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FDA warns AstraZeneca over ‘misleading claims’ about COPD drug
Promotional materials for the drug Breztri (budesonide/formoterol fumarate/glycopyrrolate inhaled) suggest that the drug has a positive effect on all-cause mortality for COPD patients, but the referenced clinical trial does not support that claim, the FDA letter states.
The FDA issued the warning letter on Aug. 4 and published the letter online on Aug. 15.
The sales aid highlights a 49% observed relative difference in time to all-cause mortality (ACM) over 1 year between Breztri and long-acting muscarinic antagonist/long-acting beta agonist (LAMA/LABA) inhalers.
Because of “statistical testing hierarchy failure” as well as confounding factors such as the removal of patients from inhaled corticosteroids (ICS) prior to entering the treatment arm of the trial, “no conclusions about the effect of Breztri on ACM can be drawn from the [clinical] trial,” the FDA wrote. “To date, no drug has been shown to improve ACM in COPD.”
The Breztri sales aid also states that there was a 20% reduction of severe exacerbations in patients using Breztri compared with patients using ICS/LABA. However, in the cited clinical trial, “the reduction in severe exacerbations was not statistically significant for patients treated with Breztri relative to comparator groups,” according to the FDA.
AstraZeneca has 15 working days from the receipt of the letter to respond in writing with “any plan for discontinuing use of such communications, or for ceasing distribution of Breztri,” the agency wrote.
A version of this article appeared on Medscape.com.
Promotional materials for the drug Breztri (budesonide/formoterol fumarate/glycopyrrolate inhaled) suggest that the drug has a positive effect on all-cause mortality for COPD patients, but the referenced clinical trial does not support that claim, the FDA letter states.
The FDA issued the warning letter on Aug. 4 and published the letter online on Aug. 15.
The sales aid highlights a 49% observed relative difference in time to all-cause mortality (ACM) over 1 year between Breztri and long-acting muscarinic antagonist/long-acting beta agonist (LAMA/LABA) inhalers.
Because of “statistical testing hierarchy failure” as well as confounding factors such as the removal of patients from inhaled corticosteroids (ICS) prior to entering the treatment arm of the trial, “no conclusions about the effect of Breztri on ACM can be drawn from the [clinical] trial,” the FDA wrote. “To date, no drug has been shown to improve ACM in COPD.”
The Breztri sales aid also states that there was a 20% reduction of severe exacerbations in patients using Breztri compared with patients using ICS/LABA. However, in the cited clinical trial, “the reduction in severe exacerbations was not statistically significant for patients treated with Breztri relative to comparator groups,” according to the FDA.
AstraZeneca has 15 working days from the receipt of the letter to respond in writing with “any plan for discontinuing use of such communications, or for ceasing distribution of Breztri,” the agency wrote.
A version of this article appeared on Medscape.com.
Promotional materials for the drug Breztri (budesonide/formoterol fumarate/glycopyrrolate inhaled) suggest that the drug has a positive effect on all-cause mortality for COPD patients, but the referenced clinical trial does not support that claim, the FDA letter states.
The FDA issued the warning letter on Aug. 4 and published the letter online on Aug. 15.
The sales aid highlights a 49% observed relative difference in time to all-cause mortality (ACM) over 1 year between Breztri and long-acting muscarinic antagonist/long-acting beta agonist (LAMA/LABA) inhalers.
Because of “statistical testing hierarchy failure” as well as confounding factors such as the removal of patients from inhaled corticosteroids (ICS) prior to entering the treatment arm of the trial, “no conclusions about the effect of Breztri on ACM can be drawn from the [clinical] trial,” the FDA wrote. “To date, no drug has been shown to improve ACM in COPD.”
The Breztri sales aid also states that there was a 20% reduction of severe exacerbations in patients using Breztri compared with patients using ICS/LABA. However, in the cited clinical trial, “the reduction in severe exacerbations was not statistically significant for patients treated with Breztri relative to comparator groups,” according to the FDA.
AstraZeneca has 15 working days from the receipt of the letter to respond in writing with “any plan for discontinuing use of such communications, or for ceasing distribution of Breztri,” the agency wrote.
A version of this article appeared on Medscape.com.
Generic inhalers for COPD support hold their own
Sometimes we get what we pay for. Other times we pay too much.
That’s the message of a study published in Annals of Internal Medicine, which finds that a generic maintenance inhaler is as effective at managing symptoms of chronic obstructive pulmonary disorder (COPD) as a pricier branded alternative.
In 2019, the Food and Drug Administration approved Wixela Inhub (the combination corticosteroid/long-acting beta2 adrenergic agonist fluticasone-salmeterol; Viatris) as a generic dry powder inhaler for managing symptoms of COPD. This approval was based on evidence of the generic’s effectiveness against asthma, although COPD also was on the product label. The study authors compared Wixela’s effectiveness in controlling symptoms of COPD with that of the brand name inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline), which uses the same active ingredients.
The result: “The generic looks to be as safe and effective as the brand name. I don’t see a clinical reason why one would ever need to get the brand name over the generic version,” said study author William Feldman, MD, DPhil, MPH, a health services researcher and pulmonologist at Harvard Medical School and Brigham and Women’s Hospital, both in Boston.
Same types of patients, different inhalers, same outcomes
Dr. Feldman and colleagues compared the medical records of 10,000 patients with COPD who began using the branded inhaler to the records of another 10,000 patients with COPD who opted for the generic alternative. Participants in the two groups were evenly matched by age, sex, race, and ethnicity, region, severity of COPD, and presence of other comorbidities, according to the researchers. Participants were all older than age 40, and the average age in both groups was 72 years.
The researchers looked for a difference in a first episode of a moderate exacerbation of COPD, defined as requiring a course of prednisone for 5-14 days. They also looked for cases of severe COPD exacerbation requiring hospitalization in the year after people began using either the generic or brand name inhaler. And they looked for differences across 1 year in rates of hospitalization for pneumonia.
For none of those outcomes, however, did the type of inhaler appear to matter. Compared with the brand-name drug, using the generic was associated with nearly identical rates of moderate or severe COPD exacerbation (hazard ratio, 0.97; 95% confidence interval, 0.90-1.04. The same was true for the proportion of people who went to the hospital for pneumonia at least once (HR, 0.99; 95% CI, 0.86-1.15).
“To get through the FDA as an interchangeable generic, the generic firms have to show that their product can be used in just the same way as the brand-name version,” Dr. Feldman said, which may explain why the generic and brand-name versions of the inhaler performed so similarly.
Dr. Feldman cautioned that the price savings for patients who opt for the generic over the branded product are hard to determine, given the vagaries of different insurance plans and potential rebates when using the branded project. As a general matter, having a single generic competitor will not lower costs much, Dr. Feldman noted, pointing to 2017 research from Harvard that found a profusion of generic competitors is needed to significantly lower health care costs.
“I don’t want to in any way underestimate the importance of getting that first generic onto the market, because it sets the stage for future generics,” Dr. Feldman said.
“There are very few generic options for patients with COPD,” said Surya Bhatt, MD, director of the Pulmonary Function and Exercise Physiology Lab at the University of Alabama at Birmingham. Even the rescue inhalers that people with COPD use to manage acute episodes of the condition are usually branded at this time, Dr. Bhatt noted, with few generic options.*
“The results are quite compelling,” said Dr. Bhatt, who was not involved in the research. Although the trial was not randomized, he commended the researchers for stratifying participants in the two groups to be as comparable as possible.
