid poisoning, and they’re often the first to give naloxone, a potentially lifesaving medication,” said Christopher E. Gaw, MD, MPH, MBE, assistant professor of pediatrics at The Ohio State University College of Medicine and an emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

Ohio State University

“Our study highlights and underscores its safety of use in the prehospital setting, and this is also supported by other data,” Gaw said. “Efforts to support public distribution and education on naloxone can really help each and every one of us as individual citizens prevent pediatric harm from the opioid crisis.”

Additional research at the meeting showed that teens’ knowledge, attitudes, and confidence about recognizing overdoses and assisting with naloxone administration improved following a peer-to-peer training program, suggesting that teens can play an important role in reducing youth mortality from overdoses.

An average of 22 American teens died from overdose every week in 2022, and as counterfeit pill use has increased among youth, research has found that fentanyl was detected in 93% of overdose deaths with counterfeit pills, according to Talia Puzantian, PharmD, BCPP, of the Keck Graduate Institute School of Pharmacy, Claremont, California, who led the study on peer education. Yet a recent survey had found that less than a third of teens (30%) knew what naloxone was, and only 14% knew how to administer it.

“Ensuring that adolescents have easy and confidential access to naloxone is important and can save lives,” said Taylor Nichols, MD, assistant clinical professor at the University of California San Francisco and an emergency medicine and addiction medicine–certified physician. “I have had teen patients who have told me that they have had to use naloxone obtained from our clinic on friends when they have accidentally overdosed.”

University of California

EMS Naloxone Administration to Youth

EMS clinicians are often the first healthcare providers to respond to an opioid overdose or poisoning event, and evidence-based guidelines for EMS naloxone administration were developed in 2019 to support this intervention. Gaw’s team investigated the frequency and demographics of pediatric administration of naloxone.

They analyzed data from the National Emergency Medical Services Information System on EMS activations for administration of at least one dose of naloxone during 2022 to those aged 0-17. There were 6215 EMS pediatric administrations of naloxone that year, and in the vast majority of cases (82%), the patient had not received a naloxone injection prior to EMS’s arrival.

Most patients (79%) were aged 13-17 years, but 10% were in the 6-12 age group. The remaining patients included 6% infants younger than 1 year and 4% aged 6-12 years. Just over half were for males (55%), and most were dispatched to a home or residential setting (61%). One in five incidents (22%) occurred at a non-healthcare business, 9% on a street or highway, and the rest at a healthcare facility or another location.

Most of the incidents occurred in urban areas (86%), followed by rural (7%), suburban (6%), and wilderness (1.4%). More occurred in the US South (42%) than in the West (29%), Midwest (22%), or Northeast (7.5%).

A key takeaway of those demographic findings is that ingestions and accidental poisonings with opioids can occur in children of any age, Nichols said. “Every single home that has any opioids in the home should absolutely have naloxone immediately available as well,” he said. “Every single person who is prescribed opioids should also have naloxone available and accessible and to be sure that the naloxone is not expired or otherwise tampered with and update that every few years.” He noted that Narcan expiration was recently extended from 3 years to 4 years by the US Food and Drug Administration (FDA).

“I always advise that people who have opioid medications keep them stored safely and securely,” Nichols said. “However, I also acknowledge that even perfect systems fail and that people make mistakes and may accidentally leave medication out, within reach, or otherwise unsecured. If that happens, and someone were to intentionally or unintentionally get into that medication and potentially overdose as a result, we want to have that reversal medication immediately available to reverse the overdose.”

In nearly all cases (91%), EMS provided advanced life support, with only 7.5% patients receiving basic life support and 1.5% receiving specialty critical care. Just under a third (29%) of the dispatch calls were for “overdose/poisoning/ingestion.” Other dispatch calls included “unconscious/fainting/near-fainting” (21%) or “cardiac arrest/death” (17%), but the frequency of each dispatch label varied by age groups.

For example, 38% of calls for infants were for cardiac arrest, compared with 15% of calls for older teens and 18% of calls for 6-12 year olds. An overdose/poisoning dispatch was meanwhile more common for teens (32%) than for infants (13%), younger children (23%), and older children/tweens (18%). Other dispatch complaints included “sick person/person down/unknown problem” (12%) and “breathing problem” (5%).

A possible reason for these variations is that “an overdose might be mistaken for another medical emergency, or vice versa, because opioid poisonings can be challenging to recognize, especially in young children and in the pediatric population,” Gaw said. “Both the public and emergency responders should maintain a high level of suspicion” of possible overdose for children with the signs or symptoms of it, such as low breathing, unresponsiveness, or small pupils.

In most cases (87%), the patient was not in cardiac arrest, though the patient had entered cardiac arrest before EMS’s arrival in 11.5% of cases. Two thirds of cases only involved one dose of naloxone, while the other 33% involved two doses.

Ryan Marino, MD, an addiction medicine specialist and an associate professor of emergency medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio, who was not involved in the study, took note of the high proportion of cases in which two doses were administered.

“While there is, in my professional opinion, almost no downside to giving naloxone in situations like this, and everybody should have it available and know how to use it, I would caution people on the risk of anchor bias, especially when more than two doses of naloxone are given, since we know that one should be an effective amount for any known opioid overdose,” Marino said. Anchoring bias refers to the tendency for individuals to rely more heavily on the first piece of information they receive about a topic or situation.

