Pulmonology

Almost all patients with both obstructive sleep apnea syndrome and severe asthma fell into the obesity phenotype, not the allergy phenotype, based on data from nearly 1,500 adults.

Both asthma and sleep-disordered breathing are common conditions worldwide, and previous research suggests that obstructive sleep apnea syndrome (OSAS) and severe asthma in particular could be associated, wrote Laurent Portel, MD, of Centre Hospitalier de Libourne, France, and colleagues.

“Even if the underlying mechanisms are not well established, it is clear that both OSAS and obesity act to aggravate existing asthma, making it more difficult to control,” they said. However, the pathology of this relationship is not well-understood, and data on severe asthma phenotypes and OSAS are limited, they said.

In a study published in Respiratory Medicine and Research, the investigators reviewed data from 1,465 patients older than 18 years with severe asthma who were part of a larger, prospective multicenter study of the management of asthma patients. The larger study, developed by the Collège des Pneumologues des Hôpitaux Généraux (CPHG) is known as the FASE-CPHG (France Asthme SEvère-CPHG) and includes 104 nonacademic hospitals in France.

Diagnosis of OSAS was reported by physicians; diagnosis of severe asthma was based on the Global Initiative for Asthma criteria. The average age of the patients was 54.4 years, 63% were women, and 60% were nonsmokers.

A total of 161 patients were diagnosed with OSAS. The researchers conducted a cluster analysis on 1,424 patients, including 156 of the OSAS patients. They identified five clusters: early-onset atopic asthma (690 patients), obese asthma (153 patients), late-onset asthma (299 patients), eosinophilic asthma (143 patients), and aspirin sensitivity asthma (139 patients).

All 153 patients in the obese asthma cluster had OSAS, by contrast, none of the patients in the early atopic asthma cluster had OSAS.

Overall, obesity, male sex, high blood pressure, depression, late-onset asthma, and early-onset atopic asthma were independently associated with OSAS, with odds ratios of 5.782, 3.047, 2.875, 2.552, 1.789, and 0.622, respectively.

Notably, OSAS patients were more frequently treated with long-term oral corticosteroids than those without OSAS (30% vs. 15%, P < .0001), the researchers said. “It is possible that this treatment may be responsible for obesity, and it represents a well-known risk factor for developing OSAS,” they wrote.

Uncontrolled asthma was significantly more common in OSAS patients than in those without OSAS (77.7% vs. 69%, P = .03), and significantly more OSAS patients reported no or occasional physical activity (79.8% vs. 68.2%, P ≤ .001).

The study findings were limited by several factors including the lack of patients from primary care or university hospitals, which may limit the generalizability of the results, the reliance on physician statements for diagnosis of OSAS, and the lack of data on OSAS severity or treatment, the researchers noted.

However, the results fill a needed gap in the literature because of the limited data on severe asthma patients in real life, and identifying severe asthma patients by phenotype may help identify those at greatest risk for OSAS, they said.

“Identified patients could more easily benefit from specific examinations such as poly(somno)graphy and, consequently, could benefit from a better management of both asthma and OSAS,” they emphasized.

The larger FASE-CPHG study was supported in part by ALK, AstraZeneca, Boehringer Ingelheim, GSK, and Le Nouveau Souffle. The researchers had no financial conflicts to disclose.

Almost all patients with both obstructive sleep apnea syndrome and severe asthma fell into the obesity phenotype, not the allergy phenotype, based on data from nearly 1,500 adults.

Both asthma and sleep-disordered breathing are common conditions worldwide, and previous research suggests that obstructive sleep apnea syndrome (OSAS) and severe asthma in particular could be associated, wrote Laurent Portel, MD, of Centre Hospitalier de Libourne, France, and colleagues.

“Even if the underlying mechanisms are not well established, it is clear that both OSAS and obesity act to aggravate existing asthma, making it more difficult to control,” they said. However, the pathology of this relationship is not well-understood, and data on severe asthma phenotypes and OSAS are limited, they said.

In a study published in Respiratory Medicine and Research, the investigators reviewed data from 1,465 patients older than 18 years with severe asthma who were part of a larger, prospective multicenter study of the management of asthma patients. The larger study, developed by the Collège des Pneumologues des Hôpitaux Généraux (CPHG) is known as the FASE-CPHG (France Asthme SEvère-CPHG) and includes 104 nonacademic hospitals in France.

Diagnosis of OSAS was reported by physicians; diagnosis of severe asthma was based on the Global Initiative for Asthma criteria. The average age of the patients was 54.4 years, 63% were women, and 60% were nonsmokers.

A total of 161 patients were diagnosed with OSAS. The researchers conducted a cluster analysis on 1,424 patients, including 156 of the OSAS patients. They identified five clusters: early-onset atopic asthma (690 patients), obese asthma (153 patients), late-onset asthma (299 patients), eosinophilic asthma (143 patients), and aspirin sensitivity asthma (139 patients).

All 153 patients in the obese asthma cluster had OSAS, by contrast, none of the patients in the early atopic asthma cluster had OSAS.

Overall, obesity, male sex, high blood pressure, depression, late-onset asthma, and early-onset atopic asthma were independently associated with OSAS, with odds ratios of 5.782, 3.047, 2.875, 2.552, 1.789, and 0.622, respectively.

Notably, OSAS patients were more frequently treated with long-term oral corticosteroids than those without OSAS (30% vs. 15%, P < .0001), the researchers said. “It is possible that this treatment may be responsible for obesity, and it represents a well-known risk factor for developing OSAS,” they wrote.

Uncontrolled asthma was significantly more common in OSAS patients than in those without OSAS (77.7% vs. 69%, P = .03), and significantly more OSAS patients reported no or occasional physical activity (79.8% vs. 68.2%, P ≤ .001).

The study findings were limited by several factors including the lack of patients from primary care or university hospitals, which may limit the generalizability of the results, the reliance on physician statements for diagnosis of OSAS, and the lack of data on OSAS severity or treatment, the researchers noted.

However, the results fill a needed gap in the literature because of the limited data on severe asthma patients in real life, and identifying severe asthma patients by phenotype may help identify those at greatest risk for OSAS, they said.

“Identified patients could more easily benefit from specific examinations such as poly(somno)graphy and, consequently, could benefit from a better management of both asthma and OSAS,” they emphasized.

The larger FASE-CPHG study was supported in part by ALK, AstraZeneca, Boehringer Ingelheim, GSK, and Le Nouveau Souffle. The researchers had no financial conflicts to disclose.

Almost all patients with both obstructive sleep apnea syndrome and severe asthma fell into the obesity phenotype, not the allergy phenotype, based on data from nearly 1,500 adults.

Both asthma and sleep-disordered breathing are common conditions worldwide, and previous research suggests that obstructive sleep apnea syndrome (OSAS) and severe asthma in particular could be associated, wrote Laurent Portel, MD, of Centre Hospitalier de Libourne, France, and colleagues.

“Even if the underlying mechanisms are not well established, it is clear that both OSAS and obesity act to aggravate existing asthma, making it more difficult to control,” they said. However, the pathology of this relationship is not well-understood, and data on severe asthma phenotypes and OSAS are limited, they said.

In a study published in Respiratory Medicine and Research, the investigators reviewed data from 1,465 patients older than 18 years with severe asthma who were part of a larger, prospective multicenter study of the management of asthma patients. The larger study, developed by the Collège des Pneumologues des Hôpitaux Généraux (CPHG) is known as the FASE-CPHG (France Asthme SEvère-CPHG) and includes 104 nonacademic hospitals in France.

Diagnosis of OSAS was reported by physicians; diagnosis of severe asthma was based on the Global Initiative for Asthma criteria. The average age of the patients was 54.4 years, 63% were women, and 60% were nonsmokers.

A total of 161 patients were diagnosed with OSAS. The researchers conducted a cluster analysis on 1,424 patients, including 156 of the OSAS patients. They identified five clusters: early-onset atopic asthma (690 patients), obese asthma (153 patients), late-onset asthma (299 patients), eosinophilic asthma (143 patients), and aspirin sensitivity asthma (139 patients).

All 153 patients in the obese asthma cluster had OSAS, by contrast, none of the patients in the early atopic asthma cluster had OSAS.

Overall, obesity, male sex, high blood pressure, depression, late-onset asthma, and early-onset atopic asthma were independently associated with OSAS, with odds ratios of 5.782, 3.047, 2.875, 2.552, 1.789, and 0.622, respectively.

Notably, OSAS patients were more frequently treated with long-term oral corticosteroids than those without OSAS (30% vs. 15%, P < .0001), the researchers said. “It is possible that this treatment may be responsible for obesity, and it represents a well-known risk factor for developing OSAS,” they wrote.

Uncontrolled asthma was significantly more common in OSAS patients than in those without OSAS (77.7% vs. 69%, P = .03), and significantly more OSAS patients reported no or occasional physical activity (79.8% vs. 68.2%, P ≤ .001).

The study findings were limited by several factors including the lack of patients from primary care or university hospitals, which may limit the generalizability of the results, the reliance on physician statements for diagnosis of OSAS, and the lack of data on OSAS severity or treatment, the researchers noted.

However, the results fill a needed gap in the literature because of the limited data on severe asthma patients in real life, and identifying severe asthma patients by phenotype may help identify those at greatest risk for OSAS, they said.

“Identified patients could more easily benefit from specific examinations such as poly(somno)graphy and, consequently, could benefit from a better management of both asthma and OSAS,” they emphasized.

