Asthma

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.

Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.

Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.

“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.

12 Months of COPD, Triple Inhaler Therapy

In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.

The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.

The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.

At 52 weeks, the annualized rate of moderate or severe exacerbations was significantly lower (34%) in the dupilumab group than in the placebo group (0.86 vs 1.30, P < .001).

Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).

Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).

Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.

The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.

Data May Drive US Food and Drug Administration (FDA) Approval

In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.

With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.

Potential Change in Patient Management

Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.

The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.

If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.

“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.

In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.

Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.

A version of this article appeared on Medscape.com.

Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.

Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.

Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.

“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.

12 Months of COPD, Triple Inhaler Therapy

In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.

The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.

The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.

At 52 weeks, the annualized rate of moderate or severe exacerbations was significantly lower (34%) in the dupilumab group than in the placebo group (0.86 vs 1.30, P < .001).

Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).

Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).

Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.

The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.

Data May Drive US Food and Drug Administration (FDA) Approval

In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.

With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.

Potential Change in Patient Management

Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.

The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.

If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.

“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.

In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.

Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.

A version of this article appeared on Medscape.com.

Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.

Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.

Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.

“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.

12 Months of COPD, Triple Inhaler Therapy

In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.

The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.

The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.

At 52 weeks, the annualized rate of moderate or severe exacerbations was significantly lower (34%) in the dupilumab group than in the placebo group (0.86 vs 1.30, P < .001).

Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).

Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).

Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.

The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.

Data May Drive US Food and Drug Administration (FDA) Approval

In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.

With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.

Potential Change in Patient Management

Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.

The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.

If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.

“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.

In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.

Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.

A version of this article appeared on Medscape.com.

SAN DIEGO — You can’t treat patients if you can’t find them. But as investigators in a randomized controlled trial showed, a case-finding method based on spirometry results can identify individuals in the community with undiagnosed chronic obstructive pulmonary disease (COPD) or asthma whose lives could be significantly improved with proper care.

Once they have been identified and randomly assigned to be treated by a pulmonologist and asthma-COPD educator according to clinical guidelines, these previously undiagnosed patients have significant improvements in health care utilization, lung function, symptoms, and quality of life compared with patients randomly assigned to treatment by a general practitioner.

“By diagnosing people early and treating them intensively, you can really improve their quality of life,” said lead investigator Shawn D. Aaron, MD, from the Ottawa Hospital Research Institute and University of Ottawa, Ontario, Canada.

Even those patients in the study who were randomly assigned to receive care from a general practice physician had improvements in lung function and quality of life, although on a smaller scale than patients assigned to a specialty team, Dr. Aaron said at the American Thoracic Society’s international conference.

He reported results of the study in a late-breaking oral abstract session. The study findings were also published online in The New England Journal of Medicine.
 

Undiagnosed diseases

“The simple problem is that 70% of individuals with asthma or COPD are likely undiagnosed,” Dr. Aaron said.

He noted that the 2007-2012 US National Health and Nutritional Examination Survey found obstructive lung disease in 13% of randomly selected US adults, but 71% of these people had never been diagnosed with asthma or COPD.

“So our questions were in this study: One, can we find adults with undiagnosed asthma or COPD in the community? The second question was: If we find them, are they sick? And the third and most important question was: Can we treat them early and improve their health outcomes?” he said.

Asthma and COPD both present with similar respiratory symptoms, including dyspnea, cough, wheeze, and/or chest tightness, and the two conditions share expiratory airflow obstruction as a common physiologic impairment that can be detected with spirometry.
 

Study details

To identify participants, the investigators hired a commercial survey firm to contact households asking whether any member aged 18 years or older had respiratory symptoms such as shortness of breath, wheezing, increased mucus or sputum production, or prolonged cough in the past 6 months. Those who responded yes were then contacted by a trial coordinator, and the symptomatic household member was asked to complete the Asthma Screening Questionnaire over the phone. Participants aged 60 years or older and those younger than 60 years with a score of 6 or higher on the asthma screen also completed the COPD Diagnostic Questionnaire.

Those with a score of 6 or higher on the asthma screen or 20 or higher on the COPD screen were invited to undergo spirometry at a trial site.

The investigators ultimately identified 508 adults with undiagnosed asthma or COPD and randomly assigned them on an equal basis to an intervention group (253 patients) or control group (255 patients).

In the intervention group treatment was provided by a study pulmonologist and asthma-COPD educator who started guideline-based care. Patients were prescribed inhalers and were taught how to use them, and many were given action plans that included smoking cessation aids, exercise and weight counseling, and vaccinations against influenza and pneumonia.

Participants assigned to the control group would receive usual care provided by their primary care practitioner.
 

Improvements abound

During the 12 months of the study, 92% of patients in the intervention group and 60% in the control group were started on new medications for their condition. 

Only 13.4% of those in the intervention group received either no respiratory treatments or a short-acting beta 2 agonist only during the entire trial period compared with 49.8% of controls, “so the usual care arm was undertreated relative to the intervention arm, and because of that under-treatment we saw a tremendous difference in the primary outcome,” Dr. Aaron said.

The primary outcome, the annualized rate of patient-initiated healthcare utilization for respiratory illness, was significantly lower in the intervention group, translating into an incidence rate ratio of 0.48 (P < .001).

Secondary outcomes were also better in the intervention group. For example, total scores on the St. George Respiratory Questionnaire (SGRQ) declined by 10.2 points from baseline in intervention group compared with a 6.8-point drop in the usual-care group. The mean difference was 3.5 points (P = .009). Lower scores on the 0-100 SGRQ scale indicate better health status.

Similarly, total scores on the COPD Assessment Test, a scale of 0-40 with lower scores indicating better health, declined by 3.8 points and 2.6 points, respectively, over 12 months, for a mean difference of 1.3 points (P = .03).

In addition, those in the intervention arm had a 119-mL improvement in forced expiratory volume in 1 second over the 12 months of the study compared with only a 22-mL improvement in the usual-care group.
 

Translatable results?

Dr. Aaron acknowledged that the investigators could have chosen to keep those who were assigned to the control group unaware of their diagnosis during the study but because all patients enrolled were symptomatic, it would have been unethical to do so. All participants were informed of their diagnosis at randomization, and the information was conveyed to each patient’s primary care practitioner as well.

In fact, many patients in the control group decided to seek treatment for either asthma or COPD after learning of their diagnosis, which may have contributed to improved outcomes in the control arm, he said.

“What this means is if you make the diagnosis early in the community, and at least have them see a primary care practitioner, they will improve their quality of life and their health status,” he concluded.

Ravi Kalhan, MD, MS, from the Northwestern University Feinberg School Of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the case-finding model used in the trial would be difficult to replicate elsewhere.

“This idea of seeking out undiagnosed people by doing spirometry, so-called ‘case finding’ as they described it, testing highly symptomatic people with spirometry, is really challenging in the US, because symptoms are not collected proactively very much,” he said.

Persons with acute respiratory symptoms in the US typically seek healthcare at urgent-care clinics or have unscheduled visits with their primary care physicians, “and by all accounts those people should have spirometry, but they just don’t in the US, as best as I can tell,” he added.

He agreed that getting patients to a specialist can result in better outcomes but said that implementing a systematic approach such as the one described in the study would be extremely difficult in the fragmented US healthcare system.

Dr. Kalhan’s co-moderator, Nuala J. Meyer, MD, MS, from the Hospital of the University of Pennsylvania, Philadelphia, told Chest Physician that “it was interesting that even those who were not in the intervention group but had these details passed on to their primary care physicians still had improvements,” and that it would be beneficial if primary care practitioners were routinely informed about the results of urgent care visits.

She added, however, that in the US the flow of information between urgent care clinics, primary care offices, and specialty clinics is problematic, suggesting that symptomatic patients may not always receive the additional care that they need.

The study was supported by the Canadian Institutes of Health Research. Dr. Aaron, Dr. Kalhan, and Dr. Meyer all reported having no relevant disclosures. 

A version of this article appeared on Medscape.com.

SAN DIEGO — You can’t treat patients if you can’t find them. But as investigators in a randomized controlled trial showed, a case-finding method based on spirometry results can identify individuals in the community with undiagnosed chronic obstructive pulmonary disease (COPD) or asthma whose lives could be significantly improved with proper care.

Once they have been identified and randomly assigned to be treated by a pulmonologist and asthma-COPD educator according to clinical guidelines, these previously undiagnosed patients have significant improvements in health care utilization, lung function, symptoms, and quality of life compared with patients randomly assigned to treatment by a general practitioner.

“By diagnosing people early and treating them intensively, you can really improve their quality of life,” said lead investigator Shawn D. Aaron, MD, from the Ottawa Hospital Research Institute and University of Ottawa, Ontario, Canada.

Even those patients in the study who were randomly assigned to receive care from a general practice physician had improvements in lung function and quality of life, although on a smaller scale than patients assigned to a specialty team, Dr. Aaron said at the American Thoracic Society’s international conference.

He reported results of the study in a late-breaking oral abstract session. The study findings were also published online in The New England Journal of Medicine.
 

Undiagnosed diseases

“The simple problem is that 70% of individuals with asthma or COPD are likely undiagnosed,” Dr. Aaron said.

He noted that the 2007-2012 US National Health and Nutritional Examination Survey found obstructive lung disease in 13% of randomly selected US adults, but 71% of these people had never been diagnosed with asthma or COPD.

“So our questions were in this study: One, can we find adults with undiagnosed asthma or COPD in the community? The second question was: If we find them, are they sick? And the third and most important question was: Can we treat them early and improve their health outcomes?” he said.

Asthma and COPD both present with similar respiratory symptoms, including dyspnea, cough, wheeze, and/or chest tightness, and the two conditions share expiratory airflow obstruction as a common physiologic impairment that can be detected with spirometry.
 

Study details

To identify participants, the investigators hired a commercial survey firm to contact households asking whether any member aged 18 years or older had respiratory symptoms such as shortness of breath, wheezing, increased mucus or sputum production, or prolonged cough in the past 6 months. Those who responded yes were then contacted by a trial coordinator, and the symptomatic household member was asked to complete the Asthma Screening Questionnaire over the phone. Participants aged 60 years or older and those younger than 60 years with a score of 6 or higher on the asthma screen also completed the COPD Diagnostic Questionnaire.

Those with a score of 6 or higher on the asthma screen or 20 or higher on the COPD screen were invited to undergo spirometry at a trial site.

The investigators ultimately identified 508 adults with undiagnosed asthma or COPD and randomly assigned them on an equal basis to an intervention group (253 patients) or control group (255 patients).

In the intervention group treatment was provided by a study pulmonologist and asthma-COPD educator who started guideline-based care. Patients were prescribed inhalers and were taught how to use them, and many were given action plans that included smoking cessation aids, exercise and weight counseling, and vaccinations against influenza and pneumonia.

Participants assigned to the control group would receive usual care provided by their primary care practitioner.
 

Improvements abound

During the 12 months of the study, 92% of patients in the intervention group and 60% in the control group were started on new medications for their condition. 

Only 13.4% of those in the intervention group received either no respiratory treatments or a short-acting beta 2 agonist only during the entire trial period compared with 49.8% of controls, “so the usual care arm was undertreated relative to the intervention arm, and because of that under-treatment we saw a tremendous difference in the primary outcome,” Dr. Aaron said.

The primary outcome, the annualized rate of patient-initiated healthcare utilization for respiratory illness, was significantly lower in the intervention group, translating into an incidence rate ratio of 0.48 (P < .001).

Secondary outcomes were also better in the intervention group. For example, total scores on the St. George Respiratory Questionnaire (SGRQ) declined by 10.2 points from baseline in intervention group compared with a 6.8-point drop in the usual-care group. The mean difference was 3.5 points (P = .009). Lower scores on the 0-100 SGRQ scale indicate better health status.

Similarly, total scores on the COPD Assessment Test, a scale of 0-40 with lower scores indicating better health, declined by 3.8 points and 2.6 points, respectively, over 12 months, for a mean difference of 1.3 points (P = .03).

In addition, those in the intervention arm had a 119-mL improvement in forced expiratory volume in 1 second over the 12 months of the study compared with only a 22-mL improvement in the usual-care group.
 

Translatable results?

Dr. Aaron acknowledged that the investigators could have chosen to keep those who were assigned to the control group unaware of their diagnosis during the study but because all patients enrolled were symptomatic, it would have been unethical to do so. All participants were informed of their diagnosis at randomization, and the information was conveyed to each patient’s primary care practitioner as well.

In fact, many patients in the control group decided to seek treatment for either asthma or COPD after learning of their diagnosis, which may have contributed to improved outcomes in the control arm, he said.

“What this means is if you make the diagnosis early in the community, and at least have them see a primary care practitioner, they will improve their quality of life and their health status,” he concluded.

Ravi Kalhan, MD, MS, from the Northwestern University Feinberg School Of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the case-finding model used in the trial would be difficult to replicate elsewhere.

“This idea of seeking out undiagnosed people by doing spirometry, so-called ‘case finding’ as they described it, testing highly symptomatic people with spirometry, is really challenging in the US, because symptoms are not collected proactively very much,” he said.

Persons with acute respiratory symptoms in the US typically seek healthcare at urgent-care clinics or have unscheduled visits with their primary care physicians, “and by all accounts those people should have spirometry, but they just don’t in the US, as best as I can tell,” he added.

He agreed that getting patients to a specialist can result in better outcomes but said that implementing a systematic approach such as the one described in the study would be extremely difficult in the fragmented US healthcare system.

Dr. Kalhan’s co-moderator, Nuala J. Meyer, MD, MS, from the Hospital of the University of Pennsylvania, Philadelphia, told Chest Physician that “it was interesting that even those who were not in the intervention group but had these details passed on to their primary care physicians still had improvements,” and that it would be beneficial if primary care practitioners were routinely informed about the results of urgent care visits.

She added, however, that in the US the flow of information between urgent care clinics, primary care offices, and specialty clinics is problematic, suggesting that symptomatic patients may not always receive the additional care that they need.

