Asthma

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PHOENIX – Before considering oral steroids or biologic therapies, many people with difficult-to-control asthma can reduce symptoms by addressing medication adherence and inhaler technique – and digital monitoring devices can play a key role.

Often physicians “will approach a patient about a biologic if they’re not responding to standard therapy. But we need to sometimes go back to those basic building blocks, like, are you taking the standard therapy?” William C. Anderson, MD, codirector of the multidisciplinary asthma clinic at Children’s Hospital Colorado, Aurora, said in an interview.

At the annual meeting of the American Academy of Allergy, Asthma, and Immunology, he and others presented data highlighting the diagnostic and therapeutic potential of digital monitoring devices for difficult-to-control asthma, the theme of the 2022s meeting.

The Global Initiative for Asthma (GINA) defines asthma as “difficult to control” if it remains uncontrolled despite medium- or high-dose inhaled corticosteroids with a second controller or with maintenance oral steroids, or if the asthma requires high-dose treatment to curb symptoms and exacerbations. About 17% of adult asthma patients have difficult-to-control asthma, according to the 2021 GINA report. 

However, correcting for inhaling technique and adherence cuts the 17% down to just 3.7%, Giselle Mosnaim, MD, an allergist at NorthShore University HealthSystem outside Chicago and AAAAI immediate past president, told attendees at a Feb. 25 session on digital technologies for asthma management.

The CRITIKAL study, which reviewed data from more than 5,000 asthma patients, “showed that, if you have critical errors in inhaler technique, this leads to worse asthma outcomes and increased asthma exacerbations,” Dr. Mosnaim said. Sadly, it also shows that, from 1975 to 2014, despite new devices and new technologies, “we still have poor inhaler technique.”

As for ways to measure adherence, physician judgments tend to be inaccurate, patient self-reporting has proved unreliable, and prescription refill data doesn’t indicate whether patients actually used the medications. “The ideal measure of adherence should be objective, accurate and unobtrusive to minimize impact on patient behavior and allow reliable data collection in real-world settings,” Dr. Mosnaim said. “So electronic medication monitors are the gold standard.” 
 

Tracking adherence

A closing afternoon session featured three presentations on research tracking adherence and outcomes in difficult-to-treat asthma patients – two pediatric cohorts and one across all ages. All studies used the Propeller Health sensor, a Food and Drug Administration–cleared device that attaches to the patient’s inhaler and automatically collects information on where, when, and how often they use their medication. The sensor then sends that information to a data cloud accessible to the patient and their health care professional.

Dr. Anderson’s team scoured a nationwide Propeller Health database for 8,000 patients using the digital monitors with controller therapies for asthma or chronic obstructive pulmonary disease (COPD). The study explored whether adherence differed for once-daily versus twice-daily medications, and if adherence differed based on patient age (4-60+ years).

For both asthma and COPD patients, those on once-daily regimens had higher medication adherence, compared with those who were prescribed twice-daily therapies. Plus, a greater proportion of once-daily patients met the prespecified 80% adherence threshold.

Looking across ages, medication use in the youngest group (aged 4-11 years) looked comparable with 30-somethings, “probably because parents are the ones giving the drug,” Dr. Anderson said. Mirroring patterns from other studies, adherence levels dipped in adolescents and young adults, relative to other age subsets.

Since this population-level analysis didn’t include individualized data on exacerbations or asthma control, “we can’t relate this to outcomes,” Dr. Anderson noted. But he said the data correlating medication use with adherence suggest that once-daily formulations may be the better option.

In one of the two pediatric studies, Matt McCulloch, MD, an allergy and immunology fellow working with Dr. Anderson, and colleagues reviewed charts of 40 children who received care at the Colorado Children’s multidisciplinary asthma clinic between 2018 and 2021. Half of these patients used Propeller Health sensors with their daily inhaled controller; the other patients were matched for age, ethnicity, sex, medication level, and disease control and severity – but had no electronic monitoring device.

On the whole, children who used digital monitoring for 12 months did not fare much better than matched controls on lung function (judged by forced expiratory volume) or asthma control (measured by Asthma Control Test scores).

However, within the digital monitoring group, patients who stayed on the Propeller system for 12 months did have better asthma control, fewer exacerbations, and improved asthma severity scores (measured by the Composite Asthma Severity Index), compared with when they first began digital monitoring. These children had all received care at the clinic for a while before their families opted for the electronic sensor, so “the effect wouldn’t have just been from starting in the clinic,” Dr. McCulloch said in an interview.

The gains came despite waning medication adherence. Similar to other digital monitoring studies, use of daily controller therapies in this retrospective analysis began at 50%-80% but dropped considerably during the first 4-5 months before settling into the 20%-30% range by 1 year.

Rachelle Ramsey, PhD, a pediatric research psychologist at Cincinnati Children’s Hospital Medical Center, presented data from 20 children with difficult-to-treat asthma who received 8 weeks of a digital adherence intervention during a 12-month treatment period. They analyzed three subsets – each with interventions based on how well the patients were managing daily controller therapy at baseline.

One patient with high (>80%) baseline adherence just received digital monitoring. The seven patients who began the study with intermediate (50%-80%) adherence received digital monitoring plus prescriptive text messaging. And the 12 children with poorest (<50%) baseline adherence received digital monitoring and a telehealth session in which a behavioral health specialist helped them set goals and create strategies to overcome barriers – for example, keeping the inhaler near their toothbrush in order to pair medication use with a daily habit.