“For first responders and healthcare professionals, the importance of additional resuscitation measures like oxygenation and ventilation are just as crucial,” Marino said. “People should not be discouraged if someone doesn’t immediately respond to naloxone as overdose physiology can cause mental status to stay impaired for other reasons beyond direct drug effect, such as hypercarbia, but continue to seek and/or provide additional emergency care in these situations.”

Patients improved after one dose in just over half the cases (54%), and their conditions were unchanged in 46% of cases. There were only 11 cases in which the patient’s condition worsened after a naloxone dose (0.2%). Most of the cases (88%) were transported by EMS, and there were 13 total deaths at the scene (0.2%).

Nichols found the low incidence of worsening clinical status particularly striking. “This is further evidence of a critically important point — naloxone is purely an opioid antagonist, and only binds to opioid receptors, such that if a person has not overdosed on opioids or does not otherwise have opioids in their system, naloxone will not have a significant effect and will not cause them harm,” Nichols said.

“The most common causes of harm are due to rapid reversal of overdose and the potential risks involved in the rapid reversal of opioid effects and potentially precipitating withdrawal, and as this paper demonstrates, these are exceedingly rare,” he said. “Given that, we should have an incredibly low barrier to administer naloxone appropriately.”

The study was limited by inability to know how many true pediatric opioid poisonings are managed by EMS, so future research could look at linking EMS and emergency room hospital databases.
 

Improved Self-Efficacy in Teens

Another study showed that a peer-to-peer training program increased teens’ knowledge about overdoses from 34% before training to 79% after (P < .0001), and it substantially improved their confidence in recognizing an overdose and administering naloxone.

Nichols said the study shows the importance of ensuring “that adolescents know how to keep themselves and their friends safe in the case that they or anyone they know does end up using illicit substances which either intentionally or unintentionally contain opioids.”

This study assessed a training program with 206 students in a Los Angeles County high school who were trained by their peers between November 2023 and March 2024. The training included trends in teen overdose deaths, defining what opioids and fentanyl are, recognizing an overdose, and responding to one with naloxone.

The teens were an average 16 years old, about evenly split between boys and girls, and mostly in 11th (40%) or 12th (28%) grade, though nearly a third (29%) were 9th graders.

The students’ knowledge about fentanyl’s presence in counterfeit pills increased from 21% before the training to 68% afterward, and their correct identification of an overdose increased from 47% of participants to 90%.

The students’ confidence and attitudes toward helping with an overdose also improved substantially after the training. About two thirds agreed that non-medical people should be able to carry naloxone before the training, and that rose to 88% agreeing after the training. The proportion who agreed they would be willing to assist in an overdose rose from 77% before to 89% after training.

More dramatically, the teens’ confidence after training more than doubled in recognizing an overdose (from 31% to 81%) and more than tripled in their ability to give naloxone during an overdose (from 26% to 83%).

“The critical piece to keep in mind is that the concern about opioid overdose is respiratory depression leading to a lack of oxygen getting to the brain,” Nichols explained. “In the event of an overdose, time is brain — the longer the brain is deprived of oxygen, the lower the chance of survival. There is no specific time at which naloxone would become less effective at reversing an overdose.”

Therefore, people do not need to know the exact time that someone may have overdosed or how long they have been passed out in order to administer naloxone, he said. “The sooner naloxone is administered to someone who is unresponsive and who may have overdosed on opioids, the higher the likelihood of a successful reversal of an overdose and of saving a life.”

The peer-to-peer program was sponsored by the CARLOW Center for Medical Innovation, and the EMS study used no external funding. The authors of both studies and Marino had no disclosures. Nichols has consulted or clinically advised TV shows and health tech startup companies and has no disclosures related to naloxone or the pharmaceutical industry.
 

A version of this article first appeared on Medscape.com.

ORLANDO — More than half of youth improved after receiving a dose of naloxone by emergency medical services (EMS) after an emergency dispatch call, according to research presented at the American Academy of Pediatrics 2024 National Conference.

“Emergency responders or EMS are often the first to arrive to an opioid poisoning, and they’re often the first to give naloxone, a potentially lifesaving medication,” said Christopher E. Gaw, MD, MPH, MBE, assistant professor of pediatrics at The Ohio State University College of Medicine and an emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

Ohio State University

“Our study highlights and underscores its safety of use in the prehospital setting, and this is also supported by other data,” Gaw said. “Efforts to support public distribution and education on naloxone can really help each and every one of us as individual citizens prevent pediatric harm from the opioid crisis.”

Additional research at the meeting showed that teens’ knowledge, attitudes, and confidence about recognizing overdoses and assisting with naloxone administration improved following a peer-to-peer training program, suggesting that teens can play an important role in reducing youth mortality from overdoses.

An average of 22 American teens died from overdose every week in 2022, and as counterfeit pill use has increased among youth, research has found that fentanyl was detected in 93% of overdose deaths with counterfeit pills, according to Talia Puzantian, PharmD, BCPP, of the Keck Graduate Institute School of Pharmacy, Claremont, California, who led the study on peer education. Yet a recent survey had found that less than a third of teens (30%) knew what naloxone was, and only 14% knew how to administer it.

“Ensuring that adolescents have easy and confidential access to naloxone is important and can save lives,” said Taylor Nichols, MD, assistant clinical professor at the University of California San Francisco and an emergency medicine and addiction medicine–certified physician. “I have had teen patients who have told me that they have had to use naloxone obtained from our clinic on friends when they have accidentally overdosed.”

