Pulmonology

Reducing exposure to tobacco smoke may reduce the burden of chronic obstructive pulmonary disease, and public health measures are needed, according to a new Tobacco Knowledge Summary from the World Health Organization.

“Smoking is a major risk factor for COPD and leads to airway inflammation and remodeling associated with lung destruction,” and contributes to approximately 70% of COPD cases worldwide, according to the statement.

Types of tobacco exposure include not only traditional smoked tobacco products (cigarettes, cigars, pipes, water pipes, kreteks, and bidis), but also smokeless tobacco, heated tobacco products, and electronic nicotine delivery systems; the addition of chemicals and flavors can increase the appeal of tobacco products and promote addiction, the authors wrote. Hookahs and water pipes “are at least as detrimental to lung health as smoking cigarettes and should not be considered as a safe alternative,” they added.

The risk of COPD extends to new e-cigarette products, the authors noted. A study in the American Journal of Preventive Medicine showed that current users of e-cigarettes had a 75% increased risk of developing COPD compared with individuals who have never used e-cigarettes.

Individuals with COPD also face an increased risk of cardiovascular disease and type 2 diabetes, and smokers with COPD who quit not only improve their COPD but also reduce their risk of developing these conditions, the authors said.
 

Mechanism of action explored

The authors noted how tobacco smoking may cause COPD when inhaled particles are deposited through the airway.

Growing evidence suggests that extracellular vesicles may play a role in the development of lung disorders such as COPD, and cigarette smoke can have an impact through this channel. A study published in the American Journal of Respiratory and Critical Care Medicine offered evidence of a potential link between exposure to cigarette smoke and the generation of a unique extracellular vesicle population that could promote the development of lung damage. In the study, Matthew C. Madison, MD, of the University of Alabama, Birmingham, and colleagues examined activity in extracellular vesicles from the bronchoalveolar lavage (BAL) fluid of smoke-exposed mice and human smokers who were otherwise healthy.

The researchers found that airway extracellular vesicles in mice or humans exposed to cigarette smoke had the ability to cause rapid lung damage when transferred into naive recipient mice. The results provide a new model that can inform preclinical COPD research, they wrote.
 

Public health action needed

“In recognition of COPD and Lung Cancer Awareness Month, the World Health Organization (WHO) emphasizes the impact of various forms of tobacco use on COPD,” Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

“This article focuses on the different types of tobacco exposure, the health care burden associated with COPD, and the risk of developing lung cancer. It also addresses the high-risk groups, especially youth, underscoring the importance of public education and the implementation of restrictions on tobacco use to combat these growing concerns,” she said.

“Education, awareness, and targeted interventions are essential for smoking cessation and COPD management,” said Dr. Narendra. “These elements are key to informing the public about smoking risks, encouraging behavioral change, and ultimately reducing the incidence of smoking-related diseases,” she emphasized.

The WHO statement called for population-level interventions including brief advice to tobacco users, toll-free quit lines, pharmacological interventions, use of messaging and chatbots to provide quit support, and the WHO quit tobacco mobile app.

“It is imperative that all tobacco users, particularly those living in low- to middle-income countries, have access to comprehensive cessation support aligned with WHO recommendations,” the authors wrote.

Finally, the authors emphasized the need to protect children and teens from the dangers of tobacco use through product regulation and to expose the tobacco industry’s marketing tactics.

“The article offers a comprehensive look at different types of tobacco exposure and their contribution to the development of COPD,” Dr. Narendra told this news organization. “Notably, it presents groundbreaking evidence of a strong association between the use of electronic nicotine delivery systems (ENDS) and heated tobacco products to development of COPD; additionally, it provides valuable guidance on smoking cessation resources for physicians to help patients quit smoking,” she said.

Looking ahead, more research is needed on “developing and sustaining state-specific or population-specific interventions for effective smoking cessation programs, and reducing the burden of COPD,” Dr. Narendra said.

The study by Madison and colleagues was supported by the National Heart, Lung, and Blood Institute, the National Institute of General Medical Science, the U.S. Veterans Affairs Administration, the Cystic Fibrosis Foundation Research Development Program, and the Veterans Affairs Merit grant.

Additional financial support came from Imperial College London, a Wellcome Trust Senior Research Fellowship, and Rosetrees Trust/The Stoneygate Trust.

Dr. Narendra had no financial conflicts to disclose but serves as a member of the editorial board of CHEST Physician.

Reducing exposure to tobacco smoke may reduce the burden of chronic obstructive pulmonary disease, and public health measures are needed, according to a new Tobacco Knowledge Summary from the World Health Organization.

“Smoking is a major risk factor for COPD and leads to airway inflammation and remodeling associated with lung destruction,” and contributes to approximately 70% of COPD cases worldwide, according to the statement.