“Overall, we found that matching Propeller with a behavioral intervention really improved adherence,” Dr. Ramsey said in an interview. While patients were receiving the intervention, adherence averaged across all groups increased from 39% to 76%. However, once the intervention period ended, the group’s adherence regressed toward baseline (36%).

Although adherence did not associate with clinical gains in this small study, the use of digital monitoring to improve medication adherence has translated to better outcomes in other recent efforts.
 

Remote monitoring

In a quality improvement project in the United Kingdom, nurses asked difficult-to-control asthma patients if they understood how to use their corticosteroid/long-acting beta₂-agonist (LABA) inhalers and if they were adhering to treatment guidelines.

Those who answered yes to these questions were invited to a 28-day study that involved swapping their steroid/LABA inhalers for a different controller/bronchodilator (fluticasone/salmeterol) with INCA (Inhaler Compliance Assessment), a device that not only tracks adherence but also uses acoustics to gauge inhaler technique.

Among the 23 patients who participated, many had better clinical outcomes after 28 days of INCA monitoring. As Dr. Mosnaim told attendees, “what was amazing is so many of the patients that had been these difficult-to-control asthmatics who would have gone on to oral steroids or perhaps a biologic – lo and behold, you put them on a digital inhaler, and what do you see?” In two-thirds of the patients, “you see FeNo [a test that measures airway inflammation by detecting nitric oxide in exhalations] goes down. You see spirometry improve. You see the asthma control questionnaire improve. You see blood eosinophils go down.”

And in a 2020 randomized trial, Dr. Mosnaim and colleagues recruited 100 adults with uncontrolled asthma who had prescriptions for a daily inhaled corticosteroid and a short-acting beta-agonist (SABA) inhaler. Participants received Propeller sensors for their steroid and SABA inhalers. After a 2-week run-in period to calculate baseline corticosteroid adherence and SABA use for all participants, half the participants were randomly assigned to the control group, which had the app and sensor in silent mode, merely to collect data on medication use – whereas the treatment group received reminders, alerts, and monthly phone calls from providers who gave feedback on adherence and technique.

After 3 months of digital monitoring, patients didn’t use their rescue medication quite as often – as judged by a rise in the percentage of SABA-free days, compared with when they began the study. But the change in SABA-free days relative to baseline was more pronounced in the treatment group (19%) than in the control group (6%).

As seen in the other digital monitoring studies, adherence to daily corticosteroids fell with time, but the drop was milder in treated participants (2%) versus the control group (17%). So in this study, digital monitoring plus mobile app reminders and clinician feedback “prevented against fall in adherence to inhaled steroids over time,” Dr. Mosnaim said.

These results are “very encouraging” and offer “proof of concept that this type of remote monitoring could work,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., said in an interview. One limitation was that the study was too short to measure exacerbation rates. A yearlong analysis would be “really fascinating because you’d catch all the seasons of the year – all the pollen seasons, all these things that could exacerbate you. Some people’s asthma can be quite seasonal.”

More important, the clinical utility of digital sensors will depend on how physicians choose to use them. If the doctor puts out a “blanket recommendation for using it but doesn’t ask you about it or doesn’t use the data to inform your care, then I think people just lose engagement and lose excitement over it,” Dr. Ramsey said. But if the health care team “asks you about the data or looks at the data with you or shows you how valuable this can be to your care, then I think that changes things.”

Building these analyses and interactions into the clinic workflow isn’t trivial. “If you have this wealth of data coming in, how are you going to look at it? Are you going to have an individual person assigned to this role? How are you going to respond to alerts?” Dr. Anderson asked.

In addition, because some digital monitors issue alerts when a patient’s asthma is not well controlled, some providers worry about liability if “something bad were to happen if you had that data but didn’t act upon it,” he said. Yet he noted that remote data monitoring is already used routinely in other areas of medicine, such as managing diabetes and heart conditions, “and it’s not like people are getting dinged for that stuff.”

Another issue is cost. Insurance only covers digital monitors in select cases, but it’s a bit of a catch-22. Insurers “don’t want to cover it until they get the data, but you can’t get the data until insurance covers it,” said Dr. Anderson, who added that “this year we finally got CPT reimbursement codes for monitoring devices.”

On the whole, studies of digital medication monitors suggest that better outcomes require “a good partnership between the health care provider and the patient,” Dr. Pongdee said. “It wasn’t like you could just put these things on and expect them to help. You still need that personal relationship to get the optimal results. We can have all this technology, but you still can’t take the people out of it.”

Dr. Mosnaim reported receiving current research grant support from GlaxoSmithKline, Novartis, Sanofi-Regeneron, and Teva; and past research grant support from AstraZeneca, Alk-Abello, and Genentech. She is immediate past president of the AAAAI, and directs the board of directors for the American Board of Allergy and Immunology. Dr. Anderson has served as a consultant for Regeneron, GlaxoSmithKline, and AstraZeneca, and has received research support from Colorado Medicaid. Dr. McCulloch and Dr. Ramsey disclosed no relevant financial relationships. Dr. Pongdee serves as an at-large director on the American Academy of Allergy, Asthma and Immunology board of directors. He receives grant funding from GlaxoSmithKline, and the Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

PHOENIX – Before considering oral steroids or biologic therapies, many people with difficult-to-control asthma can reduce symptoms by addressing medication adherence and inhaler technique – and digital monitoring devices can play a key role.