Dr. Bhatt noted that the FDA’s 2019 approval – given that the agency requires bioequivalence studies between branded and generic products – was enough to cause him to begin prescribing the generic inhaler. The fact that this approval was based on asthma but not also COPD is not a concern.
“There are so many similarities between asthma, COPD, and some obstructive lung diseases,” Dr. Bhatt noted.
In his experience, the only time someone with COPD continues using the branded inhaler – now that a potentially cheaper generic is available – is when their insurance plan makes their out-of-pocket cost minimal. Otherwise, brand loyalty does not exist.
“Patients are generally okay with being on a generic for inhalers, just because of the high cost,” Dr. Bhatt said.
The study was primarily supported by the National Heart, Lung, and Blood Institute. Dr. Feldman reported funding from Arnold Ventures, the Commonwealth Fund, and the FDA, and consulting relationships with Alosa Health and Aetion. Dr. Bhatt reported no relevant financial relationships.
*Correction, 8/16/23: An earlier version of this article mischaracterized Dr. Bhatt's comments on the availability of generic options.
A version of this article first appeared on Medscape.com.
Sometimes we get what we pay for. Other times we pay too much.
That’s the message of a study published in Annals of Internal Medicine, which finds that a generic maintenance inhaler is as effective at managing symptoms of chronic obstructive pulmonary disorder (COPD) as a pricier branded alternative.
In 2019, the Food and Drug Administration approved Wixela Inhub (the combination corticosteroid/long-acting beta2 adrenergic agonist fluticasone-salmeterol; Viatris) as a generic dry powder inhaler for managing symptoms of COPD. This approval was based on evidence of the generic’s effectiveness against asthma, although COPD also was on the product label. The study authors compared Wixela’s effectiveness in controlling symptoms of COPD with that of the brand name inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline), which uses the same active ingredients.
The result: “The generic looks to be as safe and effective as the brand name. I don’t see a clinical reason why one would ever need to get the brand name over the generic version,” said study author William Feldman, MD, DPhil, MPH, a health services researcher and pulmonologist at Harvard Medical School and Brigham and Women’s Hospital, both in Boston.
Same types of patients, different inhalers, same outcomes
Dr. Feldman and colleagues compared the medical records of 10,000 patients with COPD who began using the branded inhaler to the records of another 10,000 patients with COPD who opted for the generic alternative. Participants in the two groups were evenly matched by age, sex, race, and ethnicity, region, severity of COPD, and presence of other comorbidities, according to the researchers. Participants were all older than age 40, and the average age in both groups was 72 years.
The researchers looked for a difference in a first episode of a moderate exacerbation of COPD, defined as requiring a course of prednisone for 5-14 days. They also looked for cases of severe COPD exacerbation requiring hospitalization in the year after people began using either the generic or brand name inhaler. And they looked for differences across 1 year in rates of hospitalization for pneumonia.
For none of those outcomes, however, did the type of inhaler appear to matter. Compared with the brand-name drug, using the generic was associated with nearly identical rates of moderate or severe COPD exacerbation (hazard ratio, 0.97; 95% confidence interval, 0.90-1.04. The same was true for the proportion of people who went to the hospital for pneumonia at least once (HR, 0.99; 95% CI, 0.86-1.15).
“To get through the FDA as an interchangeable generic, the generic firms have to show that their product can be used in just the same way as the brand-name version,” Dr. Feldman said, which may explain why the generic and brand-name versions of the inhaler performed so similarly.
Dr. Feldman cautioned that the price savings for patients who opt for the generic over the branded product are hard to determine, given the vagaries of different insurance plans and potential rebates when using the branded project. As a general matter, having a single generic competitor will not lower costs much, Dr. Feldman noted, pointing to 2017 research from Harvard that found a profusion of generic competitors is needed to significantly lower health care costs.
“I don’t want to in any way underestimate the importance of getting that first generic onto the market, because it sets the stage for future generics,” Dr. Feldman said.
“There are very few generic options for patients with COPD,” said Surya Bhatt, MD, director of the Pulmonary Function and Exercise Physiology Lab at the University of Alabama at Birmingham. Even the rescue inhalers that people with COPD use to manage acute episodes of the condition are usually branded at this time, Dr. Bhatt noted, with few generic options.*
“The results are quite compelling,” said Dr. Bhatt, who was not involved in the research. Although the trial was not randomized, he commended the researchers for stratifying participants in the two groups to be as comparable as possible.
Dr. Bhatt noted that the FDA’s 2019 approval – given that the agency requires bioequivalence studies between branded and generic products – was enough to cause him to begin prescribing the generic inhaler. The fact that this approval was based on asthma but not also COPD is not a concern.
“There are so many similarities between asthma, COPD, and some obstructive lung diseases,” Dr. Bhatt noted.
In his experience, the only time someone with COPD continues using the branded inhaler – now that a potentially cheaper generic is available – is when their insurance plan makes their out-of-pocket cost minimal. Otherwise, brand loyalty does not exist.
“Patients are generally okay with being on a generic for inhalers, just because of the high cost,” Dr. Bhatt said.
The study was primarily supported by the National Heart, Lung, and Blood Institute. Dr. Feldman reported funding from Arnold Ventures, the Commonwealth Fund, and the FDA, and consulting relationships with Alosa Health and Aetion. Dr. Bhatt reported no relevant financial relationships.
*Correction, 8/16/23: An earlier version of this article mischaracterized Dr. Bhatt's comments on the availability of generic options.
A version of this article first appeared on Medscape.com.
Sometimes we get what we pay for. Other times we pay too much.
That’s the message of a study published in Annals of Internal Medicine, which finds that a generic maintenance inhaler is as effective at managing symptoms of chronic obstructive pulmonary disorder (COPD) as a pricier branded alternative.
In 2019, the Food and Drug Administration approved Wixela Inhub (the combination corticosteroid/long-acting beta2 adrenergic agonist fluticasone-salmeterol; Viatris) as a generic dry powder inhaler for managing symptoms of COPD. This approval was based on evidence of the generic’s effectiveness against asthma, although COPD also was on the product label. The study authors compared Wixela’s effectiveness in controlling symptoms of COPD with that of the brand name inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline), which uses the same active ingredients.
The result: “The generic looks to be as safe and effective as the brand name. I don’t see a clinical reason why one would ever need to get the brand name over the generic version,” said study author William Feldman, MD, DPhil, MPH, a health services researcher and pulmonologist at Harvard Medical School and Brigham and Women’s Hospital, both in Boston.
Same types of patients, different inhalers, same outcomes
Dr. Feldman and colleagues compared the medical records of 10,000 patients with COPD who began using the branded inhaler to the records of another 10,000 patients with COPD who opted for the generic alternative. Participants in the two groups were evenly matched by age, sex, race, and ethnicity, region, severity of COPD, and presence of other comorbidities, according to the researchers. Participants were all older than age 40, and the average age in both groups was 72 years.
The researchers looked for a difference in a first episode of a moderate exacerbation of COPD, defined as requiring a course of prednisone for 5-14 days. They also looked for cases of severe COPD exacerbation requiring hospitalization in the year after people began using either the generic or brand name inhaler. And they looked for differences across 1 year in rates of hospitalization for pneumonia.
