Pulmonology

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

Offering lung cancer screening to everyone with a 20-year smoking history could expand access to screening, identify more cancers, and reduce disparities, new research suggests.

In an analysis of nearly 1 million US veterans, researchers estimated that a simplified approach to lung cancer screening — based on smoking duration rather than pack-years — would expand screening eligibility by nearly 30% and reduce potentially missed lung cancers by over 70%.

Those shifts would be especially pronounced among women and Black individuals — 2 groups that are underserved by current screening criteria.

The results, presented at the American Society of Clinical Oncology (ASCO) 2026, come at a time when some groups are revisiting their lung cancer screening guidelines.

And they support smoking duration as a “simpler, more sensitive, and more equitable metric for screening eligibility,” researcher Brendan T. Heiden, MD, MPHS, Washington University School of Medicine in St. Louis, St. Louis, told meeting attendees.

Toward a Better Metric

Current guidelines from the US Preventive Services Task Force (USPSTF) recommend annual lung cancer screening with low-dose CT for adults aged 50-80 years who have at least a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

The 20 pack-year metric is equivalent to smoking a pack of cigarettes per day for 20 years. Because it requires patients to remember their smoking intensity over decades, it can be challenging to calculate and translate into care, Heiden said.

As it stands, few Americans who are eligible under current USPSTF guidelines actually undergo lung cancer screening, at about 15%-20%, Heiden noted. Meanwhile, mounting evidence suggests that many lung cancers occur in individuals who never meet those eligibility criteria.

Boosting screening uptake, Heiden said, is not enough: There’s a need to revisit eligibility itself to reach more high-risk individuals.

Some groups are already taking steps in that direction. Recently updated guidelines from the National Comprehensive Cancer Network (NCCN) added a category 2B recommendation supporting screening for individuals with at least a 20-year smoking history, regardless of pack-years. (The guidelines also say former smokers are eligible no matter how long ago they quit.)

For their study, Heiden’s team sought to estimate the performance of that smoking-duration metric against current USPSTF pack-year criteria. They used Veterans Health Administration data on over 980,000 veterans whose smoking histories were prospectively collected; lung cancer diagnoses were identified through the Veterans Affairs Central Cancer Registry.

Most of the included veterans (67%) had a smoking history; their mean age was 64 years, and 21% were Black.

Overall, the researchers found that basing eligibility on 20-year smoking duration would substantially expand access to screening: Among veterans with a smoking history, 68% qualified for screening under current USPSTF criteria compared with 87% using the smoking-duration approach.

The gains were especially pronounced among women and Black individuals (who, based on prior research, typically smoke less intensely than White males). Under USPSTF criteria, only about 55% of female and Black veterans qualified for screening compared with 83% for both groups under the smoking-duration criterion.

Importantly, Heiden said, people meeting the smoking-duration threshold remained at substantially elevated risk for lung cancer, suggesting the broader screening criteria were not merely capturing low-risk smokers.

The 5-year lung cancer incidence among veterans eligible under the smoking-duration approach was 1.59% — 11 times the rate of 0.14% among never smokers.

Perhaps most striking, Heiden said, the proportion of potentially missed cancers dropped from 13% with the pack-year metric to just 4% using the smoking-duration metric — a relative reduction of more than 70%.

Again, women and Black individuals would see the largest gains: Among Black veterans, potentially missed cancers fell from 25% to 6%, whereas among female veterans they declined from 22% to 7%.

Optimal Approach Still Unclear

The analysis had limitations, including a predominantly male veteran population whose smoking exposure was far greater than that of the general US population, indicating high inherent lung cancer risk.

But the results support what the NCCN has already done, according to Mary Reid, PhD, MSPH, BSN, a member of the group’s lung cancer screening guideline panel and chief of cancer screening, survivorship and mentorship at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Doing the calculation for pack-years can be difficult,” Reid told Medscape Medical News. “Smoking duration is easier to calculate and really the way to go.”

The USPSTF does not comment on individual studies outside of its recommendation development process.

At the meeting, study discussant Katharine A. Rendle, PhD, called the work “impressive,” citing the size of the cohort and strength of the data.

It’s particularly noteworthy that the simpler screening criteria improved sensitivity for all veterans, while largely eliminating disparities, according to Rendle, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Still, she said, further research could better define the optimal screening strategy.

“Smoking duration is a promising approach, but in my opinion, guidelines likely need to account for the underlying risk in the population,” Rendle said, noting that current smoking prevalence in the US population is about 10%.

She suggested future studies consider other smoking-duration thresholds, such as 30 or 40 years, and look at other outcomes, including life-years gained.

“It’s critical that we prioritize strategies that maximize potential benefit from screening — not just identify those at lung cancer risk — given downstream costs and burden on populations and health care systems,” Rendle said.

The study had no commercial funding. Heiden, Rendle, and Reid had no relevant disclosures.

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

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

A pharmacist-driven Veterans Health Administration (VHA) care program for veterans recovering from hospital visits for chronic obstructive pulmonary disease (COPD) is helping reduce symptom burden, a new retrospective cohort study finds. 

Of 286 patients with COPD who participated in the program and reported outcomes, 62.6% said their symptoms improved, 28.7% said they had no change, and 8.7% reported worsening symptoms, according to Edward Portillo, PharmD, and colleagues in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. Patients whose medications were changed by VHA pharmacists with prescribing authority were more likely to experience clinically meaningful improvement in symptoms compared to those without this medication change (66.3% vs. 46.6%, respectively, P < .001).

“If you had a debilitating lung disease that was affecting your ability to breathe all day, affected your ability to go to the grocery store, made it hard for you to see your grandkids, and all of a sudden you had this visit and a month to 2 months later reported feeling a heck of a lot better—that’s a really big deal,” Portillo said in an interview with Federal Practitioner. 

COPD, a progressive and irreversible lung disease that encompasses emphysema and chronic bronchitis, is the fifth-leading cause of death in the US according to the most recently available data. Research has suggested that many patients do not receive guidance-concordant care. 

“The prevalence of COPD among our veteran population is threefold greater than in the civilian population, and 1 in 4 veterans have a COPD diagnosis,” noted Portillo a pharmacist at the William S. Middleton Veterans Affairs (VA) Hospital and an associate professor at the University of Wisconsin, Madison School of Pharmacy.

In 2015, Portillo developed a program called COPD Coordinated Access to Reduce Exacerbations (COPD CARE). The program, now operating at 50 VA medical centers, allows pharmacists to optimize medication, order spirometry, assess symptoms, place referrals for pulmonary rehabilitation, and support inhaler adherence and tobacco cessation. The pharmacists work with other members of the patient care teams such as primary care physicians and nurses.

“It's integrated within the teams themselves that serve our veterans, which is very unique for a service like this,” Portillo said.

The program is especially beneficial for patients within their first 30 to 90 days posthospitalization when they may not normally be seen in the clinic, Portillo said.

“We use a national dashboard to identify patients who left the [emergency department] or hospital, and then we assess if they’d be appropriate candidates for the program,” he said. “Our goal is to see patients as fast as 30 days and as late as 90 days, but ideally within 30 to 60 days of discharge.”

An initial in-person visit of ≤ 30 minutes is followed by a 15-minute follow-up phone call in 30 days to see if interventions have been continued, he said. 

The study analyzed data from September 2020 to February 2024 from 28 VA medical centers that administer the COPD CARE program. All patients had an initial wellness visit within 90 days of hospitalization and 2 COPD Assessment Test (CAT) scores. Among 326 patients, the average age was 73.2 years; 95.7% were male; 77.9% were White, 15.6% were Black, and 2.1% had Hispanic ethnicity. 

At the time of the wellness visit, patients mean CAT score was 18.4. It improved to 15.2 by follow-up, with especially large improvements in limitations (2.5 to 2.0), tightness (1.7 to 1.2), cough (2.5 to 2.1), energy (2.9 to 2.5), phlegm (2.4 to 2.0), and sleep (1.9 to 1.5).

Pharmacists created 236 COPD action plans, changed 208 medications, provided 151 service referrals, identified 117 nonadherent patients, and identified 62 incorrect techniques. 

But only 1 intervention – medication change – was linked to clinically meaningful improvements in symptoms.

“This is not a disease that's easy to change symptomatically,” Portillo said. “My hope is that over time, and with multiple visits, those patients shift into a mode of ‘I am actually feeling much better now.’” 

Suzanne Bollmeier, PharmD, professor of Pharmacy Practice at the University of Health Sciences and Pharmacy in St. Louis, who is familiar with the study but did not take part in it, told Federal Practitioner that the results align with previous research.

Bollmeier mentioned several studies that link pharmacist interventions to better health outcomes, including inhalation technique and medication adherence.

“Pharmacists are well-positioned within the health care team to help care for patients with COPD,” she said. “Pharmacists can help with patient adherence, inhaler education, and reduction in disease risk but also identify drug-related problems and modify respiratory regimens to better optimize patient outcomes.”

Moving forward, she said, “it would be interesting to see what specific medication regimen changes were made in this present study that led to improvement in symptoms.”

The study was funded by the VA Office of Rural Health and the University of Wisconsin Institute for Clinical and Translational Research, which is supported by the National Center for Advancing Translational Sciences. The study authors and Bollmeier had no disclosures.

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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

ORLANDO, Fla. — The Centers for Medicare & Medicaid Services (CMS) will not cover continuous positive airway pressure (CPAP) treatment for people who are nonadherent by 90 days. However, that requirement is too stringent, said researchers who found more than one third of adults who struggled with adherence initially still used the therapy 1 year later at levels associated with clinical benefit.

To test the requirement, investigators assessed 132,492 patients in the Kaiser Permanente Southern California system. The patients were issued CPAP devices to treat obstructive sleep apnea from 2015 to 2023. At 1 year, 36% who would have failed the CMS requirement were still using their CPAP.

The results counter CMS’ assumption that poor early CPAP use always leads to long-term abandonment, said Dennis Hwang, MD, co-chair of Sleep Medicine and medical director of the Sleep Disorders Center at Kaiser Permanente Southern California in Fontana, California.

"We should transition away from a one-size-fits-all definition of success," Hwang added at the American Thoracic Society (ATS) 2026 International Conference.

Background and Methodology

The 90-day adherence requirement does not only apply to Medicare or Medicaid recipients, Hwang said; many private insurers have adopted the same policy. In contrast, Kaiser Permanente Southern California does not restrict usage based on early adherence.

Hwang et al considered any Kaiser Permanente member with any CPAP usage during the 12 months after being issued a device an active user. They tracked mean nightly minutes of use and the percentage of nights with ≥ 2 and ≥ 4 hours of average use.

Overall, 49% would have met the CMS criteria and used the therapy ≥ 4 hours on average each night for 70% of nights during the first 90 days. Kaiser Permanente members aged ≥ 65 years were more compliant, with 54% meeting the CMS benchmarks. ATS guidelines recognize that even ≥ 2 hours of CPAP per night on average can confer some benefits.

The average age in the study was 55 years, and the mean apnea-hypopnea index was 32-33 events per hour, suggesting severe obstructive sleep apnea at baseline. The cohort was diverse, with 42% White, 35% Hispanic, 10% Black, 9% Asian, and 4% other race or ethnicity.

Key Findings

A total of 64,568 adults would have been CMS adherent at 90 days; investigators compared outcomes at 12 months with another 67,867 nonadherent adults.

There were some significant differences between groups. The mean age was 56.4 years vs 53.7 years in the adherent group vs the nonadherent group; men made up a greater proportion of the adherent group, 68.5% vs 62.6%; and the mean number of events per hour was 35 vs 30 (P < .001 for all).

Among the 90-day nonadherent group, about 21% met the 2-hour or greater adherence benchmark, and approximately 14% used CPAP an average of ≥ 4 hours.

“Still a substantial number of [non-CMS adherent] patients are using CPAP,” Hwang said.

Failure to meet CMS adherence was associated with younger age, female sex, non-White race or ethnicity, lower socioeconomic status, and lower severity of obstructive sleep apnea.

“There is also an equity dimension. Whites had better adherence rates during the first 90 days, so there is already a disparity here in terms of outcomes,” Hwang said. Policy changes could improve access to long-term therapy on a more equitable basis, he added. For example, a 2023 ATS policy statement calls for a more patient-centric approach and a focus on reducing inequities.

An Arbitrary Requirement

The 90-day requirement seems a little short, said session co-moderator Oren Cohen, MD, assistant professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine at Icahn School of Medicine at Mount Sinai in New York City, when asked to comment. “It can take longer to get a patient back into the clinic and go through a lot of the trial and error that it takes to do a mask fitting and adjust the pressures.”

If a patient is using their CPAP device for fewer than 4 hours a night in the early period, it doesn’t mean things are failing, Cohen said. “It’s just that you’ve got to keep trying and pushing forward.”

Nonetheless, there are some long-term noncompliant patients, Cohen said. “I certainly don’t think that somebody who’s not using the device for years should continue to hold on to it. That resource can be reallocated to somebody who would get more benefit from it. But I think setting a 90-day and 4-hour rule seems arbitrary…and there should be more leeway there.”

The study was independently supported.

Hwang and Cohen reported having no relevant financial disclosures.

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

TOPLINE: Serum P21 Activated Kinase 6 (PAK6) demonstrated diagnostic accuracy comparable to pro-gastrin-releasing peptide (ProGRP) for small cell lung cancer (SCLC), with area under the curve (AUC) values of 0.892 and 0.935, respectively, in a study of 109 patients with SCLC. Combining PAK6, ProGRP, and neuron-specific enolase (NSE) achieved diagnostic efficiency of 0.98. Elevated baseline PAK6 levels correlated with shorter progression-free survival and increased risk for disease progression.

METHODOLOGY:

• Participants included 380 people in China: 109 with SCLC, 92 with non–small cell lung cancer (NSCLC), 85 with benign pulmonary nodules, and 94 healthy controls who received routine physical examinations. 

• Laboratory testing measured serum PAK6 by ELISA, while NSE, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and ProGRP were quantified by chemiluminescence. 

• Pretreatment and posttreatment serum samples from 56 patients with SCLC were analyzed to evaluate changes in biomarker levels following 3 months of treatment. 

• Progression-free survival data were collected through case review and follow-up, defined as time from treatment initiation to radiographic disease progression per RECIST 1.1 criteria or death from any cause.