Often physicians “will approach a patient about a biologic if they’re not responding to standard therapy. But we need to sometimes go back to those basic building blocks, like, are you taking the standard therapy?” William C. Anderson, MD, codirector of the multidisciplinary asthma clinic at Children’s Hospital Colorado, Aurora, said in an interview.

At the annual meeting of the American Academy of Allergy, Asthma, and Immunology, he and others presented data highlighting the diagnostic and therapeutic potential of digital monitoring devices for difficult-to-control asthma, the theme of the 2022s meeting.

The Global Initiative for Asthma (GINA) defines asthma as “difficult to control” if it remains uncontrolled despite medium- or high-dose inhaled corticosteroids with a second controller or with maintenance oral steroids, or if the asthma requires high-dose treatment to curb symptoms and exacerbations. About 17% of adult asthma patients have difficult-to-control asthma, according to the 2021 GINA report. 

However, correcting for inhaling technique and adherence cuts the 17% down to just 3.7%, Giselle Mosnaim, MD, an allergist at NorthShore University HealthSystem outside Chicago and AAAAI immediate past president, told attendees at a Feb. 25 session on digital technologies for asthma management.

The CRITIKAL study, which reviewed data from more than 5,000 asthma patients, “showed that, if you have critical errors in inhaler technique, this leads to worse asthma outcomes and increased asthma exacerbations,” Dr. Mosnaim said. Sadly, it also shows that, from 1975 to 2014, despite new devices and new technologies, “we still have poor inhaler technique.”

As for ways to measure adherence, physician judgments tend to be inaccurate, patient self-reporting has proved unreliable, and prescription refill data doesn’t indicate whether patients actually used the medications. “The ideal measure of adherence should be objective, accurate and unobtrusive to minimize impact on patient behavior and allow reliable data collection in real-world settings,” Dr. Mosnaim said. “So electronic medication monitors are the gold standard.” 
 

Tracking adherence

A closing afternoon session featured three presentations on research tracking adherence and outcomes in difficult-to-treat asthma patients – two pediatric cohorts and one across all ages. All studies used the Propeller Health sensor, a Food and Drug Administration–cleared device that attaches to the patient’s inhaler and automatically collects information on where, when, and how often they use their medication. The sensor then sends that information to a data cloud accessible to the patient and their health care professional.

Dr. Anderson’s team scoured a nationwide Propeller Health database for 8,000 patients using the digital monitors with controller therapies for asthma or chronic obstructive pulmonary disease (COPD). The study explored whether adherence differed for once-daily versus twice-daily medications, and if adherence differed based on patient age (4-60+ years).

For both asthma and COPD patients, those on once-daily regimens had higher medication adherence, compared with those who were prescribed twice-daily therapies. Plus, a greater proportion of once-daily patients met the prespecified 80% adherence threshold.

Looking across ages, medication use in the youngest group (aged 4-11 years) looked comparable with 30-somethings, “probably because parents are the ones giving the drug,” Dr. Anderson said. Mirroring patterns from other studies, adherence levels dipped in adolescents and young adults, relative to other age subsets.

Since this population-level analysis didn’t include individualized data on exacerbations or asthma control, “we can’t relate this to outcomes,” Dr. Anderson noted. But he said the data correlating medication use with adherence suggest that once-daily formulations may be the better option.

In one of the two pediatric studies, Matt McCulloch, MD, an allergy and immunology fellow working with Dr. Anderson, and colleagues reviewed charts of 40 children who received care at the Colorado Children’s multidisciplinary asthma clinic between 2018 and 2021. Half of these patients used Propeller Health sensors with their daily inhaled controller; the other patients were matched for age, ethnicity, sex, medication level, and disease control and severity – but had no electronic monitoring device.

On the whole, children who used digital monitoring for 12 months did not fare much better than matched controls on lung function (judged by forced expiratory volume) or asthma control (measured by Asthma Control Test scores).

However, within the digital monitoring group, patients who stayed on the Propeller system for 12 months did have better asthma control, fewer exacerbations, and improved asthma severity scores (measured by the Composite Asthma Severity Index), compared with when they first began digital monitoring. These children had all received care at the clinic for a while before their families opted for the electronic sensor, so “the effect wouldn’t have just been from starting in the clinic,” Dr. McCulloch said in an interview.

The gains came despite waning medication adherence. Similar to other digital monitoring studies, use of daily controller therapies in this retrospective analysis began at 50%-80% but dropped considerably during the first 4-5 months before settling into the 20%-30% range by 1 year.

Rachelle Ramsey, PhD, a pediatric research psychologist at Cincinnati Children’s Hospital Medical Center, presented data from 20 children with difficult-to-treat asthma who received 8 weeks of a digital adherence intervention during a 12-month treatment period. They analyzed three subsets – each with interventions based on how well the patients were managing daily controller therapy at baseline.

One patient with high (>80%) baseline adherence just received digital monitoring. The seven patients who began the study with intermediate (50%-80%) adherence received digital monitoring plus prescriptive text messaging. And the 12 children with poorest (<50%) baseline adherence received digital monitoring and a telehealth session in which a behavioral health specialist helped them set goals and create strategies to overcome barriers – for example, keeping the inhaler near their toothbrush in order to pair medication use with a daily habit.

“Overall, we found that matching Propeller with a behavioral intervention really improved adherence,” Dr. Ramsey said in an interview. While patients were receiving the intervention, adherence averaged across all groups increased from 39% to 76%. However, once the intervention period ended, the group’s adherence regressed toward baseline (36%).