Types of tobacco exposure include not only traditional smoked tobacco products (cigarettes, cigars, pipes, water pipes, kreteks, and bidis), but also smokeless tobacco, heated tobacco products, and electronic nicotine delivery systems; the addition of chemicals and flavors can increase the appeal of tobacco products and promote addiction, the authors wrote. Hookahs and water pipes “are at least as detrimental to lung health as smoking cigarettes and should not be considered as a safe alternative,” they added.

The risk of COPD extends to new e-cigarette products, the authors noted. A study in the American Journal of Preventive Medicine showed that current users of e-cigarettes had a 75% increased risk of developing COPD compared with individuals who have never used e-cigarettes.

Individuals with COPD also face an increased risk of cardiovascular disease and type 2 diabetes, and smokers with COPD who quit not only improve their COPD but also reduce their risk of developing these conditions, the authors said.
 

Mechanism of action explored

The authors noted how tobacco smoking may cause COPD when inhaled particles are deposited through the airway.

Growing evidence suggests that extracellular vesicles may play a role in the development of lung disorders such as COPD, and cigarette smoke can have an impact through this channel. A study published in the American Journal of Respiratory and Critical Care Medicine offered evidence of a potential link between exposure to cigarette smoke and the generation of a unique extracellular vesicle population that could promote the development of lung damage. In the study, Matthew C. Madison, MD, of the University of Alabama, Birmingham, and colleagues examined activity in extracellular vesicles from the bronchoalveolar lavage (BAL) fluid of smoke-exposed mice and human smokers who were otherwise healthy.

The researchers found that airway extracellular vesicles in mice or humans exposed to cigarette smoke had the ability to cause rapid lung damage when transferred into naive recipient mice. The results provide a new model that can inform preclinical COPD research, they wrote.
 

Public health action needed

“In recognition of COPD and Lung Cancer Awareness Month, the World Health Organization (WHO) emphasizes the impact of various forms of tobacco use on COPD,” Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

“This article focuses on the different types of tobacco exposure, the health care burden associated with COPD, and the risk of developing lung cancer. It also addresses the high-risk groups, especially youth, underscoring the importance of public education and the implementation of restrictions on tobacco use to combat these growing concerns,” she said.

“Education, awareness, and targeted interventions are essential for smoking cessation and COPD management,” said Dr. Narendra. “These elements are key to informing the public about smoking risks, encouraging behavioral change, and ultimately reducing the incidence of smoking-related diseases,” she emphasized.

The WHO statement called for population-level interventions including brief advice to tobacco users, toll-free quit lines, pharmacological interventions, use of messaging and chatbots to provide quit support, and the WHO quit tobacco mobile app.

“It is imperative that all tobacco users, particularly those living in low- to middle-income countries, have access to comprehensive cessation support aligned with WHO recommendations,” the authors wrote.

Finally, the authors emphasized the need to protect children and teens from the dangers of tobacco use through product regulation and to expose the tobacco industry’s marketing tactics.

“The article offers a comprehensive look at different types of tobacco exposure and their contribution to the development of COPD,” Dr. Narendra told this news organization. “Notably, it presents groundbreaking evidence of a strong association between the use of electronic nicotine delivery systems (ENDS) and heated tobacco products to development of COPD; additionally, it provides valuable guidance on smoking cessation resources for physicians to help patients quit smoking,” she said.

Looking ahead, more research is needed on “developing and sustaining state-specific or population-specific interventions for effective smoking cessation programs, and reducing the burden of COPD,” Dr. Narendra said.

The study by Madison and colleagues was supported by the National Heart, Lung, and Blood Institute, the National Institute of General Medical Science, the U.S. Veterans Affairs Administration, the Cystic Fibrosis Foundation Research Development Program, and the Veterans Affairs Merit grant.

Additional financial support came from Imperial College London, a Wellcome Trust Senior Research Fellowship, and Rosetrees Trust/The Stoneygate Trust.

Dr. Narendra had no financial conflicts to disclose but serves as a member of the editorial board of CHEST Physician.

Reducing exposure to tobacco smoke may reduce the burden of chronic obstructive pulmonary disease, and public health measures are needed, according to a new Tobacco Knowledge Summary from the World Health Organization.

“Smoking is a major risk factor for COPD and leads to airway inflammation and remodeling associated with lung destruction,” and contributes to approximately 70% of COPD cases worldwide, according to the statement.

Types of tobacco exposure include not only traditional smoked tobacco products (cigarettes, cigars, pipes, water pipes, kreteks, and bidis), but also smokeless tobacco, heated tobacco products, and electronic nicotine delivery systems; the addition of chemicals and flavors can increase the appeal of tobacco products and promote addiction, the authors wrote. Hookahs and water pipes “are at least as detrimental to lung health as smoking cigarettes and should not be considered as a safe alternative,” they added.

The risk of COPD extends to new e-cigarette products, the authors noted. A study in the American Journal of Preventive Medicine showed that current users of e-cigarettes had a 75% increased risk of developing COPD compared with individuals who have never used e-cigarettes.