The study was supported by the Canadian Institutes of Health Research. Dr. Aaron, Dr. Kalhan, and Dr. Meyer all reported having no relevant disclosures. 

A version of this article appeared on Medscape.com.

SAN DIEGO — You can’t treat patients if you can’t find them. But as investigators in a randomized controlled trial showed, a case-finding method based on spirometry results can identify individuals in the community with undiagnosed chronic obstructive pulmonary disease (COPD) or asthma whose lives could be significantly improved with proper care.

Once they have been identified and randomly assigned to be treated by a pulmonologist and asthma-COPD educator according to clinical guidelines, these previously undiagnosed patients have significant improvements in health care utilization, lung function, symptoms, and quality of life compared with patients randomly assigned to treatment by a general practitioner.

“By diagnosing people early and treating them intensively, you can really improve their quality of life,” said lead investigator Shawn D. Aaron, MD, from the Ottawa Hospital Research Institute and University of Ottawa, Ontario, Canada.

Even those patients in the study who were randomly assigned to receive care from a general practice physician had improvements in lung function and quality of life, although on a smaller scale than patients assigned to a specialty team, Dr. Aaron said at the American Thoracic Society’s international conference.

He reported results of the study in a late-breaking oral abstract session. The study findings were also published online in The New England Journal of Medicine.
 

Undiagnosed diseases

“The simple problem is that 70% of individuals with asthma or COPD are likely undiagnosed,” Dr. Aaron said.

He noted that the 2007-2012 US National Health and Nutritional Examination Survey found obstructive lung disease in 13% of randomly selected US adults, but 71% of these people had never been diagnosed with asthma or COPD.

“So our questions were in this study: One, can we find adults with undiagnosed asthma or COPD in the community? The second question was: If we find them, are they sick? And the third and most important question was: Can we treat them early and improve their health outcomes?” he said.

Asthma and COPD both present with similar respiratory symptoms, including dyspnea, cough, wheeze, and/or chest tightness, and the two conditions share expiratory airflow obstruction as a common physiologic impairment that can be detected with spirometry.
 

Study details

To identify participants, the investigators hired a commercial survey firm to contact households asking whether any member aged 18 years or older had respiratory symptoms such as shortness of breath, wheezing, increased mucus or sputum production, or prolonged cough in the past 6 months. Those who responded yes were then contacted by a trial coordinator, and the symptomatic household member was asked to complete the Asthma Screening Questionnaire over the phone. Participants aged 60 years or older and those younger than 60 years with a score of 6 or higher on the asthma screen also completed the COPD Diagnostic Questionnaire.

Those with a score of 6 or higher on the asthma screen or 20 or higher on the COPD screen were invited to undergo spirometry at a trial site.

The investigators ultimately identified 508 adults with undiagnosed asthma or COPD and randomly assigned them on an equal basis to an intervention group (253 patients) or control group (255 patients).

In the intervention group treatment was provided by a study pulmonologist and asthma-COPD educator who started guideline-based care. Patients were prescribed inhalers and were taught how to use them, and many were given action plans that included smoking cessation aids, exercise and weight counseling, and vaccinations against influenza and pneumonia.

Participants assigned to the control group would receive usual care provided by their primary care practitioner.
 

Improvements abound

During the 12 months of the study, 92% of patients in the intervention group and 60% in the control group were started on new medications for their condition. 

Only 13.4% of those in the intervention group received either no respiratory treatments or a short-acting beta 2 agonist only during the entire trial period compared with 49.8% of controls, “so the usual care arm was undertreated relative to the intervention arm, and because of that under-treatment we saw a tremendous difference in the primary outcome,” Dr. Aaron said.

The primary outcome, the annualized rate of patient-initiated healthcare utilization for respiratory illness, was significantly lower in the intervention group, translating into an incidence rate ratio of 0.48 (P < .001).

Secondary outcomes were also better in the intervention group. For example, total scores on the St. George Respiratory Questionnaire (SGRQ) declined by 10.2 points from baseline in intervention group compared with a 6.8-point drop in the usual-care group. The mean difference was 3.5 points (P = .009). Lower scores on the 0-100 SGRQ scale indicate better health status.

Similarly, total scores on the COPD Assessment Test, a scale of 0-40 with lower scores indicating better health, declined by 3.8 points and 2.6 points, respectively, over 12 months, for a mean difference of 1.3 points (P = .03).

In addition, those in the intervention arm had a 119-mL improvement in forced expiratory volume in 1 second over the 12 months of the study compared with only a 22-mL improvement in the usual-care group.
 

Translatable results?

Dr. Aaron acknowledged that the investigators could have chosen to keep those who were assigned to the control group unaware of their diagnosis during the study but because all patients enrolled were symptomatic, it would have been unethical to do so. All participants were informed of their diagnosis at randomization, and the information was conveyed to each patient’s primary care practitioner as well.

In fact, many patients in the control group decided to seek treatment for either asthma or COPD after learning of their diagnosis, which may have contributed to improved outcomes in the control arm, he said.

“What this means is if you make the diagnosis early in the community, and at least have them see a primary care practitioner, they will improve their quality of life and their health status,” he concluded.

Ravi Kalhan, MD, MS, from the Northwestern University Feinberg School Of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the case-finding model used in the trial would be difficult to replicate elsewhere.

“This idea of seeking out undiagnosed people by doing spirometry, so-called ‘case finding’ as they described it, testing highly symptomatic people with spirometry, is really challenging in the US, because symptoms are not collected proactively very much,” he said.

Persons with acute respiratory symptoms in the US typically seek healthcare at urgent-care clinics or have unscheduled visits with their primary care physicians, “and by all accounts those people should have spirometry, but they just don’t in the US, as best as I can tell,” he added.

He agreed that getting patients to a specialist can result in better outcomes but said that implementing a systematic approach such as the one described in the study would be extremely difficult in the fragmented US healthcare system.

Dr. Kalhan’s co-moderator, Nuala J. Meyer, MD, MS, from the Hospital of the University of Pennsylvania, Philadelphia, told Chest Physician that “it was interesting that even those who were not in the intervention group but had these details passed on to their primary care physicians still had improvements,” and that it would be beneficial if primary care practitioners were routinely informed about the results of urgent care visits.

She added, however, that in the US the flow of information between urgent care clinics, primary care offices, and specialty clinics is problematic, suggesting that symptomatic patients may not always receive the additional care that they need.

The study was supported by the Canadian Institutes of Health Research. Dr. Aaron, Dr. Kalhan, and Dr. Meyer all reported having no relevant disclosures. 

A version of this article appeared on Medscape.com.

SAN DIEGO – No matter where on earth you live, there’s likely to be an eye in the sky hovering overhead, and that’s a good thing, at least when it comes to satellite monitoring of air quality, said scientists from the National Aeronautics and Space Administration (NASA).

In a special symposium held at the American Thoracic Society’s international conference, NASA health and air quality specialists described the use of space-based systems and earth science applications to improve understanding of respiratory health risks worldwide, and to help enrich pulmonary research with galaxies of data.

“Every day we download over 25 terabytes of data,” said John Haynes, MS, program manager for Health and Air Quality Applications in the Earth Action Program of the NASA Earth Science Division in Washington.

Neil Osterweil/MDedge News

“Many of the observation data sets are critical for healthy air quality applications: observation of land surface temperature, sea surface temperature, precipitation, fires and thermal anomalies, aerosols, just to name a few, and the really awesome news is this offering from our constellation of satellites is free and open access, available to everyone across the globe,” he said.

The mission of NASA’s Earth Action Program is “to enable people and organizations to apply insights from Earth science to benefit the economy, health, quality of life, and environment.”

Program staff work with both industry and nonprofit environmental advocacy and health groups to help inform their decisions and actions with Earth science information.

NASA supports the use of Earth observations to help monitor and manage infectious diseases and environmental health, toxins and pathogens that affect health, air quality standards, and to assess the effects of climate change on air quality and public health.

Mr. Haynes noted that worldwide, six major cities have incorporated NASA data on fine particulate matter smaller than 2.5 microns (PM2.5) into their climate action plans. These cities include Accra, Ghana; Addis Ababa, Ethiopia; Buenos Aires, Argentina; Guadalajara, Mexico; Lima, Peru; and Johannesburg, South Africa.
 

Monitoring pollution with TEMPO

There are more than 30 Earth-monitoring systems currently in orbit or soon to be launched, including NASA’s Tropospheric Emissions: Monitoring of Pollution (TEMPO), launched in April 2023, with first operations in August 2023. The instrument is in a geostationary orbit about 22,236 miles above the equator at longitudes that allow it to survey virtually all of North America — from coast to coast, and from southern Mexico, Cuba, Puerto Rico, and the Bahamas to Northern Canada.

TEMPO is part of a geostationary air quality satellite “constellation” or group that provides daylight observation over the entire Northern Hemisphere, explained Aaron Naeger, PhD, MS, mission applications lead for TEMPO at the NASA Marshall Space Flight Center in Huntsville, Alabama.

Until TEMPO, space-based instruments had relatively low spatial resolution and could only capture one image each day. In contrast, TEMPO can scan east-west each daylight hour across its entire coverage area (known as the Field of Regard), and even more frequently during early morning and late afternoon. This allows researchers to measure volumes of pollution, sources, and how these pollution levels vary over time. The system measures ozone levels, nitrogen dioxide (NO₂,) formaldehyde, and aerosols.

More than 100 federal, state, local and tribal air quality agencies use the data captured by TEMPO to inform public health efforts.

Dr. Naeger gave examples of how the system can help identify public health hazards, including scans that showed high NO₂ levels from cities, traffic corridors, power plants, oil and gas fields, and fires.

Similarly, the system detected unhealthy ozone and PM2.5 levels during prescribed burns in April 2024, as well as notable differences between weekdays and weekends in NO₂ concentrations across California and the Front Range in Colorado. These showed higher levels along traffic corridors during weekdays related to increased traffic volumes and tailpipe emissions.
 

Fire and heat

Other NASA health and air quality initiatives include the FireAQ project, based at the University of Iowa in Iowa City, which provides free online weekly briefings on fire-related air quality concerns using data from TEMPO and other NASA satellite systems. The FireAQ project was described by Jun Wang, PhD, from the University of Iowa in Iowa City.

NASA also fosters collaborations to reduce health disparities in air quality and respiratory health in urban heat islands and other areas affected by extreme temperatures due to climate change, as discussed by Christopher K. Uejio, PhD, from Florida State University in Tallahassee.

Air pollution expert George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the session, said that the PM2.5 standard includes nontoxic particulate matter, such as soil, and misses sub-micron sized particles, and asked Mr. Haynes whether smaller particles were being measured in the studies he described.

Mr. Haynes replied that the systems do not directly measure PM2.5 but instead rely on aerosol optical depth, a measure of the extent to which atmospheric particles absorb or scatter sunlight.

Dr. Thurston, who in 1987 was coauthor of groundbreaking study showing the link between PM2.5 levels and mortality, is now an advocate for a tougher standard of measuring ambient ultrafine particles with an aerodynamic diameter less than .1 microns in size (PM1).

NASA health and climate data are available at https://www.earthdata.nasa.gov/.

Mr. Haynes and Dr. Naeger are NASA employees. Dr. Thurston had no relevant disclosures.

SAN DIEGO – No matter where on earth you live, there’s likely to be an eye in the sky hovering overhead, and that’s a good thing, at least when it comes to satellite monitoring of air quality, said scientists from the National Aeronautics and Space Administration (NASA).

In a special symposium held at the American Thoracic Society’s international conference, NASA health and air quality specialists described the use of space-based systems and earth science applications to improve understanding of respiratory health risks worldwide, and to help enrich pulmonary research with galaxies of data.

“Every day we download over 25 terabytes of data,” said John Haynes, MS, program manager for Health and Air Quality Applications in the Earth Action Program of the NASA Earth Science Division in Washington.

Neil Osterweil/MDedge News

“Many of the observation data sets are critical for healthy air quality applications: observation of land surface temperature, sea surface temperature, precipitation, fires and thermal anomalies, aerosols, just to name a few, and the really awesome news is this offering from our constellation of satellites is free and open access, available to everyone across the globe,” he said.

The mission of NASA’s Earth Action Program is “to enable people and organizations to apply insights from Earth science to benefit the economy, health, quality of life, and environment.”

Program staff work with both industry and nonprofit environmental advocacy and health groups to help inform their decisions and actions with Earth science information.

NASA supports the use of Earth observations to help monitor and manage infectious diseases and environmental health, toxins and pathogens that affect health, air quality standards, and to assess the effects of climate change on air quality and public health.

Mr. Haynes noted that worldwide, six major cities have incorporated NASA data on fine particulate matter smaller than 2.5 microns (PM2.5) into their climate action plans. These cities include Accra, Ghana; Addis Ababa, Ethiopia; Buenos Aires, Argentina; Guadalajara, Mexico; Lima, Peru; and Johannesburg, South Africa.
 

Monitoring pollution with TEMPO

There are more than 30 Earth-monitoring systems currently in orbit or soon to be launched, including NASA’s Tropospheric Emissions: Monitoring of Pollution (TEMPO), launched in April 2023, with first operations in August 2023. The instrument is in a geostationary orbit about 22,236 miles above the equator at longitudes that allow it to survey virtually all of North America — from coast to coast, and from southern Mexico, Cuba, Puerto Rico, and the Bahamas to Northern Canada.

TEMPO is part of a geostationary air quality satellite “constellation” or group that provides daylight observation over the entire Northern Hemisphere, explained Aaron Naeger, PhD, MS, mission applications lead for TEMPO at the NASA Marshall Space Flight Center in Huntsville, Alabama.