Although adherence did not associate with clinical gains in this small study, the use of digital monitoring to improve medication adherence has translated to better outcomes in other recent efforts.
 

Remote monitoring

In a quality improvement project in the United Kingdom, nurses asked difficult-to-control asthma patients if they understood how to use their corticosteroid/long-acting beta₂-agonist (LABA) inhalers and if they were adhering to treatment guidelines.

Those who answered yes to these questions were invited to a 28-day study that involved swapping their steroid/LABA inhalers for a different controller/bronchodilator (fluticasone/salmeterol) with INCA (Inhaler Compliance Assessment), a device that not only tracks adherence but also uses acoustics to gauge inhaler technique.

Among the 23 patients who participated, many had better clinical outcomes after 28 days of INCA monitoring. As Dr. Mosnaim told attendees, “what was amazing is so many of the patients that had been these difficult-to-control asthmatics who would have gone on to oral steroids or perhaps a biologic – lo and behold, you put them on a digital inhaler, and what do you see?” In two-thirds of the patients, “you see FeNo [a test that measures airway inflammation by detecting nitric oxide in exhalations] goes down. You see spirometry improve. You see the asthma control questionnaire improve. You see blood eosinophils go down.”

And in a 2020 randomized trial, Dr. Mosnaim and colleagues recruited 100 adults with uncontrolled asthma who had prescriptions for a daily inhaled corticosteroid and a short-acting beta-agonist (SABA) inhaler. Participants received Propeller sensors for their steroid and SABA inhalers. After a 2-week run-in period to calculate baseline corticosteroid adherence and SABA use for all participants, half the participants were randomly assigned to the control group, which had the app and sensor in silent mode, merely to collect data on medication use – whereas the treatment group received reminders, alerts, and monthly phone calls from providers who gave feedback on adherence and technique.

After 3 months of digital monitoring, patients didn’t use their rescue medication quite as often – as judged by a rise in the percentage of SABA-free days, compared with when they began the study. But the change in SABA-free days relative to baseline was more pronounced in the treatment group (19%) than in the control group (6%).

As seen in the other digital monitoring studies, adherence to daily corticosteroids fell with time, but the drop was milder in treated participants (2%) versus the control group (17%). So in this study, digital monitoring plus mobile app reminders and clinician feedback “prevented against fall in adherence to inhaled steroids over time,” Dr. Mosnaim said.

These results are “very encouraging” and offer “proof of concept that this type of remote monitoring could work,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., said in an interview. One limitation was that the study was too short to measure exacerbation rates. A yearlong analysis would be “really fascinating because you’d catch all the seasons of the year – all the pollen seasons, all these things that could exacerbate you. Some people’s asthma can be quite seasonal.”

More important, the clinical utility of digital sensors will depend on how physicians choose to use them. If the doctor puts out a “blanket recommendation for using it but doesn’t ask you about it or doesn’t use the data to inform your care, then I think people just lose engagement and lose excitement over it,” Dr. Ramsey said. But if the health care team “asks you about the data or looks at the data with you or shows you how valuable this can be to your care, then I think that changes things.”

Building these analyses and interactions into the clinic workflow isn’t trivial. “If you have this wealth of data coming in, how are you going to look at it? Are you going to have an individual person assigned to this role? How are you going to respond to alerts?” Dr. Anderson asked.

In addition, because some digital monitors issue alerts when a patient’s asthma is not well controlled, some providers worry about liability if “something bad were to happen if you had that data but didn’t act upon it,” he said. Yet he noted that remote data monitoring is already used routinely in other areas of medicine, such as managing diabetes and heart conditions, “and it’s not like people are getting dinged for that stuff.”

Another issue is cost. Insurance only covers digital monitors in select cases, but it’s a bit of a catch-22. Insurers “don’t want to cover it until they get the data, but you can’t get the data until insurance covers it,” said Dr. Anderson, who added that “this year we finally got CPT reimbursement codes for monitoring devices.”

On the whole, studies of digital medication monitors suggest that better outcomes require “a good partnership between the health care provider and the patient,” Dr. Pongdee said. “It wasn’t like you could just put these things on and expect them to help. You still need that personal relationship to get the optimal results. We can have all this technology, but you still can’t take the people out of it.”

Dr. Mosnaim reported receiving current research grant support from GlaxoSmithKline, Novartis, Sanofi-Regeneron, and Teva; and past research grant support from AstraZeneca, Alk-Abello, and Genentech. She is immediate past president of the AAAAI, and directs the board of directors for the American Board of Allergy and Immunology. Dr. Anderson has served as a consultant for Regeneron, GlaxoSmithKline, and AstraZeneca, and has received research support from Colorado Medicaid. Dr. McCulloch and Dr. Ramsey disclosed no relevant financial relationships. Dr. Pongdee serves as an at-large director on the American Academy of Allergy, Asthma and Immunology board of directors. He receives grant funding from GlaxoSmithKline, and the Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

PHOENIX – Before considering oral steroids or biologic therapies, many people with difficult-to-control asthma can reduce symptoms by addressing medication adherence and inhaler technique – and digital monitoring devices can play a key role.

Often physicians “will approach a patient about a biologic if they’re not responding to standard therapy. But we need to sometimes go back to those basic building blocks, like, are you taking the standard therapy?” William C. Anderson, MD, codirector of the multidisciplinary asthma clinic at Children’s Hospital Colorado, Aurora, said in an interview.