For none of those outcomes, however, did the type of inhaler appear to matter. Compared with the brand-name drug, using the generic was associated with nearly identical rates of moderate or severe COPD exacerbation (hazard ratio, 0.97; 95% confidence interval, 0.90-1.04. The same was true for the proportion of people who went to the hospital for pneumonia at least once (HR, 0.99; 95% CI, 0.86-1.15).
“To get through the FDA as an interchangeable generic, the generic firms have to show that their product can be used in just the same way as the brand-name version,” Dr. Feldman said, which may explain why the generic and brand-name versions of the inhaler performed so similarly.
Dr. Feldman cautioned that the price savings for patients who opt for the generic over the branded product are hard to determine, given the vagaries of different insurance plans and potential rebates when using the branded project. As a general matter, having a single generic competitor will not lower costs much, Dr. Feldman noted, pointing to 2017 research from Harvard that found a profusion of generic competitors is needed to significantly lower health care costs.
“I don’t want to in any way underestimate the importance of getting that first generic onto the market, because it sets the stage for future generics,” Dr. Feldman said.
“There are very few generic options for patients with COPD,” said Surya Bhatt, MD, director of the Pulmonary Function and Exercise Physiology Lab at the University of Alabama at Birmingham. Even the rescue inhalers that people with COPD use to manage acute episodes of the condition are usually branded at this time, Dr. Bhatt noted, with few generic options.*
“The results are quite compelling,” said Dr. Bhatt, who was not involved in the research. Although the trial was not randomized, he commended the researchers for stratifying participants in the two groups to be as comparable as possible.
Dr. Bhatt noted that the FDA’s 2019 approval – given that the agency requires bioequivalence studies between branded and generic products – was enough to cause him to begin prescribing the generic inhaler. The fact that this approval was based on asthma but not also COPD is not a concern.
“There are so many similarities between asthma, COPD, and some obstructive lung diseases,” Dr. Bhatt noted.
In his experience, the only time someone with COPD continues using the branded inhaler – now that a potentially cheaper generic is available – is when their insurance plan makes their out-of-pocket cost minimal. Otherwise, brand loyalty does not exist.
“Patients are generally okay with being on a generic for inhalers, just because of the high cost,” Dr. Bhatt said.
The study was primarily supported by the National Heart, Lung, and Blood Institute. Dr. Feldman reported funding from Arnold Ventures, the Commonwealth Fund, and the FDA, and consulting relationships with Alosa Health and Aetion. Dr. Bhatt reported no relevant financial relationships.
*Correction, 8/16/23: An earlier version of this article mischaracterized Dr. Bhatt's comments on the availability of generic options.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
COPD plus PRISm may promote frailty progression
Chronic obstructive pulmonary disease and a new phenotype of lung function impairment predicted progression of frailty in older adults, based on data from more than 5,000 individuals.
COPD has been associated with frailty, but longitudinal data on the association of COPD with progression of frailty are limited, as are data on the potential association of preserved ratio impaired spirometry (PRISm) with frailty progression, wrote Di He, BS, of Zhejiang University, China, and colleagues.
PRISm has been defined in recent studies as “proportional impairments in FEV1 and FVC, resulting in the normal ratio of FEV1 and FVC.” Individuals with PRISm may transition to normal spirometry or COPD over time, the researchers wrote.
In a study published in the journal Chest, the researchers reviewed data from 5,901 adults aged 50 years and older who were participating on the English Longitudinal Study of Ageing (ELSA), a prospective cohort study. Of these, 3,765 were included in an additional analysis of the association between transitions from normal spirometry to PRISm and the progression of frailty. The mean age of the participants was 65.5 years; 54.9% were women.
The median follow-up period for analysis with frailty progression was 9.5 years for PRISm and COPD and 5.8 years for PRISm transitions. Lung function data were collected at baseline. Based on spirometry data, participants were divided into three lung function groups – normal spirometry, PRISm, and COPD – and each of these was classified based on severity. Frailty was assessed using the frailty index (FI) during the follow-up period.
with additional annual increases of 0.301 and 0.172, respectively (P < .001 for both).
When stratified by severity, individuals with more severe PRISm and with more COPD had higher baseline FI and faster FI progression, compared with those with mild PRISm and COPD.
PRISm transitions were assessed over a 4-year interval at the start of the ELSA. Individuals with normal spirometry who transitioned to PRISm during the study had accelerated progression of frailty, as did those with COPD who transitioned to PRISm. However, no significant frailty progression occurred in those who changed from PRISm to normal spirometry.
The mechanisms behind the associations of PRISm and COPD with frailty remain unclear, but the results were consistent after controlling for multiple confounders, “suggesting PRISm and COPD had independent pathophysiological mechanisms for frailty,” the researchers write in their discussion. Other recent studies have identified sarcopenia as a complication for individuals with lung function impairment, they noted. “Therefore, another plausible explanation could be that PRISm and COPD caused sarcopenia, which accelerated frailty progression,” they say.
The findings were limited by several factors, including the observational design and the potential underestimation of lung function in participants with reversible airflow obstruction because of the use of prebronchodilator spirometry in the cohort study, the researchers noted.
However, the results were strengthened by the large sample size and high-quality data from the ELSA, as well as by the repeat measures of FI and lung function. The results were consistent after controlling for multiple confounders, and support the need for more research to explore the causality behind the association of PRISm and COPD with frailty, the researchers concluded.
The study was supported by the Zhejiang Provincial Basic Public Welfare Research Project, the Zhoushan Science and Technology Project, and the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province. The researchers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Chronic obstructive pulmonary disease and a new phenotype of lung function impairment predicted progression of frailty in older adults, based on data from more than 5,000 individuals.
COPD has been associated with frailty, but longitudinal data on the association of COPD with progression of frailty are limited, as are data on the potential association of preserved ratio impaired spirometry (PRISm) with frailty progression, wrote Di He, BS, of Zhejiang University, China, and colleagues.
PRISm has been defined in recent studies as “proportional impairments in FEV1 and FVC, resulting in the normal ratio of FEV1 and FVC.” Individuals with PRISm may transition to normal spirometry or COPD over time, the researchers wrote.
In a study published in the journal Chest, the researchers reviewed data from 5,901 adults aged 50 years and older who were participating on the English Longitudinal Study of Ageing (ELSA), a prospective cohort study. Of these, 3,765 were included in an additional analysis of the association between transitions from normal spirometry to PRISm and the progression of frailty. The mean age of the participants was 65.5 years; 54.9% were women.
The median follow-up period for analysis with frailty progression was 9.5 years for PRISm and COPD and 5.8 years for PRISm transitions. Lung function data were collected at baseline. Based on spirometry data, participants were divided into three lung function groups – normal spirometry, PRISm, and COPD – and each of these was classified based on severity. Frailty was assessed using the frailty index (FI) during the follow-up period.
with additional annual increases of 0.301 and 0.172, respectively (P < .001 for both).
When stratified by severity, individuals with more severe PRISm and with more COPD had higher baseline FI and faster FI progression, compared with those with mild PRISm and COPD.
PRISm transitions were assessed over a 4-year interval at the start of the ELSA. Individuals with normal spirometry who transitioned to PRISm during the study had accelerated progression of frailty, as did those with COPD who transitioned to PRISm. However, no significant frailty progression occurred in those who changed from PRISm to normal spirometry.