Until TEMPO, space-based instruments had relatively low spatial resolution and could only capture one image each day. In contrast, TEMPO can scan east-west each daylight hour across its entire coverage area (known as the Field of Regard), and even more frequently during early morning and late afternoon. This allows researchers to measure volumes of pollution, sources, and how these pollution levels vary over time. The system measures ozone levels, nitrogen dioxide (NO₂,) formaldehyde, and aerosols.

More than 100 federal, state, local and tribal air quality agencies use the data captured by TEMPO to inform public health efforts.

Dr. Naeger gave examples of how the system can help identify public health hazards, including scans that showed high NO₂ levels from cities, traffic corridors, power plants, oil and gas fields, and fires.

Similarly, the system detected unhealthy ozone and PM2.5 levels during prescribed burns in April 2024, as well as notable differences between weekdays and weekends in NO₂ concentrations across California and the Front Range in Colorado. These showed higher levels along traffic corridors during weekdays related to increased traffic volumes and tailpipe emissions.
 

Fire and heat

Other NASA health and air quality initiatives include the FireAQ project, based at the University of Iowa in Iowa City, which provides free online weekly briefings on fire-related air quality concerns using data from TEMPO and other NASA satellite systems. The FireAQ project was described by Jun Wang, PhD, from the University of Iowa in Iowa City.

NASA also fosters collaborations to reduce health disparities in air quality and respiratory health in urban heat islands and other areas affected by extreme temperatures due to climate change, as discussed by Christopher K. Uejio, PhD, from Florida State University in Tallahassee.

Air pollution expert George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the session, said that the PM2.5 standard includes nontoxic particulate matter, such as soil, and misses sub-micron sized particles, and asked Mr. Haynes whether smaller particles were being measured in the studies he described.

Mr. Haynes replied that the systems do not directly measure PM2.5 but instead rely on aerosol optical depth, a measure of the extent to which atmospheric particles absorb or scatter sunlight.

Dr. Thurston, who in 1987 was coauthor of groundbreaking study showing the link between PM2.5 levels and mortality, is now an advocate for a tougher standard of measuring ambient ultrafine particles with an aerodynamic diameter less than .1 microns in size (PM1).

NASA health and climate data are available at https://www.earthdata.nasa.gov/.

Mr. Haynes and Dr. Naeger are NASA employees. Dr. Thurston had no relevant disclosures.

SAN DIEGO – No matter where on earth you live, there’s likely to be an eye in the sky hovering overhead, and that’s a good thing, at least when it comes to satellite monitoring of air quality, said scientists from the National Aeronautics and Space Administration (NASA).

In a special symposium held at the American Thoracic Society’s international conference, NASA health and air quality specialists described the use of space-based systems and earth science applications to improve understanding of respiratory health risks worldwide, and to help enrich pulmonary research with galaxies of data.

“Every day we download over 25 terabytes of data,” said John Haynes, MS, program manager for Health and Air Quality Applications in the Earth Action Program of the NASA Earth Science Division in Washington.

Neil Osterweil/MDedge News

“Many of the observation data sets are critical for healthy air quality applications: observation of land surface temperature, sea surface temperature, precipitation, fires and thermal anomalies, aerosols, just to name a few, and the really awesome news is this offering from our constellation of satellites is free and open access, available to everyone across the globe,” he said.

The mission of NASA’s Earth Action Program is “to enable people and organizations to apply insights from Earth science to benefit the economy, health, quality of life, and environment.”

Program staff work with both industry and nonprofit environmental advocacy and health groups to help inform their decisions and actions with Earth science information.

NASA supports the use of Earth observations to help monitor and manage infectious diseases and environmental health, toxins and pathogens that affect health, air quality standards, and to assess the effects of climate change on air quality and public health.

Mr. Haynes noted that worldwide, six major cities have incorporated NASA data on fine particulate matter smaller than 2.5 microns (PM2.5) into their climate action plans. These cities include Accra, Ghana; Addis Ababa, Ethiopia; Buenos Aires, Argentina; Guadalajara, Mexico; Lima, Peru; and Johannesburg, South Africa.
 

Monitoring pollution with TEMPO

There are more than 30 Earth-monitoring systems currently in orbit or soon to be launched, including NASA’s Tropospheric Emissions: Monitoring of Pollution (TEMPO), launched in April 2023, with first operations in August 2023. The instrument is in a geostationary orbit about 22,236 miles above the equator at longitudes that allow it to survey virtually all of North America — from coast to coast, and from southern Mexico, Cuba, Puerto Rico, and the Bahamas to Northern Canada.

TEMPO is part of a geostationary air quality satellite “constellation” or group that provides daylight observation over the entire Northern Hemisphere, explained Aaron Naeger, PhD, MS, mission applications lead for TEMPO at the NASA Marshall Space Flight Center in Huntsville, Alabama.

Until TEMPO, space-based instruments had relatively low spatial resolution and could only capture one image each day. In contrast, TEMPO can scan east-west each daylight hour across its entire coverage area (known as the Field of Regard), and even more frequently during early morning and late afternoon. This allows researchers to measure volumes of pollution, sources, and how these pollution levels vary over time. The system measures ozone levels, nitrogen dioxide (NO₂,) formaldehyde, and aerosols.

More than 100 federal, state, local and tribal air quality agencies use the data captured by TEMPO to inform public health efforts.

Dr. Naeger gave examples of how the system can help identify public health hazards, including scans that showed high NO₂ levels from cities, traffic corridors, power plants, oil and gas fields, and fires.

Similarly, the system detected unhealthy ozone and PM2.5 levels during prescribed burns in April 2024, as well as notable differences between weekdays and weekends in NO₂ concentrations across California and the Front Range in Colorado. These showed higher levels along traffic corridors during weekdays related to increased traffic volumes and tailpipe emissions.
 

Fire and heat

Other NASA health and air quality initiatives include the FireAQ project, based at the University of Iowa in Iowa City, which provides free online weekly briefings on fire-related air quality concerns using data from TEMPO and other NASA satellite systems. The FireAQ project was described by Jun Wang, PhD, from the University of Iowa in Iowa City.

NASA also fosters collaborations to reduce health disparities in air quality and respiratory health in urban heat islands and other areas affected by extreme temperatures due to climate change, as discussed by Christopher K. Uejio, PhD, from Florida State University in Tallahassee.

Air pollution expert George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the session, said that the PM2.5 standard includes nontoxic particulate matter, such as soil, and misses sub-micron sized particles, and asked Mr. Haynes whether smaller particles were being measured in the studies he described.

Mr. Haynes replied that the systems do not directly measure PM2.5 but instead rely on aerosol optical depth, a measure of the extent to which atmospheric particles absorb or scatter sunlight.

Dr. Thurston, who in 1987 was coauthor of groundbreaking study showing the link between PM2.5 levels and mortality, is now an advocate for a tougher standard of measuring ambient ultrafine particles with an aerodynamic diameter less than .1 microns in size (PM1).

NASA health and climate data are available at https://www.earthdata.nasa.gov/.

Mr. Haynes and Dr. Naeger are NASA employees. Dr. Thurston had no relevant disclosures.

PARIS — While anaphylaxis requires immediate adrenaline administration through autoinjection, the use of this treatment is not optimal. Therefore, the development of new adrenaline formulations (such as for intranasal, sublingual, and transcutaneous routes) aims to facilitate the drug’s use and reduce persistent delays in administration by patients and caregivers. An overview of the research was presented at the 19th French-speaking Congress of Allergology.

Anaphylaxis is a severe and potentially fatal immediate hypersensitivity reaction with highly variable and dynamic clinical presentations. It requires prompt recognition for immediate treatment with intramuscular (IM) adrenaline (at the anterolateral aspect of the mid-thigh).

One might think that this reflex is acquired, but in France, while the number of prescribed adrenaline autoinjection (AAI) devices has been increasing for a decade, reaching 965,944 units in 2022, this first-line treatment is underused. Anapen (150, 300, and 500 µg), EpiPen (150 and 300 µg), Jext (150 µg and 300 µg), and Emerade (150, 300, and 500 µg) are the four products marketed in France in 2024.

“Only 17.3% of individuals presenting to the emergency department in the Lorraine region used it in 2015,” said Catherine Neukirch, MD, a pneumologist at Hôpital Bichat–Claude Bernard in Paris, France, with rates of 11.3% for children and 20.3% for adults.
 

Anaphylaxis Incidence Increasing

Approximately 0.3% (95% CI, 0.1-0.5) of the population will experience an anaphylaxis episode in their lifetime. Incidence in Europe, across all causes, is estimated between 1.5 and 7.9 cases per 100,000 inhabitants per year. Although anaphylaxis is on the rise, its associated mortality remains low, ranging between 0.05 and 0.51 per million per year for drugs, between 0.03 and 0.32 per million per year for foods, and between 0.09 and 0.13 per million per year for hymenopteran venoms.

Data from the European Anaphylaxis Registry indicate that anaphylaxis manifests rapidly after allergen exposure: 55% of cases occur within 10 minutes and 80% within 30 minutes. In addition, a biphasic reaction, which can occur up to 72 hours after exposure, is observed in < 5% of cases.

While a delay in adrenaline use is associated with risk for increased morbidity and mortality, AAI significantly reduces error rates compared with manual treatments involving ampoules, needles, and syringes. It also reduces the associated panic risks. However, there are multiple barriers to adrenaline use. The clinical symptoms of anaphylaxis may be misleading, especially if it occurs without cutaneous and urticarial manifestations but with only acute bronchospasm. It may present as isolated laryngeal edema without digestive involvement, hypotension, or other respiratory problems.

Other limitations to adrenaline use include technical difficulties and the possibility of incorrect administration, the need for appropriate needle sizes for patients with obesity, needle phobia, potential adverse effects of adrenaline injections, failure to carry two autoinjectors, constraints related to storage and bulky transport, as well as the need for training and practice.

“These factors contribute to underuse of adrenaline by patients and caregivers,” said Dr. Neukirch, which results in delays in necessary administration.
 

Adrenaline Treatment Criteria?

An analysis published in 2023 based on pharmacovigilance data from 30 regional French centers from 1984 to 2022 included 42 reported cases (average age, 33 years; 26% children) of reactions to AAI, which probably is an underestimate. About 40% of AAI uses occurred during anaphylaxis. The remaining 60% were triggered outside of reactions. The main reasons were accidental injections, mainly in the fingers, and cases of not triggering the autoinjector, underlining the importance of patient education.

In 2015, the European Medicines Agency required pharmacological studies for injectable adrenaline on healthy volunteers. These studies include ultrasound measurements of bolus injection, pharmacokinetics (ie, absorption, distribution, metabolism, and excretion), and pharmacodynamics (ie, the effect of the drug and the mechanism of action in the body), with precise evaluation of cardiovascular effects (eg, systolic and diastolic blood pressures and heart rate).

Among the information collected with the different products, ultrasound studies have shown a different localization of the adrenaline bolus (ie, in muscle in patients with normal BMI and mostly in adipose tissue in patients with BMI indicating overweight and obesity). The consequences of this finding are still unknown.

In a study with 500 µg Anapen, women with overweight or obesity showed different pharmacokinetic or pharmacodynamic profiles from those in men with normal weight, with an increase in the area under the curve (0-240 min) and marked changes in the heart rate time curve.

IM administration of 0.5 mg produces rapid pharmacokinetic effects in patients with normal weight, overweight, or obesity, with a delay for the second peak in the latter case. This delay perhaps results from initial local vasoconstriction due to adrenaline.

The early peak plasma concentration occurs at 5-10 minutes for AAI, with a faster speed for Anapen and EpiPen.

Moreover, needle size is not the most important factor. Rather, it is the strength and speed of injection, which can vary depending on the AAI.

Also, the optimal plasma concentration of adrenaline to treat anaphylaxis is not known; studies cannot be conducted during anaphylaxis. In terms of pharmacokinetics, a small series discovered that increased skin or muscle thickness delays the absorption of EpiPen AAI.
 

Intranasal Adrenaline

To facilitate rapid adrenaline use and convince reluctant patients to carry and use adrenaline, intranasal, sublingual, or transcutaneous forms are under development.

Three intranasal forms of adrenaline are already well advanced, including Neffy from ARS Pharma, epinephrine sprays from Bryn Pharma and Hikma, and Oxero from Oragoo, which contains dry powder.

A comparison of intranasal adrenaline Neffy and AAI shows that the former has satisfactory pharmacokinetic and pharmacodynamic effects.

In a phase 1 randomized crossover study of 42 healthy adults comparing the pharmacokinetic effects of Neffy adrenaline (2 mg) and EpiPen (0.3 mg), as well as IM epinephrine 0.3 mg, several observations were made. For a single dose, the maximum concentration (Cmax) of Neffy was lower than that of EpiPen.

However, with repeated doses administered 10 minutes apart, the Cmax of Neffy was higher than that of EpiPen. At this stage, pharmacodynamic responses to intranasal products are at least comparable with those of approved injectable products.

A comparison of the pharmacodynamic effects, such as systolic and diastolic blood pressures and heart rate, of Neffy adrenaline and AAI concluded that the profile of Neffy is comparable with that of EpiPen and superior to that of IM epinephrine.

In patients with a history of allergic rhinitis, adrenaline Cmax appears to be increased, while time to peak plasma concentration (Tmax) is reduced. Low blood pressure does not prevent Neffy absorption. Neffy is currently under review by the American and European health authorities.

Intranasal absorption of dry powder adrenaline appears to be faster than that of EpiPen, thus offering a clinical advantage in the short therapeutic window for anaphylaxis treatment.

In an open-label trial conducted on 12 adults with seasonal allergic rhinitis without asthma, the pharmacokinetics, pharmacodynamics, and safety of adrenaline were compared between FMXIN002 (1.6 and 3.2 mg), which was administered intranasally with or without nasal allergen challenge, and IM EpiPen 0.3 mg. Pharmacokinetics varied by patient. Nevertheless, nasal FMXIN002 had a shorter Tmax, a doubled Cmax after the allergen challenge peak, and a higher area under the curve in the 8 hours following administration compared with EpiPen. Pharmacodynamic effects comparable with those of EpiPen were noted at 15 minutes to 4 hours after administration. The tolerance was good, with mild and local side effects. The powder seems to deposit slightly better in the nasal cavity. It remains stable for 6 months at a temperature of 40 °C and relative humidity of 75% and for 2 years at a temperature of 25 °C and relative humidity of 60%.
 