The larger FASE-CPHG study was supported in part by ALK, AstraZeneca, Boehringer Ingelheim, GSK, and Le Nouveau Souffle. The researchers had no financial conflicts to disclose.

In assessing and managing patients presenting with acute, life-threatening asthma, if the exacerbation does not resolve relatively quickly, clinicians need to start looking for other causes of the patient’s respiratory distress, a review of the literature suggests.

“I think one of the most important points of this review is that asthma is a self-limiting disease, and it’s important to understand that with appropriate treatment and immediate response to it, exacerbations will get better with time,” Orlando Garner, MD, Baylor College of Medicine, Houston, said in an interview.

“So I think one of the key points is, if these exacerbations do not resolve within 24-48 hours, clinicians need to start thinking: ‘This could be something else,’ and not get stuck in the diagnosis that this is an asthmatic patient who is having an exacerbation. If the distress doesn’t resolve within 48 hours, it’s time to look for other clues,” he stressed.

The study was published online in the journal CHEST^®.

Appropriate triage

Appropriate triage is key in the management of acute asthma, Dr. Garner and colleagues pointed out. A simplified severity score for the evaluation of asthma in the ED can help in this regard. Depending on the presence or absence of a number of key signs and symptoms, patients can be readily categorized as having mild, moderate, or severe asthma. “Static assessments and dynamic assessments of acute asthma exacerbation in the ED can also help triage patients,” the authors added.

Static assessment involves assessing the severity at presentation, which in turn determines the aggressiveness of initial treatment. Objective static assessments include the measurement of peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV₁). A severe exacerbation is usually defined as a PEF or an FEV₁ of less than 50%-60% of predicted normal values, the authors noted.

Dynamic assessment is more helpful than static assessment because it gauges response to treatment. “A lack of improvement in expiratory flow rates after initial bronchodilator therapy with continuous or worsening symptoms suggests need for hospitalization,” Dr. Garner and colleagues observed. The main treatment goals for patients with acute asthma are reversal of bronchospasm and correction of hypoxemia.

These are achieved at least initially with conventional agents, such as repeated doses of inhaled short-acting beta₂-agonists, inhaled short-acting anticholinergics, systemic corticosteroids, and occasionally intravenous magnesium sulfate. If there is concomitant hypoxemia, oxygen therapy should be initiated as well. Patients who have evidence of hypercapnic respiratory failure or diaphragmatic fatigue need to be admitted to the intensive care unit, the authors indicated.

For these patients, clinicians need to remember that there are therapies other than inhalers, such as epinephrine and systemic terbutaline. During a life-threatening asthma episode, airflow in the medium and small airways often becomes turbulent, increasing the work of breathing, the researchers pointed out.

Heliox, a combination of helium and oxygen, reduces turbulent flow, they noted, although FiO₂ requirements need to be less than 30% in order for it to work. “Heliox can be used in patients with severe bronchospasm who do not respond to the conventional therapies,” the authors noted, “[but] therapy should be abandoned if there is no clinical improvement after 15 minutes of use.”

Although none of the biologics such as dupilumab (Dupixent) has yet been approved for the treatment of acute exacerbations, Dr. Garner predicts they will become the “future of medicine” for patients with severe asthma as well.
 

Ventilation in life-threatening asthma

Rapid sequence intubation is generally recommended for patients who require mechanical ventilation, but as an alternative, “we are advocating a slower approach, where we get patients to slow down their breathing and relax them with something like ketamine infusions and wait before we given them a paralytic to see if the work of breathing improves,” Dr. Garner said. Bag-mask ventilation should be avoided because it can worsen dynamic hyperinflation or cause barotrauma.

Salvage therapies such as the use of bronchoscopy with N-acetylcysteine instilled directly into the airway is another option in cases in which mucus plugging is considered to be the main driver of airflow limitation.

Asked to comment, Brit Long, MD, an emergency medicine physician at the Brooke Army Medical Center in San Antonio, Tex., felt the review was extremely useful and well done.

“We see these patients very frequently, and being able to assess them right away and get an accurate picture of what’s going on is very important,” he said in an interview. The one thing that is often more difficult, at least in the ED, is obtaining a PEF or the FEV₁ – “both very helpful if the patient can do them, but if the patient is critically ill, it’s more likely you will not be able to get those assessments, and if patients are speaking in one-word sentences and are working really hard to breathe, that’s a severe exacerbation, and they need immediate intervention.” Dr. Long also liked all the essential treatments the authors recommended that patients be given immediately, although he noted that Heliox is not going to be available in most EDs.

On the other hand, he agreed with the authors’ recommendation to take a slower approach to mechanical ventilation, if it is needed at all. “I try my best to absolutely avoid intubating these patients – you are not fixing the issue with mechanical ventilation, you are just creating further problems.

“And while I see the entire spectrum of asthma patients from very mild to severe patients, these authors did a good job in explaining what the goals of treatment are and what to do with the severe ones,” he said.

Dr. Garner and Dr. Long disclosed no relevant financial relationships.

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

In assessing and managing patients presenting with acute, life-threatening asthma, if the exacerbation does not resolve relatively quickly, clinicians need to start looking for other causes of the patient’s respiratory distress, a review of the literature suggests.

“I think one of the most important points of this review is that asthma is a self-limiting disease, and it’s important to understand that with appropriate treatment and immediate response to it, exacerbations will get better with time,” Orlando Garner, MD, Baylor College of Medicine, Houston, said in an interview.

“So I think one of the key points is, if these exacerbations do not resolve within 24-48 hours, clinicians need to start thinking: ‘This could be something else,’ and not get stuck in the diagnosis that this is an asthmatic patient who is having an exacerbation. If the distress doesn’t resolve within 48 hours, it’s time to look for other clues,” he stressed.

The study was published online in the journal CHEST^®.

Appropriate triage

Appropriate triage is key in the management of acute asthma, Dr. Garner and colleagues pointed out. A simplified severity score for the evaluation of asthma in the ED can help in this regard. Depending on the presence or absence of a number of key signs and symptoms, patients can be readily categorized as having mild, moderate, or severe asthma. “Static assessments and dynamic assessments of acute asthma exacerbation in the ED can also help triage patients,” the authors added.

Static assessment involves assessing the severity at presentation, which in turn determines the aggressiveness of initial treatment. Objective static assessments include the measurement of peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV₁). A severe exacerbation is usually defined as a PEF or an FEV₁ of less than 50%-60% of predicted normal values, the authors noted.

Dynamic assessment is more helpful than static assessment because it gauges response to treatment. “A lack of improvement in expiratory flow rates after initial bronchodilator therapy with continuous or worsening symptoms suggests need for hospitalization,” Dr. Garner and colleagues observed. The main treatment goals for patients with acute asthma are reversal of bronchospasm and correction of hypoxemia.

These are achieved at least initially with conventional agents, such as repeated doses of inhaled short-acting beta₂-agonists, inhaled short-acting anticholinergics, systemic corticosteroids, and occasionally intravenous magnesium sulfate. If there is concomitant hypoxemia, oxygen therapy should be initiated as well. Patients who have evidence of hypercapnic respiratory failure or diaphragmatic fatigue need to be admitted to the intensive care unit, the authors indicated.

For these patients, clinicians need to remember that there are therapies other than inhalers, such as epinephrine and systemic terbutaline. During a life-threatening asthma episode, airflow in the medium and small airways often becomes turbulent, increasing the work of breathing, the researchers pointed out.

Heliox, a combination of helium and oxygen, reduces turbulent flow, they noted, although FiO₂ requirements need to be less than 30% in order for it to work. “Heliox can be used in patients with severe bronchospasm who do not respond to the conventional therapies,” the authors noted, “[but] therapy should be abandoned if there is no clinical improvement after 15 minutes of use.”

Although none of the biologics such as dupilumab (Dupixent) has yet been approved for the treatment of acute exacerbations, Dr. Garner predicts they will become the “future of medicine” for patients with severe asthma as well.
 

Ventilation in life-threatening asthma

Rapid sequence intubation is generally recommended for patients who require mechanical ventilation, but as an alternative, “we are advocating a slower approach, where we get patients to slow down their breathing and relax them with something like ketamine infusions and wait before we given them a paralytic to see if the work of breathing improves,” Dr. Garner said. Bag-mask ventilation should be avoided because it can worsen dynamic hyperinflation or cause barotrauma.

Salvage therapies such as the use of bronchoscopy with N-acetylcysteine instilled directly into the airway is another option in cases in which mucus plugging is considered to be the main driver of airflow limitation.

Asked to comment, Brit Long, MD, an emergency medicine physician at the Brooke Army Medical Center in San Antonio, Tex., felt the review was extremely useful and well done.

“We see these patients very frequently, and being able to assess them right away and get an accurate picture of what’s going on is very important,” he said in an interview. The one thing that is often more difficult, at least in the ED, is obtaining a PEF or the FEV₁ – “both very helpful if the patient can do them, but if the patient is critically ill, it’s more likely you will not be able to get those assessments, and if patients are speaking in one-word sentences and are working really hard to breathe, that’s a severe exacerbation, and they need immediate intervention.” Dr. Long also liked all the essential treatments the authors recommended that patients be given immediately, although he noted that Heliox is not going to be available in most EDs.