At the annual meeting of the American Academy of Allergy, Asthma, and Immunology, he and others presented data highlighting the diagnostic and therapeutic potential of digital monitoring devices for difficult-to-control asthma, the theme of the 2022s meeting.

The Global Initiative for Asthma (GINA) defines asthma as “difficult to control” if it remains uncontrolled despite medium- or high-dose inhaled corticosteroids with a second controller or with maintenance oral steroids, or if the asthma requires high-dose treatment to curb symptoms and exacerbations. About 17% of adult asthma patients have difficult-to-control asthma, according to the 2021 GINA report. 

However, correcting for inhaling technique and adherence cuts the 17% down to just 3.7%, Giselle Mosnaim, MD, an allergist at NorthShore University HealthSystem outside Chicago and AAAAI immediate past president, told attendees at a Feb. 25 session on digital technologies for asthma management.

The CRITIKAL study, which reviewed data from more than 5,000 asthma patients, “showed that, if you have critical errors in inhaler technique, this leads to worse asthma outcomes and increased asthma exacerbations,” Dr. Mosnaim said. Sadly, it also shows that, from 1975 to 2014, despite new devices and new technologies, “we still have poor inhaler technique.”

As for ways to measure adherence, physician judgments tend to be inaccurate, patient self-reporting has proved unreliable, and prescription refill data doesn’t indicate whether patients actually used the medications. “The ideal measure of adherence should be objective, accurate and unobtrusive to minimize impact on patient behavior and allow reliable data collection in real-world settings,” Dr. Mosnaim said. “So electronic medication monitors are the gold standard.” 
 

Tracking adherence

A closing afternoon session featured three presentations on research tracking adherence and outcomes in difficult-to-treat asthma patients – two pediatric cohorts and one across all ages. All studies used the Propeller Health sensor, a Food and Drug Administration–cleared device that attaches to the patient’s inhaler and automatically collects information on where, when, and how often they use their medication. The sensor then sends that information to a data cloud accessible to the patient and their health care professional.

Dr. Anderson’s team scoured a nationwide Propeller Health database for 8,000 patients using the digital monitors with controller therapies for asthma or chronic obstructive pulmonary disease (COPD). The study explored whether adherence differed for once-daily versus twice-daily medications, and if adherence differed based on patient age (4-60+ years).

For both asthma and COPD patients, those on once-daily regimens had higher medication adherence, compared with those who were prescribed twice-daily therapies. Plus, a greater proportion of once-daily patients met the prespecified 80% adherence threshold.

Looking across ages, medication use in the youngest group (aged 4-11 years) looked comparable with 30-somethings, “probably because parents are the ones giving the drug,” Dr. Anderson said. Mirroring patterns from other studies, adherence levels dipped in adolescents and young adults, relative to other age subsets.

Since this population-level analysis didn’t include individualized data on exacerbations or asthma control, “we can’t relate this to outcomes,” Dr. Anderson noted. But he said the data correlating medication use with adherence suggest that once-daily formulations may be the better option.

In one of the two pediatric studies, Matt McCulloch, MD, an allergy and immunology fellow working with Dr. Anderson, and colleagues reviewed charts of 40 children who received care at the Colorado Children’s multidisciplinary asthma clinic between 2018 and 2021. Half of these patients used Propeller Health sensors with their daily inhaled controller; the other patients were matched for age, ethnicity, sex, medication level, and disease control and severity – but had no electronic monitoring device.

On the whole, children who used digital monitoring for 12 months did not fare much better than matched controls on lung function (judged by forced expiratory volume) or asthma control (measured by Asthma Control Test scores).

However, within the digital monitoring group, patients who stayed on the Propeller system for 12 months did have better asthma control, fewer exacerbations, and improved asthma severity scores (measured by the Composite Asthma Severity Index), compared with when they first began digital monitoring. These children had all received care at the clinic for a while before their families opted for the electronic sensor, so “the effect wouldn’t have just been from starting in the clinic,” Dr. McCulloch said in an interview.

The gains came despite waning medication adherence. Similar to other digital monitoring studies, use of daily controller therapies in this retrospective analysis began at 50%-80% but dropped considerably during the first 4-5 months before settling into the 20%-30% range by 1 year.

Rachelle Ramsey, PhD, a pediatric research psychologist at Cincinnati Children’s Hospital Medical Center, presented data from 20 children with difficult-to-treat asthma who received 8 weeks of a digital adherence intervention during a 12-month treatment period. They analyzed three subsets – each with interventions based on how well the patients were managing daily controller therapy at baseline.

One patient with high (>80%) baseline adherence just received digital monitoring. The seven patients who began the study with intermediate (50%-80%) adherence received digital monitoring plus prescriptive text messaging. And the 12 children with poorest (<50%) baseline adherence received digital monitoring and a telehealth session in which a behavioral health specialist helped them set goals and create strategies to overcome barriers – for example, keeping the inhaler near their toothbrush in order to pair medication use with a daily habit.

“Overall, we found that matching Propeller with a behavioral intervention really improved adherence,” Dr. Ramsey said in an interview. While patients were receiving the intervention, adherence averaged across all groups increased from 39% to 76%. However, once the intervention period ended, the group’s adherence regressed toward baseline (36%).

Although adherence did not associate with clinical gains in this small study, the use of digital monitoring to improve medication adherence has translated to better outcomes in other recent efforts.
 

Remote monitoring

In a quality improvement project in the United Kingdom, nurses asked difficult-to-control asthma patients if they understood how to use their corticosteroid/long-acting beta₂-agonist (LABA) inhalers and if they were adhering to treatment guidelines.