Sublingual Adrenaline Film

AQST-109 is a sublingual film that is intended to allow rapid administration of epinephrine 1, which is a prodrug of adrenaline. The product is the size of a postage stamp, weighs < 30 g, and dissolves on contact with the tongue.

The EPIPHAST II study was a phase 1, multiperiod, crossover study conducted on 24 healthy adults (age, 24-49 years) who were randomly assigned to receive either 12 or 0.3 mg of AQST-109  of manual IM adrenaline in the first two periods. All participants received 0.3 mg of EpiPen in the last period.

EpiPen 0.3 mg resulted in a higher Cmax than AQST-109 12 mg. AQST-109 12 mg had the fastest median Tmax of 12 minutes. The areas under the curve of AQST-109 12 mg fell between those of EpiPen 0.3 mg and manual IM adrenaline 0.3 mg.

Early increases in systolic blood pressure, diastolic blood pressure, and heart rate were observed with AQST-109 12 mg. Changes were more pronounced with AQST-109 12 mg despite a higher Cmax with EpiPen 0.3 mg.

Part 3 of the EPIPHAST study evaluated the impact of food exposure (ie, a peanut butter sandwich) on the pharmacokinetics of AQST-109 12 mg in 24 healthy adults. Oral food residues did not significantly affect pharmacodynamic parameters, and no treatment-related adverse events were reported.

Researchers concluded that AQST-109 12 mg absorption would not be altered by “real” situations if used during meals. “These results suggest that the sublingual adrenaline film could be promising in real situations,” said Dr. Neukirch, especially in cases of food allergy with recent ingestion of the allergenic food.
 

Transcutaneous Adrenaline

A transcutaneous form of adrenaline that uses the Zeneo device developed by Crossject, a company based in Dijon, France, comes in the form of an AAI that requires no needle. This project, funded by the European Union, uses a gas generator to propel the drug at very high speed through the skin in 50 milliseconds. This method allows for extended drug storage.

Dr. Neukirch reported financial relationships with Viatris, Stallergènes, ALK, Astrazeneca, Sanofi, GSK, and Novartis.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — While anaphylaxis requires immediate adrenaline administration through autoinjection, the use of this treatment is not optimal. Therefore, the development of new adrenaline formulations (such as for intranasal, sublingual, and transcutaneous routes) aims to facilitate the drug’s use and reduce persistent delays in administration by patients and caregivers. An overview of the research was presented at the 19th French-speaking Congress of Allergology.

Anaphylaxis is a severe and potentially fatal immediate hypersensitivity reaction with highly variable and dynamic clinical presentations. It requires prompt recognition for immediate treatment with intramuscular (IM) adrenaline (at the anterolateral aspect of the mid-thigh).

One might think that this reflex is acquired, but in France, while the number of prescribed adrenaline autoinjection (AAI) devices has been increasing for a decade, reaching 965,944 units in 2022, this first-line treatment is underused. Anapen (150, 300, and 500 µg), EpiPen (150 and 300 µg), Jext (150 µg and 300 µg), and Emerade (150, 300, and 500 µg) are the four products marketed in France in 2024.

“Only 17.3% of individuals presenting to the emergency department in the Lorraine region used it in 2015,” said Catherine Neukirch, MD, a pneumologist at Hôpital Bichat–Claude Bernard in Paris, France, with rates of 11.3% for children and 20.3% for adults.
 

Anaphylaxis Incidence Increasing

Approximately 0.3% (95% CI, 0.1-0.5) of the population will experience an anaphylaxis episode in their lifetime. Incidence in Europe, across all causes, is estimated between 1.5 and 7.9 cases per 100,000 inhabitants per year. Although anaphylaxis is on the rise, its associated mortality remains low, ranging between 0.05 and 0.51 per million per year for drugs, between 0.03 and 0.32 per million per year for foods, and between 0.09 and 0.13 per million per year for hymenopteran venoms.

Data from the European Anaphylaxis Registry indicate that anaphylaxis manifests rapidly after allergen exposure: 55% of cases occur within 10 minutes and 80% within 30 minutes. In addition, a biphasic reaction, which can occur up to 72 hours after exposure, is observed in < 5% of cases.

While a delay in adrenaline use is associated with risk for increased morbidity and mortality, AAI significantly reduces error rates compared with manual treatments involving ampoules, needles, and syringes. It also reduces the associated panic risks. However, there are multiple barriers to adrenaline use. The clinical symptoms of anaphylaxis may be misleading, especially if it occurs without cutaneous and urticarial manifestations but with only acute bronchospasm. It may present as isolated laryngeal edema without digestive involvement, hypotension, or other respiratory problems.

Other limitations to adrenaline use include technical difficulties and the possibility of incorrect administration, the need for appropriate needle sizes for patients with obesity, needle phobia, potential adverse effects of adrenaline injections, failure to carry two autoinjectors, constraints related to storage and bulky transport, as well as the need for training and practice.

“These factors contribute to underuse of adrenaline by patients and caregivers,” said Dr. Neukirch, which results in delays in necessary administration.
 

Adrenaline Treatment Criteria?

An analysis published in 2023 based on pharmacovigilance data from 30 regional French centers from 1984 to 2022 included 42 reported cases (average age, 33 years; 26% children) of reactions to AAI, which probably is an underestimate. About 40% of AAI uses occurred during anaphylaxis. The remaining 60% were triggered outside of reactions. The main reasons were accidental injections, mainly in the fingers, and cases of not triggering the autoinjector, underlining the importance of patient education.

In 2015, the European Medicines Agency required pharmacological studies for injectable adrenaline on healthy volunteers. These studies include ultrasound measurements of bolus injection, pharmacokinetics (ie, absorption, distribution, metabolism, and excretion), and pharmacodynamics (ie, the effect of the drug and the mechanism of action in the body), with precise evaluation of cardiovascular effects (eg, systolic and diastolic blood pressures and heart rate).

Among the information collected with the different products, ultrasound studies have shown a different localization of the adrenaline bolus (ie, in muscle in patients with normal BMI and mostly in adipose tissue in patients with BMI indicating overweight and obesity). The consequences of this finding are still unknown.

In a study with 500 µg Anapen, women with overweight or obesity showed different pharmacokinetic or pharmacodynamic profiles from those in men with normal weight, with an increase in the area under the curve (0-240 min) and marked changes in the heart rate time curve.

IM administration of 0.5 mg produces rapid pharmacokinetic effects in patients with normal weight, overweight, or obesity, with a delay for the second peak in the latter case. This delay perhaps results from initial local vasoconstriction due to adrenaline.

The early peak plasma concentration occurs at 5-10 minutes for AAI, with a faster speed for Anapen and EpiPen.

Moreover, needle size is not the most important factor. Rather, it is the strength and speed of injection, which can vary depending on the AAI.

Also, the optimal plasma concentration of adrenaline to treat anaphylaxis is not known; studies cannot be conducted during anaphylaxis. In terms of pharmacokinetics, a small series discovered that increased skin or muscle thickness delays the absorption of EpiPen AAI.
 

Intranasal Adrenaline

To facilitate rapid adrenaline use and convince reluctant patients to carry and use adrenaline, intranasal, sublingual, or transcutaneous forms are under development.

Three intranasal forms of adrenaline are already well advanced, including Neffy from ARS Pharma, epinephrine sprays from Bryn Pharma and Hikma, and Oxero from Oragoo, which contains dry powder.

A comparison of intranasal adrenaline Neffy and AAI shows that the former has satisfactory pharmacokinetic and pharmacodynamic effects.

In a phase 1 randomized crossover study of 42 healthy adults comparing the pharmacokinetic effects of Neffy adrenaline (2 mg) and EpiPen (0.3 mg), as well as IM epinephrine 0.3 mg, several observations were made. For a single dose, the maximum concentration (Cmax) of Neffy was lower than that of EpiPen.

However, with repeated doses administered 10 minutes apart, the Cmax of Neffy was higher than that of EpiPen. At this stage, pharmacodynamic responses to intranasal products are at least comparable with those of approved injectable products.

A comparison of the pharmacodynamic effects, such as systolic and diastolic blood pressures and heart rate, of Neffy adrenaline and AAI concluded that the profile of Neffy is comparable with that of EpiPen and superior to that of IM epinephrine.

In patients with a history of allergic rhinitis, adrenaline Cmax appears to be increased, while time to peak plasma concentration (Tmax) is reduced. Low blood pressure does not prevent Neffy absorption. Neffy is currently under review by the American and European health authorities.

Intranasal absorption of dry powder adrenaline appears to be faster than that of EpiPen, thus offering a clinical advantage in the short therapeutic window for anaphylaxis treatment.

In an open-label trial conducted on 12 adults with seasonal allergic rhinitis without asthma, the pharmacokinetics, pharmacodynamics, and safety of adrenaline were compared between FMXIN002 (1.6 and 3.2 mg), which was administered intranasally with or without nasal allergen challenge, and IM EpiPen 0.3 mg. Pharmacokinetics varied by patient. Nevertheless, nasal FMXIN002 had a shorter Tmax, a doubled Cmax after the allergen challenge peak, and a higher area under the curve in the 8 hours following administration compared with EpiPen. Pharmacodynamic effects comparable with those of EpiPen were noted at 15 minutes to 4 hours after administration. The tolerance was good, with mild and local side effects. The powder seems to deposit slightly better in the nasal cavity. It remains stable for 6 months at a temperature of 40 °C and relative humidity of 75% and for 2 years at a temperature of 25 °C and relative humidity of 60%.
 

Sublingual Adrenaline Film

AQST-109 is a sublingual film that is intended to allow rapid administration of epinephrine 1, which is a prodrug of adrenaline. The product is the size of a postage stamp, weighs < 30 g, and dissolves on contact with the tongue.

The EPIPHAST II study was a phase 1, multiperiod, crossover study conducted on 24 healthy adults (age, 24-49 years) who were randomly assigned to receive either 12 or 0.3 mg of AQST-109  of manual IM adrenaline in the first two periods. All participants received 0.3 mg of EpiPen in the last period.

EpiPen 0.3 mg resulted in a higher Cmax than AQST-109 12 mg. AQST-109 12 mg had the fastest median Tmax of 12 minutes. The areas under the curve of AQST-109 12 mg fell between those of EpiPen 0.3 mg and manual IM adrenaline 0.3 mg.

Early increases in systolic blood pressure, diastolic blood pressure, and heart rate were observed with AQST-109 12 mg. Changes were more pronounced with AQST-109 12 mg despite a higher Cmax with EpiPen 0.3 mg.

Part 3 of the EPIPHAST study evaluated the impact of food exposure (ie, a peanut butter sandwich) on the pharmacokinetics of AQST-109 12 mg in 24 healthy adults. Oral food residues did not significantly affect pharmacodynamic parameters, and no treatment-related adverse events were reported.

Researchers concluded that AQST-109 12 mg absorption would not be altered by “real” situations if used during meals. “These results suggest that the sublingual adrenaline film could be promising in real situations,” said Dr. Neukirch, especially in cases of food allergy with recent ingestion of the allergenic food.
 

Transcutaneous Adrenaline

A transcutaneous form of adrenaline that uses the Zeneo device developed by Crossject, a company based in Dijon, France, comes in the form of an AAI that requires no needle. This project, funded by the European Union, uses a gas generator to propel the drug at very high speed through the skin in 50 milliseconds. This method allows for extended drug storage.

Dr. Neukirch reported financial relationships with Viatris, Stallergènes, ALK, Astrazeneca, Sanofi, GSK, and Novartis.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — While anaphylaxis requires immediate adrenaline administration through autoinjection, the use of this treatment is not optimal. Therefore, the development of new adrenaline formulations (such as for intranasal, sublingual, and transcutaneous routes) aims to facilitate the drug’s use and reduce persistent delays in administration by patients and caregivers. An overview of the research was presented at the 19th French-speaking Congress of Allergology.

Anaphylaxis is a severe and potentially fatal immediate hypersensitivity reaction with highly variable and dynamic clinical presentations. It requires prompt recognition for immediate treatment with intramuscular (IM) adrenaline (at the anterolateral aspect of the mid-thigh).

One might think that this reflex is acquired, but in France, while the number of prescribed adrenaline autoinjection (AAI) devices has been increasing for a decade, reaching 965,944 units in 2022, this first-line treatment is underused. Anapen (150, 300, and 500 µg), EpiPen (150 and 300 µg), Jext (150 µg and 300 µg), and Emerade (150, 300, and 500 µg) are the four products marketed in France in 2024.

“Only 17.3% of individuals presenting to the emergency department in the Lorraine region used it in 2015,” said Catherine Neukirch, MD, a pneumologist at Hôpital Bichat–Claude Bernard in Paris, France, with rates of 11.3% for children and 20.3% for adults.
 

Anaphylaxis Incidence Increasing

Approximately 0.3% (95% CI, 0.1-0.5) of the population will experience an anaphylaxis episode in their lifetime. Incidence in Europe, across all causes, is estimated between 1.5 and 7.9 cases per 100,000 inhabitants per year. Although anaphylaxis is on the rise, its associated mortality remains low, ranging between 0.05 and 0.51 per million per year for drugs, between 0.03 and 0.32 per million per year for foods, and between 0.09 and 0.13 per million per year for hymenopteran venoms.

Data from the European Anaphylaxis Registry indicate that anaphylaxis manifests rapidly after allergen exposure: 55% of cases occur within 10 minutes and 80% within 30 minutes. In addition, a biphasic reaction, which can occur up to 72 hours after exposure, is observed in < 5% of cases.