TAKEAWAY:

• Median serum PAK6 is reported as 56.44 ng/L in SCLC vs 41.06 ng/L in NSCLC, 37.82 ng/L in pulmonary nodules, and 34.75 ng/L in healthy controls (P < .01). 

• PAK6 demonstrated diagnostic efficacy with and AUC of 0.892 (95% CI, 0.857-0.927), sensitivity of 0.82, and specificity of 0.86 at optimal cut-off value of 47.30 ng/L, comparable to ProGRP (AUC, 0.935) and superior to CEA (AUC, 0.676) and CA19-9 (AUC, 0.611). 

• In 56 paired SCLC samples, PAK6, NSE, and ProGRP decrease after 3 months of treatment (P < .001), while CEA and CA19-9 display no meaningful change. 

• Elevated baseline PAK6 expression correlated with shorter progression-free survival, with high-expression patients demonstrating median survival of 92 days vs 194 days in low-expression patients (HR, 2.02; 95% CI, 1.33-3.07; P = .001).

IN PRACTICE: “We identify PAK6 as a multi-faceted biomarker for SCLC with diagnostic, prognostic, and therapeutic monitoring value. Its cost-effective ELISA quantification facilitates clinical translation,” wrote the authors of the study. “Integrating PAK6 with emerging technologies could further refine SCLC management paradigms.”

SOURCE:The study was led by Simei Chen, Department of Blood Transfusion, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University in Nanchang, China. It was published online in PeerJ.

LIMITATIONS: A single-center design and modest sample size may limit generalizability of the diagnostic and prognostic estimates. The authors also note the absence of immunohistochemical validation, leaving tissue-level correlation of PAK6 unaddressed. Finally, insufficient overall survival data were reported, which constrains interpretation beyond PFS and supports the need for prospective follow-up and larger multi-center validation.

DISCLOSURES: Grant support came from the Science and Technology Program Project of Jiangxi Provincial Administration of Traditional Chinese Medicine (Grant 2024B1433). The authors stated the funders had no role in study design, data collection and analysis, the decision to publish, or manuscript preparation. No competing interests were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Serum P21 Activated Kinase 6 (PAK6) demonstrated diagnostic accuracy comparable to pro-gastrin-releasing peptide (ProGRP) for small cell lung cancer (SCLC), with area under the curve (AUC) values of 0.892 and 0.935, respectively, in a study of 109 patients with SCLC. Combining PAK6, ProGRP, and neuron-specific enolase (NSE) achieved diagnostic efficiency of 0.98. Elevated baseline PAK6 levels correlated with shorter progression-free survival and increased risk for disease progression.

METHODOLOGY:

• Participants included 380 people in China: 109 with SCLC, 92 with non–small cell lung cancer (NSCLC), 85 with benign pulmonary nodules, and 94 healthy controls who received routine physical examinations. 

• Laboratory testing measured serum PAK6 by ELISA, while NSE, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and ProGRP were quantified by chemiluminescence. 

• Pretreatment and posttreatment serum samples from 56 patients with SCLC were analyzed to evaluate changes in biomarker levels following 3 months of treatment. 

• Progression-free survival data were collected through case review and follow-up, defined as time from treatment initiation to radiographic disease progression per RECIST 1.1 criteria or death from any cause.

TAKEAWAY:

• Median serum PAK6 is reported as 56.44 ng/L in SCLC vs 41.06 ng/L in NSCLC, 37.82 ng/L in pulmonary nodules, and 34.75 ng/L in healthy controls (P < .01). 

• PAK6 demonstrated diagnostic efficacy with and AUC of 0.892 (95% CI, 0.857-0.927), sensitivity of 0.82, and specificity of 0.86 at optimal cut-off value of 47.30 ng/L, comparable to ProGRP (AUC, 0.935) and superior to CEA (AUC, 0.676) and CA19-9 (AUC, 0.611). 

• In 56 paired SCLC samples, PAK6, NSE, and ProGRP decrease after 3 months of treatment (P < .001), while CEA and CA19-9 display no meaningful change. 

• Elevated baseline PAK6 expression correlated with shorter progression-free survival, with high-expression patients demonstrating median survival of 92 days vs 194 days in low-expression patients (HR, 2.02; 95% CI, 1.33-3.07; P = .001).

IN PRACTICE: “We identify PAK6 as a multi-faceted biomarker for SCLC with diagnostic, prognostic, and therapeutic monitoring value. Its cost-effective ELISA quantification facilitates clinical translation,” wrote the authors of the study. “Integrating PAK6 with emerging technologies could further refine SCLC management paradigms.”

SOURCE:The study was led by Simei Chen, Department of Blood Transfusion, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University in Nanchang, China. It was published online in PeerJ.

LIMITATIONS: A single-center design and modest sample size may limit generalizability of the diagnostic and prognostic estimates. The authors also note the absence of immunohistochemical validation, leaving tissue-level correlation of PAK6 unaddressed. Finally, insufficient overall survival data were reported, which constrains interpretation beyond PFS and supports the need for prospective follow-up and larger multi-center validation.

DISCLOSURES: Grant support came from the Science and Technology Program Project of Jiangxi Provincial Administration of Traditional Chinese Medicine (Grant 2024B1433). The authors stated the funders had no role in study design, data collection and analysis, the decision to publish, or manuscript preparation. No competing interests were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Serum P21 Activated Kinase 6 (PAK6) demonstrated diagnostic accuracy comparable to pro-gastrin-releasing peptide (ProGRP) for small cell lung cancer (SCLC), with area under the curve (AUC) values of 0.892 and 0.935, respectively, in a study of 109 patients with SCLC. Combining PAK6, ProGRP, and neuron-specific enolase (NSE) achieved diagnostic efficiency of 0.98. Elevated baseline PAK6 levels correlated with shorter progression-free survival and increased risk for disease progression.

METHODOLOGY:

• Participants included 380 people in China: 109 with SCLC, 92 with non–small cell lung cancer (NSCLC), 85 with benign pulmonary nodules, and 94 healthy controls who received routine physical examinations. 

• Laboratory testing measured serum PAK6 by ELISA, while NSE, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and ProGRP were quantified by chemiluminescence. 

• Pretreatment and posttreatment serum samples from 56 patients with SCLC were analyzed to evaluate changes in biomarker levels following 3 months of treatment. 

• Progression-free survival data were collected through case review and follow-up, defined as time from treatment initiation to radiographic disease progression per RECIST 1.1 criteria or death from any cause.

TAKEAWAY:

• Median serum PAK6 is reported as 56.44 ng/L in SCLC vs 41.06 ng/L in NSCLC, 37.82 ng/L in pulmonary nodules, and 34.75 ng/L in healthy controls (P < .01). 

• PAK6 demonstrated diagnostic efficacy with and AUC of 0.892 (95% CI, 0.857-0.927), sensitivity of 0.82, and specificity of 0.86 at optimal cut-off value of 47.30 ng/L, comparable to ProGRP (AUC, 0.935) and superior to CEA (AUC, 0.676) and CA19-9 (AUC, 0.611). 

• In 56 paired SCLC samples, PAK6, NSE, and ProGRP decrease after 3 months of treatment (P < .001), while CEA and CA19-9 display no meaningful change. 

• Elevated baseline PAK6 expression correlated with shorter progression-free survival, with high-expression patients demonstrating median survival of 92 days vs 194 days in low-expression patients (HR, 2.02; 95% CI, 1.33-3.07; P = .001).

IN PRACTICE: “We identify PAK6 as a multi-faceted biomarker for SCLC with diagnostic, prognostic, and therapeutic monitoring value. Its cost-effective ELISA quantification facilitates clinical translation,” wrote the authors of the study. “Integrating PAK6 with emerging technologies could further refine SCLC management paradigms.”

SOURCE:The study was led by Simei Chen, Department of Blood Transfusion, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University in Nanchang, China. It was published online in PeerJ.

LIMITATIONS: A single-center design and modest sample size may limit generalizability of the diagnostic and prognostic estimates. The authors also note the absence of immunohistochemical validation, leaving tissue-level correlation of PAK6 unaddressed. Finally, insufficient overall survival data were reported, which constrains interpretation beyond PFS and supports the need for prospective follow-up and larger multi-center validation.

DISCLOSURES: Grant support came from the Science and Technology Program Project of Jiangxi Provincial Administration of Traditional Chinese Medicine (Grant 2024B1433). The authors stated the funders had no role in study design, data collection and analysis, the decision to publish, or manuscript preparation. No competing interests were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Asthma biologics significantly improved lung function in children with asthma using race-based reference points, based on new data from 115 individuals.

Data on the effect of biologics on lung function in pediatric asthma are limited, and the main previous study of this relationship, the VOYAGE trial, was limited by its reliance on older, race-specific spirometry equations, according to Ken Wu, medical student at Indiana University School of Medicine in Indianapolis.

Newer, race-neutral reference equations prevent the systematic underestimation of asthma severity in Black patients and consequently provide a more accurate assessment of therapeutic benefits, said Wu. “Our study offers a novel contribution to the literature as the first known to utilize race-neutral equations to evaluate lung function following biologic therapy in a pediatric asthma population,” he said.

In a new study, presented at the American Thoracic Society (ATS) 2026 International Conference, the researchers conducted a real-world analysis with race-neutral reference equations developed by the Global Lung Function Initiative to assess the effect of biologics on lung function. They reviewed data from 115 pediatric patients with asthma who started biologics for the first time between 2015 and 2025. Their analysis included height, weight, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratios. The mean age of the patients was 11.4 years, 52% were male, and 62% were Black. A majority (97 patients) received dupilumab; 13 received omalizumab, and 5 received mepolizumab.

The analysis included an average of three spirometry measures 1 year before starting biologics and an average of four measures during the year after starting biologics.

Treatment with dupilumab was associated with a significant improvement in lung function, with an increase in the average FEV₁ from 86.4 percent-predicted prior to biologics to 91.7 after biologics (mean difference, 5.31; P = .044). No significant differences appeared among omalizumab or mepolizumab patients, likely because of the small numbers, the researchers noted.

Overall, in a linear mixed model adjusting for biologic type, FEV₁ remained significantly higher after use of biologics than in the period prior to use (97.9 vs. 92.5), with a mean difference of 5.37 (P = .039).

The primary finding that dupilumab improved the percent-predicted FEV₁ by 5.31 is considered a modest effect size and mainly aligns with previous research, said Wu. “We are currently in the process of conducting additional analysis of whether there is a difference in lung function when we use the older race-specific equations versus our current findings with the newer race-neutral equations,” he said.

The findings were limited by several factors, including the relatively small study population and inclusion of only 3 types of biologics, with samples of omalizumab and mepolizumab that were underpowered to detect differences in lung function, said Wu. Additional studies with larger sample sizes, more biologics (including benralizumab and tezepelumab), and longer follow-up periods are needed to compare benefits across agents, he said.

Promising Implications for Practice

The ATS has recommended abandoning the previous race-adjusted pulmonary function test norms, said Timothy Joos, MD, who practices internal medicine and pediatrics at a community health center in Seattle.

These norms assigned smaller lung volumes to Black and Asian individuals and tended to underestimate lung disease in these populations, said Joos, who was not involved in the new study.

The current study, though small, showed with race-neutral reference equations that biologic agents significantly improved FEV1 values in children with severe asthma, said Joos. The association was especially strong with dupilumab, used by 85% of the patients, he noted. However, additional studies are needed with larger patient populations and other biologic agents to confirm the results, he said.

The study was supported by the Indiana Clinical and Translational Sciences Institute. The previous VOYAGE trial received funding from Sanofi and Regeneron Pharmaceuticals. The researchers reported having no financial conflicts to disclose. Joos reported having no financial conflicts to disclose.

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

Asthma biologics significantly improved lung function in children with asthma using race-based reference points, based on new data from 115 individuals.

Data on the effect of biologics on lung function in pediatric asthma are limited, and the main previous study of this relationship, the VOYAGE trial, was limited by its reliance on older, race-specific spirometry equations, according to Ken Wu, medical student at Indiana University School of Medicine in Indianapolis.

Newer, race-neutral reference equations prevent the systematic underestimation of asthma severity in Black patients and consequently provide a more accurate assessment of therapeutic benefits, said Wu. “Our study offers a novel contribution to the literature as the first known to utilize race-neutral equations to evaluate lung function following biologic therapy in a pediatric asthma population,” he said.

In a new study, presented at the American Thoracic Society (ATS) 2026 International Conference, the researchers conducted a real-world analysis with race-neutral reference equations developed by the Global Lung Function Initiative to assess the effect of biologics on lung function. They reviewed data from 115 pediatric patients with asthma who started biologics for the first time between 2015 and 2025. Their analysis included height, weight, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratios. The mean age of the patients was 11.4 years, 52% were male, and 62% were Black. A majority (97 patients) received dupilumab; 13 received omalizumab, and 5 received mepolizumab.

The analysis included an average of three spirometry measures 1 year before starting biologics and an average of four measures during the year after starting biologics.

Treatment with dupilumab was associated with a significant improvement in lung function, with an increase in the average FEV₁ from 86.4 percent-predicted prior to biologics to 91.7 after biologics (mean difference, 5.31; P = .044). No significant differences appeared among omalizumab or mepolizumab patients, likely because of the small numbers, the researchers noted.

Overall, in a linear mixed model adjusting for biologic type, FEV₁ remained significantly higher after use of biologics than in the period prior to use (97.9 vs. 92.5), with a mean difference of 5.37 (P = .039).

The primary finding that dupilumab improved the percent-predicted FEV₁ by 5.31 is considered a modest effect size and mainly aligns with previous research, said Wu. “We are currently in the process of conducting additional analysis of whether there is a difference in lung function when we use the older race-specific equations versus our current findings with the newer race-neutral equations,” he said.

The findings were limited by several factors, including the relatively small study population and inclusion of only 3 types of biologics, with samples of omalizumab and mepolizumab that were underpowered to detect differences in lung function, said Wu. Additional studies with larger sample sizes, more biologics (including benralizumab and tezepelumab), and longer follow-up periods are needed to compare benefits across agents, he said.

Promising Implications for Practice

The ATS has recommended abandoning the previous race-adjusted pulmonary function test norms, said Timothy Joos, MD, who practices internal medicine and pediatrics at a community health center in Seattle.