Those who answered yes to these questions were invited to a 28-day study that involved swapping their steroid/LABA inhalers for a different controller/bronchodilator (fluticasone/salmeterol) with INCA (Inhaler Compliance Assessment), a device that not only tracks adherence but also uses acoustics to gauge inhaler technique.

Among the 23 patients who participated, many had better clinical outcomes after 28 days of INCA monitoring. As Dr. Mosnaim told attendees, “what was amazing is so many of the patients that had been these difficult-to-control asthmatics who would have gone on to oral steroids or perhaps a biologic – lo and behold, you put them on a digital inhaler, and what do you see?” In two-thirds of the patients, “you see FeNo [a test that measures airway inflammation by detecting nitric oxide in exhalations] goes down. You see spirometry improve. You see the asthma control questionnaire improve. You see blood eosinophils go down.”

And in a 2020 randomized trial, Dr. Mosnaim and colleagues recruited 100 adults with uncontrolled asthma who had prescriptions for a daily inhaled corticosteroid and a short-acting beta-agonist (SABA) inhaler. Participants received Propeller sensors for their steroid and SABA inhalers. After a 2-week run-in period to calculate baseline corticosteroid adherence and SABA use for all participants, half the participants were randomly assigned to the control group, which had the app and sensor in silent mode, merely to collect data on medication use – whereas the treatment group received reminders, alerts, and monthly phone calls from providers who gave feedback on adherence and technique.

After 3 months of digital monitoring, patients didn’t use their rescue medication quite as often – as judged by a rise in the percentage of SABA-free days, compared with when they began the study. But the change in SABA-free days relative to baseline was more pronounced in the treatment group (19%) than in the control group (6%).

As seen in the other digital monitoring studies, adherence to daily corticosteroids fell with time, but the drop was milder in treated participants (2%) versus the control group (17%). So in this study, digital monitoring plus mobile app reminders and clinician feedback “prevented against fall in adherence to inhaled steroids over time,” Dr. Mosnaim said.

These results are “very encouraging” and offer “proof of concept that this type of remote monitoring could work,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., said in an interview. One limitation was that the study was too short to measure exacerbation rates. A yearlong analysis would be “really fascinating because you’d catch all the seasons of the year – all the pollen seasons, all these things that could exacerbate you. Some people’s asthma can be quite seasonal.”

More important, the clinical utility of digital sensors will depend on how physicians choose to use them. If the doctor puts out a “blanket recommendation for using it but doesn’t ask you about it or doesn’t use the data to inform your care, then I think people just lose engagement and lose excitement over it,” Dr. Ramsey said. But if the health care team “asks you about the data or looks at the data with you or shows you how valuable this can be to your care, then I think that changes things.”

Building these analyses and interactions into the clinic workflow isn’t trivial. “If you have this wealth of data coming in, how are you going to look at it? Are you going to have an individual person assigned to this role? How are you going to respond to alerts?” Dr. Anderson asked.

In addition, because some digital monitors issue alerts when a patient’s asthma is not well controlled, some providers worry about liability if “something bad were to happen if you had that data but didn’t act upon it,” he said. Yet he noted that remote data monitoring is already used routinely in other areas of medicine, such as managing diabetes and heart conditions, “and it’s not like people are getting dinged for that stuff.”

Another issue is cost. Insurance only covers digital monitors in select cases, but it’s a bit of a catch-22. Insurers “don’t want to cover it until they get the data, but you can’t get the data until insurance covers it,” said Dr. Anderson, who added that “this year we finally got CPT reimbursement codes for monitoring devices.”

On the whole, studies of digital medication monitors suggest that better outcomes require “a good partnership between the health care provider and the patient,” Dr. Pongdee said. “It wasn’t like you could just put these things on and expect them to help. You still need that personal relationship to get the optimal results. We can have all this technology, but you still can’t take the people out of it.”

Dr. Mosnaim reported receiving current research grant support from GlaxoSmithKline, Novartis, Sanofi-Regeneron, and Teva; and past research grant support from AstraZeneca, Alk-Abello, and Genentech. She is immediate past president of the AAAAI, and directs the board of directors for the American Board of Allergy and Immunology. Dr. Anderson has served as a consultant for Regeneron, GlaxoSmithKline, and AstraZeneca, and has received research support from Colorado Medicaid. Dr. McCulloch and Dr. Ramsey disclosed no relevant financial relationships. Dr. Pongdee serves as an at-large director on the American Academy of Allergy, Asthma and Immunology board of directors. He receives grant funding from GlaxoSmithKline, and the Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

A large-scale analysis of the genetic underpinnings of the overlap between asthma and chronic obstructive pulmonary disease (COPD) has identified eight novel signals that may be linked to inflammation and worse asthma outcomes, according to an international team of investigators.

They conducted a genome-wide association study (GWAS) of 8,068 individuals with asthma-COPD overlap (ACO) and 40,360 controls with either asthma or COPD alone and identified genetic variants that could predispose patients to ACO.

The findings by Catherine John, MBBChir, from the University of Leicester, England, and colleagues from Europe, the United States, and Canada were published online in Chest.

“Our study contributes to understanding the genetic landscape of asthma and COPD at the population level,” explained coauthor Lystra P. Hayden, MD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, in an email.

“It provides evidence for shared genetic influence ranging from variants implicated in asthma to those implicated in fixed airflow obstruction and specifically those which influence an intermediate phenotype with features of both, which was the focus of this investigation,” she wrote.