On the other hand, he agreed with the authors’ recommendation to take a slower approach to mechanical ventilation, if it is needed at all. “I try my best to absolutely avoid intubating these patients – you are not fixing the issue with mechanical ventilation, you are just creating further problems.

“And while I see the entire spectrum of asthma patients from very mild to severe patients, these authors did a good job in explaining what the goals of treatment are and what to do with the severe ones,” he said.

Dr. Garner and Dr. Long disclosed no relevant financial relationships.

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

In assessing and managing patients presenting with acute, life-threatening asthma, if the exacerbation does not resolve relatively quickly, clinicians need to start looking for other causes of the patient’s respiratory distress, a review of the literature suggests.

“I think one of the most important points of this review is that asthma is a self-limiting disease, and it’s important to understand that with appropriate treatment and immediate response to it, exacerbations will get better with time,” Orlando Garner, MD, Baylor College of Medicine, Houston, said in an interview.

“So I think one of the key points is, if these exacerbations do not resolve within 24-48 hours, clinicians need to start thinking: ‘This could be something else,’ and not get stuck in the diagnosis that this is an asthmatic patient who is having an exacerbation. If the distress doesn’t resolve within 48 hours, it’s time to look for other clues,” he stressed.

The study was published online in the journal CHEST^®.

Appropriate triage

Appropriate triage is key in the management of acute asthma, Dr. Garner and colleagues pointed out. A simplified severity score for the evaluation of asthma in the ED can help in this regard. Depending on the presence or absence of a number of key signs and symptoms, patients can be readily categorized as having mild, moderate, or severe asthma. “Static assessments and dynamic assessments of acute asthma exacerbation in the ED can also help triage patients,” the authors added.

Static assessment involves assessing the severity at presentation, which in turn determines the aggressiveness of initial treatment. Objective static assessments include the measurement of peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV₁). A severe exacerbation is usually defined as a PEF or an FEV₁ of less than 50%-60% of predicted normal values, the authors noted.

Dynamic assessment is more helpful than static assessment because it gauges response to treatment. “A lack of improvement in expiratory flow rates after initial bronchodilator therapy with continuous or worsening symptoms suggests need for hospitalization,” Dr. Garner and colleagues observed. The main treatment goals for patients with acute asthma are reversal of bronchospasm and correction of hypoxemia.

These are achieved at least initially with conventional agents, such as repeated doses of inhaled short-acting beta₂-agonists, inhaled short-acting anticholinergics, systemic corticosteroids, and occasionally intravenous magnesium sulfate. If there is concomitant hypoxemia, oxygen therapy should be initiated as well. Patients who have evidence of hypercapnic respiratory failure or diaphragmatic fatigue need to be admitted to the intensive care unit, the authors indicated.

For these patients, clinicians need to remember that there are therapies other than inhalers, such as epinephrine and systemic terbutaline. During a life-threatening asthma episode, airflow in the medium and small airways often becomes turbulent, increasing the work of breathing, the researchers pointed out.

Heliox, a combination of helium and oxygen, reduces turbulent flow, they noted, although FiO₂ requirements need to be less than 30% in order for it to work. “Heliox can be used in patients with severe bronchospasm who do not respond to the conventional therapies,” the authors noted, “[but] therapy should be abandoned if there is no clinical improvement after 15 minutes of use.”

Although none of the biologics such as dupilumab (Dupixent) has yet been approved for the treatment of acute exacerbations, Dr. Garner predicts they will become the “future of medicine” for patients with severe asthma as well.
 

Ventilation in life-threatening asthma

Rapid sequence intubation is generally recommended for patients who require mechanical ventilation, but as an alternative, “we are advocating a slower approach, where we get patients to slow down their breathing and relax them with something like ketamine infusions and wait before we given them a paralytic to see if the work of breathing improves,” Dr. Garner said. Bag-mask ventilation should be avoided because it can worsen dynamic hyperinflation or cause barotrauma.

Salvage therapies such as the use of bronchoscopy with N-acetylcysteine instilled directly into the airway is another option in cases in which mucus plugging is considered to be the main driver of airflow limitation.

Asked to comment, Brit Long, MD, an emergency medicine physician at the Brooke Army Medical Center in San Antonio, Tex., felt the review was extremely useful and well done.

“We see these patients very frequently, and being able to assess them right away and get an accurate picture of what’s going on is very important,” he said in an interview. The one thing that is often more difficult, at least in the ED, is obtaining a PEF or the FEV₁ – “both very helpful if the patient can do them, but if the patient is critically ill, it’s more likely you will not be able to get those assessments, and if patients are speaking in one-word sentences and are working really hard to breathe, that’s a severe exacerbation, and they need immediate intervention.” Dr. Long also liked all the essential treatments the authors recommended that patients be given immediately, although he noted that Heliox is not going to be available in most EDs.

On the other hand, he agreed with the authors’ recommendation to take a slower approach to mechanical ventilation, if it is needed at all. “I try my best to absolutely avoid intubating these patients – you are not fixing the issue with mechanical ventilation, you are just creating further problems.

“And while I see the entire spectrum of asthma patients from very mild to severe patients, these authors did a good job in explaining what the goals of treatment are and what to do with the severe ones,” he said.

Dr. Garner and Dr. Long disclosed no relevant financial relationships.

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

New studies show that chronic exposure to air pollution is associated with increased risk of autoimmune disease in adults and depression in adolescents.

Other analyses of data have found environmental air pollution from sources such as car exhaust and factory output can trigger an inflammatory response in the body. What’s new about a study published in RMD Open is that it explored an association between long-term exposure to pollution and risk of autoimmune diseases, wrote Giovanni Adami, MD, of the University of Verona (Italy) and colleagues.

“Environmental air pollution, according to the World Health Organization, is a major risk to health and 99% of the population worldwide is living in places where recommendations for air quality are not met,” said Dr. Adami in an interview. The limited data on the precise role of air pollution on rheumatic diseases in particular prompted the study, he said.

To explore the potential link between air pollution exposure and autoimmune disease, the researchers reviewed medical information from 81,363 adults via a national medical database in Italy; the data were submitted between June 2016 and November 2020.

The average age of the study population was 65 years, and 92% were women; 22% had at least one coexisting health condition. Each study participant was linked to local environmental monitoring via their residential postcode. 

The researchers obtained details about concentrations of particulate matter in the environment from the Italian Institute of Environmental Protection that included 617 monitoring stations in 110 Italian provinces. They focused on concentrations of 10 and 2.5 (PM10 and PM2.5).

Exposure thresholds of 30 mcg/m³ for PM10 and 20 mcg/m³ for PM2.5 are generally considered harmful to health, they noted. On average, the long-term exposure was 16 mcg/m³ for PM2.5 and 25 mcg/m³ for PM10 between 2013 and 2019.

Overall, 9,723 individuals (12%) were diagnosed with an autoimmune disease between 2016 and 2020.

Exposure to PM10 was associated with a 7% higher risk of diagnosis with any autoimmune disease for every 10 mcg/m³ increase in concentration, but no association appeared between PM2.5 exposure and increased risk of autoimmune diseases.

However, in an adjusted model, chronic exposure to PM10 above 30 mcg/m³ and to PM2.5 above 20 mcg/m³ were associated with a 12% and 13% higher risk, respectively, of any autoimmune disease. 

Chronic exposure to high levels of PM10 was specifically associated with a higher risk of rheumatoid arthritis, but no other autoimmune diseases. Chronic exposure to high levels of PM2.5 was associated with a higher risk of rheumatoid arthritis, connective tissue diseases, and inflammatory bowel diseases.

In their discussion, the researchers noted that the smaller diameter of PM2.5 molecules fluctuate less in response to rain and other weather, compared with PM10 molecules, which might make them a more accurate predictor of exposure to chronic air pollution.

The study findings were limited by several factors including the observational design, which prohibits the establishment of cause, and a lack of data on the start of symptoms and dates of diagnoses for autoimmune diseases, the researchers noted. Other limitations include the high percentage of older women in the study, which may limit generalizability, and the inability to account for additional personal exposure to pollutants outside of the environmental exposure, they said.

However, the results were strengthened by the large sample size and wide geographic distribution with variable pollution exposure, they said.

“Unfortunately, we were not surprised at all,” by the findings, Dr. Adami said in an interview.

“The biological rationale underpinning our findings is strong. Nevertheless, the magnitude of the effect was overwhelming. In addition, we saw an effect even at threshold of exposure that is widely considered as safe,” Dr. Adami noted.

Clinicians have been taught to consider cigarette smoking or other lifestyle behaviors as major risk factors for the development of several autoimmune diseases, said Dr. Adami. “In the future, we probably should include air pollution exposure as a risk factor as well. Interestingly, there is also accumulating evidence linking acute exposure to environmental air pollution with flares of chronic arthritis,” he said.

“Our study could have direct societal and political consequences,” and might help direct policy makers’ decisions on addressing strategies aimed to reduce fossil emissions, he said. As for additional research, “we certainly need multination studies to confirm our results on a larger scale,” Dr. Adami emphasized. “In addition, it is time to take action and start designing interventions aimed to reduce acute and chronic exposure to air pollution in patients suffering from RMDs.”

Consider the big picture of air quality

The Italian study is especially timely “given our evolving and emerging understanding of environmental risk factors for acute and chronic diseases, which we must first understand before we can address,” said Eileen Barrett, MD, of the University of New Mexico, Albuquerque, in an interview.