While a delay in adrenaline use is associated with risk for increased morbidity and mortality, AAI significantly reduces error rates compared with manual treatments involving ampoules, needles, and syringes. It also reduces the associated panic risks. However, there are multiple barriers to adrenaline use. The clinical symptoms of anaphylaxis may be misleading, especially if it occurs without cutaneous and urticarial manifestations but with only acute bronchospasm. It may present as isolated laryngeal edema without digestive involvement, hypotension, or other respiratory problems.

Other limitations to adrenaline use include technical difficulties and the possibility of incorrect administration, the need for appropriate needle sizes for patients with obesity, needle phobia, potential adverse effects of adrenaline injections, failure to carry two autoinjectors, constraints related to storage and bulky transport, as well as the need for training and practice.

“These factors contribute to underuse of adrenaline by patients and caregivers,” said Dr. Neukirch, which results in delays in necessary administration.
 

Adrenaline Treatment Criteria?

An analysis published in 2023 based on pharmacovigilance data from 30 regional French centers from 1984 to 2022 included 42 reported cases (average age, 33 years; 26% children) of reactions to AAI, which probably is an underestimate. About 40% of AAI uses occurred during anaphylaxis. The remaining 60% were triggered outside of reactions. The main reasons were accidental injections, mainly in the fingers, and cases of not triggering the autoinjector, underlining the importance of patient education.

In 2015, the European Medicines Agency required pharmacological studies for injectable adrenaline on healthy volunteers. These studies include ultrasound measurements of bolus injection, pharmacokinetics (ie, absorption, distribution, metabolism, and excretion), and pharmacodynamics (ie, the effect of the drug and the mechanism of action in the body), with precise evaluation of cardiovascular effects (eg, systolic and diastolic blood pressures and heart rate).

Among the information collected with the different products, ultrasound studies have shown a different localization of the adrenaline bolus (ie, in muscle in patients with normal BMI and mostly in adipose tissue in patients with BMI indicating overweight and obesity). The consequences of this finding are still unknown.

In a study with 500 µg Anapen, women with overweight or obesity showed different pharmacokinetic or pharmacodynamic profiles from those in men with normal weight, with an increase in the area under the curve (0-240 min) and marked changes in the heart rate time curve.

IM administration of 0.5 mg produces rapid pharmacokinetic effects in patients with normal weight, overweight, or obesity, with a delay for the second peak in the latter case. This delay perhaps results from initial local vasoconstriction due to adrenaline.

The early peak plasma concentration occurs at 5-10 minutes for AAI, with a faster speed for Anapen and EpiPen.

Moreover, needle size is not the most important factor. Rather, it is the strength and speed of injection, which can vary depending on the AAI.

Also, the optimal plasma concentration of adrenaline to treat anaphylaxis is not known; studies cannot be conducted during anaphylaxis. In terms of pharmacokinetics, a small series discovered that increased skin or muscle thickness delays the absorption of EpiPen AAI.
 

Intranasal Adrenaline

To facilitate rapid adrenaline use and convince reluctant patients to carry and use adrenaline, intranasal, sublingual, or transcutaneous forms are under development.

Three intranasal forms of adrenaline are already well advanced, including Neffy from ARS Pharma, epinephrine sprays from Bryn Pharma and Hikma, and Oxero from Oragoo, which contains dry powder.

A comparison of intranasal adrenaline Neffy and AAI shows that the former has satisfactory pharmacokinetic and pharmacodynamic effects.

In a phase 1 randomized crossover study of 42 healthy adults comparing the pharmacokinetic effects of Neffy adrenaline (2 mg) and EpiPen (0.3 mg), as well as IM epinephrine 0.3 mg, several observations were made. For a single dose, the maximum concentration (Cmax) of Neffy was lower than that of EpiPen.

However, with repeated doses administered 10 minutes apart, the Cmax of Neffy was higher than that of EpiPen. At this stage, pharmacodynamic responses to intranasal products are at least comparable with those of approved injectable products.

A comparison of the pharmacodynamic effects, such as systolic and diastolic blood pressures and heart rate, of Neffy adrenaline and AAI concluded that the profile of Neffy is comparable with that of EpiPen and superior to that of IM epinephrine.

In patients with a history of allergic rhinitis, adrenaline Cmax appears to be increased, while time to peak plasma concentration (Tmax) is reduced. Low blood pressure does not prevent Neffy absorption. Neffy is currently under review by the American and European health authorities.

Intranasal absorption of dry powder adrenaline appears to be faster than that of EpiPen, thus offering a clinical advantage in the short therapeutic window for anaphylaxis treatment.

In an open-label trial conducted on 12 adults with seasonal allergic rhinitis without asthma, the pharmacokinetics, pharmacodynamics, and safety of adrenaline were compared between FMXIN002 (1.6 and 3.2 mg), which was administered intranasally with or without nasal allergen challenge, and IM EpiPen 0.3 mg. Pharmacokinetics varied by patient. Nevertheless, nasal FMXIN002 had a shorter Tmax, a doubled Cmax after the allergen challenge peak, and a higher area under the curve in the 8 hours following administration compared with EpiPen. Pharmacodynamic effects comparable with those of EpiPen were noted at 15 minutes to 4 hours after administration. The tolerance was good, with mild and local side effects. The powder seems to deposit slightly better in the nasal cavity. It remains stable for 6 months at a temperature of 40 °C and relative humidity of 75% and for 2 years at a temperature of 25 °C and relative humidity of 60%.
 

Sublingual Adrenaline Film

AQST-109 is a sublingual film that is intended to allow rapid administration of epinephrine 1, which is a prodrug of adrenaline. The product is the size of a postage stamp, weighs < 30 g, and dissolves on contact with the tongue.

The EPIPHAST II study was a phase 1, multiperiod, crossover study conducted on 24 healthy adults (age, 24-49 years) who were randomly assigned to receive either 12 or 0.3 mg of AQST-109  of manual IM adrenaline in the first two periods. All participants received 0.3 mg of EpiPen in the last period.

EpiPen 0.3 mg resulted in a higher Cmax than AQST-109 12 mg. AQST-109 12 mg had the fastest median Tmax of 12 minutes. The areas under the curve of AQST-109 12 mg fell between those of EpiPen 0.3 mg and manual IM adrenaline 0.3 mg.

Early increases in systolic blood pressure, diastolic blood pressure, and heart rate were observed with AQST-109 12 mg. Changes were more pronounced with AQST-109 12 mg despite a higher Cmax with EpiPen 0.3 mg.

Part 3 of the EPIPHAST study evaluated the impact of food exposure (ie, a peanut butter sandwich) on the pharmacokinetics of AQST-109 12 mg in 24 healthy adults. Oral food residues did not significantly affect pharmacodynamic parameters, and no treatment-related adverse events were reported.

Researchers concluded that AQST-109 12 mg absorption would not be altered by “real” situations if used during meals. “These results suggest that the sublingual adrenaline film could be promising in real situations,” said Dr. Neukirch, especially in cases of food allergy with recent ingestion of the allergenic food.
 

Transcutaneous Adrenaline

A transcutaneous form of adrenaline that uses the Zeneo device developed by Crossject, a company based in Dijon, France, comes in the form of an AAI that requires no needle. This project, funded by the European Union, uses a gas generator to propel the drug at very high speed through the skin in 50 milliseconds. This method allows for extended drug storage.

Dr. Neukirch reported financial relationships with Viatris, Stallergènes, ALK, Astrazeneca, Sanofi, GSK, and Novartis.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

SAN DIEGO — While there is currently no smoking gun definitively showing that indoor nitrogen dioxide (NO₂) concentrations from gas appliances are a cause of pulmonary diseases, the circumstantial evidence of the baleful effects of gas stoves on lung function is pretty compelling, said participants in a pro-con debate.

In what the moderator called “one of the most agreeable debates yet,” experts presented their views on the risks that cooking with natural gas pose on pulmonary health, and discussed ways for mitigating that harm. The debate was held at the American Thoracic Society’s international conference.
 

PRO: Gas stoves cause lung disease

Arguing for the “pro” side, John R. Balmes, MD of the University of California, San Francisco, and a physician member of the California Air Resources Board, began by admitting that “I would never have said gas stoves cause lung disease, but that’s what they assigned me.”

Gamely proceeding anyway, Dr. Balmes noted that natural gas — methane — is a potent greenhouse gas, and that cooking with natural gas leads to generation of NO₂ with high peak concentrations in the home, especially in the kitchen, but in other rooms as well.

Neil Osterweil/MDedge News

Con: More evidence needed

Arguing for the “con” side of the question, Meredith C. McCormack, MD, MHS, professor of medicine in the pulmonary and critical care division at Johns Hopkins University in Baltimore, said that “more definitive evidence is needed to define whether gas stoves cause lung disease.”

But Dr. McCormack didn’t let the natural gas industry off the hook, noting that a systematic review and meta-analysis of cooking with gas in high-, middle-, and low-income countries showed that domestic use of gas fuels vs. electric was associated with increased risk of asthma (1.11 overall), COPD (1.15), and pneumonia (1.26).

Neil Osterweil/MDedge News

On common ground

Environmental interventions that can benefit all members of a household — not just those with obstructive pulmonary disease — include smoking cessation, charcoal filter-equipped air cleaners, stove hoods that vent outdoors, integrated pest management, hypoallergenic pillow and mattress covers, high efficiency particulate air (HEPA) vacuums, and mold and radon abatement.

Both Dr. Balmes and Dr. McCormack agreed in the end that gas stoves contribute to respiratory morbidity, and that both state and national policy changes are needed to support transition to cleaner indoor air, with financial incentives available for households with more modest incomes.

“For everyone, there is a climate-change mitigation imperative to transition away from gas appliances if we want to tackle the climate emergency,” Dr. Balmes said.
 

End indoor combustion

George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the debate, told Chest Physician that the participants talked about NO₂ but didn’t touch on particulate pollution generated by gas stoves.

Burning natural gas produces particles that are very similar in composition to those produced by burning coal, oil, or diesel fuel, Dr. Thurston said, and he pointed out that interventions such as range hoods work only if they actually vent outdoors, and aren’t simply fans that recirculate the air within the home. And even when ventilation works as it should to move air out of the house, it only pumps it back into the atmosphere, where it contributes to climate change.

“We need combustion-free homes. That’s the unifying principle. We have to keep our eyes on that prize,” he said.

Dr. Balmes, Dr. McCormack, and Dr. Thurston all reported having no relevant disclosures.

SAN DIEGO — While there is currently no smoking gun definitively showing that indoor nitrogen dioxide (NO₂) concentrations from gas appliances are a cause of pulmonary diseases, the circumstantial evidence of the baleful effects of gas stoves on lung function is pretty compelling, said participants in a pro-con debate.

In what the moderator called “one of the most agreeable debates yet,” experts presented their views on the risks that cooking with natural gas pose on pulmonary health, and discussed ways for mitigating that harm. The debate was held at the American Thoracic Society’s international conference.
 

PRO: Gas stoves cause lung disease

Arguing for the “pro” side, John R. Balmes, MD of the University of California, San Francisco, and a physician member of the California Air Resources Board, began by admitting that “I would never have said gas stoves cause lung disease, but that’s what they assigned me.”

Gamely proceeding anyway, Dr. Balmes noted that natural gas — methane — is a potent greenhouse gas, and that cooking with natural gas leads to generation of NO₂ with high peak concentrations in the home, especially in the kitchen, but in other rooms as well.

Neil Osterweil/MDedge News

Con: More evidence needed

Arguing for the “con” side of the question, Meredith C. McCormack, MD, MHS, professor of medicine in the pulmonary and critical care division at Johns Hopkins University in Baltimore, said that “more definitive evidence is needed to define whether gas stoves cause lung disease.”

But Dr. McCormack didn’t let the natural gas industry off the hook, noting that a systematic review and meta-analysis of cooking with gas in high-, middle-, and low-income countries showed that domestic use of gas fuels vs. electric was associated with increased risk of asthma (1.11 overall), COPD (1.15), and pneumonia (1.26).

Neil Osterweil/MDedge News

On common ground

Environmental interventions that can benefit all members of a household — not just those with obstructive pulmonary disease — include smoking cessation, charcoal filter-equipped air cleaners, stove hoods that vent outdoors, integrated pest management, hypoallergenic pillow and mattress covers, high efficiency particulate air (HEPA) vacuums, and mold and radon abatement.

Both Dr. Balmes and Dr. McCormack agreed in the end that gas stoves contribute to respiratory morbidity, and that both state and national policy changes are needed to support transition to cleaner indoor air, with financial incentives available for households with more modest incomes.

“For everyone, there is a climate-change mitigation imperative to transition away from gas appliances if we want to tackle the climate emergency,” Dr. Balmes said.
 

End indoor combustion

George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the debate, told Chest Physician that the participants talked about NO₂ but didn’t touch on particulate pollution generated by gas stoves.

Burning natural gas produces particles that are very similar in composition to those produced by burning coal, oil, or diesel fuel, Dr. Thurston said, and he pointed out that interventions such as range hoods work only if they actually vent outdoors, and aren’t simply fans that recirculate the air within the home. And even when ventilation works as it should to move air out of the house, it only pumps it back into the atmosphere, where it contributes to climate change.

“We need combustion-free homes. That’s the unifying principle. We have to keep our eyes on that prize,” he said.

Dr. Balmes, Dr. McCormack, and Dr. Thurston all reported having no relevant disclosures.

SAN DIEGO — While there is currently no smoking gun definitively showing that indoor nitrogen dioxide (NO₂) concentrations from gas appliances are a cause of pulmonary diseases, the circumstantial evidence of the baleful effects of gas stoves on lung function is pretty compelling, said participants in a pro-con debate.

In what the moderator called “one of the most agreeable debates yet,” experts presented their views on the risks that cooking with natural gas pose on pulmonary health, and discussed ways for mitigating that harm. The debate was held at the American Thoracic Society’s international conference.
 