These norms assigned smaller lung volumes to Black and Asian individuals and tended to underestimate lung disease in these populations, said Joos, who was not involved in the new study.

The current study, though small, showed with race-neutral reference equations that biologic agents significantly improved FEV1 values in children with severe asthma, said Joos. The association was especially strong with dupilumab, used by 85% of the patients, he noted. However, additional studies are needed with larger patient populations and other biologic agents to confirm the results, he said.

The study was supported by the Indiana Clinical and Translational Sciences Institute. The previous VOYAGE trial received funding from Sanofi and Regeneron Pharmaceuticals. The researchers reported having no financial conflicts to disclose. Joos reported having no financial conflicts to disclose.

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

Asthma biologics significantly improved lung function in children with asthma using race-based reference points, based on new data from 115 individuals.

Data on the effect of biologics on lung function in pediatric asthma are limited, and the main previous study of this relationship, the VOYAGE trial, was limited by its reliance on older, race-specific spirometry equations, according to Ken Wu, medical student at Indiana University School of Medicine in Indianapolis.

Newer, race-neutral reference equations prevent the systematic underestimation of asthma severity in Black patients and consequently provide a more accurate assessment of therapeutic benefits, said Wu. “Our study offers a novel contribution to the literature as the first known to utilize race-neutral equations to evaluate lung function following biologic therapy in a pediatric asthma population,” he said.

In a new study, presented at the American Thoracic Society (ATS) 2026 International Conference, the researchers conducted a real-world analysis with race-neutral reference equations developed by the Global Lung Function Initiative to assess the effect of biologics on lung function. They reviewed data from 115 pediatric patients with asthma who started biologics for the first time between 2015 and 2025. Their analysis included height, weight, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratios. The mean age of the patients was 11.4 years, 52% were male, and 62% were Black. A majority (97 patients) received dupilumab; 13 received omalizumab, and 5 received mepolizumab.

The analysis included an average of three spirometry measures 1 year before starting biologics and an average of four measures during the year after starting biologics.

Treatment with dupilumab was associated with a significant improvement in lung function, with an increase in the average FEV₁ from 86.4 percent-predicted prior to biologics to 91.7 after biologics (mean difference, 5.31; P = .044). No significant differences appeared among omalizumab or mepolizumab patients, likely because of the small numbers, the researchers noted.

Overall, in a linear mixed model adjusting for biologic type, FEV₁ remained significantly higher after use of biologics than in the period prior to use (97.9 vs. 92.5), with a mean difference of 5.37 (P = .039).

The primary finding that dupilumab improved the percent-predicted FEV₁ by 5.31 is considered a modest effect size and mainly aligns with previous research, said Wu. “We are currently in the process of conducting additional analysis of whether there is a difference in lung function when we use the older race-specific equations versus our current findings with the newer race-neutral equations,” he said.

The findings were limited by several factors, including the relatively small study population and inclusion of only 3 types of biologics, with samples of omalizumab and mepolizumab that were underpowered to detect differences in lung function, said Wu. Additional studies with larger sample sizes, more biologics (including benralizumab and tezepelumab), and longer follow-up periods are needed to compare benefits across agents, he said.

Promising Implications for Practice

The ATS has recommended abandoning the previous race-adjusted pulmonary function test norms, said Timothy Joos, MD, who practices internal medicine and pediatrics at a community health center in Seattle.

These norms assigned smaller lung volumes to Black and Asian individuals and tended to underestimate lung disease in these populations, said Joos, who was not involved in the new study.

The current study, though small, showed with race-neutral reference equations that biologic agents significantly improved FEV1 values in children with severe asthma, said Joos. The association was especially strong with dupilumab, used by 85% of the patients, he noted. However, additional studies are needed with larger patient populations and other biologic agents to confirm the results, he said.

The study was supported by the Indiana Clinical and Translational Sciences Institute. The previous VOYAGE trial received funding from Sanofi and Regeneron Pharmaceuticals. The researchers reported having no financial conflicts to disclose. Joos reported having no financial conflicts to disclose.

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

Approximately 20% of adults screened for early lung cancer met criteria undiagnosed chronic obstructive pulmonary disease (COPD), based on new data from approximately 300 individuals presented at the American Thoracic Society (ATS) 2026 International Conference.

“Patients undergoing lung cancer screening with low-dose CT scans represent a high-risk population for smoking-related lung disease, including COPD,” said lead author Stephen Dachert, MD, assistant professor of clinical thoracic medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia.

“While lung cancer screening programs are well established, COPD remains frequently underrecognized despite many patients having respiratory symptoms, airflow obstruction, and structural lung abnormalities detectable during screening,” Dachert told Medscape Medical News. Currently, the US Preventive Services Task Force does not recommend routine COPD screening, he noted.

To evaluate how often COPD was being missed and whether patients were receiving appropriate therapy, a particular concern in underserved populations, Dachert and colleagues reviewed data from electronic medical record, and pre-bronchodilator spirometry data were collected for 305 adults enrolled in the Temple Healthy Chest Initiative. Symptom burden was assessed using questionnaires about prior inhaler use and the COPD Airway Assessment Test (CAAT). The median age of the participants was 63 years; 182 were women, and 187 were active smokers. Most of the participants (228) self-identified as Black/African American, 42 as non-Caucasian Hispanic, and 31 as White/Caucasian.

About half of the participants (52%) had no previous COPD diagnosis. Of these, 49 (31.2%) had evidence of airflow obstruction, and almost all (97%) had symptoms defined as CAAT scores of > 1 for mucus, cough, or breathlessness.

Overall, “Twenty-one percent met criteria for undiagnosed COPD based on airflow obstruction and positive CAAT symptoms, and many had moderate disease severity by GOLD COPD classification,” Dachert said.

The high prevalence of previously undiagnosed COPD, despite a substantial symptom burden, was a striking finding, Dachert told Medscape Medical News. “We were also struck by the degree of undertreatment, with more than 60% of these patients not receiving any inhaler therapy,” he added. Among the 48 undiagnosed COPD patients in the total cohort, approximately 10% had received short-acting beta 2-agonist-only therapy.

“While prior studies have suggested underdiagnosis in lung cancer screening populations, the magnitude seen in this predominantly minority cohort reinforces how common missed opportunities for diagnosis remain in clinical practice,” Dachert said.

The findings were limited by the use of data from a single region and may not be generalized to other areas. However, the results suggest that lung cancer screening (LCS) programs are an opportunity to identify and treat chronic smoking-related lung disease, Dachert said. “Incorporating spirometry, symptom assessment, and review of respiratory therapies into LCS programs may help identify patients with clinically significant but previously unrecognized COPD, and earlier diagnosis could allow for smoking cessation reinforcement, initiation of evidence-based inhaler therapy, symptom improvement, and potentially reduction in exacerbations and health care utilization,” he said.

“Future studies should evaluate whether systematic COPD screening embedded within lung cancer screening programs improves clinical outcomes such as quality of life, exacerbations, hospitalizations, and healthcare utilization,” Dachert said. Additional work is needed to determine the best combination of screening tools to efficiently identify high-risk patients, which may include spirometry, quantitative CT imaging, symptom questionnaires, and biomarkers, he noted. “Longitudinal studies may help clarify whether earlier identification during lung cancer screening changes disease trajectory over time,” Dachert added.

Value Added for Underserved Populations

The new study’s results suggest that incorporating routine symptom assessment and spirometry into LCS pathways may improve earlier diagnosis and optimization of COPD management, said Jesse R. Sherratt, DO, a pulmonologist and critical care specialist at the University of Texas Health Science Center at San Antonio.

“Individuals undergoing lung cancer screening are at particularly high risk for smoking-related lung disease, yet COPD frequently remains unrecognized and untreated in this population,” said Sherratt, who was not involved in the study. The current study highlights the potential value, particularly among underserved populations, of incorporating spirometry and symptom assessment into LCS programs for earlier identification of patients with clinically significant COPD, he said.

The high rates of undiagnosed COPD and undertreatment were not unexpected, given the substantial smoking exposure and high-risk characteristics of patients undergoing LCS, said Sherratt. “However, the degree of symptom burden and the disproportionate impact on minority populations were especially notable and emphasize ongoing disparities in respiratory healthcare access and diagnosis,” he said.

“Additional studies are needed to determine whether integrating spirometry and structured COPD screening into lung cancer screening programs improves long-term clinical outcomes, healthcare utilization, and quality of life,” Sherratt noted. Further research also should evaluate strategies to reduce disparities in COPD diagnosis and treatment among minority populations, he said.

The study was supported by grants from AstraZeneca and the Temple Lung Center. AstraZeneca collaborators participated in the study as coauthors. Sherratt had no financial conflicts to disclose.

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

Approximately 20% of adults screened for early lung cancer met criteria undiagnosed chronic obstructive pulmonary disease (COPD), based on new data from approximately 300 individuals presented at the American Thoracic Society (ATS) 2026 International Conference.

“Patients undergoing lung cancer screening with low-dose CT scans represent a high-risk population for smoking-related lung disease, including COPD,” said lead author Stephen Dachert, MD, assistant professor of clinical thoracic medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia.

“While lung cancer screening programs are well established, COPD remains frequently underrecognized despite many patients having respiratory symptoms, airflow obstruction, and structural lung abnormalities detectable during screening,” Dachert told Medscape Medical News. Currently, the US Preventive Services Task Force does not recommend routine COPD screening, he noted.

To evaluate how often COPD was being missed and whether patients were receiving appropriate therapy, a particular concern in underserved populations, Dachert and colleagues reviewed data from electronic medical record, and pre-bronchodilator spirometry data were collected for 305 adults enrolled in the Temple Healthy Chest Initiative. Symptom burden was assessed using questionnaires about prior inhaler use and the COPD Airway Assessment Test (CAAT). The median age of the participants was 63 years; 182 were women, and 187 were active smokers. Most of the participants (228) self-identified as Black/African American, 42 as non-Caucasian Hispanic, and 31 as White/Caucasian.

About half of the participants (52%) had no previous COPD diagnosis. Of these, 49 (31.2%) had evidence of airflow obstruction, and almost all (97%) had symptoms defined as CAAT scores of > 1 for mucus, cough, or breathlessness.

Overall, “Twenty-one percent met criteria for undiagnosed COPD based on airflow obstruction and positive CAAT symptoms, and many had moderate disease severity by GOLD COPD classification,” Dachert said.

The high prevalence of previously undiagnosed COPD, despite a substantial symptom burden, was a striking finding, Dachert told Medscape Medical News. “We were also struck by the degree of undertreatment, with more than 60% of these patients not receiving any inhaler therapy,” he added. Among the 48 undiagnosed COPD patients in the total cohort, approximately 10% had received short-acting beta 2-agonist-only therapy.

“While prior studies have suggested underdiagnosis in lung cancer screening populations, the magnitude seen in this predominantly minority cohort reinforces how common missed opportunities for diagnosis remain in clinical practice,” Dachert said.

The findings were limited by the use of data from a single region and may not be generalized to other areas. However, the results suggest that lung cancer screening (LCS) programs are an opportunity to identify and treat chronic smoking-related lung disease, Dachert said. “Incorporating spirometry, symptom assessment, and review of respiratory therapies into LCS programs may help identify patients with clinically significant but previously unrecognized COPD, and earlier diagnosis could allow for smoking cessation reinforcement, initiation of evidence-based inhaler therapy, symptom improvement, and potentially reduction in exacerbations and health care utilization,” he said.

“Future studies should evaluate whether systematic COPD screening embedded within lung cancer screening programs improves clinical outcomes such as quality of life, exacerbations, hospitalizations, and healthcare utilization,” Dachert said. Additional work is needed to determine the best combination of screening tools to efficiently identify high-risk patients, which may include spirometry, quantitative CT imaging, symptom questionnaires, and biomarkers, he noted. “Longitudinal studies may help clarify whether earlier identification during lung cancer screening changes disease trajectory over time,” Dachert added.

Value Added for Underserved Populations

The new study’s results suggest that incorporating routine symptom assessment and spirometry into LCS pathways may improve earlier diagnosis and optimization of COPD management, said Jesse R. Sherratt, DO, a pulmonologist and critical care specialist at the University of Texas Health Science Center at San Antonio.

“Individuals undergoing lung cancer screening are at particularly high risk for smoking-related lung disease, yet COPD frequently remains unrecognized and untreated in this population,” said Sherratt, who was not involved in the study. The current study highlights the potential value, particularly among underserved populations, of incorporating spirometry and symptom assessment into LCS programs for earlier identification of patients with clinically significant COPD, he said.

The high rates of undiagnosed COPD and undertreatment were not unexpected, given the substantial smoking exposure and high-risk characteristics of patients undergoing LCS, said Sherratt. “However, the degree of symptom burden and the disproportionate impact on minority populations were especially notable and emphasize ongoing disparities in respiratory healthcare access and diagnosis,” he said.

“Additional studies are needed to determine whether integrating spirometry and structured COPD screening into lung cancer screening programs improves long-term clinical outcomes, healthcare utilization, and quality of life,” Sherratt noted. Further research also should evaluate strategies to reduce disparities in COPD diagnosis and treatment among minority populations, he said.

The study was supported by grants from AstraZeneca and the Temple Lung Center. AstraZeneca collaborators participated in the study as coauthors. Sherratt had no financial conflicts to disclose.

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

Approximately 20% of adults screened for early lung cancer met criteria undiagnosed chronic obstructive pulmonary disease (COPD), based on new data from approximately 300 individuals presented at the American Thoracic Society (ATS) 2026 International Conference.

“Patients undergoing lung cancer screening with low-dose CT scans represent a high-risk population for smoking-related lung disease, including COPD,” said lead author Stephen Dachert, MD, assistant professor of clinical thoracic medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia.

“While lung cancer screening programs are well established, COPD remains frequently underrecognized despite many patients having respiratory symptoms, airflow obstruction, and structural lung abnormalities detectable during screening,” Dachert told Medscape Medical News. Currently, the US Preventive Services Task Force does not recommend routine COPD screening, he noted.