“I am largely surprised about the findings, as most physicians aren’t studying ambient air quality and risk for autoimmune disease,” said Dr. Barrett. “More often we think of air quality when we think of risk for respiratory diseases than autoimmune diseases, per se,” she said.

“There are several take-home messages from this study,” said Dr. Barrett. “The first is that we need more research to understand the consequences of air pollutants on health. Second, this study reminds us to think broadly about how air quality and our environment can affect health. And third, all clinicians should be committed to promoting science that can improve public health and reduce death and disability,” she emphasized.

The findings do not specifically reflect associations between pollution and other conditions such as chronic obstructive pulmonary disease and asthma although previous studies have shown an association between asthma and COPD exacerbations and air pollution, Dr. Barrett said.

“Further research will be needed to confirm the associations reported in this study,” Dr. Barrett said.

More research in other countries, including research related to other autoimmune diseases, and with other datasets on population and community level risks from poor air quality, would be helpful, and that information could be used to advise smart public policy, Dr. Barrett added.

Air pollution’s mental health impact

Air pollution’s effects extend beyond physical to the psychological, a new study of depression in teenagers showed. This study was published in Developmental Psychology.

Previous research on the environmental factors associated with depressive symptoms in teens has focused mainly on individual and family level contributors; the impact of the physical environment has not been well studied, the investigators, Erika M. Manczak, PhD, of the University of Denver and colleagues, wrote.

In their paper, the authors found a significant impact of neighborhood ozone exposure on the trajectory of depressive symptoms in teens over a 4-year period.

“Given that inhaling pollution activates biological pathways implicated in the development of depression, including immune, cardiovascular, and neurodevelopmental processes, exposure to ambient air pollution may influence the development and/or trajectory of depressive symptoms in youth,” they said.

The researchers recruited 213 adolescents in the San Francisco Bay area through local advertisements. The participants were aged 9-13 years at baseline, with an average age of 11 years. A total of 121 were female, 47% were white, 8.5% were African American, 12.3% were Asian, 10.4% were nonwhite Latin, and 21.7% were biracial or another ethnicity. The participants self-reported depressive symptoms and other psychopathology symptoms up to three times during the study period. Ozone exposure was calculated based on home addresses.

After controlling for other personal, family, and neighborhood variables, the researchers found that higher levels of ozone exposure were significantly associated with increased depressive symptoms over time, and the slope of trajectory of depressive symptoms became steeper as the ozone levels increased (P less than .001). Ozone did not significantly predict the trajectory of any other psychopathology symptoms.

“The results of this study provide preliminary support for the possibility that ozone is an overlooked contributor to the development or course of youth depressive symptoms,” the researchers wrote in their discussion.

“Interestingly, the association between ozone and symptom trajectories as measured by Anxious/Depressed subscale of the [Youth Self-Report] was not as strong as it was for the [Children’s Depression Inventory-Short Version] or Withdrawn/Depressed scales, suggesting that associations are more robust for behavioral withdrawal symptoms of depression than for other types of symptoms,” they noted.

The study findings were limited by the use of self-reports and by the inability of the study design to show causality, the researchers said. Other limitations include the use of average assessments of ozone that are less precise, lack of assessment of biological pathways for risk, lack of formal psychiatric diagnoses, and the small geographic region included in the study, they said.

However, the results provide preliminary evidence that ozone exposure is a potential contributing factor to depressive symptoms in youth, and serve as a jumping-off point for future research, they noted. Future studies should address changes in systemic inflammation, neurodevelopment, or stress reactivity, as well as concurrent psychosocial or biological factors, and temporal associations between air pollution and mental health symptoms, they concluded.

Environmental factors drive inflammatory responses

Peter L. Loper Jr., MD, considers the findings of the Developmental Psychology study to be unsurprising but important – because air pollution is simply getting worse.

“As the study authors cite, there is sufficient data correlating ozone to negative physical health outcomes in youth, but a paucity of data exploring the impact of poor air quality on mental health outcomes in this demographic,” noted Dr. Loper, of the University of South Carolina, Columbia, in an interview.

“As discussed by the study researchers, any environmental exposure that increases immune-mediated inflammation can result in negative health outcomes. In fact, there is already data to suggest that similar cytokines, or immune cell signalers, that get released by our immune system due to environmental exposures and that contribute to asthma, may also be implicated in depression and other mental health problems,” he noted.

“Just like downstream symptom indicators of physical illnesses such as asthma are secondary to immune-mediated pulmonary inflammation, downstream symptom indicators of mental illness, such as depression, are secondary to immune-mediated neuroinflammation,” Dr. Loper emphasized. “The most well-characterized upstream phenomenon perpetuating the downstream symptom indicators of depression involve neuroinflammatory states due to psychosocial and relational factors such as chronic stress, poor relationships, or substance use. However, any environmental factor that triggers an immune response and inflammation can promote neuroinflammation that manifests as symptoms of mental illness.”

The message for teens with depression and their families is that “we are a product of our environment,” Dr. Loper said. “When our environments are proinflammatory, or cause our immune system to become overactive, then we will develop illness; however, the most potent mediator of inflammation in the brain, and the downstream symptoms of depression, is our relationships with those we love most,” he said.

Dr. Loper suggested research aimed at identifying other sources of immune-mediated inflammation caused by physical environments and better understanding how environmental phenomenon like ozone may compound previously established risk factors for mental illness could be useful.

The RMD Open study received no outside funding, and its authors had no financial conflicts.

The Developmental Psychology study was supported by the National Institute of Mental Health and the Stanford University Precision Health and Integrated Diagnostics Center. The researchers for that report, and Dr. Loper and Dr. Barrett had no conflicts to disclose.

New studies show that chronic exposure to air pollution is associated with increased risk of autoimmune disease in adults and depression in adolescents.

Other analyses of data have found environmental air pollution from sources such as car exhaust and factory output can trigger an inflammatory response in the body. What’s new about a study published in RMD Open is that it explored an association between long-term exposure to pollution and risk of autoimmune diseases, wrote Giovanni Adami, MD, of the University of Verona (Italy) and colleagues.

“Environmental air pollution, according to the World Health Organization, is a major risk to health and 99% of the population worldwide is living in places where recommendations for air quality are not met,” said Dr. Adami in an interview. The limited data on the precise role of air pollution on rheumatic diseases in particular prompted the study, he said.

To explore the potential link between air pollution exposure and autoimmune disease, the researchers reviewed medical information from 81,363 adults via a national medical database in Italy; the data were submitted between June 2016 and November 2020.

The average age of the study population was 65 years, and 92% were women; 22% had at least one coexisting health condition. Each study participant was linked to local environmental monitoring via their residential postcode. 

The researchers obtained details about concentrations of particulate matter in the environment from the Italian Institute of Environmental Protection that included 617 monitoring stations in 110 Italian provinces. They focused on concentrations of 10 and 2.5 (PM10 and PM2.5).

Exposure thresholds of 30 mcg/m³ for PM10 and 20 mcg/m³ for PM2.5 are generally considered harmful to health, they noted. On average, the long-term exposure was 16 mcg/m³ for PM2.5 and 25 mcg/m³ for PM10 between 2013 and 2019.

Overall, 9,723 individuals (12%) were diagnosed with an autoimmune disease between 2016 and 2020.

Exposure to PM10 was associated with a 7% higher risk of diagnosis with any autoimmune disease for every 10 mcg/m³ increase in concentration, but no association appeared between PM2.5 exposure and increased risk of autoimmune diseases.

However, in an adjusted model, chronic exposure to PM10 above 30 mcg/m³ and to PM2.5 above 20 mcg/m³ were associated with a 12% and 13% higher risk, respectively, of any autoimmune disease. 

Chronic exposure to high levels of PM10 was specifically associated with a higher risk of rheumatoid arthritis, but no other autoimmune diseases. Chronic exposure to high levels of PM2.5 was associated with a higher risk of rheumatoid arthritis, connective tissue diseases, and inflammatory bowel diseases.

In their discussion, the researchers noted that the smaller diameter of PM2.5 molecules fluctuate less in response to rain and other weather, compared with PM10 molecules, which might make them a more accurate predictor of exposure to chronic air pollution.

The study findings were limited by several factors including the observational design, which prohibits the establishment of cause, and a lack of data on the start of symptoms and dates of diagnoses for autoimmune diseases, the researchers noted. Other limitations include the high percentage of older women in the study, which may limit generalizability, and the inability to account for additional personal exposure to pollutants outside of the environmental exposure, they said.

However, the results were strengthened by the large sample size and wide geographic distribution with variable pollution exposure, they said.

“Unfortunately, we were not surprised at all,” by the findings, Dr. Adami said in an interview.

“The biological rationale underpinning our findings is strong. Nevertheless, the magnitude of the effect was overwhelming. In addition, we saw an effect even at threshold of exposure that is widely considered as safe,” Dr. Adami noted.

Clinicians have been taught to consider cigarette smoking or other lifestyle behaviors as major risk factors for the development of several autoimmune diseases, said Dr. Adami. “In the future, we probably should include air pollution exposure as a risk factor as well. Interestingly, there is also accumulating evidence linking acute exposure to environmental air pollution with flares of chronic arthritis,” he said.

“Our study could have direct societal and political consequences,” and might help direct policy makers’ decisions on addressing strategies aimed to reduce fossil emissions, he said. As for additional research, “we certainly need multination studies to confirm our results on a larger scale,” Dr. Adami emphasized. “In addition, it is time to take action and start designing interventions aimed to reduce acute and chronic exposure to air pollution in patients suffering from RMDs.”