University of California

EMS Naloxone Administration to Youth

EMS clinicians are often the first healthcare providers to respond to an opioid overdose or poisoning event, and evidence-based guidelines for EMS naloxone administration were developed in 2019 to support this intervention. Gaw’s team investigated the frequency and demographics of pediatric administration of naloxone.

They analyzed data from the National Emergency Medical Services Information System on EMS activations for administration of at least one dose of naloxone during 2022 to those aged 0-17. There were 6215 EMS pediatric administrations of naloxone that year, and in the vast majority of cases (82%), the patient had not received a naloxone injection prior to EMS’s arrival.

Most patients (79%) were aged 13-17 years, but 10% were in the 6-12 age group. The remaining patients included 6% infants younger than 1 year and 4% aged 6-12 years. Just over half were for males (55%), and most were dispatched to a home or residential setting (61%). One in five incidents (22%) occurred at a non-healthcare business, 9% on a street or highway, and the rest at a healthcare facility or another location.

Most of the incidents occurred in urban areas (86%), followed by rural (7%), suburban (6%), and wilderness (1.4%). More occurred in the US South (42%) than in the West (29%), Midwest (22%), or Northeast (7.5%).

A key takeaway of those demographic findings is that ingestions and accidental poisonings with opioids can occur in children of any age, Nichols said. “Every single home that has any opioids in the home should absolutely have naloxone immediately available as well,” he said. “Every single person who is prescribed opioids should also have naloxone available and accessible and to be sure that the naloxone is not expired or otherwise tampered with and update that every few years.” He noted that Narcan expiration was recently extended from 3 years to 4 years by the US Food and Drug Administration (FDA).

“I always advise that people who have opioid medications keep them stored safely and securely,” Nichols said. “However, I also acknowledge that even perfect systems fail and that people make mistakes and may accidentally leave medication out, within reach, or otherwise unsecured. If that happens, and someone were to intentionally or unintentionally get into that medication and potentially overdose as a result, we want to have that reversal medication immediately available to reverse the overdose.”

In nearly all cases (91%), EMS provided advanced life support, with only 7.5% patients receiving basic life support and 1.5% receiving specialty critical care. Just under a third (29%) of the dispatch calls were for “overdose/poisoning/ingestion.” Other dispatch calls included “unconscious/fainting/near-fainting” (21%) or “cardiac arrest/death” (17%), but the frequency of each dispatch label varied by age groups.

For example, 38% of calls for infants were for cardiac arrest, compared with 15% of calls for older teens and 18% of calls for 6-12 year olds. An overdose/poisoning dispatch was meanwhile more common for teens (32%) than for infants (13%), younger children (23%), and older children/tweens (18%). Other dispatch complaints included “sick person/person down/unknown problem” (12%) and “breathing problem” (5%).

A possible reason for these variations is that “an overdose might be mistaken for another medical emergency, or vice versa, because opioid poisonings can be challenging to recognize, especially in young children and in the pediatric population,” Gaw said. “Both the public and emergency responders should maintain a high level of suspicion” of possible overdose for children with the signs or symptoms of it, such as low breathing, unresponsiveness, or small pupils.

In most cases (87%), the patient was not in cardiac arrest, though the patient had entered cardiac arrest before EMS’s arrival in 11.5% of cases. Two thirds of cases only involved one dose of naloxone, while the other 33% involved two doses.

Ryan Marino, MD, an addiction medicine specialist and an associate professor of emergency medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio, who was not involved in the study, took note of the high proportion of cases in which two doses were administered.

“While there is, in my professional opinion, almost no downside to giving naloxone in situations like this, and everybody should have it available and know how to use it, I would caution people on the risk of anchor bias, especially when more than two doses of naloxone are given, since we know that one should be an effective amount for any known opioid overdose,” Marino said. Anchoring bias refers to the tendency for individuals to rely more heavily on the first piece of information they receive about a topic or situation.

“For first responders and healthcare professionals, the importance of additional resuscitation measures like oxygenation and ventilation are just as crucial,” Marino said. “People should not be discouraged if someone doesn’t immediately respond to naloxone as overdose physiology can cause mental status to stay impaired for other reasons beyond direct drug effect, such as hypercarbia, but continue to seek and/or provide additional emergency care in these situations.”

Patients improved after one dose in just over half the cases (54%), and their conditions were unchanged in 46% of cases. There were only 11 cases in which the patient’s condition worsened after a naloxone dose (0.2%). Most of the cases (88%) were transported by EMS, and there were 13 total deaths at the scene (0.2%).

Nichols found the low incidence of worsening clinical status particularly striking. “This is further evidence of a critically important point — naloxone is purely an opioid antagonist, and only binds to opioid receptors, such that if a person has not overdosed on opioids or does not otherwise have opioids in their system, naloxone will not have a significant effect and will not cause them harm,” Nichols said.

“The most common causes of harm are due to rapid reversal of overdose and the potential risks involved in the rapid reversal of opioid effects and potentially precipitating withdrawal, and as this paper demonstrates, these are exceedingly rare,” he said. “Given that, we should have an incredibly low barrier to administer naloxone appropriately.”

The study was limited by inability to know how many true pediatric opioid poisonings are managed by EMS, so future research could look at linking EMS and emergency room hospital databases.
 

Improved Self-Efficacy in Teens

Another study showed that a peer-to-peer training program increased teens’ knowledge about overdoses from 34% before training to 79% after (P < .0001), and it substantially improved their confidence in recognizing an overdose and administering naloxone.

Nichols said the study shows the importance of ensuring “that adolescents know how to keep themselves and their friends safe in the case that they or anyone they know does end up using illicit substances which either intentionally or unintentionally contain opioids.”