The mechanisms behind the associations of PRISm and COPD with frailty remain unclear, but the results were consistent after controlling for multiple confounders, “suggesting PRISm and COPD had independent pathophysiological mechanisms for frailty,” the researchers write in their discussion. Other recent studies have identified sarcopenia as a complication for individuals with lung function impairment, they noted. “Therefore, another plausible explanation could be that PRISm and COPD caused sarcopenia, which accelerated frailty progression,” they say.
The findings were limited by several factors, including the observational design and the potential underestimation of lung function in participants with reversible airflow obstruction because of the use of prebronchodilator spirometry in the cohort study, the researchers noted.
However, the results were strengthened by the large sample size and high-quality data from the ELSA, as well as by the repeat measures of FI and lung function. The results were consistent after controlling for multiple confounders, and support the need for more research to explore the causality behind the association of PRISm and COPD with frailty, the researchers concluded.
The study was supported by the Zhejiang Provincial Basic Public Welfare Research Project, the Zhoushan Science and Technology Project, and the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province. The researchers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Chronic obstructive pulmonary disease and a new phenotype of lung function impairment predicted progression of frailty in older adults, based on data from more than 5,000 individuals.
COPD has been associated with frailty, but longitudinal data on the association of COPD with progression of frailty are limited, as are data on the potential association of preserved ratio impaired spirometry (PRISm) with frailty progression, wrote Di He, BS, of Zhejiang University, China, and colleagues.
PRISm has been defined in recent studies as “proportional impairments in FEV1 and FVC, resulting in the normal ratio of FEV1 and FVC.” Individuals with PRISm may transition to normal spirometry or COPD over time, the researchers wrote.
In a study published in the journal Chest, the researchers reviewed data from 5,901 adults aged 50 years and older who were participating on the English Longitudinal Study of Ageing (ELSA), a prospective cohort study. Of these, 3,765 were included in an additional analysis of the association between transitions from normal spirometry to PRISm and the progression of frailty. The mean age of the participants was 65.5 years; 54.9% were women.
The median follow-up period for analysis with frailty progression was 9.5 years for PRISm and COPD and 5.8 years for PRISm transitions. Lung function data were collected at baseline. Based on spirometry data, participants were divided into three lung function groups – normal spirometry, PRISm, and COPD – and each of these was classified based on severity. Frailty was assessed using the frailty index (FI) during the follow-up period.
with additional annual increases of 0.301 and 0.172, respectively (P < .001 for both).
When stratified by severity, individuals with more severe PRISm and with more COPD had higher baseline FI and faster FI progression, compared with those with mild PRISm and COPD.
PRISm transitions were assessed over a 4-year interval at the start of the ELSA. Individuals with normal spirometry who transitioned to PRISm during the study had accelerated progression of frailty, as did those with COPD who transitioned to PRISm. However, no significant frailty progression occurred in those who changed from PRISm to normal spirometry.
The mechanisms behind the associations of PRISm and COPD with frailty remain unclear, but the results were consistent after controlling for multiple confounders, “suggesting PRISm and COPD had independent pathophysiological mechanisms for frailty,” the researchers write in their discussion. Other recent studies have identified sarcopenia as a complication for individuals with lung function impairment, they noted. “Therefore, another plausible explanation could be that PRISm and COPD caused sarcopenia, which accelerated frailty progression,” they say.
The findings were limited by several factors, including the observational design and the potential underestimation of lung function in participants with reversible airflow obstruction because of the use of prebronchodilator spirometry in the cohort study, the researchers noted.
However, the results were strengthened by the large sample size and high-quality data from the ELSA, as well as by the repeat measures of FI and lung function. The results were consistent after controlling for multiple confounders, and support the need for more research to explore the causality behind the association of PRISm and COPD with frailty, the researchers concluded.
The study was supported by the Zhejiang Provincial Basic Public Welfare Research Project, the Zhoushan Science and Technology Project, and the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province. The researchers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL CHEST
Classification of COPD exacerbation predicts prognosis
Adults with exacerbations of chronic obstructive pulmonary disease (ECOPD) whose condition was classified as severe using the Rome criteria had a higher risk of death at 1 year than those who were classified as having moderate or mild disease, as determined from data from more than 300 individuals.
Patients hospitalized with severe exacerbations of ECOPD are at increased risk for worse clinical outcomes and death, so early identification is important, Ernesto Crisafulli, MD, of the University of Verona (Italy) and Azienda Ospedaliera Universitaria Integrata of Verona, and colleagues wrote.
which grades ECOPD as mild, moderate, or severe on the basis of more objective and disease-related aspects. However, data on the clinical usefulness of the Rome criteria are limited.
In a study published in the journal Chest, the researchers retrospectively categorized 347 adults hospitalized with ECOPD using the Rome severity classifications of mild, moderate, and severe.
Classifications were made using baseline, clinical and microbiological factors, as well as gas analysis and laboratory variables. The researchers also reviewed data on the length of hospital stay and mortality (in-hospital and over a follow-up of 6 months to 3 years).
Approximately one-third of the patients (39%) were classified as having mild disease, 31% as having moderate disease, and 30% as having severe illness. Overall, hospital stay was significantly longer for the patients with severe disease, although in-hospital mortality was similar across all three groups.
Patients classified as having severe disease also had a worse prognosis at all follow-up time points, and severe classification was significantly associated with worse cumulative survival at 1 year and 3 years (Gehan-Breslow-Wilson test, P = .032 and P = .004, respectively).
In a multivariate analysis, the risk of death at 1 year was significantly higher among patients classified as severe or moderate (hazard ratio, 1.99 and 1.47, respectively), compared with those classified as mild.
Mortality risk also was higher among patients aged 80 years and older and among those requiring long-term oxygen therapy or with a history of ECOPD episodes, the researchers noted. Body mass index in the range of 25-29 kg/m2 was associated with lower risk.
The study was limited by several factors, including the replacement of dyspnea perception in the Rome classification with other objective measures, the researchers wrote. Other limitations include the retrospective design, small sample size, use of data from a single center, and lack of data on causes of mortality. Women were underrepresented in the study, and so additional research involving women is needed.
The results suggest that the Rome classification allows for the effective identification of patients with ECOPD who have a worse prognosis. The Rome classification may help guide disease management through targeted interventions and personalized care programs for this population, the researchers concluded.
The study received no outside funding. The researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adults with exacerbations of chronic obstructive pulmonary disease (ECOPD) whose condition was classified as severe using the Rome criteria had a higher risk of death at 1 year than those who were classified as having moderate or mild disease, as determined from data from more than 300 individuals.
Patients hospitalized with severe exacerbations of ECOPD are at increased risk for worse clinical outcomes and death, so early identification is important, Ernesto Crisafulli, MD, of the University of Verona (Italy) and Azienda Ospedaliera Universitaria Integrata of Verona, and colleagues wrote.
which grades ECOPD as mild, moderate, or severe on the basis of more objective and disease-related aspects. However, data on the clinical usefulness of the Rome criteria are limited.
In a study published in the journal Chest, the researchers retrospectively categorized 347 adults hospitalized with ECOPD using the Rome severity classifications of mild, moderate, and severe.