Consider the big picture of air quality

The Italian study is especially timely “given our evolving and emerging understanding of environmental risk factors for acute and chronic diseases, which we must first understand before we can address,” said Eileen Barrett, MD, of the University of New Mexico, Albuquerque, in an interview.

“I am largely surprised about the findings, as most physicians aren’t studying ambient air quality and risk for autoimmune disease,” said Dr. Barrett. “More often we think of air quality when we think of risk for respiratory diseases than autoimmune diseases, per se,” she said.

“There are several take-home messages from this study,” said Dr. Barrett. “The first is that we need more research to understand the consequences of air pollutants on health. Second, this study reminds us to think broadly about how air quality and our environment can affect health. And third, all clinicians should be committed to promoting science that can improve public health and reduce death and disability,” she emphasized.

The findings do not specifically reflect associations between pollution and other conditions such as chronic obstructive pulmonary disease and asthma although previous studies have shown an association between asthma and COPD exacerbations and air pollution, Dr. Barrett said.

“Further research will be needed to confirm the associations reported in this study,” Dr. Barrett said.

More research in other countries, including research related to other autoimmune diseases, and with other datasets on population and community level risks from poor air quality, would be helpful, and that information could be used to advise smart public policy, Dr. Barrett added.

Air pollution’s mental health impact

Air pollution’s effects extend beyond physical to the psychological, a new study of depression in teenagers showed. This study was published in Developmental Psychology.

Previous research on the environmental factors associated with depressive symptoms in teens has focused mainly on individual and family level contributors; the impact of the physical environment has not been well studied, the investigators, Erika M. Manczak, PhD, of the University of Denver and colleagues, wrote.

In their paper, the authors found a significant impact of neighborhood ozone exposure on the trajectory of depressive symptoms in teens over a 4-year period.

“Given that inhaling pollution activates biological pathways implicated in the development of depression, including immune, cardiovascular, and neurodevelopmental processes, exposure to ambient air pollution may influence the development and/or trajectory of depressive symptoms in youth,” they said.

The researchers recruited 213 adolescents in the San Francisco Bay area through local advertisements. The participants were aged 9-13 years at baseline, with an average age of 11 years. A total of 121 were female, 47% were white, 8.5% were African American, 12.3% were Asian, 10.4% were nonwhite Latin, and 21.7% were biracial or another ethnicity. The participants self-reported depressive symptoms and other psychopathology symptoms up to three times during the study period. Ozone exposure was calculated based on home addresses.

After controlling for other personal, family, and neighborhood variables, the researchers found that higher levels of ozone exposure were significantly associated with increased depressive symptoms over time, and the slope of trajectory of depressive symptoms became steeper as the ozone levels increased (P less than .001). Ozone did not significantly predict the trajectory of any other psychopathology symptoms.

“The results of this study provide preliminary support for the possibility that ozone is an overlooked contributor to the development or course of youth depressive symptoms,” the researchers wrote in their discussion.

“Interestingly, the association between ozone and symptom trajectories as measured by Anxious/Depressed subscale of the [Youth Self-Report] was not as strong as it was for the [Children’s Depression Inventory-Short Version] or Withdrawn/Depressed scales, suggesting that associations are more robust for behavioral withdrawal symptoms of depression than for other types of symptoms,” they noted.

The study findings were limited by the use of self-reports and by the inability of the study design to show causality, the researchers said. Other limitations include the use of average assessments of ozone that are less precise, lack of assessment of biological pathways for risk, lack of formal psychiatric diagnoses, and the small geographic region included in the study, they said.

However, the results provide preliminary evidence that ozone exposure is a potential contributing factor to depressive symptoms in youth, and serve as a jumping-off point for future research, they noted. Future studies should address changes in systemic inflammation, neurodevelopment, or stress reactivity, as well as concurrent psychosocial or biological factors, and temporal associations between air pollution and mental health symptoms, they concluded.

Environmental factors drive inflammatory responses

Peter L. Loper Jr., MD, considers the findings of the Developmental Psychology study to be unsurprising but important – because air pollution is simply getting worse.

“As the study authors cite, there is sufficient data correlating ozone to negative physical health outcomes in youth, but a paucity of data exploring the impact of poor air quality on mental health outcomes in this demographic,” noted Dr. Loper, of the University of South Carolina, Columbia, in an interview.

“As discussed by the study researchers, any environmental exposure that increases immune-mediated inflammation can result in negative health outcomes. In fact, there is already data to suggest that similar cytokines, or immune cell signalers, that get released by our immune system due to environmental exposures and that contribute to asthma, may also be implicated in depression and other mental health problems,” he noted.

“Just like downstream symptom indicators of physical illnesses such as asthma are secondary to immune-mediated pulmonary inflammation, downstream symptom indicators of mental illness, such as depression, are secondary to immune-mediated neuroinflammation,” Dr. Loper emphasized. “The most well-characterized upstream phenomenon perpetuating the downstream symptom indicators of depression involve neuroinflammatory states due to psychosocial and relational factors such as chronic stress, poor relationships, or substance use. However, any environmental factor that triggers an immune response and inflammation can promote neuroinflammation that manifests as symptoms of mental illness.”

The message for teens with depression and their families is that “we are a product of our environment,” Dr. Loper said. “When our environments are proinflammatory, or cause our immune system to become overactive, then we will develop illness; however, the most potent mediator of inflammation in the brain, and the downstream symptoms of depression, is our relationships with those we love most,” he said.

Dr. Loper suggested research aimed at identifying other sources of immune-mediated inflammation caused by physical environments and better understanding how environmental phenomenon like ozone may compound previously established risk factors for mental illness could be useful.

The RMD Open study received no outside funding, and its authors had no financial conflicts.

The Developmental Psychology study was supported by the National Institute of Mental Health and the Stanford University Precision Health and Integrated Diagnostics Center. The researchers for that report, and Dr. Loper and Dr. Barrett had no conflicts to disclose.

New studies show that chronic exposure to air pollution is associated with increased risk of autoimmune disease in adults and depression in adolescents.

Other analyses of data have found environmental air pollution from sources such as car exhaust and factory output can trigger an inflammatory response in the body. What’s new about a study published in RMD Open is that it explored an association between long-term exposure to pollution and risk of autoimmune diseases, wrote Giovanni Adami, MD, of the University of Verona (Italy) and colleagues.

“Environmental air pollution, according to the World Health Organization, is a major risk to health and 99% of the population worldwide is living in places where recommendations for air quality are not met,” said Dr. Adami in an interview. The limited data on the precise role of air pollution on rheumatic diseases in particular prompted the study, he said.

To explore the potential link between air pollution exposure and autoimmune disease, the researchers reviewed medical information from 81,363 adults via a national medical database in Italy; the data were submitted between June 2016 and November 2020.

The average age of the study population was 65 years, and 92% were women; 22% had at least one coexisting health condition. Each study participant was linked to local environmental monitoring via their residential postcode. 

The researchers obtained details about concentrations of particulate matter in the environment from the Italian Institute of Environmental Protection that included 617 monitoring stations in 110 Italian provinces. They focused on concentrations of 10 and 2.5 (PM10 and PM2.5).

Exposure thresholds of 30 mcg/m³ for PM10 and 20 mcg/m³ for PM2.5 are generally considered harmful to health, they noted. On average, the long-term exposure was 16 mcg/m³ for PM2.5 and 25 mcg/m³ for PM10 between 2013 and 2019.

Overall, 9,723 individuals (12%) were diagnosed with an autoimmune disease between 2016 and 2020.

Exposure to PM10 was associated with a 7% higher risk of diagnosis with any autoimmune disease for every 10 mcg/m³ increase in concentration, but no association appeared between PM2.5 exposure and increased risk of autoimmune diseases.

However, in an adjusted model, chronic exposure to PM10 above 30 mcg/m³ and to PM2.5 above 20 mcg/m³ were associated with a 12% and 13% higher risk, respectively, of any autoimmune disease. 

Chronic exposure to high levels of PM10 was specifically associated with a higher risk of rheumatoid arthritis, but no other autoimmune diseases. Chronic exposure to high levels of PM2.5 was associated with a higher risk of rheumatoid arthritis, connective tissue diseases, and inflammatory bowel diseases.

In their discussion, the researchers noted that the smaller diameter of PM2.5 molecules fluctuate less in response to rain and other weather, compared with PM10 molecules, which might make them a more accurate predictor of exposure to chronic air pollution.

The study findings were limited by several factors including the observational design, which prohibits the establishment of cause, and a lack of data on the start of symptoms and dates of diagnoses for autoimmune diseases, the researchers noted. Other limitations include the high percentage of older women in the study, which may limit generalizability, and the inability to account for additional personal exposure to pollutants outside of the environmental exposure, they said.

However, the results were strengthened by the large sample size and wide geographic distribution with variable pollution exposure, they said.

“Unfortunately, we were not surprised at all,” by the findings, Dr. Adami said in an interview.

“The biological rationale underpinning our findings is strong. Nevertheless, the magnitude of the effect was overwhelming. In addition, we saw an effect even at threshold of exposure that is widely considered as safe,” Dr. Adami noted.