To evaluate how often COPD was being missed and whether patients were receiving appropriate therapy, a particular concern in underserved populations, Dachert and colleagues reviewed data from electronic medical record, and pre-bronchodilator spirometry data were collected for 305 adults enrolled in the Temple Healthy Chest Initiative. Symptom burden was assessed using questionnaires about prior inhaler use and the COPD Airway Assessment Test (CAAT). The median age of the participants was 63 years; 182 were women, and 187 were active smokers. Most of the participants (228) self-identified as Black/African American, 42 as non-Caucasian Hispanic, and 31 as White/Caucasian.

About half of the participants (52%) had no previous COPD diagnosis. Of these, 49 (31.2%) had evidence of airflow obstruction, and almost all (97%) had symptoms defined as CAAT scores of > 1 for mucus, cough, or breathlessness.

Overall, “Twenty-one percent met criteria for undiagnosed COPD based on airflow obstruction and positive CAAT symptoms, and many had moderate disease severity by GOLD COPD classification,” Dachert said.

The high prevalence of previously undiagnosed COPD, despite a substantial symptom burden, was a striking finding, Dachert told Medscape Medical News. “We were also struck by the degree of undertreatment, with more than 60% of these patients not receiving any inhaler therapy,” he added. Among the 48 undiagnosed COPD patients in the total cohort, approximately 10% had received short-acting beta 2-agonist-only therapy.

“While prior studies have suggested underdiagnosis in lung cancer screening populations, the magnitude seen in this predominantly minority cohort reinforces how common missed opportunities for diagnosis remain in clinical practice,” Dachert said.

The findings were limited by the use of data from a single region and may not be generalized to other areas. However, the results suggest that lung cancer screening (LCS) programs are an opportunity to identify and treat chronic smoking-related lung disease, Dachert said. “Incorporating spirometry, symptom assessment, and review of respiratory therapies into LCS programs may help identify patients with clinically significant but previously unrecognized COPD, and earlier diagnosis could allow for smoking cessation reinforcement, initiation of evidence-based inhaler therapy, symptom improvement, and potentially reduction in exacerbations and health care utilization,” he said.

“Future studies should evaluate whether systematic COPD screening embedded within lung cancer screening programs improves clinical outcomes such as quality of life, exacerbations, hospitalizations, and healthcare utilization,” Dachert said. Additional work is needed to determine the best combination of screening tools to efficiently identify high-risk patients, which may include spirometry, quantitative CT imaging, symptom questionnaires, and biomarkers, he noted. “Longitudinal studies may help clarify whether earlier identification during lung cancer screening changes disease trajectory over time,” Dachert added.

Value Added for Underserved Populations

The new study’s results suggest that incorporating routine symptom assessment and spirometry into LCS pathways may improve earlier diagnosis and optimization of COPD management, said Jesse R. Sherratt, DO, a pulmonologist and critical care specialist at the University of Texas Health Science Center at San Antonio.

“Individuals undergoing lung cancer screening are at particularly high risk for smoking-related lung disease, yet COPD frequently remains unrecognized and untreated in this population,” said Sherratt, who was not involved in the study. The current study highlights the potential value, particularly among underserved populations, of incorporating spirometry and symptom assessment into LCS programs for earlier identification of patients with clinically significant COPD, he said.

The high rates of undiagnosed COPD and undertreatment were not unexpected, given the substantial smoking exposure and high-risk characteristics of patients undergoing LCS, said Sherratt. “However, the degree of symptom burden and the disproportionate impact on minority populations were especially notable and emphasize ongoing disparities in respiratory healthcare access and diagnosis,” he said.

“Additional studies are needed to determine whether integrating spirometry and structured COPD screening into lung cancer screening programs improves long-term clinical outcomes, healthcare utilization, and quality of life,” Sherratt noted. Further research also should evaluate strategies to reduce disparities in COPD diagnosis and treatment among minority populations, he said.

The study was supported by grants from AstraZeneca and the Temple Lung Center. AstraZeneca collaborators participated in the study as coauthors. Sherratt had no financial conflicts to disclose.

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

Treatment with ralinepag, an investigational prostacyclin receptor agonist, reduced the risk for clinical disease worsening by 55% compared to placebo in patients with pulmonary arterial hypertension (PAH), based on new data from the ADVANCE Outcomes study presented at the American Thoracic Society (ATS) 2026 International Conference.

Ralinepag works by restoring prostacyclin signaling and activating prostacyclin receptors to affect pathways that play a role in the progression of PAH. The drug was originally formulated as an immediate-release capsule but modified to the extended-release tablet used in the current study as a way to optimize once daily dosing.

“The prostacyclin pathway is foundational in the management of PAH, and advancing prostacyclin science has benefited patients over the years,” said lead author Vallerie V. McLaughlin, MD, professor of cardiovascular medicine and director of the Pulmonary Hypertension Program at the University of Michigan, Ann Arbor, Michigan, who presented the findings at the meeting. Although other oral prostacyclin pathway agents available, ralinepag has the advantages of high potency and longer half-life that could be effective and well-tolerated in a more patient-friendly once daily formulation, McLaughlin said.

The international study population included 687 adults with PAH from 30 countries across five continents. Participants were randomized to ralinepag or placebo in addition to their standard PAH background therapies. Ralinepag was orally dosed once daily and titrated for tolerability and response. The mean age of the participants was 52 years, 80% were White, and the median time since PAH diagnosis was 2.3 years. A majority of 62% had idiopathic or heritable PAH, 28.2% had PAH as a result of connective tissue disease, 4.1% had a congenital heart defect, 3.1% had drug- or toxin-induced PAH, and 2.6% had PAH as a result of HIV infection. More than two thirds were considered low risk (characterized as Functional Class II).

The primary endpoint was the time to first indication of clinical worsening, which was defined as death, hospital admission for worsening PAH, initiation of a parenteral or inhaled prostacyclin pathway agent for worsening PAH, or unsatisfactory long-term clinical response.

Overall, patients treated with ralinepag were significantly less likely to experience a clinical worsening event than placebo patients (hazard ratio [HR], 0.45; 95% CI, 0.33-0.62; P < .0001), and 47% more likely to achieve the secondary endpoint of clinical improvement (P = .015).

Patients treated with ralinepag also showed significant improvements over placebo patients in the secondary endpoints of pro-B-type natriuretic peptide levels (24.3% reduction from baseline to week 28 over placebo; P = .0013), and in the 6-minute walk test (a placebo-corrected difference of 20.4 m from baseline to week 28; P = .0033).

Although more than 90% of participants treated with ralinepag reported an adverse event related to the drug, approximately 5% experienced drug-related serious adverse events, and the overall safety profile reflected previous ralinepag studies, with a positive risk-benefit ratio, the investigators noted.

Support for Early Introduction

The researchers expected the efficacy associated with prostacyclin therapy, said McLaughlin. “We were very pleased to see such a strong treatment effect in a relatively low-risk population, primarily Functional Class II with a mean 6-minute walk of nearly 440 meters, with the majority of patients on dual oral therapy,” she said.

If approved, ralinepag could help optimized risk status in PAH, said McLaughlin. “Many patients do not get to low risk with first-line therapy, and oral and inhaled prostacyclin pathway agents are often used in addition to dual therapy with phosphodiesterase type-5 inhibitors and endothelin receptor antagonists,” she said. “The impressive treatment effect of ralinepag in patients primarily treated with dual oral therapy reflects this real-world scenario,” she added. The significant event reduction makes a case for earlier introduction of ralinepag in relatively low-risk patients; a highly effective therapy that targets the prostacyclin pathway may reduce the need for more cumbersome and invasive prostacyclin therapies, McLaughlin added.

Ralinepag remains an investigational drug, but the company plans to seek a New Drug Application from the FDA for the treatment of PAH by the second half of 2026, according to a press release.

The research team would like to continue evaluating the ADVANCE Outcomes database to learn more about dose response, tolerability, and subgroup response, said McLaughlin. At that point, real-world data would be useful, and additional research areas in that setting would include combination therapy with other agents such as sotatercept, as well as the use of ralinepag to transition patients on more complicated and invasive therapy, she said.

Attention to Adverse Effects

Prostacyclin therapies are often offered in oral, inhaled, and the most invasive intravenous/subcutaneous routes, but a gap remains between the strong efficacy seen with parenteral therapy and what many patients are willing or able to use in real-world practice, said Parth M. Rali, MD, director of the Temple University Health System Pulmonary Embolism Response Team Program, Section Temple Lung Pulmonary Vascular Disease Program, Philadelphia, who was not involved in the study.

“Ralinepag provides sustained activation of IP receptors and has very long effective half-life, giving drug exposure comparable to parenteral therapy, and offers the first daily treatment option, which is important for the patients with PAH who are often on multiple drugs therapies,” Rali said.

Given the encouraging phase 2 findings demonstrating meaningful reductions in pulmonary vascular resistance and signals toward clinical benefit, we would like to see a favorable outcome in the phase 3 program. Primary outcome studied was time to clinical worsening in the large, randomized trial that involved global populations from the US, Europe, Latin-America, and Asia Pacific Region. Ralinepag arm had 55% reduction in risk for clinical worsening (HR, ~ 0.45) compared to placebo arm. “The positive results of the trial were primarily driven by disease progression, initiation of prostacyclin therapy, and unsatisfactory long-term clinical response at 28 weeks in ralinepag group compared to placebo group,” Rali said.

Although ralinepag offers a good option for once-a-day oral prostacyclin options for the patients, the significant number of patients in the new study who discontinued because of adverse effects is notable, said Rali. “Treating clinicians will have to watch very closely, as the real-world patient population seems to be more complex than clinical trial populations,” he said. “At the same time, clinicians will have an option to weigh against growing list of inhaled prostacyclin pathway therapies that may not have systemic side effects of the oral agents,” he added.

“Given the strong scientific data in the ADVANCE trials, ralinepag may become drug of choice for oral prostacyclin pathway agents,” Rali added. However, its place in the treatment sequence, whether it is best used early in the disease course, as an add-on for patients already receiving dual oral therapy, or potentially part of upfront combination strategies, will call for some clinician judgement, Rali said. “Patient education and gradual dose titration will likely play a major role in improving adherence and limiting prostacyclin-related adverse effects,” he added.

Questions for future research include what percentage of the patients were able to tolerate the maximum dose of the drug, and whether any changes in primary or secondary outcomes occurred depending on the dose, said Rali. Other areas of interest include whether certain patient populations derive greater benefit than others, including connective tissue disease-associated PAH, idiopathic PAH, and higher-risk patient populations. “Comparative effectiveness data against currently available oral prostacyclin pathway agents and studies evaluating transition strategies from parenteral or inhaled therapies would help clinicians better understand where ralinepag ultimately fits in the PAH treatment algorithm,” Rali said. “I also would be curious to see what the authors thought of the failure to achieve the primary endpoint in cohorts of patients from Latin America and Asia Pacific regions,” he added.

The study was funded by United Therapeutics, and McLaughlin disclosed serving as a consultant for the company. Rali had no financial conflicts to disclose.

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

Treatment with ralinepag, an investigational prostacyclin receptor agonist, reduced the risk for clinical disease worsening by 55% compared to placebo in patients with pulmonary arterial hypertension (PAH), based on new data from the ADVANCE Outcomes study presented at the American Thoracic Society (ATS) 2026 International Conference.

Ralinepag works by restoring prostacyclin signaling and activating prostacyclin receptors to affect pathways that play a role in the progression of PAH. The drug was originally formulated as an immediate-release capsule but modified to the extended-release tablet used in the current study as a way to optimize once daily dosing.

“The prostacyclin pathway is foundational in the management of PAH, and advancing prostacyclin science has benefited patients over the years,” said lead author Vallerie V. McLaughlin, MD, professor of cardiovascular medicine and director of the Pulmonary Hypertension Program at the University of Michigan, Ann Arbor, Michigan, who presented the findings at the meeting. Although other oral prostacyclin pathway agents available, ralinepag has the advantages of high potency and longer half-life that could be effective and well-tolerated in a more patient-friendly once daily formulation, McLaughlin said.

The international study population included 687 adults with PAH from 30 countries across five continents. Participants were randomized to ralinepag or placebo in addition to their standard PAH background therapies. Ralinepag was orally dosed once daily and titrated for tolerability and response. The mean age of the participants was 52 years, 80% were White, and the median time since PAH diagnosis was 2.3 years. A majority of 62% had idiopathic or heritable PAH, 28.2% had PAH as a result of connective tissue disease, 4.1% had a congenital heart defect, 3.1% had drug- or toxin-induced PAH, and 2.6% had PAH as a result of HIV infection. More than two thirds were considered low risk (characterized as Functional Class II).

The primary endpoint was the time to first indication of clinical worsening, which was defined as death, hospital admission for worsening PAH, initiation of a parenteral or inhaled prostacyclin pathway agent for worsening PAH, or unsatisfactory long-term clinical response.

Overall, patients treated with ralinepag were significantly less likely to experience a clinical worsening event than placebo patients (hazard ratio [HR], 0.45; 95% CI, 0.33-0.62; P < .0001), and 47% more likely to achieve the secondary endpoint of clinical improvement (P = .015).

Patients treated with ralinepag also showed significant improvements over placebo patients in the secondary endpoints of pro-B-type natriuretic peptide levels (24.3% reduction from baseline to week 28 over placebo; P = .0013), and in the 6-minute walk test (a placebo-corrected difference of 20.4 m from baseline to week 28; P = .0033).

Although more than 90% of participants treated with ralinepag reported an adverse event related to the drug, approximately 5% experienced drug-related serious adverse events, and the overall safety profile reflected previous ralinepag studies, with a positive risk-benefit ratio, the investigators noted.

Support for Early Introduction

The researchers expected the efficacy associated with prostacyclin therapy, said McLaughlin. “We were very pleased to see such a strong treatment effect in a relatively low-risk population, primarily Functional Class II with a mean 6-minute walk of nearly 440 meters, with the majority of patients on dual oral therapy,” she said.

If approved, ralinepag could help optimized risk status in PAH, said McLaughlin. “Many patients do not get to low risk with first-line therapy, and oral and inhaled prostacyclin pathway agents are often used in addition to dual therapy with phosphodiesterase type-5 inhibitors and endothelin receptor antagonists,” she said. “The impressive treatment effect of ralinepag in patients primarily treated with dual oral therapy reflects this real-world scenario,” she added. The significant event reduction makes a case for earlier introduction of ralinepag in relatively low-risk patients; a highly effective therapy that targets the prostacyclin pathway may reduce the need for more cumbersome and invasive prostacyclin therapies, McLaughlin added.