This study assessed a training program with 206 students in a Los Angeles County high school who were trained by their peers between November 2023 and March 2024. The training included trends in teen overdose deaths, defining what opioids and fentanyl are, recognizing an overdose, and responding to one with naloxone.

The teens were an average 16 years old, about evenly split between boys and girls, and mostly in 11th (40%) or 12th (28%) grade, though nearly a third (29%) were 9th graders.

The students’ knowledge about fentanyl’s presence in counterfeit pills increased from 21% before the training to 68% afterward, and their correct identification of an overdose increased from 47% of participants to 90%.

The students’ confidence and attitudes toward helping with an overdose also improved substantially after the training. About two thirds agreed that non-medical people should be able to carry naloxone before the training, and that rose to 88% agreeing after the training. The proportion who agreed they would be willing to assist in an overdose rose from 77% before to 89% after training.

More dramatically, the teens’ confidence after training more than doubled in recognizing an overdose (from 31% to 81%) and more than tripled in their ability to give naloxone during an overdose (from 26% to 83%).

“The critical piece to keep in mind is that the concern about opioid overdose is respiratory depression leading to a lack of oxygen getting to the brain,” Nichols explained. “In the event of an overdose, time is brain — the longer the brain is deprived of oxygen, the lower the chance of survival. There is no specific time at which naloxone would become less effective at reversing an overdose.”

Therefore, people do not need to know the exact time that someone may have overdosed or how long they have been passed out in order to administer naloxone, he said. “The sooner naloxone is administered to someone who is unresponsive and who may have overdosed on opioids, the higher the likelihood of a successful reversal of an overdose and of saving a life.”

The peer-to-peer program was sponsored by the CARLOW Center for Medical Innovation, and the EMS study used no external funding. The authors of both studies and Marino had no disclosures. Nichols has consulted or clinically advised TV shows and health tech startup companies and has no disclosures related to naloxone or the pharmaceutical industry.
 

A version of this article first appeared on Medscape.com.

ORLANDO — More than half of youth improved after receiving a dose of naloxone by emergency medical services (EMS) after an emergency dispatch call, according to research presented at the American Academy of Pediatrics 2024 National Conference.

“Emergency responders or EMS are often the first to arrive to an opioid poisoning, and they’re often the first to give naloxone, a potentially lifesaving medication,” said Christopher E. Gaw, MD, MPH, MBE, assistant professor of pediatrics at The Ohio State University College of Medicine and an emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

Ohio State University

“Our study highlights and underscores its safety of use in the prehospital setting, and this is also supported by other data,” Gaw said. “Efforts to support public distribution and education on naloxone can really help each and every one of us as individual citizens prevent pediatric harm from the opioid crisis.”

Additional research at the meeting showed that teens’ knowledge, attitudes, and confidence about recognizing overdoses and assisting with naloxone administration improved following a peer-to-peer training program, suggesting that teens can play an important role in reducing youth mortality from overdoses.

An average of 22 American teens died from overdose every week in 2022, and as counterfeit pill use has increased among youth, research has found that fentanyl was detected in 93% of overdose deaths with counterfeit pills, according to Talia Puzantian, PharmD, BCPP, of the Keck Graduate Institute School of Pharmacy, Claremont, California, who led the study on peer education. Yet a recent survey had found that less than a third of teens (30%) knew what naloxone was, and only 14% knew how to administer it.

“Ensuring that adolescents have easy and confidential access to naloxone is important and can save lives,” said Taylor Nichols, MD, assistant clinical professor at the University of California San Francisco and an emergency medicine and addiction medicine–certified physician. “I have had teen patients who have told me that they have had to use naloxone obtained from our clinic on friends when they have accidentally overdosed.”

University of California

EMS Naloxone Administration to Youth

EMS clinicians are often the first healthcare providers to respond to an opioid overdose or poisoning event, and evidence-based guidelines for EMS naloxone administration were developed in 2019 to support this intervention. Gaw’s team investigated the frequency and demographics of pediatric administration of naloxone.

They analyzed data from the National Emergency Medical Services Information System on EMS activations for administration of at least one dose of naloxone during 2022 to those aged 0-17. There were 6215 EMS pediatric administrations of naloxone that year, and in the vast majority of cases (82%), the patient had not received a naloxone injection prior to EMS’s arrival.

Most patients (79%) were aged 13-17 years, but 10% were in the 6-12 age group. The remaining patients included 6% infants younger than 1 year and 4% aged 6-12 years. Just over half were for males (55%), and most were dispatched to a home or residential setting (61%). One in five incidents (22%) occurred at a non-healthcare business, 9% on a street or highway, and the rest at a healthcare facility or another location.

Most of the incidents occurred in urban areas (86%), followed by rural (7%), suburban (6%), and wilderness (1.4%). More occurred in the US South (42%) than in the West (29%), Midwest (22%), or Northeast (7.5%).

A key takeaway of those demographic findings is that ingestions and accidental poisonings with opioids can occur in children of any age, Nichols said. “Every single home that has any opioids in the home should absolutely have naloxone immediately available as well,” he said. “Every single person who is prescribed opioids should also have naloxone available and accessible and to be sure that the naloxone is not expired or otherwise tampered with and update that every few years.” He noted that Narcan expiration was recently extended from 3 years to 4 years by the US Food and Drug Administration (FDA).