PRO: Gas stoves cause lung disease

Arguing for the “pro” side, John R. Balmes, MD of the University of California, San Francisco, and a physician member of the California Air Resources Board, began by admitting that “I would never have said gas stoves cause lung disease, but that’s what they assigned me.”

Gamely proceeding anyway, Dr. Balmes noted that natural gas — methane — is a potent greenhouse gas, and that cooking with natural gas leads to generation of NO₂ with high peak concentrations in the home, especially in the kitchen, but in other rooms as well.

Neil Osterweil/MDedge News

Con: More evidence needed

Arguing for the “con” side of the question, Meredith C. McCormack, MD, MHS, professor of medicine in the pulmonary and critical care division at Johns Hopkins University in Baltimore, said that “more definitive evidence is needed to define whether gas stoves cause lung disease.”

But Dr. McCormack didn’t let the natural gas industry off the hook, noting that a systematic review and meta-analysis of cooking with gas in high-, middle-, and low-income countries showed that domestic use of gas fuels vs. electric was associated with increased risk of asthma (1.11 overall), COPD (1.15), and pneumonia (1.26).

Neil Osterweil/MDedge News

On common ground

Environmental interventions that can benefit all members of a household — not just those with obstructive pulmonary disease — include smoking cessation, charcoal filter-equipped air cleaners, stove hoods that vent outdoors, integrated pest management, hypoallergenic pillow and mattress covers, high efficiency particulate air (HEPA) vacuums, and mold and radon abatement.

Both Dr. Balmes and Dr. McCormack agreed in the end that gas stoves contribute to respiratory morbidity, and that both state and national policy changes are needed to support transition to cleaner indoor air, with financial incentives available for households with more modest incomes.

“For everyone, there is a climate-change mitigation imperative to transition away from gas appliances if we want to tackle the climate emergency,” Dr. Balmes said.
 

End indoor combustion

George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the debate, told Chest Physician that the participants talked about NO₂ but didn’t touch on particulate pollution generated by gas stoves.

Burning natural gas produces particles that are very similar in composition to those produced by burning coal, oil, or diesel fuel, Dr. Thurston said, and he pointed out that interventions such as range hoods work only if they actually vent outdoors, and aren’t simply fans that recirculate the air within the home. And even when ventilation works as it should to move air out of the house, it only pumps it back into the atmosphere, where it contributes to climate change.

“We need combustion-free homes. That’s the unifying principle. We have to keep our eyes on that prize,” he said.

Dr. Balmes, Dr. McCormack, and Dr. Thurston all reported having no relevant disclosures.

Extreme heat, wildfires, and particulate matter not from wildfires were the most studied climate issues in conjunction with increased respiratory care, based on data from more than 60 studies.

Previous research has shown that fossil fuel combustion and climate change are threats to respiratory health, but the direct impact of climate on respiratory healthcare has not been well studied, wrote Jacqueline R. Lewy, MD, who led the study while a 4th-year medical student at the University of Michigan, Ann Arbor.

Recent local events prompted Dr. Lewy and colleagues to examine the current landscape of climate change studies and respiratory healthcare.

“Last summer, when Canadian wildfire smoke enveloped the Midwest and the East Coast, patients presented with exacerbations of asthma and COPD to our clinics,” corresponding author Alexander S. Rabin, MD, of the University of Michigan, said in an interview.

“The event was a reminder of the increasing health threats that our most vulnerable patients face from climate change,” he said. “The smoke events also got us thinking about how health systems around the world are preparing, and we wanted to better understand what is known about the impacts of climate change on healthcare delivery to patients with lung disease and look for blind spots in the research,” he explained.

In the review, published in The Journal of Climate Change and Health, the researchers identified 67 studies related to climate and respiratory care; 50 of these were published between 2020 and 2023.

The most frequently studied climate and weather topics were extreme heat (31 studies), particulate matter not from wildfires (22 studies), and wildfires (19 studies).

The most common respiratory-related outcomes were respiratory-related hospital admissions (33 studies) and respiratory-related emergency department (ED) visits (24 studies).

Few studies addressed the potential impact of climate on telehealth, facility energy distribution, and pharmaceutical supplies, the researchers wrote. Notably, only one study in the review showed an association between power outages in New York City and higher chronic obstructive pulmonary disease (COPD)-related hospital admission rates, and no primary research emerged on the effects of climate change on respiratory medicine supply or distribution, they said.

Findings from studies with demographic breakdowns included evidence of greater effects of extreme weather on elderly populations compared with younger groups, and data from the seven studies focused on children showed a particular risk for climate-related respiratory exacerbations among those younger than 5 years.

The findings of the review were limited by several factors including the targeted article selection and potential misclassification bias, as respiratory outcomes often overlapped with cardiac or other outcomes, the researchers noted.

However, the results highlighted three key areas for future research. First, more studies are needed on the impact of climate on understudied populations in areas such as Africa, South America, Asia, and the Caribbean. Second, studies are needed on the impact of climate on respiratory care beyond acute care, with attention to primary and specialty respiratory care use, supply chain impacts, and effects on long-term pulmonary care and rehabilitation. Finally, more research is needed to explore solutions to the increased demands on pulmonary care in the context of climate change, including the use of telehealth, the authors wrote.
 

Limitations and Research Gaps

“While we found extensive published research chronicling the acute respiratory health impacts of climate change and extreme weather, such as heat waves and wildfires, we were surprised to find few studies on health system adaptation,” Dr. Rabin told this news organization.

“Although we know that prevention and long-term disease management are critical, studies looking at primary care impacts on respiratory care, healthcare infrastructure hardening, and medication supply chain resilience were largely absent from the literature,” he said. “We were further struck by the limited amount of research originating from the most climate-affected areas such as in the Global South, where outdoor air pollution already results in over 4 million deaths per year,” he noted.

Although clinicians increasingly recognize that climate change and extreme weather threaten lung health, solutions are needed to make health systems resilient, accessible, and adaptable, especially with the likely increase in demand for respiratory care, Dr. Rabin emphasized.

More research is needed on preventive measures that could mitigate the risk for bad air quality, heat, and other extreme climate change events on vulnerable populations, said Dr. Rabin. “Every domain of healthcare delivery, from pharmaceutical procurement to hospital heating and cooling system design, must account for these environmental changes,” he said. “More collaboration is needed with researchers and clinicians in areas of the world that are underrepresented and underresourced to help share knowledge and tools to build health system resilience.”
 

Takeaways and Next Steps

“I was struck by how many studies used healthcare metrics as a way to measure health outcomes but not to measure resilience and efficiency of healthcare systems themselves,” Dr. Lewy said in an interview. “For example, many studies used ED visits or hospital admissions as ways to measure severity of disease associated with a climate event, but the strain that increased visits or admissions have on healthcare systems was barely mentioned,” she noted.

Looking ahead, more studies that focus specifically on infrastructure as it relates to healthcare would be valuable, said Dr. Lewy. Recent research has explored virtual care as a way to mitigate climate change-associated COPD exacerbations, but virtual care may not be reliably accessible in cases of the widespread power and network outages that often accompany storms, heat waves, and other catastrophic weather events, she noted. “More research into these types of logistical factors affecting healthcare systems would be helpful,” she added.

Dr. Rabin disclosed support for the study from the US Department of Veterans Affairs but had no other financial conflicts to disclose. Dr. Lewy had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Extreme heat, wildfires, and particulate matter not from wildfires were the most studied climate issues in conjunction with increased respiratory care, based on data from more than 60 studies.

Previous research has shown that fossil fuel combustion and climate change are threats to respiratory health, but the direct impact of climate on respiratory healthcare has not been well studied, wrote Jacqueline R. Lewy, MD, who led the study while a 4th-year medical student at the University of Michigan, Ann Arbor.

Recent local events prompted Dr. Lewy and colleagues to examine the current landscape of climate change studies and respiratory healthcare.

“Last summer, when Canadian wildfire smoke enveloped the Midwest and the East Coast, patients presented with exacerbations of asthma and COPD to our clinics,” corresponding author Alexander S. Rabin, MD, of the University of Michigan, said in an interview.

“The event was a reminder of the increasing health threats that our most vulnerable patients face from climate change,” he said. “The smoke events also got us thinking about how health systems around the world are preparing, and we wanted to better understand what is known about the impacts of climate change on healthcare delivery to patients with lung disease and look for blind spots in the research,” he explained.

In the review, published in The Journal of Climate Change and Health, the researchers identified 67 studies related to climate and respiratory care; 50 of these were published between 2020 and 2023.

The most frequently studied climate and weather topics were extreme heat (31 studies), particulate matter not from wildfires (22 studies), and wildfires (19 studies).

The most common respiratory-related outcomes were respiratory-related hospital admissions (33 studies) and respiratory-related emergency department (ED) visits (24 studies).

Few studies addressed the potential impact of climate on telehealth, facility energy distribution, and pharmaceutical supplies, the researchers wrote. Notably, only one study in the review showed an association between power outages in New York City and higher chronic obstructive pulmonary disease (COPD)-related hospital admission rates, and no primary research emerged on the effects of climate change on respiratory medicine supply or distribution, they said.

Findings from studies with demographic breakdowns included evidence of greater effects of extreme weather on elderly populations compared with younger groups, and data from the seven studies focused on children showed a particular risk for climate-related respiratory exacerbations among those younger than 5 years.

The findings of the review were limited by several factors including the targeted article selection and potential misclassification bias, as respiratory outcomes often overlapped with cardiac or other outcomes, the researchers noted.

However, the results highlighted three key areas for future research. First, more studies are needed on the impact of climate on understudied populations in areas such as Africa, South America, Asia, and the Caribbean. Second, studies are needed on the impact of climate on respiratory care beyond acute care, with attention to primary and specialty respiratory care use, supply chain impacts, and effects on long-term pulmonary care and rehabilitation. Finally, more research is needed to explore solutions to the increased demands on pulmonary care in the context of climate change, including the use of telehealth, the authors wrote.
 

Limitations and Research Gaps

“While we found extensive published research chronicling the acute respiratory health impacts of climate change and extreme weather, such as heat waves and wildfires, we were surprised to find few studies on health system adaptation,” Dr. Rabin told this news organization.

“Although we know that prevention and long-term disease management are critical, studies looking at primary care impacts on respiratory care, healthcare infrastructure hardening, and medication supply chain resilience were largely absent from the literature,” he said. “We were further struck by the limited amount of research originating from the most climate-affected areas such as in the Global South, where outdoor air pollution already results in over 4 million deaths per year,” he noted.

Although clinicians increasingly recognize that climate change and extreme weather threaten lung health, solutions are needed to make health systems resilient, accessible, and adaptable, especially with the likely increase in demand for respiratory care, Dr. Rabin emphasized.

More research is needed on preventive measures that could mitigate the risk for bad air quality, heat, and other extreme climate change events on vulnerable populations, said Dr. Rabin. “Every domain of healthcare delivery, from pharmaceutical procurement to hospital heating and cooling system design, must account for these environmental changes,” he said. “More collaboration is needed with researchers and clinicians in areas of the world that are underrepresented and underresourced to help share knowledge and tools to build health system resilience.”
 

Takeaways and Next Steps

“I was struck by how many studies used healthcare metrics as a way to measure health outcomes but not to measure resilience and efficiency of healthcare systems themselves,” Dr. Lewy said in an interview. “For example, many studies used ED visits or hospital admissions as ways to measure severity of disease associated with a climate event, but the strain that increased visits or admissions have on healthcare systems was barely mentioned,” she noted.

Looking ahead, more studies that focus specifically on infrastructure as it relates to healthcare would be valuable, said Dr. Lewy. Recent research has explored virtual care as a way to mitigate climate change-associated COPD exacerbations, but virtual care may not be reliably accessible in cases of the widespread power and network outages that often accompany storms, heat waves, and other catastrophic weather events, she noted. “More research into these types of logistical factors affecting healthcare systems would be helpful,” she added.

Dr. Rabin disclosed support for the study from the US Department of Veterans Affairs but had no other financial conflicts to disclose. Dr. Lewy had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Extreme heat, wildfires, and particulate matter not from wildfires were the most studied climate issues in conjunction with increased respiratory care, based on data from more than 60 studies.

Previous research has shown that fossil fuel combustion and climate change are threats to respiratory health, but the direct impact of climate on respiratory healthcare has not been well studied, wrote Jacqueline R. Lewy, MD, who led the study while a 4th-year medical student at the University of Michigan, Ann Arbor.

Recent local events prompted Dr. Lewy and colleagues to examine the current landscape of climate change studies and respiratory healthcare.

“Last summer, when Canadian wildfire smoke enveloped the Midwest and the East Coast, patients presented with exacerbations of asthma and COPD to our clinics,” corresponding author Alexander S. Rabin, MD, of the University of Michigan, said in an interview.

“The event was a reminder of the increasing health threats that our most vulnerable patients face from climate change,” he said. “The smoke events also got us thinking about how health systems around the world are preparing, and we wanted to better understand what is known about the impacts of climate change on healthcare delivery to patients with lung disease and look for blind spots in the research,” he explained.

In the review, published in The Journal of Climate Change and Health, the researchers identified 67 studies related to climate and respiratory care; 50 of these were published between 2020 and 2023.

The most frequently studied climate and weather topics were extreme heat (31 studies), particulate matter not from wildfires (22 studies), and wildfires (19 studies).

The most common respiratory-related outcomes were respiratory-related hospital admissions (33 studies) and respiratory-related emergency department (ED) visits (24 studies).

Few studies addressed the potential impact of climate on telehealth, facility energy distribution, and pharmaceutical supplies, the researchers wrote. Notably, only one study in the review showed an association between power outages in New York City and higher chronic obstructive pulmonary disease (COPD)-related hospital admission rates, and no primary research emerged on the effects of climate change on respiratory medicine supply or distribution, they said.