Ralinepag remains an investigational drug, but the company plans to seek a New Drug Application from the FDA for the treatment of PAH by the second half of 2026, according to a press release.

The research team would like to continue evaluating the ADVANCE Outcomes database to learn more about dose response, tolerability, and subgroup response, said McLaughlin. At that point, real-world data would be useful, and additional research areas in that setting would include combination therapy with other agents such as sotatercept, as well as the use of ralinepag to transition patients on more complicated and invasive therapy, she said.

Attention to Adverse Effects

Prostacyclin therapies are often offered in oral, inhaled, and the most invasive intravenous/subcutaneous routes, but a gap remains between the strong efficacy seen with parenteral therapy and what many patients are willing or able to use in real-world practice, said Parth M. Rali, MD, director of the Temple University Health System Pulmonary Embolism Response Team Program, Section Temple Lung Pulmonary Vascular Disease Program, Philadelphia, who was not involved in the study.

“Ralinepag provides sustained activation of IP receptors and has very long effective half-life, giving drug exposure comparable to parenteral therapy, and offers the first daily treatment option, which is important for the patients with PAH who are often on multiple drugs therapies,” Rali said.

Given the encouraging phase 2 findings demonstrating meaningful reductions in pulmonary vascular resistance and signals toward clinical benefit, we would like to see a favorable outcome in the phase 3 program. Primary outcome studied was time to clinical worsening in the large, randomized trial that involved global populations from the US, Europe, Latin-America, and Asia Pacific Region. Ralinepag arm had 55% reduction in risk for clinical worsening (HR, ~ 0.45) compared to placebo arm. “The positive results of the trial were primarily driven by disease progression, initiation of prostacyclin therapy, and unsatisfactory long-term clinical response at 28 weeks in ralinepag group compared to placebo group,” Rali said.

Although ralinepag offers a good option for once-a-day oral prostacyclin options for the patients, the significant number of patients in the new study who discontinued because of adverse effects is notable, said Rali. “Treating clinicians will have to watch very closely, as the real-world patient population seems to be more complex than clinical trial populations,” he said. “At the same time, clinicians will have an option to weigh against growing list of inhaled prostacyclin pathway therapies that may not have systemic side effects of the oral agents,” he added.

“Given the strong scientific data in the ADVANCE trials, ralinepag may become drug of choice for oral prostacyclin pathway agents,” Rali added. However, its place in the treatment sequence, whether it is best used early in the disease course, as an add-on for patients already receiving dual oral therapy, or potentially part of upfront combination strategies, will call for some clinician judgement, Rali said. “Patient education and gradual dose titration will likely play a major role in improving adherence and limiting prostacyclin-related adverse effects,” he added.

Questions for future research include what percentage of the patients were able to tolerate the maximum dose of the drug, and whether any changes in primary or secondary outcomes occurred depending on the dose, said Rali. Other areas of interest include whether certain patient populations derive greater benefit than others, including connective tissue disease-associated PAH, idiopathic PAH, and higher-risk patient populations. “Comparative effectiveness data against currently available oral prostacyclin pathway agents and studies evaluating transition strategies from parenteral or inhaled therapies would help clinicians better understand where ralinepag ultimately fits in the PAH treatment algorithm,” Rali said. “I also would be curious to see what the authors thought of the failure to achieve the primary endpoint in cohorts of patients from Latin America and Asia Pacific regions,” he added.

The study was funded by United Therapeutics, and McLaughlin disclosed serving as a consultant for the company. Rali had no financial conflicts to disclose.

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

Treatment with ralinepag, an investigational prostacyclin receptor agonist, reduced the risk for clinical disease worsening by 55% compared to placebo in patients with pulmonary arterial hypertension (PAH), based on new data from the ADVANCE Outcomes study presented at the American Thoracic Society (ATS) 2026 International Conference.

Ralinepag works by restoring prostacyclin signaling and activating prostacyclin receptors to affect pathways that play a role in the progression of PAH. The drug was originally formulated as an immediate-release capsule but modified to the extended-release tablet used in the current study as a way to optimize once daily dosing.

“The prostacyclin pathway is foundational in the management of PAH, and advancing prostacyclin science has benefited patients over the years,” said lead author Vallerie V. McLaughlin, MD, professor of cardiovascular medicine and director of the Pulmonary Hypertension Program at the University of Michigan, Ann Arbor, Michigan, who presented the findings at the meeting. Although other oral prostacyclin pathway agents available, ralinepag has the advantages of high potency and longer half-life that could be effective and well-tolerated in a more patient-friendly once daily formulation, McLaughlin said.

The international study population included 687 adults with PAH from 30 countries across five continents. Participants were randomized to ralinepag or placebo in addition to their standard PAH background therapies. Ralinepag was orally dosed once daily and titrated for tolerability and response. The mean age of the participants was 52 years, 80% were White, and the median time since PAH diagnosis was 2.3 years. A majority of 62% had idiopathic or heritable PAH, 28.2% had PAH as a result of connective tissue disease, 4.1% had a congenital heart defect, 3.1% had drug- or toxin-induced PAH, and 2.6% had PAH as a result of HIV infection. More than two thirds were considered low risk (characterized as Functional Class II).

The primary endpoint was the time to first indication of clinical worsening, which was defined as death, hospital admission for worsening PAH, initiation of a parenteral or inhaled prostacyclin pathway agent for worsening PAH, or unsatisfactory long-term clinical response.

Overall, patients treated with ralinepag were significantly less likely to experience a clinical worsening event than placebo patients (hazard ratio [HR], 0.45; 95% CI, 0.33-0.62; P < .0001), and 47% more likely to achieve the secondary endpoint of clinical improvement (P = .015).

Patients treated with ralinepag also showed significant improvements over placebo patients in the secondary endpoints of pro-B-type natriuretic peptide levels (24.3% reduction from baseline to week 28 over placebo; P = .0013), and in the 6-minute walk test (a placebo-corrected difference of 20.4 m from baseline to week 28; P = .0033).

Although more than 90% of participants treated with ralinepag reported an adverse event related to the drug, approximately 5% experienced drug-related serious adverse events, and the overall safety profile reflected previous ralinepag studies, with a positive risk-benefit ratio, the investigators noted.

Support for Early Introduction

The researchers expected the efficacy associated with prostacyclin therapy, said McLaughlin. “We were very pleased to see such a strong treatment effect in a relatively low-risk population, primarily Functional Class II with a mean 6-minute walk of nearly 440 meters, with the majority of patients on dual oral therapy,” she said.

If approved, ralinepag could help optimized risk status in PAH, said McLaughlin. “Many patients do not get to low risk with first-line therapy, and oral and inhaled prostacyclin pathway agents are often used in addition to dual therapy with phosphodiesterase type-5 inhibitors and endothelin receptor antagonists,” she said. “The impressive treatment effect of ralinepag in patients primarily treated with dual oral therapy reflects this real-world scenario,” she added. The significant event reduction makes a case for earlier introduction of ralinepag in relatively low-risk patients; a highly effective therapy that targets the prostacyclin pathway may reduce the need for more cumbersome and invasive prostacyclin therapies, McLaughlin added.

Ralinepag remains an investigational drug, but the company plans to seek a New Drug Application from the FDA for the treatment of PAH by the second half of 2026, according to a press release.

The research team would like to continue evaluating the ADVANCE Outcomes database to learn more about dose response, tolerability, and subgroup response, said McLaughlin. At that point, real-world data would be useful, and additional research areas in that setting would include combination therapy with other agents such as sotatercept, as well as the use of ralinepag to transition patients on more complicated and invasive therapy, she said.

Attention to Adverse Effects

Prostacyclin therapies are often offered in oral, inhaled, and the most invasive intravenous/subcutaneous routes, but a gap remains between the strong efficacy seen with parenteral therapy and what many patients are willing or able to use in real-world practice, said Parth M. Rali, MD, director of the Temple University Health System Pulmonary Embolism Response Team Program, Section Temple Lung Pulmonary Vascular Disease Program, Philadelphia, who was not involved in the study.

“Ralinepag provides sustained activation of IP receptors and has very long effective half-life, giving drug exposure comparable to parenteral therapy, and offers the first daily treatment option, which is important for the patients with PAH who are often on multiple drugs therapies,” Rali said.

Given the encouraging phase 2 findings demonstrating meaningful reductions in pulmonary vascular resistance and signals toward clinical benefit, we would like to see a favorable outcome in the phase 3 program. Primary outcome studied was time to clinical worsening in the large, randomized trial that involved global populations from the US, Europe, Latin-America, and Asia Pacific Region. Ralinepag arm had 55% reduction in risk for clinical worsening (HR, ~ 0.45) compared to placebo arm. “The positive results of the trial were primarily driven by disease progression, initiation of prostacyclin therapy, and unsatisfactory long-term clinical response at 28 weeks in ralinepag group compared to placebo group,” Rali said.

Although ralinepag offers a good option for once-a-day oral prostacyclin options for the patients, the significant number of patients in the new study who discontinued because of adverse effects is notable, said Rali. “Treating clinicians will have to watch very closely, as the real-world patient population seems to be more complex than clinical trial populations,” he said. “At the same time, clinicians will have an option to weigh against growing list of inhaled prostacyclin pathway therapies that may not have systemic side effects of the oral agents,” he added.

“Given the strong scientific data in the ADVANCE trials, ralinepag may become drug of choice for oral prostacyclin pathway agents,” Rali added. However, its place in the treatment sequence, whether it is best used early in the disease course, as an add-on for patients already receiving dual oral therapy, or potentially part of upfront combination strategies, will call for some clinician judgement, Rali said. “Patient education and gradual dose titration will likely play a major role in improving adherence and limiting prostacyclin-related adverse effects,” he added.

Questions for future research include what percentage of the patients were able to tolerate the maximum dose of the drug, and whether any changes in primary or secondary outcomes occurred depending on the dose, said Rali. Other areas of interest include whether certain patient populations derive greater benefit than others, including connective tissue disease-associated PAH, idiopathic PAH, and higher-risk patient populations. “Comparative effectiveness data against currently available oral prostacyclin pathway agents and studies evaluating transition strategies from parenteral or inhaled therapies would help clinicians better understand where ralinepag ultimately fits in the PAH treatment algorithm,” Rali said. “I also would be curious to see what the authors thought of the failure to achieve the primary endpoint in cohorts of patients from Latin America and Asia Pacific regions,” he added.

The study was funded by United Therapeutics, and McLaughlin disclosed serving as a consultant for the company. Rali had no financial conflicts to disclose.

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

TOPLINE:

Higher baseline counts of blood eosinophils (EOS) were associated with an increased risk for exacerbations in patients with asthma over 1 year, and higher baseline levels of fractional exhaled nitric oxide (FeNO) were linked to increased odds of exacerbations treated with only oral corticosteroids (OCS) in asthma and asthma plus chronic obstructive pulmonary disease (COPD) but linked to a decreased risk for all exacerbations in COPD.

METHODOLOGY:

• Researchers analyzed data from the multinational NOVELTY study to assess whether blood EOS counts and FeNO levels, alone and together, predict the risk for future exacerbations in patients with asthma, COPD, or both.
• Overall, 4319 patients were included in the EOS analysis (2138 with asthma, 1541 with COPD, and 640 with asthma plus COPD), and 7770 patients were included in the FeNO analysis (4166 with asthma, 2588 with COPD, and 1016 with asthma plus COPD).
• Baseline data included demographics, treatments, exacerbations, and lung function (spirometry and FeNO levels).
• Outcomes were assessed over the first year of follow‑up, and patients received usual care from their treating physicians.
• Exacerbation subtypes were categorized as all exacerbations, exacerbations treated with only antibiotics, and exacerbations treated with only OCS.

TAKEAWAY:

• Higher EOS counts at baseline were associated with an increased risk for all exacerbations in asthma (incidence rate ratio [IRR], 1.09; P = .033), meaning each doubling of the count corresponded to a 9% higher exacerbation rate; a similar trend of higher risk was seen in COPD that did not reach statistical significance.
• Higher FeNO levels at baseline were associated with a lower risk for all exacerbations in COPD (IRR, 0.91; P = .025). In asthma, FeNO levels showed no association with an overall risk for exacerbations; in asthma plus COPD, neither biomarker predicted the overall risk.
• In asthma, higher FeNO levels at baseline were linked to increased odds of exacerbations treated with only OCS (odds ratio [OR], 1.16) but decreased odds of exacerbations treated with only antibiotics (OR, 0.75); in asthma plus COPD, higher FeNO levels were also linked to increased odds of exacerbations treated with only OCS (OR, 1.55; P < .05 for all).
• In an analysis including both biomarkers, higher EOS counts at baseline independently predicted all exacerbations in asthma; however, both higher EOS counts and lower FeNO levels were independently associated with a higher risk for all exacerbations in COPD (P < .05 for all).

IN PRACTICE:

“[The study] finding is of importance for future studies and daily clinical practice as it indicates that assessment of exacerbation subtype might improve personalized treatment management,” the authors wrote.

SOURCE:

This study was led by Susan Muiser, University Medical Centre Groningen, Groningen, Netherlands. It was published online on April 21, 2026, in Thorax.

LIMITATIONS:

Diagnoses were assigned by treating physicians without standardized diagnostic criteria. Physicians had access to type 2 inflammation biomarker results, which may have influenced treatment decisions. Exacerbation subtypes were categorized using medical records and patient-reported information, introducing a potential recall bias.

DISCLOSURES:

The NOVELTY study was funded by AstraZeneca. Four authors reported being employees of AstraZeneca, with 2 of them also being shareholders. Several authors disclosed receiving travel grants, research grants, consulting fees, honoraria, and support to attend meetings; serving on advisory boards; and holding stock or stock options with multiple pharmaceutical companies and organizations, including AstraZeneca and WebMD Global.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Higher baseline counts of blood eosinophils (EOS) were associated with an increased risk for exacerbations in patients with asthma over 1 year, and higher baseline levels of fractional exhaled nitric oxide (FeNO) were linked to increased odds of exacerbations treated with only oral corticosteroids (OCS) in asthma and asthma plus chronic obstructive pulmonary disease (COPD) but linked to a decreased risk for all exacerbations in COPD.