Clinicians have been taught to consider cigarette smoking or other lifestyle behaviors as major risk factors for the development of several autoimmune diseases, said Dr. Adami. “In the future, we probably should include air pollution exposure as a risk factor as well. Interestingly, there is also accumulating evidence linking acute exposure to environmental air pollution with flares of chronic arthritis,” he said.

“Our study could have direct societal and political consequences,” and might help direct policy makers’ decisions on addressing strategies aimed to reduce fossil emissions, he said. As for additional research, “we certainly need multination studies to confirm our results on a larger scale,” Dr. Adami emphasized. “In addition, it is time to take action and start designing interventions aimed to reduce acute and chronic exposure to air pollution in patients suffering from RMDs.”

Consider the big picture of air quality

The Italian study is especially timely “given our evolving and emerging understanding of environmental risk factors for acute and chronic diseases, which we must first understand before we can address,” said Eileen Barrett, MD, of the University of New Mexico, Albuquerque, in an interview.

“I am largely surprised about the findings, as most physicians aren’t studying ambient air quality and risk for autoimmune disease,” said Dr. Barrett. “More often we think of air quality when we think of risk for respiratory diseases than autoimmune diseases, per se,” she said.

“There are several take-home messages from this study,” said Dr. Barrett. “The first is that we need more research to understand the consequences of air pollutants on health. Second, this study reminds us to think broadly about how air quality and our environment can affect health. And third, all clinicians should be committed to promoting science that can improve public health and reduce death and disability,” she emphasized.

The findings do not specifically reflect associations between pollution and other conditions such as chronic obstructive pulmonary disease and asthma although previous studies have shown an association between asthma and COPD exacerbations and air pollution, Dr. Barrett said.

“Further research will be needed to confirm the associations reported in this study,” Dr. Barrett said.

More research in other countries, including research related to other autoimmune diseases, and with other datasets on population and community level risks from poor air quality, would be helpful, and that information could be used to advise smart public policy, Dr. Barrett added.

Air pollution’s mental health impact

Air pollution’s effects extend beyond physical to the psychological, a new study of depression in teenagers showed. This study was published in Developmental Psychology.

Previous research on the environmental factors associated with depressive symptoms in teens has focused mainly on individual and family level contributors; the impact of the physical environment has not been well studied, the investigators, Erika M. Manczak, PhD, of the University of Denver and colleagues, wrote.

In their paper, the authors found a significant impact of neighborhood ozone exposure on the trajectory of depressive symptoms in teens over a 4-year period.

“Given that inhaling pollution activates biological pathways implicated in the development of depression, including immune, cardiovascular, and neurodevelopmental processes, exposure to ambient air pollution may influence the development and/or trajectory of depressive symptoms in youth,” they said.

The researchers recruited 213 adolescents in the San Francisco Bay area through local advertisements. The participants were aged 9-13 years at baseline, with an average age of 11 years. A total of 121 were female, 47% were white, 8.5% were African American, 12.3% were Asian, 10.4% were nonwhite Latin, and 21.7% were biracial or another ethnicity. The participants self-reported depressive symptoms and other psychopathology symptoms up to three times during the study period. Ozone exposure was calculated based on home addresses.

After controlling for other personal, family, and neighborhood variables, the researchers found that higher levels of ozone exposure were significantly associated with increased depressive symptoms over time, and the slope of trajectory of depressive symptoms became steeper as the ozone levels increased (P less than .001). Ozone did not significantly predict the trajectory of any other psychopathology symptoms.

“The results of this study provide preliminary support for the possibility that ozone is an overlooked contributor to the development or course of youth depressive symptoms,” the researchers wrote in their discussion.

“Interestingly, the association between ozone and symptom trajectories as measured by Anxious/Depressed subscale of the [Youth Self-Report] was not as strong as it was for the [Children’s Depression Inventory-Short Version] or Withdrawn/Depressed scales, suggesting that associations are more robust for behavioral withdrawal symptoms of depression than for other types of symptoms,” they noted.

The study findings were limited by the use of self-reports and by the inability of the study design to show causality, the researchers said. Other limitations include the use of average assessments of ozone that are less precise, lack of assessment of biological pathways for risk, lack of formal psychiatric diagnoses, and the small geographic region included in the study, they said.

However, the results provide preliminary evidence that ozone exposure is a potential contributing factor to depressive symptoms in youth, and serve as a jumping-off point for future research, they noted. Future studies should address changes in systemic inflammation, neurodevelopment, or stress reactivity, as well as concurrent psychosocial or biological factors, and temporal associations between air pollution and mental health symptoms, they concluded.

Environmental factors drive inflammatory responses

Peter L. Loper Jr., MD, considers the findings of the Developmental Psychology study to be unsurprising but important – because air pollution is simply getting worse.

“As the study authors cite, there is sufficient data correlating ozone to negative physical health outcomes in youth, but a paucity of data exploring the impact of poor air quality on mental health outcomes in this demographic,” noted Dr. Loper, of the University of South Carolina, Columbia, in an interview.

“As discussed by the study researchers, any environmental exposure that increases immune-mediated inflammation can result in negative health outcomes. In fact, there is already data to suggest that similar cytokines, or immune cell signalers, that get released by our immune system due to environmental exposures and that contribute to asthma, may also be implicated in depression and other mental health problems,” he noted.

“Just like downstream symptom indicators of physical illnesses such as asthma are secondary to immune-mediated pulmonary inflammation, downstream symptom indicators of mental illness, such as depression, are secondary to immune-mediated neuroinflammation,” Dr. Loper emphasized. “The most well-characterized upstream phenomenon perpetuating the downstream symptom indicators of depression involve neuroinflammatory states due to psychosocial and relational factors such as chronic stress, poor relationships, or substance use. However, any environmental factor that triggers an immune response and inflammation can promote neuroinflammation that manifests as symptoms of mental illness.”

The message for teens with depression and their families is that “we are a product of our environment,” Dr. Loper said. “When our environments are proinflammatory, or cause our immune system to become overactive, then we will develop illness; however, the most potent mediator of inflammation in the brain, and the downstream symptoms of depression, is our relationships with those we love most,” he said.

Dr. Loper suggested research aimed at identifying other sources of immune-mediated inflammation caused by physical environments and better understanding how environmental phenomenon like ozone may compound previously established risk factors for mental illness could be useful.

The RMD Open study received no outside funding, and its authors had no financial conflicts.

The Developmental Psychology study was supported by the National Institute of Mental Health and the Stanford University Precision Health and Integrated Diagnostics Center. The researchers for that report, and Dr. Loper and Dr. Barrett had no conflicts to disclose.

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

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

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

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

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

Most lung cancer patients with interstitial lung disease will not benefit from thoracic radiotherapy, based on data from a systematic review of 24 studies.

Thoracic radiotherapy remains a key part of lung cancer treatment for early and metastatic disease. However, patients with both small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) associated with interstitial lung disease (ILD) fare worse than do those without ILD, often because of acute exacerbation of ILD and severe or fatal pneumonitis, wrote Animesh Saha, MD, of Apollo Multi-Specialty Hospitals, Kolkata, India, and colleagues. Consequently, clinicians may hesitate to offer radiotherapy to these patients.

In a review published in Clinical Oncology, the researchers identified 24 studies, including phase II and phase III randomized or nonrandomized trials, as well as prospective, observational studies and retrospective real-world studies. The goal of the review was to report the incidence and predictors of radiation pneumonitis associated with different types of thoracic radiotherapy for lung cancer patients with ILD, the researchers said. Treatment types included curative-intent fractionated radiotherapy or chemoradiotherapy or moderately hypofractionated (nonstereotactic ablative radiotherapy [SABR]) and hyperfractionated radiotherapy as well as particle beam therapies.

The studies included patients with SCLC or NSCLC and any form of ILD, including subclinical, radiologically diagnosed, or symptomatic, the researchers said.

Overall, the median incidence of grade 3 or higher radiation pneumonitis was 19.7%; the median incidence in patients treated with conventional radical radiotherapy, SABR, and particle beam therapy was 31.8%, 11.9%, and 20.25%, respectively.

Eighteen studies reported grade 5 radiation pneumonitis; the overall median incidence was 6%, but as high as 60% in some studies. When separated by treatment type, the median incidence was 2.7%, 6.25%, and 6.25%, respectively, in patients treated with radical radiotherapy (non-SABR), SABR, and particle beam therapy.

Independent predictors of severe radiation pneumonitis (grade 2 or higher and grade 3 or higher) included subclinical or radiological ILD, the researchers said. Among ILD subtypes, studies have shown increased risk for severe radiation pneumonitis among those with non-IPF or non-UIP pattern fibrosis.

In addition, patient-related factors of low forced vital capacity (FVC) and low forced expiratory volume in 1 second (FEV₁), have been associated with severe radiation pneumonitis, the researchers said. They also found increased risk for patients with lower lobe tumor location compared to other lobes.

As for treatment-related factors, a history of gemcitabine chemotherapy was associated with an increased risk of grade 3 or higher radiation pneumonitis.

“There is always concern about using thoracic radiotherapy in lung cancer patients with coexisting ILD in view of the risks involved,” the researchers wrote in their discussion of the findings. “Although thoracic radiotherapy is expected to produce similar local control, overall survival is worse in lung cancer patients with ILD than without, probably due to the poor prognosis associated with ILD and associated treatment-related mortality,” they said.

The findings were limited by several factors including the heterogeneity of the studies and study population and the retrospective design of most of the studies, the researchers noted.