“I always advise that people who have opioid medications keep them stored safely and securely,” Nichols said. “However, I also acknowledge that even perfect systems fail and that people make mistakes and may accidentally leave medication out, within reach, or otherwise unsecured. If that happens, and someone were to intentionally or unintentionally get into that medication and potentially overdose as a result, we want to have that reversal medication immediately available to reverse the overdose.”

In nearly all cases (91%), EMS provided advanced life support, with only 7.5% patients receiving basic life support and 1.5% receiving specialty critical care. Just under a third (29%) of the dispatch calls were for “overdose/poisoning/ingestion.” Other dispatch calls included “unconscious/fainting/near-fainting” (21%) or “cardiac arrest/death” (17%), but the frequency of each dispatch label varied by age groups.

For example, 38% of calls for infants were for cardiac arrest, compared with 15% of calls for older teens and 18% of calls for 6-12 year olds. An overdose/poisoning dispatch was meanwhile more common for teens (32%) than for infants (13%), younger children (23%), and older children/tweens (18%). Other dispatch complaints included “sick person/person down/unknown problem” (12%) and “breathing problem” (5%).

A possible reason for these variations is that “an overdose might be mistaken for another medical emergency, or vice versa, because opioid poisonings can be challenging to recognize, especially in young children and in the pediatric population,” Gaw said. “Both the public and emergency responders should maintain a high level of suspicion” of possible overdose for children with the signs or symptoms of it, such as low breathing, unresponsiveness, or small pupils.

In most cases (87%), the patient was not in cardiac arrest, though the patient had entered cardiac arrest before EMS’s arrival in 11.5% of cases. Two thirds of cases only involved one dose of naloxone, while the other 33% involved two doses.

Ryan Marino, MD, an addiction medicine specialist and an associate professor of emergency medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio, who was not involved in the study, took note of the high proportion of cases in which two doses were administered.

“While there is, in my professional opinion, almost no downside to giving naloxone in situations like this, and everybody should have it available and know how to use it, I would caution people on the risk of anchor bias, especially when more than two doses of naloxone are given, since we know that one should be an effective amount for any known opioid overdose,” Marino said. Anchoring bias refers to the tendency for individuals to rely more heavily on the first piece of information they receive about a topic or situation.

“For first responders and healthcare professionals, the importance of additional resuscitation measures like oxygenation and ventilation are just as crucial,” Marino said. “People should not be discouraged if someone doesn’t immediately respond to naloxone as overdose physiology can cause mental status to stay impaired for other reasons beyond direct drug effect, such as hypercarbia, but continue to seek and/or provide additional emergency care in these situations.”

Patients improved after one dose in just over half the cases (54%), and their conditions were unchanged in 46% of cases. There were only 11 cases in which the patient’s condition worsened after a naloxone dose (0.2%). Most of the cases (88%) were transported by EMS, and there were 13 total deaths at the scene (0.2%).

Nichols found the low incidence of worsening clinical status particularly striking. “This is further evidence of a critically important point — naloxone is purely an opioid antagonist, and only binds to opioid receptors, such that if a person has not overdosed on opioids or does not otherwise have opioids in their system, naloxone will not have a significant effect and will not cause them harm,” Nichols said.

“The most common causes of harm are due to rapid reversal of overdose and the potential risks involved in the rapid reversal of opioid effects and potentially precipitating withdrawal, and as this paper demonstrates, these are exceedingly rare,” he said. “Given that, we should have an incredibly low barrier to administer naloxone appropriately.”

The study was limited by inability to know how many true pediatric opioid poisonings are managed by EMS, so future research could look at linking EMS and emergency room hospital databases.
 

Improved Self-Efficacy in Teens

Another study showed that a peer-to-peer training program increased teens’ knowledge about overdoses from 34% before training to 79% after (P < .0001), and it substantially improved their confidence in recognizing an overdose and administering naloxone.

Nichols said the study shows the importance of ensuring “that adolescents know how to keep themselves and their friends safe in the case that they or anyone they know does end up using illicit substances which either intentionally or unintentionally contain opioids.”

This study assessed a training program with 206 students in a Los Angeles County high school who were trained by their peers between November 2023 and March 2024. The training included trends in teen overdose deaths, defining what opioids and fentanyl are, recognizing an overdose, and responding to one with naloxone.

The teens were an average 16 years old, about evenly split between boys and girls, and mostly in 11th (40%) or 12th (28%) grade, though nearly a third (29%) were 9th graders.

The students’ knowledge about fentanyl’s presence in counterfeit pills increased from 21% before the training to 68% afterward, and their correct identification of an overdose increased from 47% of participants to 90%.

The students’ confidence and attitudes toward helping with an overdose also improved substantially after the training. About two thirds agreed that non-medical people should be able to carry naloxone before the training, and that rose to 88% agreeing after the training. The proportion who agreed they would be willing to assist in an overdose rose from 77% before to 89% after training.

More dramatically, the teens’ confidence after training more than doubled in recognizing an overdose (from 31% to 81%) and more than tripled in their ability to give naloxone during an overdose (from 26% to 83%).

“The critical piece to keep in mind is that the concern about opioid overdose is respiratory depression leading to a lack of oxygen getting to the brain,” Nichols explained. “In the event of an overdose, time is brain — the longer the brain is deprived of oxygen, the lower the chance of survival. There is no specific time at which naloxone would become less effective at reversing an overdose.”

Therefore, people do not need to know the exact time that someone may have overdosed or how long they have been passed out in order to administer naloxone, he said. “The sooner naloxone is administered to someone who is unresponsive and who may have overdosed on opioids, the higher the likelihood of a successful reversal of an overdose and of saving a life.”