METHODOLOGY:

• Researchers analyzed data from the multinational NOVELTY study to assess whether blood EOS counts and FeNO levels, alone and together, predict the risk for future exacerbations in patients with asthma, COPD, or both.
• Overall, 4319 patients were included in the EOS analysis (2138 with asthma, 1541 with COPD, and 640 with asthma plus COPD), and 7770 patients were included in the FeNO analysis (4166 with asthma, 2588 with COPD, and 1016 with asthma plus COPD).
• Baseline data included demographics, treatments, exacerbations, and lung function (spirometry and FeNO levels).
• Outcomes were assessed over the first year of follow‑up, and patients received usual care from their treating physicians.
• Exacerbation subtypes were categorized as all exacerbations, exacerbations treated with only antibiotics, and exacerbations treated with only OCS.

TAKEAWAY:

• Higher EOS counts at baseline were associated with an increased risk for all exacerbations in asthma (incidence rate ratio [IRR], 1.09; P = .033), meaning each doubling of the count corresponded to a 9% higher exacerbation rate; a similar trend of higher risk was seen in COPD that did not reach statistical significance.
• Higher FeNO levels at baseline were associated with a lower risk for all exacerbations in COPD (IRR, 0.91; P = .025). In asthma, FeNO levels showed no association with an overall risk for exacerbations; in asthma plus COPD, neither biomarker predicted the overall risk.
• In asthma, higher FeNO levels at baseline were linked to increased odds of exacerbations treated with only OCS (odds ratio [OR], 1.16) but decreased odds of exacerbations treated with only antibiotics (OR, 0.75); in asthma plus COPD, higher FeNO levels were also linked to increased odds of exacerbations treated with only OCS (OR, 1.55; P < .05 for all).
• In an analysis including both biomarkers, higher EOS counts at baseline independently predicted all exacerbations in asthma; however, both higher EOS counts and lower FeNO levels were independently associated with a higher risk for all exacerbations in COPD (P < .05 for all).

IN PRACTICE:

“[The study] finding is of importance for future studies and daily clinical practice as it indicates that assessment of exacerbation subtype might improve personalized treatment management,” the authors wrote.

SOURCE:

This study was led by Susan Muiser, University Medical Centre Groningen, Groningen, Netherlands. It was published online on April 21, 2026, in Thorax.

LIMITATIONS:

Diagnoses were assigned by treating physicians without standardized diagnostic criteria. Physicians had access to type 2 inflammation biomarker results, which may have influenced treatment decisions. Exacerbation subtypes were categorized using medical records and patient-reported information, introducing a potential recall bias.

DISCLOSURES:

The NOVELTY study was funded by AstraZeneca. Four authors reported being employees of AstraZeneca, with 2 of them also being shareholders. Several authors disclosed receiving travel grants, research grants, consulting fees, honoraria, and support to attend meetings; serving on advisory boards; and holding stock or stock options with multiple pharmaceutical companies and organizations, including AstraZeneca and WebMD Global.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Higher baseline counts of blood eosinophils (EOS) were associated with an increased risk for exacerbations in patients with asthma over 1 year, and higher baseline levels of fractional exhaled nitric oxide (FeNO) were linked to increased odds of exacerbations treated with only oral corticosteroids (OCS) in asthma and asthma plus chronic obstructive pulmonary disease (COPD) but linked to a decreased risk for all exacerbations in COPD.

METHODOLOGY:

• Researchers analyzed data from the multinational NOVELTY study to assess whether blood EOS counts and FeNO levels, alone and together, predict the risk for future exacerbations in patients with asthma, COPD, or both.
• Overall, 4319 patients were included in the EOS analysis (2138 with asthma, 1541 with COPD, and 640 with asthma plus COPD), and 7770 patients were included in the FeNO analysis (4166 with asthma, 2588 with COPD, and 1016 with asthma plus COPD).
• Baseline data included demographics, treatments, exacerbations, and lung function (spirometry and FeNO levels).
• Outcomes were assessed over the first year of follow‑up, and patients received usual care from their treating physicians.
• Exacerbation subtypes were categorized as all exacerbations, exacerbations treated with only antibiotics, and exacerbations treated with only OCS.

TAKEAWAY:

• Higher EOS counts at baseline were associated with an increased risk for all exacerbations in asthma (incidence rate ratio [IRR], 1.09; P = .033), meaning each doubling of the count corresponded to a 9% higher exacerbation rate; a similar trend of higher risk was seen in COPD that did not reach statistical significance.
• Higher FeNO levels at baseline were associated with a lower risk for all exacerbations in COPD (IRR, 0.91; P = .025). In asthma, FeNO levels showed no association with an overall risk for exacerbations; in asthma plus COPD, neither biomarker predicted the overall risk.
• In asthma, higher FeNO levels at baseline were linked to increased odds of exacerbations treated with only OCS (odds ratio [OR], 1.16) but decreased odds of exacerbations treated with only antibiotics (OR, 0.75); in asthma plus COPD, higher FeNO levels were also linked to increased odds of exacerbations treated with only OCS (OR, 1.55; P < .05 for all).
• In an analysis including both biomarkers, higher EOS counts at baseline independently predicted all exacerbations in asthma; however, both higher EOS counts and lower FeNO levels were independently associated with a higher risk for all exacerbations in COPD (P < .05 for all).

IN PRACTICE:

“[The study] finding is of importance for future studies and daily clinical practice as it indicates that assessment of exacerbation subtype might improve personalized treatment management,” the authors wrote.

SOURCE:

This study was led by Susan Muiser, University Medical Centre Groningen, Groningen, Netherlands. It was published online on April 21, 2026, in Thorax.

LIMITATIONS:

Diagnoses were assigned by treating physicians without standardized diagnostic criteria. Physicians had access to type 2 inflammation biomarker results, which may have influenced treatment decisions. Exacerbation subtypes were categorized using medical records and patient-reported information, introducing a potential recall bias.

DISCLOSURES:

The NOVELTY study was funded by AstraZeneca. Four authors reported being employees of AstraZeneca, with 2 of them also being shareholders. Several authors disclosed receiving travel grants, research grants, consulting fees, honoraria, and support to attend meetings; serving on advisory boards; and holding stock or stock options with multiple pharmaceutical companies and organizations, including AstraZeneca and WebMD Global.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Mild asthma is not benign. Underdiagnosis in children exposes them to preventable morbidity — including impaired lung growth that can lead to fixed airway obstruction and a higher lifetime risk for chronic obstructive pulmonary disease (COPD), as well as severe exacerbations and increased need for systemic corticosteroids. Experts at the 21st Francophone Allergy Congress 2026 said preserving respiratory function depends on early diagnosis and disease control.

Mild asthma is retrospectively defined as the level of treatment required to achieve and maintain disease control. It corresponds to asthma controlled with a low dose of inhaled corticosteroids or with a combination of inhaled corticosteroids and formoterol as needed (Global Initiative for Asthma(GINA)/French Society of Pediatric Pulmonology and Allergology, steps 1-2).

Mélisande Bourgoin-Heck, MD, PhD, Department of Pediatric Allergology, Armand Trousseau University Hospital, Sorbonne University, AP-HP, Paris, France, emphasized a fundamental distinction: “While control is based on symptoms, exacerbations, activity limitations, and quality of life, severity corresponds to the level of treatment required to achieve this control. The term mild therefore depends on the treatment required and not solely on the frequency or intensity of symptoms.”

How to Identify It?

Clinically, asthma most often presents with wheezing, cough, shortness of breath, and chest tightness, with symptoms that fluctuate in frequency and severity. Nighttime symptoms are common. Symptoms often start or worsen with viral infections, physical exertion (including after exercise), laughter, or exposure to allergens or cold air. “Symptoms are often dismissed as minor and intermittent,” the pediatrician said, “which leads to delayed diagnosis.”

That’s why recognizing risk factors is important because they help guide diagnosis: male sex, a first-degree family history of asthma, exposure to secondhand smoke, prematurity, maternal obesity, living in group settings or having school-aged siblings which raise the risk for early infections, a history of severe bronchiolitis, and an atopic tendency, demonstrated by atopic dermatitis, allergic rhinitis, or sensitization to food and respiratory allergens.

How Much Should We Trust Predictive Scores?

Several clinical scores for predicting asthma exist, notably the Asthma Predictive Index, the modified Asthma Predictive Index, and the Pediatric Asthma Risk Score; the latter demonstrates better overall discrimination, making it useful for children at low-to-moderate risk.

“These scores place significant emphasis on the atopic predisposition,” noted Bourgoin-Heck, “including allergic sensitivities, allergic rhinitis, and atopic dermatitis. Their performance varies by age and clinical phenotype. They are highly specific for the diagnosis of allergic asthma, with a positive score associated with a high risk of asthma. However, their sensitivity is not up to par: A negative score does not rule out the diagnosis, leading to a risk of overlooking nonallergic forms.”

A chest x-ray is used to rule out differential diagnoses. It may be normal or reveal chest distension or bronchial signs. During follow-up, it is only recommended in cases of fever or severe illness to look for complications such as bronchopulmonary superinfection, pneumothorax, pneumomediastinum, subcutaneous emphysema and ventilation disorders/atelectasis.

Normal Spirometry: Could Asthma Really be Ruled Out?

Pulmonary function tests (PFTs) may be normal and do not rule out asthma. Spirometry can be performed around age 6 years and is often normal. “The reversibility test is a diagnostic indicator but may be negative in cases of normal forced expiratory volume in 1 second (FEV₁),” warned the specialist.

Provocation tests are useful in cases of doubt.

In children unable to perform a forced exhalation, spirometry is impossible or unreliable, which justifies the use of respiratory resistance measurements (starting at age 3). Several methods are then used: flow-interruption resistance (FIR) identifies bronchial obstruction with an expiratory FIR > 2 Z scores (how many SDs a result is from the predicted value for a child’s age/height/sex). Oscillometry, suitable for young children, is considered pathologic for values exceeding 150% of the predicted value. Plethysmography indicates obstruction with a Raw value > 150% of the predicted value or an sRaw value > 180%.

Interpretation is based on standards adapted to the technique and the study population, with thresholds varying by method (threshold values for PFTs, page e4).

When in Doubt, How Useful Are Biomarkers?

As a biomarker of atopy, a blood eosinophil count of at least 150/mm³ is associated with asthma symptoms and exacerbations. Specific Immunoglobulin E (IgE) indicates allergic sensitization associated with asthma. Finally, elevated fractional concentration of exhaled nitric oxide (> 20-25 parts per billion depending on age) is associated with wheezing, corticosteroid use, and persistent asthma. The combination of atopy markers — including maternal allergy, eczema, wheezing, positive specific IgE levels, and eosinophilia — significantly increases the likelihood of asthma.

“However, when diagnostic uncertainty persists in a child younger than 5 years (absence of atopy; normal PFTs — which is common), a trial of treatment based on initial symptoms may be recommended according to GINA 2025 (Box 10-2),” explained Bourgoin-Heck.

In the presence of mild and intermittent symptoms, a short-acting bronchodilator challenge test on demand is indicated for a maximum duration of 2-3 months. This strategy applies to infrequent wheezing episodes, without the need for emergency care and therefore without any severe exacerbations, with symptoms occurring twice or less per week. Treatment consists of administering two puffs when symptoms occur (to be repeated as needed), with an assessment of improvement within 20-60 minutes. In cases of a history of a severe wheezing episode within the past year (systemic corticosteroids, emergency department visit, and hospitalization) or symptoms more than twice a week, the therapeutic trial involves long-term inhaled corticosteroids (eg, fluticasone 100 µg/d to 250 µg/d) combined with a short-acting bronchodilator as needed for 2-3 months. If the response is favorable, treatment is adjusted to the minimum effective dose.

Monitoring of clinical progress relies on asthma control scores such as the Asthma Control Test, considering both parental perception and the child’s self-assessment. Because the goal in mild asthma is indeed to achieve complete control.

Mild Asthma: Behind the Triviality, Real Risks

Mild childhood asthma is the most common form of asthma. It is by no means benign and carries a risk for exacerbations requiring systemic corticosteroids and potential long-term consequences.

Asthma is often missed — an estimated 20% of children age ≥ 6 years to 70% by age 1 year are not identified — and therefore go untreated, leading to a lower quality of life from attacks and persistent symptoms between episodes that could limit activity and disrupt sleep.

Even seemingly mild asthma is associated with a risk for severe exacerbation, including in patients with infrequent and mild symptoms.

There is also impaired lung growth, with a decrease in peak lung function and the potential for progression to fixed bronchial obstruction, which can lead to COPD. However, it has been shown that early treatment reduces chronic inflammation, limits bronchial remodeling, and prevents the decline in lung function.

In a Danish neonatal cohort 9125 infants, were followed at 1, 3, and 6 years of age and analyzed at 50 years of age via the Danish COPD patient registry, early asthma symptoms were associated with a decrease in FEV1 (-3.36%) and the FEV1/ Forced Vital Capacity ratio (-1.28), as well as an increased risk for a COPD diagnosis in adulthood (odds ratio [OR], 1.96).

Epidemiologic data confirm this: A history of asthma increases the risk of developing COPD by 10-30 times, and a reduced peak FEV1 in early adulthood is associated with an increased risk for early‑onset COPD and greater severity.

“Asthma is associated with a decline in lung function that can begin as early as infancy,” noted the pediatrician, “or even during the prenatal period, persists throughout childhood, continues into adulthood, and predisposes individuals to established bronchial obstruction.”

Early Inhaled Corticosteroids Reduced Exacerbations

In the inhaled steroid treatment as regular therapy in early asthma trial, which enrolled about 7000 adults and children and included a subgroup of 1900 children aged < 11 years with recent-onset mild asthma, inhaled budesonide was compared with placebo. Over 3 years of follow-up, the placebo group showed poorer lung function, whereas those treated with budesonide had improved FEV1 and about a 40% reduction in severe exacerbations. A partial functional “catch-up” was observed when treatment was initiated in the third year.

However, the study does not allow for conclusions regarding the very long-term prevention of functional decline, due to the lack of sufficient follow-up time.

Delayed Treatment Increases Risks

Furthermore, delayed treatment is associated with an increased use of short-acting bronchodilators and systemic corticosteroids, carrying a risk for complications. The specialist warned: “Adverse effects appear after just a few courses of oral corticosteroids, notably an increased risk of fractures (odds ratio, 2.15 for low doses of prednisolone < 70 mg; OR, 3.09 for higher doses > 70 mg). These risks are real and emerge quickly.”