Classifications were made using baseline, clinical and microbiological factors, as well as gas analysis and laboratory variables. The researchers also reviewed data on the length of hospital stay and mortality (in-hospital and over a follow-up of 6 months to 3 years).
Approximately one-third of the patients (39%) were classified as having mild disease, 31% as having moderate disease, and 30% as having severe illness. Overall, hospital stay was significantly longer for the patients with severe disease, although in-hospital mortality was similar across all three groups.
Patients classified as having severe disease also had a worse prognosis at all follow-up time points, and severe classification was significantly associated with worse cumulative survival at 1 year and 3 years (Gehan-Breslow-Wilson test, P = .032 and P = .004, respectively).
In a multivariate analysis, the risk of death at 1 year was significantly higher among patients classified as severe or moderate (hazard ratio, 1.99 and 1.47, respectively), compared with those classified as mild.
Mortality risk also was higher among patients aged 80 years and older and among those requiring long-term oxygen therapy or with a history of ECOPD episodes, the researchers noted. Body mass index in the range of 25-29 kg/m2 was associated with lower risk.
The study was limited by several factors, including the replacement of dyspnea perception in the Rome classification with other objective measures, the researchers wrote. Other limitations include the retrospective design, small sample size, use of data from a single center, and lack of data on causes of mortality. Women were underrepresented in the study, and so additional research involving women is needed.
The results suggest that the Rome classification allows for the effective identification of patients with ECOPD who have a worse prognosis. The Rome classification may help guide disease management through targeted interventions and personalized care programs for this population, the researchers concluded.
The study received no outside funding. The researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adults with exacerbations of chronic obstructive pulmonary disease (ECOPD) whose condition was classified as severe using the Rome criteria had a higher risk of death at 1 year than those who were classified as having moderate or mild disease, as determined from data from more than 300 individuals.
Patients hospitalized with severe exacerbations of ECOPD are at increased risk for worse clinical outcomes and death, so early identification is important, Ernesto Crisafulli, MD, of the University of Verona (Italy) and Azienda Ospedaliera Universitaria Integrata of Verona, and colleagues wrote.
which grades ECOPD as mild, moderate, or severe on the basis of more objective and disease-related aspects. However, data on the clinical usefulness of the Rome criteria are limited.
In a study published in the journal Chest, the researchers retrospectively categorized 347 adults hospitalized with ECOPD using the Rome severity classifications of mild, moderate, and severe.
Classifications were made using baseline, clinical and microbiological factors, as well as gas analysis and laboratory variables. The researchers also reviewed data on the length of hospital stay and mortality (in-hospital and over a follow-up of 6 months to 3 years).
Approximately one-third of the patients (39%) were classified as having mild disease, 31% as having moderate disease, and 30% as having severe illness. Overall, hospital stay was significantly longer for the patients with severe disease, although in-hospital mortality was similar across all three groups.
Patients classified as having severe disease also had a worse prognosis at all follow-up time points, and severe classification was significantly associated with worse cumulative survival at 1 year and 3 years (Gehan-Breslow-Wilson test, P = .032 and P = .004, respectively).
In a multivariate analysis, the risk of death at 1 year was significantly higher among patients classified as severe or moderate (hazard ratio, 1.99 and 1.47, respectively), compared with those classified as mild.
Mortality risk also was higher among patients aged 80 years and older and among those requiring long-term oxygen therapy or with a history of ECOPD episodes, the researchers noted. Body mass index in the range of 25-29 kg/m2 was associated with lower risk.
The study was limited by several factors, including the replacement of dyspnea perception in the Rome classification with other objective measures, the researchers wrote. Other limitations include the retrospective design, small sample size, use of data from a single center, and lack of data on causes of mortality. Women were underrepresented in the study, and so additional research involving women is needed.
The results suggest that the Rome classification allows for the effective identification of patients with ECOPD who have a worse prognosis. The Rome classification may help guide disease management through targeted interventions and personalized care programs for this population, the researchers concluded.
The study received no outside funding. The researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL CHEST
COPD: Large-scale study suggests protective role for vitamin D
COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.
While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.
From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).
While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.
Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.
“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”
“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”
He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.”
Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.
No disclosures were reported by Dr. Zhu or by Dr. Maselli.
COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.
While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.
From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).
While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.
Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.
“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”
“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”
He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.”
Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.
No disclosures were reported by Dr. Zhu or by Dr. Maselli.
COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.
While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.
From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).
While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.
Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.
“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”
“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”
He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.”
Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.
No disclosures were reported by Dr. Zhu or by Dr. Maselli.
FROM BMJ OPEN RESPIRATORY RESEARCH
LAMA-LABA surpasses corticosteroid combination as COPD therapy
Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.
Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.
Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.
The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.
The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.
Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
Findings clarify clinical practice guidelines
“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.
“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.
However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.
“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.
The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.
Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.
Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.
Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.
Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.
The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.
The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.
Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
Findings clarify clinical practice guidelines
“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.
“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.
However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.
“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.
The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.
Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.
Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.
Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.
Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.
The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.
The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.
Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
Findings clarify clinical practice guidelines
“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.
“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.
However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.
“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.
The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.
Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.
FROM JAMA INTERNAL MEDICINE
Parsing the split-decision victory for biologics in COPD
It’s tough to keep up with the proliferation of monoclonal antibodies. Seems every day I’m confronted by a patient who’s using a new drug with a name ending in “mab.” That drug blocks a cellular receptor I haven’t heard of that’s involved in a cascade of interactions I haven’t thought about since medical school. The resulting disruption reduces disease burden, typically at great expense to the medical system, the patient, or both. We’ve truly entered the era of precision medicine. It’s not enough to understand disease; you also must know its heterogeneous expression so that you can prescribe the ‘mab that targets the biology responsible for variants in behavior. All diseases are, in fact, syndromes. This isn’t a bad thing, but it’s a challenge.
A series of ‘mabs have been approved for treating type 2 high (TH2) or eosinophilic asthma. We refer to this group of ‘mabs generically as biologics. The group includes omalizumab, mepolizumab, dupilumab, benralizumab, reslizumab, and tezepelumab. While mechanism of action varies slightly across drugs, the biologics all target a specific arm of the immune system. Efficacy is linearly related to serum eosinophil count and there’s little clinically or pharmacologically to distinguish one from another. Of course, no head-to-head comparisons of efficacy are available and there’s no financial incentive for them to be performed.
Latest research
A new randomized controlled trial (RCT) of dupilumab for chronic obstructive pulmonary disease (COPD) adds to the aforementioned biologic knowledge base. Turns out it works as long as the patients are carefully selected. Researchers enrolled GOLD D (or E depending on which iteration of the GOLD Statement you use) patients on triple inhaler therapy (inhaled corticosteroids [ICS]/long-acting beta-agonist [LABA]/long-acting muscarinic antagonist [LAMA]) with two moderate exacerbations or one exacerbation requiring hospitalization in the past year. Blood eosinophil counts were > 300 cells/mcL and chronic bronchitis was present clinically. The primary and multiple secondary outcomes were improved with dupilumab.
This is welcome news. I’ve treated countless patients with severe COPD who have repeated exacerbations despite my efforts to prevent them. These patients are on ICS/LABA/LAMA and azithromycin or roflumilast, and occasionally both. While every COPD guideline known to man forbids using chronic oral corticosteroids (OCS), I’ve prescribed them repeatedly because the benefits to keeping a recalcitrant, exacerbating patient out of the hospital seem to outweigh OCS risks. It would be nice to have a better option. Although we were taught that they were immutably distinct in medical school, every first-year pulmonary fellow knows that asthma and COPD share more similarities than differences, so it makes sense that proven asthma therapies would work for some patients with COPD.