However, the results highlight the increased risk of severe and fatal radiation pneumonitis in lung cancer patients with ILD and the need for careful patient selection and counseling if thoracic radiotherapy is to be considered, they concluded.

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

Most lung cancer patients with interstitial lung disease will not benefit from thoracic radiotherapy, based on data from a systematic review of 24 studies.

Thoracic radiotherapy remains a key part of lung cancer treatment for early and metastatic disease. However, patients with both small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) associated with interstitial lung disease (ILD) fare worse than do those without ILD, often because of acute exacerbation of ILD and severe or fatal pneumonitis, wrote Animesh Saha, MD, of Apollo Multi-Specialty Hospitals, Kolkata, India, and colleagues. Consequently, clinicians may hesitate to offer radiotherapy to these patients.

In a review published in Clinical Oncology, the researchers identified 24 studies, including phase II and phase III randomized or nonrandomized trials, as well as prospective, observational studies and retrospective real-world studies. The goal of the review was to report the incidence and predictors of radiation pneumonitis associated with different types of thoracic radiotherapy for lung cancer patients with ILD, the researchers said. Treatment types included curative-intent fractionated radiotherapy or chemoradiotherapy or moderately hypofractionated (nonstereotactic ablative radiotherapy [SABR]) and hyperfractionated radiotherapy as well as particle beam therapies.

The studies included patients with SCLC or NSCLC and any form of ILD, including subclinical, radiologically diagnosed, or symptomatic, the researchers said.

Overall, the median incidence of grade 3 or higher radiation pneumonitis was 19.7%; the median incidence in patients treated with conventional radical radiotherapy, SABR, and particle beam therapy was 31.8%, 11.9%, and 20.25%, respectively.

Eighteen studies reported grade 5 radiation pneumonitis; the overall median incidence was 6%, but as high as 60% in some studies. When separated by treatment type, the median incidence was 2.7%, 6.25%, and 6.25%, respectively, in patients treated with radical radiotherapy (non-SABR), SABR, and particle beam therapy.

Independent predictors of severe radiation pneumonitis (grade 2 or higher and grade 3 or higher) included subclinical or radiological ILD, the researchers said. Among ILD subtypes, studies have shown increased risk for severe radiation pneumonitis among those with non-IPF or non-UIP pattern fibrosis.

In addition, patient-related factors of low forced vital capacity (FVC) and low forced expiratory volume in 1 second (FEV₁), have been associated with severe radiation pneumonitis, the researchers said. They also found increased risk for patients with lower lobe tumor location compared to other lobes.

As for treatment-related factors, a history of gemcitabine chemotherapy was associated with an increased risk of grade 3 or higher radiation pneumonitis.

“There is always concern about using thoracic radiotherapy in lung cancer patients with coexisting ILD in view of the risks involved,” the researchers wrote in their discussion of the findings. “Although thoracic radiotherapy is expected to produce similar local control, overall survival is worse in lung cancer patients with ILD than without, probably due to the poor prognosis associated with ILD and associated treatment-related mortality,” they said.

The findings were limited by several factors including the heterogeneity of the studies and study population and the retrospective design of most of the studies, the researchers noted.

However, the results highlight the increased risk of severe and fatal radiation pneumonitis in lung cancer patients with ILD and the need for careful patient selection and counseling if thoracic radiotherapy is to be considered, they concluded.

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

Most lung cancer patients with interstitial lung disease will not benefit from thoracic radiotherapy, based on data from a systematic review of 24 studies.

Thoracic radiotherapy remains a key part of lung cancer treatment for early and metastatic disease. However, patients with both small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) associated with interstitial lung disease (ILD) fare worse than do those without ILD, often because of acute exacerbation of ILD and severe or fatal pneumonitis, wrote Animesh Saha, MD, of Apollo Multi-Specialty Hospitals, Kolkata, India, and colleagues. Consequently, clinicians may hesitate to offer radiotherapy to these patients.

In a review published in Clinical Oncology, the researchers identified 24 studies, including phase II and phase III randomized or nonrandomized trials, as well as prospective, observational studies and retrospective real-world studies. The goal of the review was to report the incidence and predictors of radiation pneumonitis associated with different types of thoracic radiotherapy for lung cancer patients with ILD, the researchers said. Treatment types included curative-intent fractionated radiotherapy or chemoradiotherapy or moderately hypofractionated (nonstereotactic ablative radiotherapy [SABR]) and hyperfractionated radiotherapy as well as particle beam therapies.

The studies included patients with SCLC or NSCLC and any form of ILD, including subclinical, radiologically diagnosed, or symptomatic, the researchers said.

Overall, the median incidence of grade 3 or higher radiation pneumonitis was 19.7%; the median incidence in patients treated with conventional radical radiotherapy, SABR, and particle beam therapy was 31.8%, 11.9%, and 20.25%, respectively.

Eighteen studies reported grade 5 radiation pneumonitis; the overall median incidence was 6%, but as high as 60% in some studies. When separated by treatment type, the median incidence was 2.7%, 6.25%, and 6.25%, respectively, in patients treated with radical radiotherapy (non-SABR), SABR, and particle beam therapy.

Independent predictors of severe radiation pneumonitis (grade 2 or higher and grade 3 or higher) included subclinical or radiological ILD, the researchers said. Among ILD subtypes, studies have shown increased risk for severe radiation pneumonitis among those with non-IPF or non-UIP pattern fibrosis.

In addition, patient-related factors of low forced vital capacity (FVC) and low forced expiratory volume in 1 second (FEV₁), have been associated with severe radiation pneumonitis, the researchers said. They also found increased risk for patients with lower lobe tumor location compared to other lobes.

As for treatment-related factors, a history of gemcitabine chemotherapy was associated with an increased risk of grade 3 or higher radiation pneumonitis.

“There is always concern about using thoracic radiotherapy in lung cancer patients with coexisting ILD in view of the risks involved,” the researchers wrote in their discussion of the findings. “Although thoracic radiotherapy is expected to produce similar local control, overall survival is worse in lung cancer patients with ILD than without, probably due to the poor prognosis associated with ILD and associated treatment-related mortality,” they said.

The findings were limited by several factors including the heterogeneity of the studies and study population and the retrospective design of most of the studies, the researchers noted.

However, the results highlight the increased risk of severe and fatal radiation pneumonitis in lung cancer patients with ILD and the need for careful patient selection and counseling if thoracic radiotherapy is to be considered, they concluded.

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

Continuous positive airway pressure (CPAP) may be only modestly effective for ameliorating metabolic syndrome in patients with moderate to severe obstructive sleep apnea (OSA).

That conclusion comes from investigators in a randomized controlled, trial, who found that, among 100 patients with OSA and a recent diagnosis of metabolic syndrome (MS), 18% of those assigned to use CPAP at night had a reversal of MS at 6 months of follow-up, compared with 4% of controls who were assigned to use nasal strips at night (P = .04).

The majority of patients assigned to CPAP still retained their MS diagnoses at 6 months, and CPAP did not significantly reduce individual components of the syndrome. Use of CPAP was, however, associated with small reductions in visceral fat and improvement in endothelial function, reported Sara Q.C. Giampa, PhD, from the University of São Paulo, and colleagues.

“Despite a significant rate of MS reversibility after CPAP therapy, most of the patients maintained the MS diagnosis. The modest effects of CPAP on MS reversibility underscore the need for combined therapy with CPAP, aiming to maximize metabolic syndrome recovery in parallel with improvements in OSA severity and related symptoms,” according to their study, reported in the journal CHEST^®.

Asked whether he still recommends CPAP to patients with OSA and the metabolic syndrome, given the findings, corresponding author Luciano F. Drager, MD, PhD, replied “yes, definitely.”

“Despite the modest rate in reversing metabolic syndrome after CPAP, the rate was 5-fold higher than non-effective treatment (18% vs. 4%),” he said in an interview.

Dr. Drager noted that studies of other single interventions such as physical exercise to reverse MS in patients with OSA also had modest results.

A researcher who studies the relationship between sleep, circadian rhythms, and metabolism commented that, although the patients in the CPAP group were compliant with the assigned equipment and had both reductions in apneic events and improvement in oxygen saturation, the effect of CPAP on the metabolic syndrome was rather small.

“The CPAP was doing what we thought it was supposed to do, but it didn’t have the magnitude of effect on the metabolic syndrome as I expected or I think as the authors expected,” said Deanna Arble, PhD, assistant professor of biological science at Marquette University, Milwaukee.

She noted that the study also failed to detect a significant improvement in the blood pressure component of metabolic syndrome.

“In my experience and my review of the literature, blood pressure tends to be the one that’s improved most dramatically with CPAP,” she said.

Dr. Arble was not involved in the study.

Study details

In the trial, titled TREATOSA-MS, the investigators enrolled 100 patients with a recent diagnosis of metabolic syndrome and moderate to severe OSA, defined as 15 or more apnea-hypopnea index events per hour. The patients were stratified by body mass index and then randomized to undergo therapeutic CPAP or to use nasal strips for 6 months.

At baseline and at the end of each intervention investigators measured anthropometric variables, blood pressure, glucose, and lipid profiles. They also leptin and adiponectin, body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic), and endothelial function to control for potential confounders.

As noted previously, they found that after 6 months “most patients with OSA randomized to CPAP retained the MS diagnosis, but the rate of MS reversibility was higher than observed in the placebo group.” The difference in metabolic syndrome reversal, 18% with CPAP versus 4% with nasal strips, translated into a hazard ratio favoring CPAP of 5.27 (P = .04).