Another study confirms the adverse effects of oral corticosteroid therapy: A cumulative dose of 500 mg to 1000 mg (approximately four to five courses of systemic corticosteroids over a lifetime) already increases the risk. Complications include osteoporosis, diabetes, cataracts, heart failure, and pneumonia. “Cumulative exposure, even intermittent, is associated with increased morbidity, which can be prevented through appropriate management of mild asthma,” she added. “Yet it has been clearly demonstrated that inhaled therapy reduces the need for oral corticosteroids.”

This story was translated from Medscape’s French edition.

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

Mild asthma is not benign. Underdiagnosis in children exposes them to preventable morbidity — including impaired lung growth that can lead to fixed airway obstruction and a higher lifetime risk for chronic obstructive pulmonary disease (COPD), as well as severe exacerbations and increased need for systemic corticosteroids. Experts at the 21st Francophone Allergy Congress 2026 said preserving respiratory function depends on early diagnosis and disease control.

Mild asthma is retrospectively defined as the level of treatment required to achieve and maintain disease control. It corresponds to asthma controlled with a low dose of inhaled corticosteroids or with a combination of inhaled corticosteroids and formoterol as needed (Global Initiative for Asthma(GINA)/French Society of Pediatric Pulmonology and Allergology, steps 1-2).

Mélisande Bourgoin-Heck, MD, PhD, Department of Pediatric Allergology, Armand Trousseau University Hospital, Sorbonne University, AP-HP, Paris, France, emphasized a fundamental distinction: “While control is based on symptoms, exacerbations, activity limitations, and quality of life, severity corresponds to the level of treatment required to achieve this control. The term mild therefore depends on the treatment required and not solely on the frequency or intensity of symptoms.”

How to Identify It?

Clinically, asthma most often presents with wheezing, cough, shortness of breath, and chest tightness, with symptoms that fluctuate in frequency and severity. Nighttime symptoms are common. Symptoms often start or worsen with viral infections, physical exertion (including after exercise), laughter, or exposure to allergens or cold air. “Symptoms are often dismissed as minor and intermittent,” the pediatrician said, “which leads to delayed diagnosis.”

That’s why recognizing risk factors is important because they help guide diagnosis: male sex, a first-degree family history of asthma, exposure to secondhand smoke, prematurity, maternal obesity, living in group settings or having school-aged siblings which raise the risk for early infections, a history of severe bronchiolitis, and an atopic tendency, demonstrated by atopic dermatitis, allergic rhinitis, or sensitization to food and respiratory allergens.

How Much Should We Trust Predictive Scores?

Several clinical scores for predicting asthma exist, notably the Asthma Predictive Index, the modified Asthma Predictive Index, and the Pediatric Asthma Risk Score; the latter demonstrates better overall discrimination, making it useful for children at low-to-moderate risk.

“These scores place significant emphasis on the atopic predisposition,” noted Bourgoin-Heck, “including allergic sensitivities, allergic rhinitis, and atopic dermatitis. Their performance varies by age and clinical phenotype. They are highly specific for the diagnosis of allergic asthma, with a positive score associated with a high risk of asthma. However, their sensitivity is not up to par: A negative score does not rule out the diagnosis, leading to a risk of overlooking nonallergic forms.”

A chest x-ray is used to rule out differential diagnoses. It may be normal or reveal chest distension or bronchial signs. During follow-up, it is only recommended in cases of fever or severe illness to look for complications such as bronchopulmonary superinfection, pneumothorax, pneumomediastinum, subcutaneous emphysema and ventilation disorders/atelectasis.

Normal Spirometry: Could Asthma Really be Ruled Out?

Pulmonary function tests (PFTs) may be normal and do not rule out asthma. Spirometry can be performed around age 6 years and is often normal. “The reversibility test is a diagnostic indicator but may be negative in cases of normal forced expiratory volume in 1 second (FEV₁),” warned the specialist.

Provocation tests are useful in cases of doubt.

In children unable to perform a forced exhalation, spirometry is impossible or unreliable, which justifies the use of respiratory resistance measurements (starting at age 3). Several methods are then used: flow-interruption resistance (FIR) identifies bronchial obstruction with an expiratory FIR > 2 Z scores (how many SDs a result is from the predicted value for a child’s age/height/sex). Oscillometry, suitable for young children, is considered pathologic for values exceeding 150% of the predicted value. Plethysmography indicates obstruction with a Raw value > 150% of the predicted value or an sRaw value > 180%.

Interpretation is based on standards adapted to the technique and the study population, with thresholds varying by method (threshold values for PFTs, page e4).

When in Doubt, How Useful Are Biomarkers?

As a biomarker of atopy, a blood eosinophil count of at least 150/mm³ is associated with asthma symptoms and exacerbations. Specific Immunoglobulin E (IgE) indicates allergic sensitization associated with asthma. Finally, elevated fractional concentration of exhaled nitric oxide (> 20-25 parts per billion depending on age) is associated with wheezing, corticosteroid use, and persistent asthma. The combination of atopy markers — including maternal allergy, eczema, wheezing, positive specific IgE levels, and eosinophilia — significantly increases the likelihood of asthma.

“However, when diagnostic uncertainty persists in a child younger than 5 years (absence of atopy; normal PFTs — which is common), a trial of treatment based on initial symptoms may be recommended according to GINA 2025 (Box 10-2),” explained Bourgoin-Heck.

In the presence of mild and intermittent symptoms, a short-acting bronchodilator challenge test on demand is indicated for a maximum duration of 2-3 months. This strategy applies to infrequent wheezing episodes, without the need for emergency care and therefore without any severe exacerbations, with symptoms occurring twice or less per week. Treatment consists of administering two puffs when symptoms occur (to be repeated as needed), with an assessment of improvement within 20-60 minutes. In cases of a history of a severe wheezing episode within the past year (systemic corticosteroids, emergency department visit, and hospitalization) or symptoms more than twice a week, the therapeutic trial involves long-term inhaled corticosteroids (eg, fluticasone 100 µg/d to 250 µg/d) combined with a short-acting bronchodilator as needed for 2-3 months. If the response is favorable, treatment is adjusted to the minimum effective dose.

Monitoring of clinical progress relies on asthma control scores such as the Asthma Control Test, considering both parental perception and the child’s self-assessment. Because the goal in mild asthma is indeed to achieve complete control.

Mild Asthma: Behind the Triviality, Real Risks

Mild childhood asthma is the most common form of asthma. It is by no means benign and carries a risk for exacerbations requiring systemic corticosteroids and potential long-term consequences.

Asthma is often missed — an estimated 20% of children age ≥ 6 years to 70% by age 1 year are not identified — and therefore go untreated, leading to a lower quality of life from attacks and persistent symptoms between episodes that could limit activity and disrupt sleep.

Even seemingly mild asthma is associated with a risk for severe exacerbation, including in patients with infrequent and mild symptoms.

There is also impaired lung growth, with a decrease in peak lung function and the potential for progression to fixed bronchial obstruction, which can lead to COPD. However, it has been shown that early treatment reduces chronic inflammation, limits bronchial remodeling, and prevents the decline in lung function.

In a Danish neonatal cohort 9125 infants, were followed at 1, 3, and 6 years of age and analyzed at 50 years of age via the Danish COPD patient registry, early asthma symptoms were associated with a decrease in FEV1 (-3.36%) and the FEV1/ Forced Vital Capacity ratio (-1.28), as well as an increased risk for a COPD diagnosis in adulthood (odds ratio [OR], 1.96).

Epidemiologic data confirm this: A history of asthma increases the risk of developing COPD by 10-30 times, and a reduced peak FEV1 in early adulthood is associated with an increased risk for early‑onset COPD and greater severity.

“Asthma is associated with a decline in lung function that can begin as early as infancy,” noted the pediatrician, “or even during the prenatal period, persists throughout childhood, continues into adulthood, and predisposes individuals to established bronchial obstruction.”

Early Inhaled Corticosteroids Reduced Exacerbations

In the inhaled steroid treatment as regular therapy in early asthma trial, which enrolled about 7000 adults and children and included a subgroup of 1900 children aged < 11 years with recent-onset mild asthma, inhaled budesonide was compared with placebo. Over 3 years of follow-up, the placebo group showed poorer lung function, whereas those treated with budesonide had improved FEV1 and about a 40% reduction in severe exacerbations. A partial functional “catch-up” was observed when treatment was initiated in the third year.

However, the study does not allow for conclusions regarding the very long-term prevention of functional decline, due to the lack of sufficient follow-up time.

Delayed Treatment Increases Risks

Furthermore, delayed treatment is associated with an increased use of short-acting bronchodilators and systemic corticosteroids, carrying a risk for complications. The specialist warned: “Adverse effects appear after just a few courses of oral corticosteroids, notably an increased risk of fractures (odds ratio, 2.15 for low doses of prednisolone < 70 mg; OR, 3.09 for higher doses > 70 mg). These risks are real and emerge quickly.”

Another study confirms the adverse effects of oral corticosteroid therapy: A cumulative dose of 500 mg to 1000 mg (approximately four to five courses of systemic corticosteroids over a lifetime) already increases the risk. Complications include osteoporosis, diabetes, cataracts, heart failure, and pneumonia. “Cumulative exposure, even intermittent, is associated with increased morbidity, which can be prevented through appropriate management of mild asthma,” she added. “Yet it has been clearly demonstrated that inhaled therapy reduces the need for oral corticosteroids.”

This story was translated from Medscape’s French edition.

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

Mild asthma is not benign. Underdiagnosis in children exposes them to preventable morbidity — including impaired lung growth that can lead to fixed airway obstruction and a higher lifetime risk for chronic obstructive pulmonary disease (COPD), as well as severe exacerbations and increased need for systemic corticosteroids. Experts at the 21st Francophone Allergy Congress 2026 said preserving respiratory function depends on early diagnosis and disease control.

Mild asthma is retrospectively defined as the level of treatment required to achieve and maintain disease control. It corresponds to asthma controlled with a low dose of inhaled corticosteroids or with a combination of inhaled corticosteroids and formoterol as needed (Global Initiative for Asthma(GINA)/French Society of Pediatric Pulmonology and Allergology, steps 1-2).

Mélisande Bourgoin-Heck, MD, PhD, Department of Pediatric Allergology, Armand Trousseau University Hospital, Sorbonne University, AP-HP, Paris, France, emphasized a fundamental distinction: “While control is based on symptoms, exacerbations, activity limitations, and quality of life, severity corresponds to the level of treatment required to achieve this control. The term mild therefore depends on the treatment required and not solely on the frequency or intensity of symptoms.”

How to Identify It?

Clinically, asthma most often presents with wheezing, cough, shortness of breath, and chest tightness, with symptoms that fluctuate in frequency and severity. Nighttime symptoms are common. Symptoms often start or worsen with viral infections, physical exertion (including after exercise), laughter, or exposure to allergens or cold air. “Symptoms are often dismissed as minor and intermittent,” the pediatrician said, “which leads to delayed diagnosis.”

That’s why recognizing risk factors is important because they help guide diagnosis: male sex, a first-degree family history of asthma, exposure to secondhand smoke, prematurity, maternal obesity, living in group settings or having school-aged siblings which raise the risk for early infections, a history of severe bronchiolitis, and an atopic tendency, demonstrated by atopic dermatitis, allergic rhinitis, or sensitization to food and respiratory allergens.

How Much Should We Trust Predictive Scores?

Several clinical scores for predicting asthma exist, notably the Asthma Predictive Index, the modified Asthma Predictive Index, and the Pediatric Asthma Risk Score; the latter demonstrates better overall discrimination, making it useful for children at low-to-moderate risk.

“These scores place significant emphasis on the atopic predisposition,” noted Bourgoin-Heck, “including allergic sensitivities, allergic rhinitis, and atopic dermatitis. Their performance varies by age and clinical phenotype. They are highly specific for the diagnosis of allergic asthma, with a positive score associated with a high risk of asthma. However, their sensitivity is not up to par: A negative score does not rule out the diagnosis, leading to a risk of overlooking nonallergic forms.”

A chest x-ray is used to rule out differential diagnoses. It may be normal or reveal chest distension or bronchial signs. During follow-up, it is only recommended in cases of fever or severe illness to look for complications such as bronchopulmonary superinfection, pneumothorax, pneumomediastinum, subcutaneous emphysema and ventilation disorders/atelectasis.

Normal Spirometry: Could Asthma Really be Ruled Out?

Pulmonary function tests (PFTs) may be normal and do not rule out asthma. Spirometry can be performed around age 6 years and is often normal. “The reversibility test is a diagnostic indicator but may be negative in cases of normal forced expiratory volume in 1 second (FEV₁),” warned the specialist.

Provocation tests are useful in cases of doubt.

In children unable to perform a forced exhalation, spirometry is impossible or unreliable, which justifies the use of respiratory resistance measurements (starting at age 3). Several methods are then used: flow-interruption resistance (FIR) identifies bronchial obstruction with an expiratory FIR > 2 Z scores (how many SDs a result is from the predicted value for a child’s age/height/sex). Oscillometry, suitable for young children, is considered pathologic for values exceeding 150% of the predicted value. Plethysmography indicates obstruction with a Raw value > 150% of the predicted value or an sRaw value > 180%.

Interpretation is based on standards adapted to the technique and the study population, with thresholds varying by method (threshold values for PFTs, page e4).

When in Doubt, How Useful Are Biomarkers?

As a biomarker of atopy, a blood eosinophil count of at least 150/mm³ is associated with asthma symptoms and exacerbations. Specific Immunoglobulin E (IgE) indicates allergic sensitization associated with asthma. Finally, elevated fractional concentration of exhaled nitric oxide (> 20-25 parts per billion depending on age) is associated with wheezing, corticosteroid use, and persistent asthma. The combination of atopy markers — including maternal allergy, eczema, wheezing, positive specific IgE levels, and eosinophilia — significantly increases the likelihood of asthma.

“However, when diagnostic uncertainty persists in a child younger than 5 years (absence of atopy; normal PFTs — which is common), a trial of treatment based on initial symptoms may be recommended according to GINA 2025 (Box 10-2),” explained Bourgoin-Heck.