The peer-to-peer program was sponsored by the CARLOW Center for Medical Innovation, and the EMS study used no external funding. The authors of both studies and Marino had no disclosures. Nichols has consulted or clinically advised TV shows and health tech startup companies and has no disclosures related to naloxone or the pharmaceutical industry.
 

A version of this article first appeared on Medscape.com.

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

In the article "‘Door-to-thrombectomy ’ time linked to better acute PE outcomes" in the November 2024 issue of CHEST Physician, Dr. Patel was quoted as stating, "Mechanical thrombectomy in the FLASH registry showed mortality benefit," and, "There's a mortality benefit in any case whether the patient is high risk or intermediate-high." Dr. Patel was referring to the FLASH registry as a whole and not to the registry data study described in this article. CHEST Physician regrets the error and any confusion this may have caused.

BOSTON — The sooner that patients with acute pulmonary embolism (PE) get treated with mechanical thrombectomy, the greater the likelihood that they will have favorable short- and long-term outcomes, regardless of their degree of initial risk, a study of registry data showed.

Among nearly 800 patients with acute PE whose data are recorded in the FlowTriever All-Comer Registry for Patient Safety and Hemodynamics (FLASH), a prospective multicenter registry of individuals treated with mechanical thrombectomy using the FlowTriever system (Inari Medical), shorter time from admission to mechanical thrombectomy was associated with significantly greater reductions in intraprocedural mean and systolic pulmonary artery pressures (PAP), greater reductions in the right ventricular/left ventricular (RV/LV) ratio, and longer 6-minute walk times at 6 months, reported Krunal H. Patel, MD, a pulmonary and critical care fellow at the Lewis Katz School of Medicine at Temple University Hospital in Philadelphia.

“Mechanical thrombectomy in the FLASH registry showed a mortality benefit. I think as time progresses and mechanical thrombectomy becomes more popular, we’re just going to need to figure out what is the ideal time for intervention,” he said during an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

“There’s mortality benefit in any case whether the patient is high-risk or intermediate-high. This is a thought-provoking retrospective analysis that says that early intervention is probably better than doing it late, but regardless, the FLASH registry trial showed that early thrombectomy or thrombectomy in general shows positive mortality benefit,” Patel said in an interview.

He likened the challenge for pulmonary and critical care specialists to that of interventional cardiologists, who have determined that the ideal window for starting percutaneous coronary interventions is within 90 minutes of the patient’s arrival at the facility.

“I think we have to get our ‘door-to-balloon’ time for PE care,” he said.
 

Study Details

Patel and colleague Parth M. Rali, MD, FCCP, associate professor of thoracic medicine at Temple, conducted a retrospective review of data on 787 US patients in the FLASH registry for whom time to mechanical thrombectomy data were available. They stratified the patients into short and long time to mechanical thrombectomy groups, with “short” defined as ≤ 12 hours of presentation and “long” as > 12 hours.

They found that the median time to thrombectomy was 19.68 hours. In all, 242 patients (31%) were treated within the short window, and the remaining 545 patients (69%) were treated after at least 12 hours had passed.

Comparing clinical characteristics between the groups, the investigators noted that significantly more patients in the short time group vs long time group were categorized as high-risk (11.2% vs 6.2%; P = .0026). This difference is likely due to the need for greater urgency among high-risk patients, Patel said.

Patients in the short time group also had significantly higher baseline RV/LV ratios and lactate levels, but baseline dyspnea scores and pre-procedure median and systolic PAP were similar between the groups.

The mean time to thrombectomy was 6.08 hours in the short time group vs 34.04 hours in the long time group. Their respective median times were 6.01 and 24.73 hours.

The procedural time was similar between the groups, at 45 and 42 minutes, respectively.

The location of the treated thrombus was central only in 35.1% and 26.5% patients in the short and long time groups, respectively. Lobar-only thrombi were treated in 7.9% and 14.3%, respectively, and both central and lobar thrombi were treated in 57.0% and 59.2%, respectively.

Both 48-hour and 30-day all-cause mortality rates were similar between the groups (0.4%/0.2% and 0.5%/1.0%).

Patients in the short time group had slightly but significantly longer post-procedure hospital and intensive care unit stays, but 30-day readmission rates — whether for PE- or non-PE–related causes — were similar.

Where the differences between the groups really showed, however, were PAP reductions over baseline, with decline in median pressures of −8.7 mm Hg in the short group vs −7.2 mm Hg in the long group (P = .0008), and drops in systolic PAP of −14.4 vs −12.1 mm Hg, respectively (P = .0011).

In addition, reductions in RV/LV ratios from baseline were also significantly greater among patients whose thrombectomies had been expedited at the 48-hour, 30-day, and 6-month follow-up periods.

At 6 months, patients who had received mechanical thrombectomy within 12 hours also had significantly longer 6-minute walk distances (442.2 vs 390.5 m; P = .0032).
 

Low Thrombolysis Rate

Following his presentation, session co-moderator Galina Glazman-Kuczaj, MD, from the Division of Pulmonary and Critical Care Medicine at Albany Med Health System, Albany, New York, asked Patel what percentage of patients, if any, had received thrombolytic therapy before the thrombectomy procedure.

He noted that only 1% or 2% patients in the FLASH registry received thrombolysis.