However, the dupilumab study must be placed in context. Past studies haven’t been as positive. In 2017, two separate RCTs found that mepolizumab reduced the annual rate of moderate to severe exacerbations (primary outcome) in one trial but not the other. Interpretation gets more complicated when broken down by intention to treat (ITT) vs. modified ITT and when secondary outcomes are considered. Sparing you those details, this trial does not instill confidence, leading the Food and Drug Administration to refuse approval for mepolizumab for COPD. A second RCT of benralizumab for COPD was published in 2019. Much less cognitive load was required to interpret this one; it was negative. FDA approval was not requested.
Looking through the trial designs for the three RCTs of biologics for COPD, I couldn’t find major differences that could explain the discordant results. Sample size and enrollment criteria were similar. As stated, I don’t believe that the biologic data in asthma allow for predicting efficacy in one eosinophilic patient vs. another and I assume the same would be true for COPD. All three trials found that eosinophils were eliminated, so responses were biologically equivalent.
Key takeaways
If trial design and pharmacology don’t account for the disparate outcomes, how do we explain them? More important, how do we translate these trials into clinical practice? I looked for a review or editorial by a scientist-clinician smarter than I so I could steal their ideas and express them as pedantic euphemisms here. I found it curious that I was unable to find one. A recent publication in the American Journal of Respiratory and Critical Care Medicine suggests that the answer lies within the complex lattice of eosinophil subtypes, but I’m unqualified to judge the veracity of this “phenotype within a phenotype” theory.
More trials in COPD are being done. We should have results on tezepelumab, that great savior that may cover noneosinophilic asthma phenotypes, within the next few years. Until then, we’re stuck defying guidelines with the anachronistic use of OCS for the COPD patient who exacerbates through ICS/LABA/LAMA, roflumilast, and azithromycin.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported receiving income from CHEST College, Metapharm, and WebMD.
A version of this article first appeared on Medscape.com.
It’s tough to keep up with the proliferation of monoclonal antibodies. Seems every day I’m confronted by a patient who’s using a new drug with a name ending in “mab.” That drug blocks a cellular receptor I haven’t heard of that’s involved in a cascade of interactions I haven’t thought about since medical school. The resulting disruption reduces disease burden, typically at great expense to the medical system, the patient, or both. We’ve truly entered the era of precision medicine. It’s not enough to understand disease; you also must know its heterogeneous expression so that you can prescribe the ‘mab that targets the biology responsible for variants in behavior. All diseases are, in fact, syndromes. This isn’t a bad thing, but it’s a challenge.
A series of ‘mabs have been approved for treating type 2 high (TH2) or eosinophilic asthma. We refer to this group of ‘mabs generically as biologics. The group includes omalizumab, mepolizumab, dupilumab, benralizumab, reslizumab, and tezepelumab. While mechanism of action varies slightly across drugs, the biologics all target a specific arm of the immune system. Efficacy is linearly related to serum eosinophil count and there’s little clinically or pharmacologically to distinguish one from another. Of course, no head-to-head comparisons of efficacy are available and there’s no financial incentive for them to be performed.
Latest research
A new randomized controlled trial (RCT) of dupilumab for chronic obstructive pulmonary disease (COPD) adds to the aforementioned biologic knowledge base. Turns out it works as long as the patients are carefully selected. Researchers enrolled GOLD D (or E depending on which iteration of the GOLD Statement you use) patients on triple inhaler therapy (inhaled corticosteroids [ICS]/long-acting beta-agonist [LABA]/long-acting muscarinic antagonist [LAMA]) with two moderate exacerbations or one exacerbation requiring hospitalization in the past year. Blood eosinophil counts were > 300 cells/mcL and chronic bronchitis was present clinically. The primary and multiple secondary outcomes were improved with dupilumab.
This is welcome news. I’ve treated countless patients with severe COPD who have repeated exacerbations despite my efforts to prevent them. These patients are on ICS/LABA/LAMA and azithromycin or roflumilast, and occasionally both. While every COPD guideline known to man forbids using chronic oral corticosteroids (OCS), I’ve prescribed them repeatedly because the benefits to keeping a recalcitrant, exacerbating patient out of the hospital seem to outweigh OCS risks. It would be nice to have a better option. Although we were taught that they were immutably distinct in medical school, every first-year pulmonary fellow knows that asthma and COPD share more similarities than differences, so it makes sense that proven asthma therapies would work for some patients with COPD.
However, the dupilumab study must be placed in context. Past studies haven’t been as positive. In 2017, two separate RCTs found that mepolizumab reduced the annual rate of moderate to severe exacerbations (primary outcome) in one trial but not the other. Interpretation gets more complicated when broken down by intention to treat (ITT) vs. modified ITT and when secondary outcomes are considered. Sparing you those details, this trial does not instill confidence, leading the Food and Drug Administration to refuse approval for mepolizumab for COPD. A second RCT of benralizumab for COPD was published in 2019. Much less cognitive load was required to interpret this one; it was negative. FDA approval was not requested.
Looking through the trial designs for the three RCTs of biologics for COPD, I couldn’t find major differences that could explain the discordant results. Sample size and enrollment criteria were similar. As stated, I don’t believe that the biologic data in asthma allow for predicting efficacy in one eosinophilic patient vs. another and I assume the same would be true for COPD. All three trials found that eosinophils were eliminated, so responses were biologically equivalent.
Key takeaways
If trial design and pharmacology don’t account for the disparate outcomes, how do we explain them? More important, how do we translate these trials into clinical practice? I looked for a review or editorial by a scientist-clinician smarter than I so I could steal their ideas and express them as pedantic euphemisms here. I found it curious that I was unable to find one. A recent publication in the American Journal of Respiratory and Critical Care Medicine suggests that the answer lies within the complex lattice of eosinophil subtypes, but I’m unqualified to judge the veracity of this “phenotype within a phenotype” theory.
More trials in COPD are being done. We should have results on tezepelumab, that great savior that may cover noneosinophilic asthma phenotypes, within the next few years. Until then, we’re stuck defying guidelines with the anachronistic use of OCS for the COPD patient who exacerbates through ICS/LABA/LAMA, roflumilast, and azithromycin.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported receiving income from CHEST College, Metapharm, and WebMD.
A version of this article first appeared on Medscape.com.
It’s tough to keep up with the proliferation of monoclonal antibodies. Seems every day I’m confronted by a patient who’s using a new drug with a name ending in “mab.” That drug blocks a cellular receptor I haven’t heard of that’s involved in a cascade of interactions I haven’t thought about since medical school. The resulting disruption reduces disease burden, typically at great expense to the medical system, the patient, or both. We’ve truly entered the era of precision medicine. It’s not enough to understand disease; you also must know its heterogeneous expression so that you can prescribe the ‘mab that targets the biology responsible for variants in behavior. All diseases are, in fact, syndromes. This isn’t a bad thing, but it’s a challenge.