In the presence of mild and intermittent symptoms, a short-acting bronchodilator challenge test on demand is indicated for a maximum duration of 2-3 months. This strategy applies to infrequent wheezing episodes, without the need for emergency care and therefore without any severe exacerbations, with symptoms occurring twice or less per week. Treatment consists of administering two puffs when symptoms occur (to be repeated as needed), with an assessment of improvement within 20-60 minutes. In cases of a history of a severe wheezing episode within the past year (systemic corticosteroids, emergency department visit, and hospitalization) or symptoms more than twice a week, the therapeutic trial involves long-term inhaled corticosteroids (eg, fluticasone 100 µg/d to 250 µg/d) combined with a short-acting bronchodilator as needed for 2-3 months. If the response is favorable, treatment is adjusted to the minimum effective dose.

Monitoring of clinical progress relies on asthma control scores such as the Asthma Control Test, considering both parental perception and the child’s self-assessment. Because the goal in mild asthma is indeed to achieve complete control.

Mild Asthma: Behind the Triviality, Real Risks

Mild childhood asthma is the most common form of asthma. It is by no means benign and carries a risk for exacerbations requiring systemic corticosteroids and potential long-term consequences.

Asthma is often missed — an estimated 20% of children age ≥ 6 years to 70% by age 1 year are not identified — and therefore go untreated, leading to a lower quality of life from attacks and persistent symptoms between episodes that could limit activity and disrupt sleep.

Even seemingly mild asthma is associated with a risk for severe exacerbation, including in patients with infrequent and mild symptoms.

There is also impaired lung growth, with a decrease in peak lung function and the potential for progression to fixed bronchial obstruction, which can lead to COPD. However, it has been shown that early treatment reduces chronic inflammation, limits bronchial remodeling, and prevents the decline in lung function.

In a Danish neonatal cohort 9125 infants, were followed at 1, 3, and 6 years of age and analyzed at 50 years of age via the Danish COPD patient registry, early asthma symptoms were associated with a decrease in FEV1 (-3.36%) and the FEV1/ Forced Vital Capacity ratio (-1.28), as well as an increased risk for a COPD diagnosis in adulthood (odds ratio [OR], 1.96).

Epidemiologic data confirm this: A history of asthma increases the risk of developing COPD by 10-30 times, and a reduced peak FEV1 in early adulthood is associated with an increased risk for early‑onset COPD and greater severity.

“Asthma is associated with a decline in lung function that can begin as early as infancy,” noted the pediatrician, “or even during the prenatal period, persists throughout childhood, continues into adulthood, and predisposes individuals to established bronchial obstruction.”

Early Inhaled Corticosteroids Reduced Exacerbations

In the inhaled steroid treatment as regular therapy in early asthma trial, which enrolled about 7000 adults and children and included a subgroup of 1900 children aged < 11 years with recent-onset mild asthma, inhaled budesonide was compared with placebo. Over 3 years of follow-up, the placebo group showed poorer lung function, whereas those treated with budesonide had improved FEV1 and about a 40% reduction in severe exacerbations. A partial functional “catch-up” was observed when treatment was initiated in the third year.

However, the study does not allow for conclusions regarding the very long-term prevention of functional decline, due to the lack of sufficient follow-up time.

Delayed Treatment Increases Risks

Furthermore, delayed treatment is associated with an increased use of short-acting bronchodilators and systemic corticosteroids, carrying a risk for complications. The specialist warned: “Adverse effects appear after just a few courses of oral corticosteroids, notably an increased risk of fractures (odds ratio, 2.15 for low doses of prednisolone < 70 mg; OR, 3.09 for higher doses > 70 mg). These risks are real and emerge quickly.”

Another study confirms the adverse effects of oral corticosteroid therapy: A cumulative dose of 500 mg to 1000 mg (approximately four to five courses of systemic corticosteroids over a lifetime) already increases the risk. Complications include osteoporosis, diabetes, cataracts, heart failure, and pneumonia. “Cumulative exposure, even intermittent, is associated with increased morbidity, which can be prevented through appropriate management of mild asthma,” she added. “Yet it has been clearly demonstrated that inhaled therapy reduces the need for oral corticosteroids.”

This story was translated from Medscape’s French edition.

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

TOPLINE:

Military veterans exposed to burn pits during deployment are > 4 times higher risk for persistent cough and 3 times higher risk for dyspnea and wheezing compared with unexposed veterans. Following clinical evaluation, nearly half of veterans received diagnoses of respiratory diseases, including asthma (about 30%), chronic obstructive pulmonary disease (about 13%), and bronchitis (about 12%). Diagnostic uncertainty remains common, with nearly one-third of symptomatic veterans still lacking a specific diagnosis after extensive noninvasive testing.

METHODOLOGY:

• Focused review that proposed an assessment and monitoring strategy for deployed US military veterans with unexplained dyspnea that incorporates multidisciplinary review and patient discussion.
• Analysis included data from the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures (STAMPEDE), which evaluated respiratory symptoms in military personnel within 6 months of returning from Southwest Asia.
• Registry and survey input included Airborne Hazards and Open Burn Pit Registry clinical evaluations in 24,578 veterans in addition to a survey of 479 veterans.
• Biopsy guidance emphasized case-by-case decisions after review; supporting examples include 49 symptomatic veterans undergoing high-resolution computed tomography in STAMPEDE and 38 veterans with biopsy-proven constrictive bronchiolitis, many with normal or near normal pulmonary function tests (PFTs).

TAKEAWAY: 

• Veterans with persistent unexplained cough, dyspnea, or chest tightness for > 3 months, reduced exercise tolerance, or abnormal PFTs should be referred to a pulmonary specialist for diagnostic evaluation.
• Among 380 military personnel with chronic respiratory symptoms in STAMPEDE III, 22.9% had diagnoses of asthma, 15.0% had airway hyperreactivity, 10.8% had upper and large airways disorders, and 32.0% did not meet criteria for a specific diagnosis after extensive noninvasive testing.
• Standard testing can miss disease: among 38 veterans with biopsy-proven constrictive bronchiolitis, 19 had normal or near normal PFTs compared with the general population, despite reductions vs a historical asymptomatic military cohort.
• Long-term management centers on follow-up, with proposed PFT monitoring every 6 to 12 months in symptomatic patients even when initial findings are normal.

IN PRACTICE:

“Significant gaps remain in the provision of health care and benefits,” the authors wrote. “The assessment of veterans with suspected lung disease should be comprehensive, involving a thorough medical and exposure history, as well as PFTs and imaging.

SOURCE:

The study was led by Robert M. Tighe, MD, Duke University Medical Center in Durham, North Carolina; Le Roy Torres, Burn Pits 360 in Robstown, Texas; and Robert Miller, Vanderbilt University Medical Center in Nashville, Tennessee. It was published online in Annals of the American Thoracic Society.

LIMITATIONS:

This article synthesizes existing literature and expert recommendations without presenting new primary data or statistical analyses. The review acknowledges that diagnosing deployment-related respiratory disorders can be challenging as symptoms are often nonspecific and may present months or years after deployment with variable latency. The current Post-Deployment Cardiopulmonary Evaluation Network structure does not have the capacity to evaluate the large number of veterans with respiratory disorders and is limited to those who have registered symptoms through the Airborne Hazards and Open Burn Pit Registry.

DISCLOSURES:

Writing support was provided by Julie Fleming and Wendy Morris of Fleishman-Hillard, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals. Boehringer Ingelheim was given the opportunity to review the article for medical and scientific accuracy as well as intellectual property considerations. No disclosures or conflict of interest statements for the individual authors are provided in the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Military veterans exposed to burn pits during deployment are > 4 times higher risk for persistent cough and 3 times higher risk for dyspnea and wheezing compared with unexposed veterans. Following clinical evaluation, nearly half of veterans received diagnoses of respiratory diseases, including asthma (about 30%), chronic obstructive pulmonary disease (about 13%), and bronchitis (about 12%). Diagnostic uncertainty remains common, with nearly one-third of symptomatic veterans still lacking a specific diagnosis after extensive noninvasive testing.

METHODOLOGY:

• Focused review that proposed an assessment and monitoring strategy for deployed US military veterans with unexplained dyspnea that incorporates multidisciplinary review and patient discussion.
• Analysis included data from the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures (STAMPEDE), which evaluated respiratory symptoms in military personnel within 6 months of returning from Southwest Asia.
• Registry and survey input included Airborne Hazards and Open Burn Pit Registry clinical evaluations in 24,578 veterans in addition to a survey of 479 veterans.
• Biopsy guidance emphasized case-by-case decisions after review; supporting examples include 49 symptomatic veterans undergoing high-resolution computed tomography in STAMPEDE and 38 veterans with biopsy-proven constrictive bronchiolitis, many with normal or near normal pulmonary function tests (PFTs).

TAKEAWAY: 

• Veterans with persistent unexplained cough, dyspnea, or chest tightness for > 3 months, reduced exercise tolerance, or abnormal PFTs should be referred to a pulmonary specialist for diagnostic evaluation.
• Among 380 military personnel with chronic respiratory symptoms in STAMPEDE III, 22.9% had diagnoses of asthma, 15.0% had airway hyperreactivity, 10.8% had upper and large airways disorders, and 32.0% did not meet criteria for a specific diagnosis after extensive noninvasive testing.
• Standard testing can miss disease: among 38 veterans with biopsy-proven constrictive bronchiolitis, 19 had normal or near normal PFTs compared with the general population, despite reductions vs a historical asymptomatic military cohort.
• Long-term management centers on follow-up, with proposed PFT monitoring every 6 to 12 months in symptomatic patients even when initial findings are normal.

IN PRACTICE:

“Significant gaps remain in the provision of health care and benefits,” the authors wrote. “The assessment of veterans with suspected lung disease should be comprehensive, involving a thorough medical and exposure history, as well as PFTs and imaging.

SOURCE:

The study was led by Robert M. Tighe, MD, Duke University Medical Center in Durham, North Carolina; Le Roy Torres, Burn Pits 360 in Robstown, Texas; and Robert Miller, Vanderbilt University Medical Center in Nashville, Tennessee. It was published online in Annals of the American Thoracic Society.

LIMITATIONS:

This article synthesizes existing literature and expert recommendations without presenting new primary data or statistical analyses. The review acknowledges that diagnosing deployment-related respiratory disorders can be challenging as symptoms are often nonspecific and may present months or years after deployment with variable latency. The current Post-Deployment Cardiopulmonary Evaluation Network structure does not have the capacity to evaluate the large number of veterans with respiratory disorders and is limited to those who have registered symptoms through the Airborne Hazards and Open Burn Pit Registry.

DISCLOSURES:

Writing support was provided by Julie Fleming and Wendy Morris of Fleishman-Hillard, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals. Boehringer Ingelheim was given the opportunity to review the article for medical and scientific accuracy as well as intellectual property considerations. No disclosures or conflict of interest statements for the individual authors are provided in the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Military veterans exposed to burn pits during deployment are > 4 times higher risk for persistent cough and 3 times higher risk for dyspnea and wheezing compared with unexposed veterans. Following clinical evaluation, nearly half of veterans received diagnoses of respiratory diseases, including asthma (about 30%), chronic obstructive pulmonary disease (about 13%), and bronchitis (about 12%). Diagnostic uncertainty remains common, with nearly one-third of symptomatic veterans still lacking a specific diagnosis after extensive noninvasive testing.

METHODOLOGY:

• Focused review that proposed an assessment and monitoring strategy for deployed US military veterans with unexplained dyspnea that incorporates multidisciplinary review and patient discussion.
• Analysis included data from the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures (STAMPEDE), which evaluated respiratory symptoms in military personnel within 6 months of returning from Southwest Asia.
• Registry and survey input included Airborne Hazards and Open Burn Pit Registry clinical evaluations in 24,578 veterans in addition to a survey of 479 veterans.
• Biopsy guidance emphasized case-by-case decisions after review; supporting examples include 49 symptomatic veterans undergoing high-resolution computed tomography in STAMPEDE and 38 veterans with biopsy-proven constrictive bronchiolitis, many with normal or near normal pulmonary function tests (PFTs).

TAKEAWAY: 

• Veterans with persistent unexplained cough, dyspnea, or chest tightness for > 3 months, reduced exercise tolerance, or abnormal PFTs should be referred to a pulmonary specialist for diagnostic evaluation.
• Among 380 military personnel with chronic respiratory symptoms in STAMPEDE III, 22.9% had diagnoses of asthma, 15.0% had airway hyperreactivity, 10.8% had upper and large airways disorders, and 32.0% did not meet criteria for a specific diagnosis after extensive noninvasive testing.
• Standard testing can miss disease: among 38 veterans with biopsy-proven constrictive bronchiolitis, 19 had normal or near normal PFTs compared with the general population, despite reductions vs a historical asymptomatic military cohort.
• Long-term management centers on follow-up, with proposed PFT monitoring every 6 to 12 months in symptomatic patients even when initial findings are normal.

IN PRACTICE:

“Significant gaps remain in the provision of health care and benefits,” the authors wrote. “The assessment of veterans with suspected lung disease should be comprehensive, involving a thorough medical and exposure history, as well as PFTs and imaging.

SOURCE:

The study was led by Robert M. Tighe, MD, Duke University Medical Center in Durham, North Carolina; Le Roy Torres, Burn Pits 360 in Robstown, Texas; and Robert Miller, Vanderbilt University Medical Center in Nashville, Tennessee. It was published online in Annals of the American Thoracic Society.

LIMITATIONS:

This article synthesizes existing literature and expert recommendations without presenting new primary data or statistical analyses. The review acknowledges that diagnosing deployment-related respiratory disorders can be challenging as symptoms are often nonspecific and may present months or years after deployment with variable latency. The current Post-Deployment Cardiopulmonary Evaluation Network structure does not have the capacity to evaluate the large number of veterans with respiratory disorders and is limited to those who have registered symptoms through the Airborne Hazards and Open Burn Pit Registry.

DISCLOSURES:

Writing support was provided by Julie Fleming and Wendy Morris of Fleishman-Hillard, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals. Boehringer Ingelheim was given the opportunity to review the article for medical and scientific accuracy as well as intellectual property considerations. No disclosures or conflict of interest statements for the individual authors are provided in the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.