In an interview, Glazman-Kuczaj said that “it was reassuring for [Patel] to report that it was only a small population of patients who got thrombolysis beforehand in either group because you would expect that maybe people in the group that took longer to have a thrombectomy got some thrombolysis beforehand and that perhaps they were more stable, but it seems like thrombectomy was the first-line treatment in both groups.”

The FLASH Registry is funded by Inari Medical. Patel and Glazman-Kuczaj reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

In the article "‘Door-to-thrombectomy ’ time linked to better acute PE outcomes" in the November 2024 issue of CHEST Physician, Dr. Patel was quoted as stating, "Mechanical thrombectomy in the FLASH registry showed mortality benefit," and, "There's a mortality benefit in any case whether the patient is high risk or intermediate-high." Dr. Patel was referring to the FLASH registry as a whole and not to the registry data study described in this article. CHEST Physician regrets the error and any confusion this may have caused.

BOSTON — The sooner that patients with acute pulmonary embolism (PE) get treated with mechanical thrombectomy, the greater the likelihood that they will have favorable short- and long-term outcomes, regardless of their degree of initial risk, a study of registry data showed.

Among nearly 800 patients with acute PE whose data are recorded in the FlowTriever All-Comer Registry for Patient Safety and Hemodynamics (FLASH), a prospective multicenter registry of individuals treated with mechanical thrombectomy using the FlowTriever system (Inari Medical), shorter time from admission to mechanical thrombectomy was associated with significantly greater reductions in intraprocedural mean and systolic pulmonary artery pressures (PAP), greater reductions in the right ventricular/left ventricular (RV/LV) ratio, and longer 6-minute walk times at 6 months, reported Krunal H. Patel, MD, a pulmonary and critical care fellow at the Lewis Katz School of Medicine at Temple University Hospital in Philadelphia.

“Mechanical thrombectomy in the FLASH registry showed a mortality benefit. I think as time progresses and mechanical thrombectomy becomes more popular, we’re just going to need to figure out what is the ideal time for intervention,” he said during an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

“There’s mortality benefit in any case whether the patient is high-risk or intermediate-high. This is a thought-provoking retrospective analysis that says that early intervention is probably better than doing it late, but regardless, the FLASH registry trial showed that early thrombectomy or thrombectomy in general shows positive mortality benefit,” Patel said in an interview.

He likened the challenge for pulmonary and critical care specialists to that of interventional cardiologists, who have determined that the ideal window for starting percutaneous coronary interventions is within 90 minutes of the patient’s arrival at the facility.

“I think we have to get our ‘door-to-balloon’ time for PE care,” he said.
 

Study Details

Patel and colleague Parth M. Rali, MD, FCCP, associate professor of thoracic medicine at Temple, conducted a retrospective review of data on 787 US patients in the FLASH registry for whom time to mechanical thrombectomy data were available. They stratified the patients into short and long time to mechanical thrombectomy groups, with “short” defined as ≤ 12 hours of presentation and “long” as > 12 hours.

They found that the median time to thrombectomy was 19.68 hours. In all, 242 patients (31%) were treated within the short window, and the remaining 545 patients (69%) were treated after at least 12 hours had passed.

Comparing clinical characteristics between the groups, the investigators noted that significantly more patients in the short time group vs long time group were categorized as high-risk (11.2% vs 6.2%; P = .0026). This difference is likely due to the need for greater urgency among high-risk patients, Patel said.

Patients in the short time group also had significantly higher baseline RV/LV ratios and lactate levels, but baseline dyspnea scores and pre-procedure median and systolic PAP were similar between the groups.

The mean time to thrombectomy was 6.08 hours in the short time group vs 34.04 hours in the long time group. Their respective median times were 6.01 and 24.73 hours.

The procedural time was similar between the groups, at 45 and 42 minutes, respectively.

The location of the treated thrombus was central only in 35.1% and 26.5% patients in the short and long time groups, respectively. Lobar-only thrombi were treated in 7.9% and 14.3%, respectively, and both central and lobar thrombi were treated in 57.0% and 59.2%, respectively.

Both 48-hour and 30-day all-cause mortality rates were similar between the groups (0.4%/0.2% and 0.5%/1.0%).

Patients in the short time group had slightly but significantly longer post-procedure hospital and intensive care unit stays, but 30-day readmission rates — whether for PE- or non-PE–related causes — were similar.

Where the differences between the groups really showed, however, were PAP reductions over baseline, with decline in median pressures of −8.7 mm Hg in the short group vs −7.2 mm Hg in the long group (P = .0008), and drops in systolic PAP of −14.4 vs −12.1 mm Hg, respectively (P = .0011).

In addition, reductions in RV/LV ratios from baseline were also significantly greater among patients whose thrombectomies had been expedited at the 48-hour, 30-day, and 6-month follow-up periods.

At 6 months, patients who had received mechanical thrombectomy within 12 hours also had significantly longer 6-minute walk distances (442.2 vs 390.5 m; P = .0032).
 

Low Thrombolysis Rate

Following his presentation, session co-moderator Galina Glazman-Kuczaj, MD, from the Division of Pulmonary and Critical Care Medicine at Albany Med Health System, Albany, New York, asked Patel what percentage of patients, if any, had received thrombolytic therapy before the thrombectomy procedure.

He noted that only 1% or 2% patients in the FLASH registry received thrombolysis.

In an interview, Glazman-Kuczaj said that “it was reassuring for [Patel] to report that it was only a small population of patients who got thrombolysis beforehand in either group because you would expect that maybe people in the group that took longer to have a thrombectomy got some thrombolysis beforehand and that perhaps they were more stable, but it seems like thrombectomy was the first-line treatment in both groups.”