Findings from studies with demographic breakdowns included evidence of greater effects of extreme weather on elderly populations compared with younger groups, and data from the seven studies focused on children showed a particular risk for climate-related respiratory exacerbations among those younger than 5 years.

The findings of the review were limited by several factors including the targeted article selection and potential misclassification bias, as respiratory outcomes often overlapped with cardiac or other outcomes, the researchers noted.

However, the results highlighted three key areas for future research. First, more studies are needed on the impact of climate on understudied populations in areas such as Africa, South America, Asia, and the Caribbean. Second, studies are needed on the impact of climate on respiratory care beyond acute care, with attention to primary and specialty respiratory care use, supply chain impacts, and effects on long-term pulmonary care and rehabilitation. Finally, more research is needed to explore solutions to the increased demands on pulmonary care in the context of climate change, including the use of telehealth, the authors wrote.
 

Limitations and Research Gaps

“While we found extensive published research chronicling the acute respiratory health impacts of climate change and extreme weather, such as heat waves and wildfires, we were surprised to find few studies on health system adaptation,” Dr. Rabin told this news organization.

“Although we know that prevention and long-term disease management are critical, studies looking at primary care impacts on respiratory care, healthcare infrastructure hardening, and medication supply chain resilience were largely absent from the literature,” he said. “We were further struck by the limited amount of research originating from the most climate-affected areas such as in the Global South, where outdoor air pollution already results in over 4 million deaths per year,” he noted.

Although clinicians increasingly recognize that climate change and extreme weather threaten lung health, solutions are needed to make health systems resilient, accessible, and adaptable, especially with the likely increase in demand for respiratory care, Dr. Rabin emphasized.

More research is needed on preventive measures that could mitigate the risk for bad air quality, heat, and other extreme climate change events on vulnerable populations, said Dr. Rabin. “Every domain of healthcare delivery, from pharmaceutical procurement to hospital heating and cooling system design, must account for these environmental changes,” he said. “More collaboration is needed with researchers and clinicians in areas of the world that are underrepresented and underresourced to help share knowledge and tools to build health system resilience.”
 

Takeaways and Next Steps

“I was struck by how many studies used healthcare metrics as a way to measure health outcomes but not to measure resilience and efficiency of healthcare systems themselves,” Dr. Lewy said in an interview. “For example, many studies used ED visits or hospital admissions as ways to measure severity of disease associated with a climate event, but the strain that increased visits or admissions have on healthcare systems was barely mentioned,” she noted.

Looking ahead, more studies that focus specifically on infrastructure as it relates to healthcare would be valuable, said Dr. Lewy. Recent research has explored virtual care as a way to mitigate climate change-associated COPD exacerbations, but virtual care may not be reliably accessible in cases of the widespread power and network outages that often accompany storms, heat waves, and other catastrophic weather events, she noted. “More research into these types of logistical factors affecting healthcare systems would be helpful,” she added.

Dr. Rabin disclosed support for the study from the US Department of Veterans Affairs but had no other financial conflicts to disclose. Dr. Lewy had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A recent study links waist size and a higher risk for asthma attack. After adjustments, the likelihood of asthma attacks was 1.06 times higher for every 5-cm increase in waist circumference in adults with asthma.

BMI Earlier Tied to Asthma

Previous research supports a link between increased body mass index (BMI) and asthma, but the association between abdominal obesity and asthma attacks has not been well studied.

The researchers in the current study reviewed data from the National Health and Nutrition Examination Survey for 5530 adults with asthma in the United States. Adults in the study were divided into groups based on whether they did or did not experience asthma attacks.

The median age of the study population was 43 years, the median waist circumference was 98.9 cm, and the median BMI was 28.50.
 

More Waist Inches = Asthma Attacks

Overall, patients who reported asthma attacks had a significantly higher waist circumference than those without asthma attacks (median, 102.6 cm vs 97.3 cm, P < .001).

The association between increased waist circumference and increased odds of asthma attack was significant across non-adjusted, minimally adjusted, and fully adjusted models (odds ratios, 1.7, 1.06, and 1.06, respectively). In fact, each 5-cm increase in waist circumference was associated with a 1.06 times higher likelihood of an asthma attack after full adjustment for BMI-defined obesity, age, gender, race/ethnicity, education, poverty income ratio, smoking status, and metabolic syndrome.

The relationship between increased likelihood of asthma attacks and increased waist circumference persisted in subgroup analyses based on gender, age, and smoking status.
 

Importance of Waist Size

“Our study underscores the critical role of waist circumference measurements in the routine health evaluations of individuals diagnosed with asthma, highlighting its inclusion as an essential aspect of comprehensive health assessments,” the researchers wrote.

Limited to Data Available

The study findings were limited by several factors including the use of existing database questions to evaluate asthma attacks, a lack of data on the specificity of triggers of asthma exacerbations, and an inability to distinguish the severity of asthma attacks.

The study was published online in BMC Public Health. The lead author was Xiang Liu, MD, of Qingdao Municipal Hospital, Qingdao, China.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A recent study links waist size and a higher risk for asthma attack. After adjustments, the likelihood of asthma attacks was 1.06 times higher for every 5-cm increase in waist circumference in adults with asthma.

BMI Earlier Tied to Asthma

Previous research supports a link between increased body mass index (BMI) and asthma, but the association between abdominal obesity and asthma attacks has not been well studied.

The researchers in the current study reviewed data from the National Health and Nutrition Examination Survey for 5530 adults with asthma in the United States. Adults in the study were divided into groups based on whether they did or did not experience asthma attacks.

The median age of the study population was 43 years, the median waist circumference was 98.9 cm, and the median BMI was 28.50.
 

More Waist Inches = Asthma Attacks

Overall, patients who reported asthma attacks had a significantly higher waist circumference than those without asthma attacks (median, 102.6 cm vs 97.3 cm, P < .001).

The association between increased waist circumference and increased odds of asthma attack was significant across non-adjusted, minimally adjusted, and fully adjusted models (odds ratios, 1.7, 1.06, and 1.06, respectively). In fact, each 5-cm increase in waist circumference was associated with a 1.06 times higher likelihood of an asthma attack after full adjustment for BMI-defined obesity, age, gender, race/ethnicity, education, poverty income ratio, smoking status, and metabolic syndrome.

The relationship between increased likelihood of asthma attacks and increased waist circumference persisted in subgroup analyses based on gender, age, and smoking status.
 

Importance of Waist Size

“Our study underscores the critical role of waist circumference measurements in the routine health evaluations of individuals diagnosed with asthma, highlighting its inclusion as an essential aspect of comprehensive health assessments,” the researchers wrote.

Limited to Data Available

The study findings were limited by several factors including the use of existing database questions to evaluate asthma attacks, a lack of data on the specificity of triggers of asthma exacerbations, and an inability to distinguish the severity of asthma attacks.

The study was published online in BMC Public Health. The lead author was Xiang Liu, MD, of Qingdao Municipal Hospital, Qingdao, China.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A recent study links waist size and a higher risk for asthma attack. After adjustments, the likelihood of asthma attacks was 1.06 times higher for every 5-cm increase in waist circumference in adults with asthma.

BMI Earlier Tied to Asthma

Previous research supports a link between increased body mass index (BMI) and asthma, but the association between abdominal obesity and asthma attacks has not been well studied.

The researchers in the current study reviewed data from the National Health and Nutrition Examination Survey for 5530 adults with asthma in the United States. Adults in the study were divided into groups based on whether they did or did not experience asthma attacks.

The median age of the study population was 43 years, the median waist circumference was 98.9 cm, and the median BMI was 28.50.
 

More Waist Inches = Asthma Attacks

Overall, patients who reported asthma attacks had a significantly higher waist circumference than those without asthma attacks (median, 102.6 cm vs 97.3 cm, P < .001).

The association between increased waist circumference and increased odds of asthma attack was significant across non-adjusted, minimally adjusted, and fully adjusted models (odds ratios, 1.7, 1.06, and 1.06, respectively). In fact, each 5-cm increase in waist circumference was associated with a 1.06 times higher likelihood of an asthma attack after full adjustment for BMI-defined obesity, age, gender, race/ethnicity, education, poverty income ratio, smoking status, and metabolic syndrome.

The relationship between increased likelihood of asthma attacks and increased waist circumference persisted in subgroup analyses based on gender, age, and smoking status.
 

Importance of Waist Size

“Our study underscores the critical role of waist circumference measurements in the routine health evaluations of individuals diagnosed with asthma, highlighting its inclusion as an essential aspect of comprehensive health assessments,” the researchers wrote.

Limited to Data Available

The study findings were limited by several factors including the use of existing database questions to evaluate asthma attacks, a lack of data on the specificity of triggers of asthma exacerbations, and an inability to distinguish the severity of asthma attacks.

The study was published online in BMC Public Health. The lead author was Xiang Liu, MD, of Qingdao Municipal Hospital, Qingdao, China.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

In addition to warmer weather, June will usher in changes in asthma and COPD inhaler costs for many patients, potentially reducing barriers to those seeing high prescription prices. Price ceilings have been set by some companies, likely following action earlier this year by a Senate Committee which pointed to higher costs of US inhalers compared with other countries.

Senator Sanders stated: “In my view, Americans who have asthma and COPD should not be forced to pay, in many cases, 10-70 times more for the same exact inhalers as patients in Europe and other parts of the world.”

Starting June 1, Boehringer Ingelheim will cap out-of-pocket costs for the company’s inhaler products for chronic lung disease and asthma at $35 per month, according to a March 7, 2024, press release from the German drugmaker’s US headquarters in Ridgefield, Conn. The reductions cover the full range of the company’s inhaler products for asthma and chronic obstructive pulmonary disease (COPD) including Atrovent, Combivent Respimat and Spiriva HandiHaler and Respimat, Stiolto Respimat and Striverdi Respimat. In the release, Boehringer Ingelheim USA Corporation’s President and CEO Jean-Michel Boers stated, “The US health care system is complex and often doesn’t work for patients, especially the most vulnerable. While we can’t fix the entire system alone, we are bringing forward a solution to make it fairer. We want to do our part to help patients living with COPD or asthma who struggle to pay for their medications.”

Similar announcements were made by AstraZeneca and GSK. GSK’s cap will go into effect on January 1, 2025, and includes Advair Diskus, Advair HFA, Anoro Ellipta, Arnuity Ellipta, Breo Ellipta, Incruse Ellipta, Serevent Diskus, Trelegy Ellipta, and Ventolin HFA. The AstraZeneca cap, which covers Airsupra, Bevespi Aerosphere, Breztri Aeroshpere, and Symbicort, goes into effect on June 1, 2024.
 

Senate statement on pricing

These companies plus Teva had received letters sent on January 8, 2024, by the members of the Senate Committee on Health, Education, Labor, and Pensions: senators Sanders, Baldwin, Luján and Markey. The letters cited enormous inhaler price discrepancies, for example $489 for Combivent Respimat in the United States but just $7 in France, and announced the conduct of an investigation into efforts by these companies to artificially inflate and manipulate prices of asthma inhalers that have been on the market for decades. A statement from Sen. Sanders’ office noted that AstraZeneca, GSK, and Teva made more than $25 billion in revenue from inhalers alone in the past 5 years (Boehringer Ingelheim does not provide public US inhaler revenue information).

Suit claims generic delay

A federal lawsuit filed in Boston on March 6, according to a Reuters brief from March 7, cited Boehringer for improperly submitting patents to the US Food and Drug Administration (FDA). The purpose of those patents, the suit charges, was to delay generic competition and inflate Combivent Respimat and Spiriva Respimat inhaler prices.

Inhaler prices soared in the United States, according to a March 10 U.S. News & World Report commentary by The Conversation, a nonprofit news organization, after the 2008 FDA ban on chlorofluorocarbon (CFC)-propellants led to the phase-out of CFC-containing inhalers and their replacement with hydrofluoroalkane-propellant inhalers. For the insured that meant an average out-of-pocket inhaler cost increase from $13.60 per prescription in 2004 to $25 in 2015. The current rate for the now nongeneric HFA-propelled but otherwise identical albuterol inhaler is $98. Competition from a more recently FDA-approved (2020) generic version has not been robust enough to effect meaningful price reductions, the report stated. While good insurance generally covers most of inhaler costs, the more than 25 million uninsured in 2023 faced steep market prices that put strain even on some insured, the CDC found, driving many in the United States to purchase from Mexican, Canadian, or other foreign pharmacies. The Teva QVAR REdiHaler corticosteroid inhaler, costing $9 in Germany, costs $286 in the US. Dosages, however, may not be identical. A first FDA-authorization of drug importing this past January applied only to agents for a limited number of disease states and pertained only to Florida, but may serve as a model for other states, according to the commentary.

“The announced price cap from Boehringer Ingelheim,” stated Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA) in a press release, “is a step toward improving access to essential asthma medicine and demonstrates that the voice of the asthma patient community is being heard.” The AAFA release noted further that asthma death rates, while declining overall, are triple in Blacks compared with Whites. Death rates, asthma rates, and rates of being uninsured or underinsured are much higher in Black and Puerto Rican populations than in Whites. The complex layers of the current US system, composed of pharmaceutical manufacturers, pharmacy benefit managers, insurance companies, employers, and federal policies often conspire against those people who need asthma drugs the most. AAFA research has shown that when drug prices become a barrier to treatment, people with asthma ration or simply discontinue their essential asthma medications. Beyond saved lives, access to asthma medications can reduce hospitalizations and lower the more than $82 billion in annual asthma costs to the US economy.

Sen. Sanders, on March 20, applauded the GSK announcement: “As Chairman of the Senate Health, Education, Labor, and Pensions Committee, I very much appreciate GlaxoSmithKline’s announcement today that Americans throughout the country with asthma and COPD will pay no more than $35 for the brand name inhalers they manufacture. I look forward to working with GSK to make sure that this decision reaches as many patients as possible.”