A series of ‘mabs have been approved for treating type 2 high (TH2) or eosinophilic asthma. We refer to this group of ‘mabs generically as biologics. The group includes omalizumab, mepolizumab, dupilumab, benralizumab, reslizumab, and tezepelumab. While mechanism of action varies slightly across drugs, the biologics all target a specific arm of the immune system. Efficacy is linearly related to serum eosinophil count and there’s little clinically or pharmacologically to distinguish one from another. Of course, no head-to-head comparisons of efficacy are available and there’s no financial incentive for them to be performed.
Latest research
A new randomized controlled trial (RCT) of dupilumab for chronic obstructive pulmonary disease (COPD) adds to the aforementioned biologic knowledge base. Turns out it works as long as the patients are carefully selected. Researchers enrolled GOLD D (or E depending on which iteration of the GOLD Statement you use) patients on triple inhaler therapy (inhaled corticosteroids [ICS]/long-acting beta-agonist [LABA]/long-acting muscarinic antagonist [LAMA]) with two moderate exacerbations or one exacerbation requiring hospitalization in the past year. Blood eosinophil counts were > 300 cells/mcL and chronic bronchitis was present clinically. The primary and multiple secondary outcomes were improved with dupilumab.
This is welcome news. I’ve treated countless patients with severe COPD who have repeated exacerbations despite my efforts to prevent them. These patients are on ICS/LABA/LAMA and azithromycin or roflumilast, and occasionally both. While every COPD guideline known to man forbids using chronic oral corticosteroids (OCS), I’ve prescribed them repeatedly because the benefits to keeping a recalcitrant, exacerbating patient out of the hospital seem to outweigh OCS risks. It would be nice to have a better option. Although we were taught that they were immutably distinct in medical school, every first-year pulmonary fellow knows that asthma and COPD share more similarities than differences, so it makes sense that proven asthma therapies would work for some patients with COPD.
However, the dupilumab study must be placed in context. Past studies haven’t been as positive. In 2017, two separate RCTs found that mepolizumab reduced the annual rate of moderate to severe exacerbations (primary outcome) in one trial but not the other. Interpretation gets more complicated when broken down by intention to treat (ITT) vs. modified ITT and when secondary outcomes are considered. Sparing you those details, this trial does not instill confidence, leading the Food and Drug Administration to refuse approval for mepolizumab for COPD. A second RCT of benralizumab for COPD was published in 2019. Much less cognitive load was required to interpret this one; it was negative. FDA approval was not requested.
Looking through the trial designs for the three RCTs of biologics for COPD, I couldn’t find major differences that could explain the discordant results. Sample size and enrollment criteria were similar. As stated, I don’t believe that the biologic data in asthma allow for predicting efficacy in one eosinophilic patient vs. another and I assume the same would be true for COPD. All three trials found that eosinophils were eliminated, so responses were biologically equivalent.
Key takeaways
If trial design and pharmacology don’t account for the disparate outcomes, how do we explain them? More important, how do we translate these trials into clinical practice? I looked for a review or editorial by a scientist-clinician smarter than I so I could steal their ideas and express them as pedantic euphemisms here. I found it curious that I was unable to find one. A recent publication in the American Journal of Respiratory and Critical Care Medicine suggests that the answer lies within the complex lattice of eosinophil subtypes, but I’m unqualified to judge the veracity of this “phenotype within a phenotype” theory.
More trials in COPD are being done. We should have results on tezepelumab, that great savior that may cover noneosinophilic asthma phenotypes, within the next few years. Until then, we’re stuck defying guidelines with the anachronistic use of OCS for the COPD patient who exacerbates through ICS/LABA/LAMA, roflumilast, and azithromycin.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported receiving income from CHEST College, Metapharm, and WebMD.
A version of this article first appeared on Medscape.com.
Electronic nose may sniff out early lung cancer in COPD
, based on data from a prospective study of approximately 800 individuals.
Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.
Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.
In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.
Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).
Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).
All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.
After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.
Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.
“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.
The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.
However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.
The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.
A version of this article first appeared on Medscape.com.
, based on data from a prospective study of approximately 800 individuals.
Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.
Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.
In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.
Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).
Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).
All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.
After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.
Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.
“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.
The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.
However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.
The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.
A version of this article first appeared on Medscape.com.
, based on data from a prospective study of approximately 800 individuals.
Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.
Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.
In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.
Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).
Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).
All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.
After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.
Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.
“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.
The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.
However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.
The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.
A version of this article first appeared on Medscape.com.
FROM CHEST
Antibiotics for acute exacerbation of COPD: It’s still controversial
In late 2021, the Rome Proposal for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and grading their severity was published. The 2023 Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease (GOLD) Report has adopted the Rome Proposal criteria. Given that an endorsement by GOLD is tantamount to acceptance by clinicians, researchers, and policymakers alike, I guess we’re all using them now.
Anyone who’s ever cared for patients with COPD knows that treatment and reduction of exacerbations is how we improve outcomes. AECOPD are associated with considerable morbidity, greater health care utilization and costs, and a long-term decline in lung function. While we hope our pharmacotherapies improve symptoms, we know they reduce AECOPD. If our pharmacotherapies have any impact on mortality, it’s probably via AECOPD prevention.
Since antibiotic indications are tied to severity, using the Rome Proposal criteria may affect management in unpredictable ways. As such, it’s worth reviewing the data on antibiotics for AECOPD.
What do the data reveal?
To start, it’s important to note that GOLD doesn’t equate having an AECOPD with needing an antibiotic. I myself have conflated the diagnosis with the indication and thereby overprescribed. The bar for diagnosis is quite low. In previous GOLD summaries, any “change in respiratory symptoms” would warrant the AECOPD label. Although the Rome Proposal definition is more specific, it leaves room for liberal interpretation. It’s likely to have a greater effect on research than on clinical practice. My guess is that AECOPD prevalence doesn’t change.
The antibiotic hurdle is slightly higher than that for diagnosis but is equally open to interpretation. In part, that’s related to the inherent subjectivity of judging symptoms, sputum production, and changes in color, but it’s also because the data are so poor. The meta-analyses that have been used to establish the indications include fewer than 1000 patients spread across 10 to 11 trials. Thus, the individual trials are small, and the sample size remains nominal even after adding them together. The addition of antibiotics – and it doesn’t seem to matter which class, type, or duration – will decrease mortality and hospital length of stay. One study says these effects are limited to inpatients while the other does not. After reading GOLD 2013, GOLD 2023, and both the meta-analyses they used to support their recommendations, I’m still not sure who benefits. Do you have to be hospitalized? Is some sort of ventilatory support required? Does C-reactive protein help or not?
In accordance with the classic Anthonisen criteria, GOLD relies on sputum volume and color as evidence of a bacterial infection. Soon after GOLD 2023 was published, a meta-analysis found that sputum color isn’t particularly accurate for detecting bacterial infection. Because it doesn’t seem to matter which antibiotic class is used, I always thought we were using antibiotics for their magical, pleiotropic anti-inflammatory effects anyway. I didn’t think the presence of an actual bacterial infection was important. If I saw an infiltrate on chest x-ray, I’d change my diagnosis from AECOPD to community-acquired pneumonia (CAP) and switch to CAP coverage. I’ve been doing this so long that I swear it’s in a guideline somewhere, though admittedly I couldn’t find said guideline while reading for this piece.