The FLASH Registry is funded by Inari Medical. Patel and Glazman-Kuczaj reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

In the article "‘Door-to-thrombectomy ’ time linked to better acute PE outcomes" in the November 2024 issue of CHEST Physician, Dr. Patel was quoted as stating, "Mechanical thrombectomy in the FLASH registry showed mortality benefit," and, "There's a mortality benefit in any case whether the patient is high risk or intermediate-high." Dr. Patel was referring to the FLASH registry as a whole and not to the registry data study described in this article. CHEST Physician regrets the error and any confusion this may have caused.

BOSTON — The sooner that patients with acute pulmonary embolism (PE) get treated with mechanical thrombectomy, the greater the likelihood that they will have favorable short- and long-term outcomes, regardless of their degree of initial risk, a study of registry data showed.

Among nearly 800 patients with acute PE whose data are recorded in the FlowTriever All-Comer Registry for Patient Safety and Hemodynamics (FLASH), a prospective multicenter registry of individuals treated with mechanical thrombectomy using the FlowTriever system (Inari Medical), shorter time from admission to mechanical thrombectomy was associated with significantly greater reductions in intraprocedural mean and systolic pulmonary artery pressures (PAP), greater reductions in the right ventricular/left ventricular (RV/LV) ratio, and longer 6-minute walk times at 6 months, reported Krunal H. Patel, MD, a pulmonary and critical care fellow at the Lewis Katz School of Medicine at Temple University Hospital in Philadelphia.

“Mechanical thrombectomy in the FLASH registry showed a mortality benefit. I think as time progresses and mechanical thrombectomy becomes more popular, we’re just going to need to figure out what is the ideal time for intervention,” he said during an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

“There’s mortality benefit in any case whether the patient is high-risk or intermediate-high. This is a thought-provoking retrospective analysis that says that early intervention is probably better than doing it late, but regardless, the FLASH registry trial showed that early thrombectomy or thrombectomy in general shows positive mortality benefit,” Patel said in an interview.

He likened the challenge for pulmonary and critical care specialists to that of interventional cardiologists, who have determined that the ideal window for starting percutaneous coronary interventions is within 90 minutes of the patient’s arrival at the facility.

“I think we have to get our ‘door-to-balloon’ time for PE care,” he said.
 

Study Details

Patel and colleague Parth M. Rali, MD, FCCP, associate professor of thoracic medicine at Temple, conducted a retrospective review of data on 787 US patients in the FLASH registry for whom time to mechanical thrombectomy data were available. They stratified the patients into short and long time to mechanical thrombectomy groups, with “short” defined as ≤ 12 hours of presentation and “long” as > 12 hours.

They found that the median time to thrombectomy was 19.68 hours. In all, 242 patients (31%) were treated within the short window, and the remaining 545 patients (69%) were treated after at least 12 hours had passed.

Comparing clinical characteristics between the groups, the investigators noted that significantly more patients in the short time group vs long time group were categorized as high-risk (11.2% vs 6.2%; P = .0026). This difference is likely due to the need for greater urgency among high-risk patients, Patel said.

Patients in the short time group also had significantly higher baseline RV/LV ratios and lactate levels, but baseline dyspnea scores and pre-procedure median and systolic PAP were similar between the groups.

The mean time to thrombectomy was 6.08 hours in the short time group vs 34.04 hours in the long time group. Their respective median times were 6.01 and 24.73 hours.

The procedural time was similar between the groups, at 45 and 42 minutes, respectively.

The location of the treated thrombus was central only in 35.1% and 26.5% patients in the short and long time groups, respectively. Lobar-only thrombi were treated in 7.9% and 14.3%, respectively, and both central and lobar thrombi were treated in 57.0% and 59.2%, respectively.

Both 48-hour and 30-day all-cause mortality rates were similar between the groups (0.4%/0.2% and 0.5%/1.0%).

Patients in the short time group had slightly but significantly longer post-procedure hospital and intensive care unit stays, but 30-day readmission rates — whether for PE- or non-PE–related causes — were similar.

Where the differences between the groups really showed, however, were PAP reductions over baseline, with decline in median pressures of −8.7 mm Hg in the short group vs −7.2 mm Hg in the long group (P = .0008), and drops in systolic PAP of −14.4 vs −12.1 mm Hg, respectively (P = .0011).

In addition, reductions in RV/LV ratios from baseline were also significantly greater among patients whose thrombectomies had been expedited at the 48-hour, 30-day, and 6-month follow-up periods.

At 6 months, patients who had received mechanical thrombectomy within 12 hours also had significantly longer 6-minute walk distances (442.2 vs 390.5 m; P = .0032).
 

Low Thrombolysis Rate

Following his presentation, session co-moderator Galina Glazman-Kuczaj, MD, from the Division of Pulmonary and Critical Care Medicine at Albany Med Health System, Albany, New York, asked Patel what percentage of patients, if any, had received thrombolytic therapy before the thrombectomy procedure.

He noted that only 1% or 2% patients in the FLASH registry received thrombolysis.

In an interview, Glazman-Kuczaj said that “it was reassuring for [Patel] to report that it was only a small population of patients who got thrombolysis beforehand in either group because you would expect that maybe people in the group that took longer to have a thrombectomy got some thrombolysis beforehand and that perhaps they were more stable, but it seems like thrombectomy was the first-line treatment in both groups.”

The FLASH Registry is funded by Inari Medical. Patel and Glazman-Kuczaj reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.