Although the study does not provide sufficient evidence to support patient-level genetic testing for these variants, “it does suggest potential common biological mechanisms underpinning both asthma and COPD, which in the future could inform treatments of people displaying features of both conditions,” Dr. Hayden said.

Asthma and COPD are distinct conditions but share certain features, such as airflow obstruction, inflammation, and cytokine profiles. Recent studies have suggested that patients with features of both conditions – ACO – have worse outcomes than those with either condition alone.

The authors note that recent guidelines from the Global Initiative for Chronic Obstructive Lung Disease “emphasize that asthma and COPD are different conditions but may coexist in the same patient.”

“One of the things that genetics can do is to see if there is a genetic basis to the etiology of both of these conditions,” said coauthor Sina A. Gharib, MD, professor of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle.

“Are these both just the same disease manifesting differently, or are they two really different diseases? That’s an ongoing controversy, and I don’t think this paper or any other paper that I’ve seen really settles this,” he said in an interview.

He noted that most genetic studies of asthma tend to exclude patients with COPD, and vice versa, because the complexity of the respective phenotypes can make it difficult to draw strong conclusions about genetic contributions to disease etiology.

Dr. Gharib’s group contributed data for the validation portion of the study.
 

Genetic study

The authors first drew data on the patients with ACO and controls from the UK Biobank and conducted a GWAS using a cutoff P value of less than 5x10-6 to identify “promising” signals that remained significant in analyses comparing patients with ACO with those with asthma alone and with COPD alone.

They then analyzed the variants in 12 independent cohorts and identified 31 variants they deemed to be worth a closer look.

“These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD or lung function,” they write.

The investigators also performed subgroup analyses stratified by age of asthma onset and by smoking status.

“We found that for the 31 ACO signals of interest examined, the effect sizes amongst cases with childhood-onset asthma were highly correlated to those with adult onset. Effect sizes in ever- and never-smokers were also closely correlated. Our study suggests that ACO is not due solely to smoking in people with asthma,” Dr. Hayden said.

In addition, they tested variants across a wide range of phenotypes and found that traits of eosinophil counts, atopy, and asthma were prominent.

“Our findings suggest a spectrum of shared genetic influences, from variants predominantly influencing asthma to those predominantly influencing fixed airflow obstruction. We focus on variants that tend towards an intermediate phenotype with features of both asthma and fixed airflow obstruction with pathways implicating innate and adaptive immunity and potentially bone development and signals for which the biology remains unclear,” they write.

While it’s still unclear whether ACO is a distinct entity unto itself, “we do seem to find some signals that seem to be uniquely displayed in this population that has diagnosis of asthma but also has a reduction in lung function that’s not reversible, which is what we see in COPD,” Dr. Gharib said.

Further exploration of the biology of ACO could lead to development of methods to prevent fixed airflow obstruction in patients with asthma, the authors conclude.

The study was supported by BREATHE, the Health Data Research Hub for Respiratory Health in partnership with SAIL Databank. Dr. Hayden and Dr. Gharib reported no relevant financial relationships.

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

A large-scale analysis of the genetic underpinnings of the overlap between asthma and chronic obstructive pulmonary disease (COPD) has identified eight novel signals that may be linked to inflammation and worse asthma outcomes, according to an international team of investigators.

They conducted a genome-wide association study (GWAS) of 8,068 individuals with asthma-COPD overlap (ACO) and 40,360 controls with either asthma or COPD alone and identified genetic variants that could predispose patients to ACO.

The findings by Catherine John, MBBChir, from the University of Leicester, England, and colleagues from Europe, the United States, and Canada were published online in Chest.

“Our study contributes to understanding the genetic landscape of asthma and COPD at the population level,” explained coauthor Lystra P. Hayden, MD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, in an email.

“It provides evidence for shared genetic influence ranging from variants implicated in asthma to those implicated in fixed airflow obstruction and specifically those which influence an intermediate phenotype with features of both, which was the focus of this investigation,” she wrote.

Although the study does not provide sufficient evidence to support patient-level genetic testing for these variants, “it does suggest potential common biological mechanisms underpinning both asthma and COPD, which in the future could inform treatments of people displaying features of both conditions,” Dr. Hayden said.

Asthma and COPD are distinct conditions but share certain features, such as airflow obstruction, inflammation, and cytokine profiles. Recent studies have suggested that patients with features of both conditions – ACO – have worse outcomes than those with either condition alone.

The authors note that recent guidelines from the Global Initiative for Chronic Obstructive Lung Disease “emphasize that asthma and COPD are different conditions but may coexist in the same patient.”

“One of the things that genetics can do is to see if there is a genetic basis to the etiology of both of these conditions,” said coauthor Sina A. Gharib, MD, professor of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle.

“Are these both just the same disease manifesting differently, or are they two really different diseases? That’s an ongoing controversy, and I don’t think this paper or any other paper that I’ve seen really settles this,” he said in an interview.

He noted that most genetic studies of asthma tend to exclude patients with COPD, and vice versa, because the complexity of the respective phenotypes can make it difficult to draw strong conclusions about genetic contributions to disease etiology.

Dr. Gharib’s group contributed data for the validation portion of the study.
 

Genetic study

The authors first drew data on the patients with ACO and controls from the UK Biobank and conducted a GWAS using a cutoff P value of less than 5x10-6 to identify “promising” signals that remained significant in analyses comparing patients with ACO with those with asthma alone and with COPD alone.