“Inhaled medications continue to be an essential part of the therapy for patients with asthma, COPD, and other respiratory conditions,” said Diego J. Maselli, professor and chief, Division of Pulmonary Diseases & Critical Care, UT Health at San Antonio, San Antonio, Texas, in an interview with CHEST Physician. He added, “Unfortunately, with increasing cost of these and other treatments, access has been challenging for many patients. Patients, families, and providers constantly experience frustration with the difficulties of obtaining these lifesaving medications, and cost is the main barrier. Even those with ample insurance coverage face difficult challenges, as the high prices of these medications motivate insurance carriers to constantly adjust what is the ‘preferred’ option among inhalers. Regrettably, noncompliance and nonadherence to inhaled therapies has been linked to poor patient outcomes and increased health care utilization in both asthma and COPD. Because of the high prevalence of these diseases in the US and worldwide, efforts to increase the access of these vital medications has been a priority. With the leveling of the prices of these medications across the world, we hope that there will be both improved access and, as a consequence, better patient outcomes.”

In addition to warmer weather, June will usher in changes in asthma and COPD inhaler costs for many patients, potentially reducing barriers to those seeing high prescription prices. Price ceilings have been set by some companies, likely following action earlier this year by a Senate Committee which pointed to higher costs of US inhalers compared with other countries.

Senator Sanders stated: “In my view, Americans who have asthma and COPD should not be forced to pay, in many cases, 10-70 times more for the same exact inhalers as patients in Europe and other parts of the world.”

Starting June 1, Boehringer Ingelheim will cap out-of-pocket costs for the company’s inhaler products for chronic lung disease and asthma at $35 per month, according to a March 7, 2024, press release from the German drugmaker’s US headquarters in Ridgefield, Conn. The reductions cover the full range of the company’s inhaler products for asthma and chronic obstructive pulmonary disease (COPD) including Atrovent, Combivent Respimat and Spiriva HandiHaler and Respimat, Stiolto Respimat and Striverdi Respimat. In the release, Boehringer Ingelheim USA Corporation’s President and CEO Jean-Michel Boers stated, “The US health care system is complex and often doesn’t work for patients, especially the most vulnerable. While we can’t fix the entire system alone, we are bringing forward a solution to make it fairer. We want to do our part to help patients living with COPD or asthma who struggle to pay for their medications.”

Similar announcements were made by AstraZeneca and GSK. GSK’s cap will go into effect on January 1, 2025, and includes Advair Diskus, Advair HFA, Anoro Ellipta, Arnuity Ellipta, Breo Ellipta, Incruse Ellipta, Serevent Diskus, Trelegy Ellipta, and Ventolin HFA. The AstraZeneca cap, which covers Airsupra, Bevespi Aerosphere, Breztri Aeroshpere, and Symbicort, goes into effect on June 1, 2024.
 

Senate statement on pricing

These companies plus Teva had received letters sent on January 8, 2024, by the members of the Senate Committee on Health, Education, Labor, and Pensions: senators Sanders, Baldwin, Luján and Markey. The letters cited enormous inhaler price discrepancies, for example $489 for Combivent Respimat in the United States but just $7 in France, and announced the conduct of an investigation into efforts by these companies to artificially inflate and manipulate prices of asthma inhalers that have been on the market for decades. A statement from Sen. Sanders’ office noted that AstraZeneca, GSK, and Teva made more than $25 billion in revenue from inhalers alone in the past 5 years (Boehringer Ingelheim does not provide public US inhaler revenue information).

Suit claims generic delay

A federal lawsuit filed in Boston on March 6, according to a Reuters brief from March 7, cited Boehringer for improperly submitting patents to the US Food and Drug Administration (FDA). The purpose of those patents, the suit charges, was to delay generic competition and inflate Combivent Respimat and Spiriva Respimat inhaler prices.

Inhaler prices soared in the United States, according to a March 10 U.S. News & World Report commentary by The Conversation, a nonprofit news organization, after the 2008 FDA ban on chlorofluorocarbon (CFC)-propellants led to the phase-out of CFC-containing inhalers and their replacement with hydrofluoroalkane-propellant inhalers. For the insured that meant an average out-of-pocket inhaler cost increase from $13.60 per prescription in 2004 to $25 in 2015. The current rate for the now nongeneric HFA-propelled but otherwise identical albuterol inhaler is $98. Competition from a more recently FDA-approved (2020) generic version has not been robust enough to effect meaningful price reductions, the report stated. While good insurance generally covers most of inhaler costs, the more than 25 million uninsured in 2023 faced steep market prices that put strain even on some insured, the CDC found, driving many in the United States to purchase from Mexican, Canadian, or other foreign pharmacies. The Teva QVAR REdiHaler corticosteroid inhaler, costing $9 in Germany, costs $286 in the US. Dosages, however, may not be identical. A first FDA-authorization of drug importing this past January applied only to agents for a limited number of disease states and pertained only to Florida, but may serve as a model for other states, according to the commentary.

“The announced price cap from Boehringer Ingelheim,” stated Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA) in a press release, “is a step toward improving access to essential asthma medicine and demonstrates that the voice of the asthma patient community is being heard.” The AAFA release noted further that asthma death rates, while declining overall, are triple in Blacks compared with Whites. Death rates, asthma rates, and rates of being uninsured or underinsured are much higher in Black and Puerto Rican populations than in Whites. The complex layers of the current US system, composed of pharmaceutical manufacturers, pharmacy benefit managers, insurance companies, employers, and federal policies often conspire against those people who need asthma drugs the most. AAFA research has shown that when drug prices become a barrier to treatment, people with asthma ration or simply discontinue their essential asthma medications. Beyond saved lives, access to asthma medications can reduce hospitalizations and lower the more than $82 billion in annual asthma costs to the US economy.

Sen. Sanders, on March 20, applauded the GSK announcement: “As Chairman of the Senate Health, Education, Labor, and Pensions Committee, I very much appreciate GlaxoSmithKline’s announcement today that Americans throughout the country with asthma and COPD will pay no more than $35 for the brand name inhalers they manufacture. I look forward to working with GSK to make sure that this decision reaches as many patients as possible.”

“Inhaled medications continue to be an essential part of the therapy for patients with asthma, COPD, and other respiratory conditions,” said Diego J. Maselli, professor and chief, Division of Pulmonary Diseases & Critical Care, UT Health at San Antonio, San Antonio, Texas, in an interview with CHEST Physician. He added, “Unfortunately, with increasing cost of these and other treatments, access has been challenging for many patients. Patients, families, and providers constantly experience frustration with the difficulties of obtaining these lifesaving medications, and cost is the main barrier. Even those with ample insurance coverage face difficult challenges, as the high prices of these medications motivate insurance carriers to constantly adjust what is the ‘preferred’ option among inhalers. Regrettably, noncompliance and nonadherence to inhaled therapies has been linked to poor patient outcomes and increased health care utilization in both asthma and COPD. Because of the high prevalence of these diseases in the US and worldwide, efforts to increase the access of these vital medications has been a priority. With the leveling of the prices of these medications across the world, we hope that there will be both improved access and, as a consequence, better patient outcomes.”

In addition to warmer weather, June will usher in changes in asthma and COPD inhaler costs for many patients, potentially reducing barriers to those seeing high prescription prices. Price ceilings have been set by some companies, likely following action earlier this year by a Senate Committee which pointed to higher costs of US inhalers compared with other countries.

Senator Sanders stated: “In my view, Americans who have asthma and COPD should not be forced to pay, in many cases, 10-70 times more for the same exact inhalers as patients in Europe and other parts of the world.”

Starting June 1, Boehringer Ingelheim will cap out-of-pocket costs for the company’s inhaler products for chronic lung disease and asthma at $35 per month, according to a March 7, 2024, press release from the German drugmaker’s US headquarters in Ridgefield, Conn. The reductions cover the full range of the company’s inhaler products for asthma and chronic obstructive pulmonary disease (COPD) including Atrovent, Combivent Respimat and Spiriva HandiHaler and Respimat, Stiolto Respimat and Striverdi Respimat. In the release, Boehringer Ingelheim USA Corporation’s President and CEO Jean-Michel Boers stated, “The US health care system is complex and often doesn’t work for patients, especially the most vulnerable. While we can’t fix the entire system alone, we are bringing forward a solution to make it fairer. We want to do our part to help patients living with COPD or asthma who struggle to pay for their medications.”

Similar announcements were made by AstraZeneca and GSK. GSK’s cap will go into effect on January 1, 2025, and includes Advair Diskus, Advair HFA, Anoro Ellipta, Arnuity Ellipta, Breo Ellipta, Incruse Ellipta, Serevent Diskus, Trelegy Ellipta, and Ventolin HFA. The AstraZeneca cap, which covers Airsupra, Bevespi Aerosphere, Breztri Aeroshpere, and Symbicort, goes into effect on June 1, 2024.
 

Senate statement on pricing

These companies plus Teva had received letters sent on January 8, 2024, by the members of the Senate Committee on Health, Education, Labor, and Pensions: senators Sanders, Baldwin, Luján and Markey. The letters cited enormous inhaler price discrepancies, for example $489 for Combivent Respimat in the United States but just $7 in France, and announced the conduct of an investigation into efforts by these companies to artificially inflate and manipulate prices of asthma inhalers that have been on the market for decades. A statement from Sen. Sanders’ office noted that AstraZeneca, GSK, and Teva made more than $25 billion in revenue from inhalers alone in the past 5 years (Boehringer Ingelheim does not provide public US inhaler revenue information).

Suit claims generic delay

A federal lawsuit filed in Boston on March 6, according to a Reuters brief from March 7, cited Boehringer for improperly submitting patents to the US Food and Drug Administration (FDA). The purpose of those patents, the suit charges, was to delay generic competition and inflate Combivent Respimat and Spiriva Respimat inhaler prices.

Inhaler prices soared in the United States, according to a March 10 U.S. News & World Report commentary by The Conversation, a nonprofit news organization, after the 2008 FDA ban on chlorofluorocarbon (CFC)-propellants led to the phase-out of CFC-containing inhalers and their replacement with hydrofluoroalkane-propellant inhalers. For the insured that meant an average out-of-pocket inhaler cost increase from $13.60 per prescription in 2004 to $25 in 2015. The current rate for the now nongeneric HFA-propelled but otherwise identical albuterol inhaler is $98. Competition from a more recently FDA-approved (2020) generic version has not been robust enough to effect meaningful price reductions, the report stated. While good insurance generally covers most of inhaler costs, the more than 25 million uninsured in 2023 faced steep market prices that put strain even on some insured, the CDC found, driving many in the United States to purchase from Mexican, Canadian, or other foreign pharmacies. The Teva QVAR REdiHaler corticosteroid inhaler, costing $9 in Germany, costs $286 in the US. Dosages, however, may not be identical. A first FDA-authorization of drug importing this past January applied only to agents for a limited number of disease states and pertained only to Florida, but may serve as a model for other states, according to the commentary.

“The announced price cap from Boehringer Ingelheim,” stated Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA) in a press release, “is a step toward improving access to essential asthma medicine and demonstrates that the voice of the asthma patient community is being heard.” The AAFA release noted further that asthma death rates, while declining overall, are triple in Blacks compared with Whites. Death rates, asthma rates, and rates of being uninsured or underinsured are much higher in Black and Puerto Rican populations than in Whites. The complex layers of the current US system, composed of pharmaceutical manufacturers, pharmacy benefit managers, insurance companies, employers, and federal policies often conspire against those people who need asthma drugs the most. AAFA research has shown that when drug prices become a barrier to treatment, people with asthma ration or simply discontinue their essential asthma medications. Beyond saved lives, access to asthma medications can reduce hospitalizations and lower the more than $82 billion in annual asthma costs to the US economy.

Sen. Sanders, on March 20, applauded the GSK announcement: “As Chairman of the Senate Health, Education, Labor, and Pensions Committee, I very much appreciate GlaxoSmithKline’s announcement today that Americans throughout the country with asthma and COPD will pay no more than $35 for the brand name inhalers they manufacture. I look forward to working with GSK to make sure that this decision reaches as many patients as possible.”

“Inhaled medications continue to be an essential part of the therapy for patients with asthma, COPD, and other respiratory conditions,” said Diego J. Maselli, professor and chief, Division of Pulmonary Diseases & Critical Care, UT Health at San Antonio, San Antonio, Texas, in an interview with CHEST Physician. He added, “Unfortunately, with increasing cost of these and other treatments, access has been challenging for many patients. Patients, families, and providers constantly experience frustration with the difficulties of obtaining these lifesaving medications, and cost is the main barrier. Even those with ample insurance coverage face difficult challenges, as the high prices of these medications motivate insurance carriers to constantly adjust what is the ‘preferred’ option among inhalers. Regrettably, noncompliance and nonadherence to inhaled therapies has been linked to poor patient outcomes and increased health care utilization in both asthma and COPD. Because of the high prevalence of these diseases in the US and worldwide, efforts to increase the access of these vital medications has been a priority. With the leveling of the prices of these medications across the world, we hope that there will be both improved access and, as a consequence, better patient outcomes.”

On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler^® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.

“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
 

Digital App Companion to Inhaler

The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth^® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.

Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.

When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
 

Possibility for Objective Data

“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.

“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
 

CONNECT2: Better Asthma Control at 24 Weeks

Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.

Lack of Inhaler Uptake

“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”

Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”

The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.

On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler^® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.

“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
 

Digital App Companion to Inhaler

The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth^® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.

Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.

When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
 

Possibility for Objective Data

“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.

“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
 

CONNECT2: Better Asthma Control at 24 Weeks

Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.

Lack of Inhaler Uptake

“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”

Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”

The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.

On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler^® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.

“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
 

Digital App Companion to Inhaler

The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth^® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.

Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.

When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
 

Possibility for Objective Data

“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.

“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
 

CONNECT2: Better Asthma Control at 24 Weeks

Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.

Lack of Inhaler Uptake

“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”

Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”

The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.