Key takeaways
In summary, I believe that the guidance reflects the data, which is muddy. The Rome Proposal should be seen as just that – a framework for moving forward with AECOPD classification and antibiotic indications that will need to be refined over time as better data become available. In fact, they allow for a more objective, point-of-care assessment of severity that can be validated and tied to antibiotic benefits. The Rome criteria aren’t evidence-based; they’re a necessary first step toward creating the evidence.
In the meantime, if your AECOPD patients are hospitalized, they probably warrant an antibiotic. If they’re not, sputum changes may be a reasonable surrogate for a bacterial infection. Considerable uncertainty remains.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
In late 2021, the Rome Proposal for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and grading their severity was published. The 2023 Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease (GOLD) Report has adopted the Rome Proposal criteria. Given that an endorsement by GOLD is tantamount to acceptance by clinicians, researchers, and policymakers alike, I guess we’re all using them now.
Anyone who’s ever cared for patients with COPD knows that treatment and reduction of exacerbations is how we improve outcomes. AECOPD are associated with considerable morbidity, greater health care utilization and costs, and a long-term decline in lung function. While we hope our pharmacotherapies improve symptoms, we know they reduce AECOPD. If our pharmacotherapies have any impact on mortality, it’s probably via AECOPD prevention.
Since antibiotic indications are tied to severity, using the Rome Proposal criteria may affect management in unpredictable ways. As such, it’s worth reviewing the data on antibiotics for AECOPD.
What do the data reveal?
To start, it’s important to note that GOLD doesn’t equate having an AECOPD with needing an antibiotic. I myself have conflated the diagnosis with the indication and thereby overprescribed. The bar for diagnosis is quite low. In previous GOLD summaries, any “change in respiratory symptoms” would warrant the AECOPD label. Although the Rome Proposal definition is more specific, it leaves room for liberal interpretation. It’s likely to have a greater effect on research than on clinical practice. My guess is that AECOPD prevalence doesn’t change.
The antibiotic hurdle is slightly higher than that for diagnosis but is equally open to interpretation. In part, that’s related to the inherent subjectivity of judging symptoms, sputum production, and changes in color, but it’s also because the data are so poor. The meta-analyses that have been used to establish the indications include fewer than 1000 patients spread across 10 to 11 trials. Thus, the individual trials are small, and the sample size remains nominal even after adding them together. The addition of antibiotics – and it doesn’t seem to matter which class, type, or duration – will decrease mortality and hospital length of stay. One study says these effects are limited to inpatients while the other does not. After reading GOLD 2013, GOLD 2023, and both the meta-analyses they used to support their recommendations, I’m still not sure who benefits. Do you have to be hospitalized? Is some sort of ventilatory support required? Does C-reactive protein help or not?
In accordance with the classic Anthonisen criteria, GOLD relies on sputum volume and color as evidence of a bacterial infection. Soon after GOLD 2023 was published, a meta-analysis found that sputum color isn’t particularly accurate for detecting bacterial infection. Because it doesn’t seem to matter which antibiotic class is used, I always thought we were using antibiotics for their magical, pleiotropic anti-inflammatory effects anyway. I didn’t think the presence of an actual bacterial infection was important. If I saw an infiltrate on chest x-ray, I’d change my diagnosis from AECOPD to community-acquired pneumonia (CAP) and switch to CAP coverage. I’ve been doing this so long that I swear it’s in a guideline somewhere, though admittedly I couldn’t find said guideline while reading for this piece.
Key takeaways
In summary, I believe that the guidance reflects the data, which is muddy. The Rome Proposal should be seen as just that – a framework for moving forward with AECOPD classification and antibiotic indications that will need to be refined over time as better data become available. In fact, they allow for a more objective, point-of-care assessment of severity that can be validated and tied to antibiotic benefits. The Rome criteria aren’t evidence-based; they’re a necessary first step toward creating the evidence.
In the meantime, if your AECOPD patients are hospitalized, they probably warrant an antibiotic. If they’re not, sputum changes may be a reasonable surrogate for a bacterial infection. Considerable uncertainty remains.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
In late 2021, the Rome Proposal for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and grading their severity was published. The 2023 Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease (GOLD) Report has adopted the Rome Proposal criteria. Given that an endorsement by GOLD is tantamount to acceptance by clinicians, researchers, and policymakers alike, I guess we’re all using them now.
Anyone who’s ever cared for patients with COPD knows that treatment and reduction of exacerbations is how we improve outcomes. AECOPD are associated with considerable morbidity, greater health care utilization and costs, and a long-term decline in lung function. While we hope our pharmacotherapies improve symptoms, we know they reduce AECOPD. If our pharmacotherapies have any impact on mortality, it’s probably via AECOPD prevention.
Since antibiotic indications are tied to severity, using the Rome Proposal criteria may affect management in unpredictable ways. As such, it’s worth reviewing the data on antibiotics for AECOPD.
What do the data reveal?
To start, it’s important to note that GOLD doesn’t equate having an AECOPD with needing an antibiotic. I myself have conflated the diagnosis with the indication and thereby overprescribed. The bar for diagnosis is quite low. In previous GOLD summaries, any “change in respiratory symptoms” would warrant the AECOPD label. Although the Rome Proposal definition is more specific, it leaves room for liberal interpretation. It’s likely to have a greater effect on research than on clinical practice. My guess is that AECOPD prevalence doesn’t change.
The antibiotic hurdle is slightly higher than that for diagnosis but is equally open to interpretation. In part, that’s related to the inherent subjectivity of judging symptoms, sputum production, and changes in color, but it’s also because the data are so poor. The meta-analyses that have been used to establish the indications include fewer than 1000 patients spread across 10 to 11 trials. Thus, the individual trials are small, and the sample size remains nominal even after adding them together. The addition of antibiotics – and it doesn’t seem to matter which class, type, or duration – will decrease mortality and hospital length of stay. One study says these effects are limited to inpatients while the other does not. After reading GOLD 2013, GOLD 2023, and both the meta-analyses they used to support their recommendations, I’m still not sure who benefits. Do you have to be hospitalized? Is some sort of ventilatory support required? Does C-reactive protein help or not?
In accordance with the classic Anthonisen criteria, GOLD relies on sputum volume and color as evidence of a bacterial infection. Soon after GOLD 2023 was published, a meta-analysis found that sputum color isn’t particularly accurate for detecting bacterial infection. Because it doesn’t seem to matter which antibiotic class is used, I always thought we were using antibiotics for their magical, pleiotropic anti-inflammatory effects anyway. I didn’t think the presence of an actual bacterial infection was important. If I saw an infiltrate on chest x-ray, I’d change my diagnosis from AECOPD to community-acquired pneumonia (CAP) and switch to CAP coverage. I’ve been doing this so long that I swear it’s in a guideline somewhere, though admittedly I couldn’t find said guideline while reading for this piece.
Key takeaways
In summary, I believe that the guidance reflects the data, which is muddy. The Rome Proposal should be seen as just that – a framework for moving forward with AECOPD classification and antibiotic indications that will need to be refined over time as better data become available. In fact, they allow for a more objective, point-of-care assessment of severity that can be validated and tied to antibiotic benefits. The Rome criteria aren’t evidence-based; they’re a necessary first step toward creating the evidence.
In the meantime, if your AECOPD patients are hospitalized, they probably warrant an antibiotic. If they’re not, sputum changes may be a reasonable surrogate for a bacterial infection. Considerable uncertainty remains.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
The breathtaking effects of climate change
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.