They then analyzed the variants in 12 independent cohorts and identified 31 variants they deemed to be worth a closer look.

“These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD or lung function,” they write.

The investigators also performed subgroup analyses stratified by age of asthma onset and by smoking status.

“We found that for the 31 ACO signals of interest examined, the effect sizes amongst cases with childhood-onset asthma were highly correlated to those with adult onset. Effect sizes in ever- and never-smokers were also closely correlated. Our study suggests that ACO is not due solely to smoking in people with asthma,” Dr. Hayden said.

In addition, they tested variants across a wide range of phenotypes and found that traits of eosinophil counts, atopy, and asthma were prominent.

“Our findings suggest a spectrum of shared genetic influences, from variants predominantly influencing asthma to those predominantly influencing fixed airflow obstruction. We focus on variants that tend towards an intermediate phenotype with features of both asthma and fixed airflow obstruction with pathways implicating innate and adaptive immunity and potentially bone development and signals for which the biology remains unclear,” they write.

While it’s still unclear whether ACO is a distinct entity unto itself, “we do seem to find some signals that seem to be uniquely displayed in this population that has diagnosis of asthma but also has a reduction in lung function that’s not reversible, which is what we see in COPD,” Dr. Gharib said.

Further exploration of the biology of ACO could lead to development of methods to prevent fixed airflow obstruction in patients with asthma, the authors conclude.

The study was supported by BREATHE, the Health Data Research Hub for Respiratory Health in partnership with SAIL Databank. Dr. Hayden and Dr. Gharib reported no relevant financial relationships.

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

A large-scale analysis of the genetic underpinnings of the overlap between asthma and chronic obstructive pulmonary disease (COPD) has identified eight novel signals that may be linked to inflammation and worse asthma outcomes, according to an international team of investigators.

They conducted a genome-wide association study (GWAS) of 8,068 individuals with asthma-COPD overlap (ACO) and 40,360 controls with either asthma or COPD alone and identified genetic variants that could predispose patients to ACO.

The findings by Catherine John, MBBChir, from the University of Leicester, England, and colleagues from Europe, the United States, and Canada were published online in Chest.

“Our study contributes to understanding the genetic landscape of asthma and COPD at the population level,” explained coauthor Lystra P. Hayden, MD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, in an email.

“It provides evidence for shared genetic influence ranging from variants implicated in asthma to those implicated in fixed airflow obstruction and specifically those which influence an intermediate phenotype with features of both, which was the focus of this investigation,” she wrote.

Although the study does not provide sufficient evidence to support patient-level genetic testing for these variants, “it does suggest potential common biological mechanisms underpinning both asthma and COPD, which in the future could inform treatments of people displaying features of both conditions,” Dr. Hayden said.

Asthma and COPD are distinct conditions but share certain features, such as airflow obstruction, inflammation, and cytokine profiles. Recent studies have suggested that patients with features of both conditions – ACO – have worse outcomes than those with either condition alone.

The authors note that recent guidelines from the Global Initiative for Chronic Obstructive Lung Disease “emphasize that asthma and COPD are different conditions but may coexist in the same patient.”

“One of the things that genetics can do is to see if there is a genetic basis to the etiology of both of these conditions,” said coauthor Sina A. Gharib, MD, professor of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle.

“Are these both just the same disease manifesting differently, or are they two really different diseases? That’s an ongoing controversy, and I don’t think this paper or any other paper that I’ve seen really settles this,” he said in an interview.

He noted that most genetic studies of asthma tend to exclude patients with COPD, and vice versa, because the complexity of the respective phenotypes can make it difficult to draw strong conclusions about genetic contributions to disease etiology.

Dr. Gharib’s group contributed data for the validation portion of the study.
 

Genetic study

The authors first drew data on the patients with ACO and controls from the UK Biobank and conducted a GWAS using a cutoff P value of less than 5x10-6 to identify “promising” signals that remained significant in analyses comparing patients with ACO with those with asthma alone and with COPD alone.

They then analyzed the variants in 12 independent cohorts and identified 31 variants they deemed to be worth a closer look.

“These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD or lung function,” they write.

The investigators also performed subgroup analyses stratified by age of asthma onset and by smoking status.

“We found that for the 31 ACO signals of interest examined, the effect sizes amongst cases with childhood-onset asthma were highly correlated to those with adult onset. Effect sizes in ever- and never-smokers were also closely correlated. Our study suggests that ACO is not due solely to smoking in people with asthma,” Dr. Hayden said.

In addition, they tested variants across a wide range of phenotypes and found that traits of eosinophil counts, atopy, and asthma were prominent.

“Our findings suggest a spectrum of shared genetic influences, from variants predominantly influencing asthma to those predominantly influencing fixed airflow obstruction. We focus on variants that tend towards an intermediate phenotype with features of both asthma and fixed airflow obstruction with pathways implicating innate and adaptive immunity and potentially bone development and signals for which the biology remains unclear,” they write.

While it’s still unclear whether ACO is a distinct entity unto itself, “we do seem to find some signals that seem to be uniquely displayed in this population that has diagnosis of asthma but also has a reduction in lung function that’s not reversible, which is what we see in COPD,” Dr. Gharib said.

Further exploration of the biology of ACO could lead to development of methods to prevent fixed airflow obstruction in patients with asthma, the authors conclude.

The study was supported by BREATHE, the Health Data Research Hub for Respiratory Health in partnership with SAIL Databank. Dr. Hayden and Dr. Gharib reported no relevant financial relationships.

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

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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