Also as noted, in analyses adjusted for baseline values, CPAP did not significantly improve either weight, liver fat, lip profiles, or the adiposity biomarkers leptin and adiponectin, but did have “very modest” influence on reducing visceral fat and improving endothelial function.
 

Rigorous study

Dr. Arble said that most studies of the association between OSA and metabolic syndrome have focused on only one or two of the parameters that were included in the TREATOSA-MS study, giving the findings additional weight.

“This could potentially be a very good, carefully controlled first insight into how obstructive sleep apnea is related to the metabolic syndrome,” she said.

The study was funded by grants Fundação de Amparo Q22 à Pesquisa do Estado de São Paulo and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. The authors and Dr. Arble reported having no conflicts of interest to disclose.

Continuous positive airway pressure (CPAP) may be only modestly effective for ameliorating metabolic syndrome in patients with moderate to severe obstructive sleep apnea (OSA).

That conclusion comes from investigators in a randomized controlled, trial, who found that, among 100 patients with OSA and a recent diagnosis of metabolic syndrome (MS), 18% of those assigned to use CPAP at night had a reversal of MS at 6 months of follow-up, compared with 4% of controls who were assigned to use nasal strips at night (P = .04).

The majority of patients assigned to CPAP still retained their MS diagnoses at 6 months, and CPAP did not significantly reduce individual components of the syndrome. Use of CPAP was, however, associated with small reductions in visceral fat and improvement in endothelial function, reported Sara Q.C. Giampa, PhD, from the University of São Paulo, and colleagues.

“Despite a significant rate of MS reversibility after CPAP therapy, most of the patients maintained the MS diagnosis. The modest effects of CPAP on MS reversibility underscore the need for combined therapy with CPAP, aiming to maximize metabolic syndrome recovery in parallel with improvements in OSA severity and related symptoms,” according to their study, reported in the journal CHEST^®.

Asked whether he still recommends CPAP to patients with OSA and the metabolic syndrome, given the findings, corresponding author Luciano F. Drager, MD, PhD, replied “yes, definitely.”

“Despite the modest rate in reversing metabolic syndrome after CPAP, the rate was 5-fold higher than non-effective treatment (18% vs. 4%),” he said in an interview.

Dr. Drager noted that studies of other single interventions such as physical exercise to reverse MS in patients with OSA also had modest results.

A researcher who studies the relationship between sleep, circadian rhythms, and metabolism commented that, although the patients in the CPAP group were compliant with the assigned equipment and had both reductions in apneic events and improvement in oxygen saturation, the effect of CPAP on the metabolic syndrome was rather small.

“The CPAP was doing what we thought it was supposed to do, but it didn’t have the magnitude of effect on the metabolic syndrome as I expected or I think as the authors expected,” said Deanna Arble, PhD, assistant professor of biological science at Marquette University, Milwaukee.

She noted that the study also failed to detect a significant improvement in the blood pressure component of metabolic syndrome.

“In my experience and my review of the literature, blood pressure tends to be the one that’s improved most dramatically with CPAP,” she said.

Dr. Arble was not involved in the study.

Study details

In the trial, titled TREATOSA-MS, the investigators enrolled 100 patients with a recent diagnosis of metabolic syndrome and moderate to severe OSA, defined as 15 or more apnea-hypopnea index events per hour. The patients were stratified by body mass index and then randomized to undergo therapeutic CPAP or to use nasal strips for 6 months.

At baseline and at the end of each intervention investigators measured anthropometric variables, blood pressure, glucose, and lipid profiles. They also leptin and adiponectin, body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic), and endothelial function to control for potential confounders.

As noted previously, they found that after 6 months “most patients with OSA randomized to CPAP retained the MS diagnosis, but the rate of MS reversibility was higher than observed in the placebo group.” The difference in metabolic syndrome reversal, 18% with CPAP versus 4% with nasal strips, translated into a hazard ratio favoring CPAP of 5.27 (P = .04).

Also as noted, in analyses adjusted for baseline values, CPAP did not significantly improve either weight, liver fat, lip profiles, or the adiposity biomarkers leptin and adiponectin, but did have “very modest” influence on reducing visceral fat and improving endothelial function.
 

Rigorous study

Dr. Arble said that most studies of the association between OSA and metabolic syndrome have focused on only one or two of the parameters that were included in the TREATOSA-MS study, giving the findings additional weight.

“This could potentially be a very good, carefully controlled first insight into how obstructive sleep apnea is related to the metabolic syndrome,” she said.

The study was funded by grants Fundação de Amparo Q22 à Pesquisa do Estado de São Paulo and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. The authors and Dr. Arble reported having no conflicts of interest to disclose.

Continuous positive airway pressure (CPAP) may be only modestly effective for ameliorating metabolic syndrome in patients with moderate to severe obstructive sleep apnea (OSA).

That conclusion comes from investigators in a randomized controlled, trial, who found that, among 100 patients with OSA and a recent diagnosis of metabolic syndrome (MS), 18% of those assigned to use CPAP at night had a reversal of MS at 6 months of follow-up, compared with 4% of controls who were assigned to use nasal strips at night (P = .04).

The majority of patients assigned to CPAP still retained their MS diagnoses at 6 months, and CPAP did not significantly reduce individual components of the syndrome. Use of CPAP was, however, associated with small reductions in visceral fat and improvement in endothelial function, reported Sara Q.C. Giampa, PhD, from the University of São Paulo, and colleagues.

“Despite a significant rate of MS reversibility after CPAP therapy, most of the patients maintained the MS diagnosis. The modest effects of CPAP on MS reversibility underscore the need for combined therapy with CPAP, aiming to maximize metabolic syndrome recovery in parallel with improvements in OSA severity and related symptoms,” according to their study, reported in the journal CHEST^®.

Asked whether he still recommends CPAP to patients with OSA and the metabolic syndrome, given the findings, corresponding author Luciano F. Drager, MD, PhD, replied “yes, definitely.”

“Despite the modest rate in reversing metabolic syndrome after CPAP, the rate was 5-fold higher than non-effective treatment (18% vs. 4%),” he said in an interview.

Dr. Drager noted that studies of other single interventions such as physical exercise to reverse MS in patients with OSA also had modest results.

A researcher who studies the relationship between sleep, circadian rhythms, and metabolism commented that, although the patients in the CPAP group were compliant with the assigned equipment and had both reductions in apneic events and improvement in oxygen saturation, the effect of CPAP on the metabolic syndrome was rather small.

“The CPAP was doing what we thought it was supposed to do, but it didn’t have the magnitude of effect on the metabolic syndrome as I expected or I think as the authors expected,” said Deanna Arble, PhD, assistant professor of biological science at Marquette University, Milwaukee.

She noted that the study also failed to detect a significant improvement in the blood pressure component of metabolic syndrome.

“In my experience and my review of the literature, blood pressure tends to be the one that’s improved most dramatically with CPAP,” she said.

Dr. Arble was not involved in the study.

Study details

In the trial, titled TREATOSA-MS, the investigators enrolled 100 patients with a recent diagnosis of metabolic syndrome and moderate to severe OSA, defined as 15 or more apnea-hypopnea index events per hour. The patients were stratified by body mass index and then randomized to undergo therapeutic CPAP or to use nasal strips for 6 months.

At baseline and at the end of each intervention investigators measured anthropometric variables, blood pressure, glucose, and lipid profiles. They also leptin and adiponectin, body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic), and endothelial function to control for potential confounders.

As noted previously, they found that after 6 months “most patients with OSA randomized to CPAP retained the MS diagnosis, but the rate of MS reversibility was higher than observed in the placebo group.” The difference in metabolic syndrome reversal, 18% with CPAP versus 4% with nasal strips, translated into a hazard ratio favoring CPAP of 5.27 (P = .04).

Also as noted, in analyses adjusted for baseline values, CPAP did not significantly improve either weight, liver fat, lip profiles, or the adiposity biomarkers leptin and adiponectin, but did have “very modest” influence on reducing visceral fat and improving endothelial function.
 

Rigorous study

Dr. Arble said that most studies of the association between OSA and metabolic syndrome have focused on only one or two of the parameters that were included in the TREATOSA-MS study, giving the findings additional weight.

“This could potentially be a very good, carefully controlled first insight into how obstructive sleep apnea is related to the metabolic syndrome,” she said.

The study was funded by grants Fundação de Amparo Q22 à Pesquisa do Estado de São Paulo and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. The authors and Dr. Arble reported having no conflicts of interest to disclose.

Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.

The research was published online Jan. 29 in Materials Today Chemistry.

The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.

“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.

All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.

The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.

Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.

“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
 

In vivo evaluation

Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.

The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.

Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.

“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
 

Pediatric airway obstruction

Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.

“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).

When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.

In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.

The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.

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

Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.

The research was published online Jan. 29 in Materials Today Chemistry.

The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.

“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.

All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.

The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.

Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.

“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
 

In vivo evaluation

Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.

The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.

Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.

“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
 

Pediatric airway obstruction

Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.

“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).

When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.

In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.

The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.

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

Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.

The research was published online Jan. 29 in Materials Today Chemistry.

The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.

“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.

All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.

The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.

Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.

“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
 

In vivo evaluation

Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.

The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.

Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.

“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
 

Pediatric airway obstruction

Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.

“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).

When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.

In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.

The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.

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

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.