Individuals with COPD also face an increased risk of cardiovascular disease and type 2 diabetes, and smokers with COPD who quit not only improve their COPD but also reduce their risk of developing these conditions, the authors said.
 

Mechanism of action explored

The authors noted how tobacco smoking may cause COPD when inhaled particles are deposited through the airway.

Growing evidence suggests that extracellular vesicles may play a role in the development of lung disorders such as COPD, and cigarette smoke can have an impact through this channel. A study published in the American Journal of Respiratory and Critical Care Medicine offered evidence of a potential link between exposure to cigarette smoke and the generation of a unique extracellular vesicle population that could promote the development of lung damage. In the study, Matthew C. Madison, MD, of the University of Alabama, Birmingham, and colleagues examined activity in extracellular vesicles from the bronchoalveolar lavage (BAL) fluid of smoke-exposed mice and human smokers who were otherwise healthy.

The researchers found that airway extracellular vesicles in mice or humans exposed to cigarette smoke had the ability to cause rapid lung damage when transferred into naive recipient mice. The results provide a new model that can inform preclinical COPD research, they wrote.
 

Public health action needed

“In recognition of COPD and Lung Cancer Awareness Month, the World Health Organization (WHO) emphasizes the impact of various forms of tobacco use on COPD,” Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

“This article focuses on the different types of tobacco exposure, the health care burden associated with COPD, and the risk of developing lung cancer. It also addresses the high-risk groups, especially youth, underscoring the importance of public education and the implementation of restrictions on tobacco use to combat these growing concerns,” she said.

“Education, awareness, and targeted interventions are essential for smoking cessation and COPD management,” said Dr. Narendra. “These elements are key to informing the public about smoking risks, encouraging behavioral change, and ultimately reducing the incidence of smoking-related diseases,” she emphasized.

The WHO statement called for population-level interventions including brief advice to tobacco users, toll-free quit lines, pharmacological interventions, use of messaging and chatbots to provide quit support, and the WHO quit tobacco mobile app.

“It is imperative that all tobacco users, particularly those living in low- to middle-income countries, have access to comprehensive cessation support aligned with WHO recommendations,” the authors wrote.

Finally, the authors emphasized the need to protect children and teens from the dangers of tobacco use through product regulation and to expose the tobacco industry’s marketing tactics.

“The article offers a comprehensive look at different types of tobacco exposure and their contribution to the development of COPD,” Dr. Narendra told this news organization. “Notably, it presents groundbreaking evidence of a strong association between the use of electronic nicotine delivery systems (ENDS) and heated tobacco products to development of COPD; additionally, it provides valuable guidance on smoking cessation resources for physicians to help patients quit smoking,” she said.

Looking ahead, more research is needed on “developing and sustaining state-specific or population-specific interventions for effective smoking cessation programs, and reducing the burden of COPD,” Dr. Narendra said.

The study by Madison and colleagues was supported by the National Heart, Lung, and Blood Institute, the National Institute of General Medical Science, the U.S. Veterans Affairs Administration, the Cystic Fibrosis Foundation Research Development Program, and the Veterans Affairs Merit grant.

Additional financial support came from Imperial College London, a Wellcome Trust Senior Research Fellowship, and Rosetrees Trust/The Stoneygate Trust.

Dr. Narendra had no financial conflicts to disclose but serves as a member of the editorial board of CHEST Physician.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

SAN DIEGO – In the spring of 2024, the American College of Rheumatology is expected to release guidelines to help inform the screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs).

The guidelines, which were previewed during a session at the ACR’s annual meeting, will include 50 recommendations, 3 of which met criteria for a strong rating:

• For people with SARDs at increased risk of developing ILD, the authors strongly recommend against screening with surgical lung biopsy.
• For people with systemic sclerosis (SSc)-related ILD, the authors strongly recommend against glucocorticoids as a first-line ILD treatment.
• For people with SSc-related ILD progression despite an initial ILD treatment, the authors strongly recommend against using long-term glucocorticoids.

Elana J. Bernstein, MD, MSc, a rheumatologist who directs the Columbia/New York-Presbyterian Scleroderma Center, and Sindhu R. Johnson, MD, a rheumatologist who directs the Toronto Scleroderma Program at the University of Toronto, provided a sneak peek of the recommendations to attendees before anticipated publication in Arthritis & Rheumatology and Arthritis Care & Research. For now, guideline summaries for screening and monitoring and treatment are currently available, and three manuscripts are under peer review: one about screening and monitoring, one about treatment, and one about the patient panel that participated in the effort.

Pediatric patients with SARDs excluded

The guidelines’ population of interest was people 17 years of age and older who were diagnosed with SARDs with a high risk of ILD. Pediatric patients with SARDs were excluded from the endeavor, as were those with systemic lupus erythematosus, antineutrophil cytoplasmic antibody–associated vasculitis, sarcoidosis, ankylosing spondylitis, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features, and those with unclassifiable ILD.

In the realm of screening, the guideline authors conditionally recommend two screening tests for patients considered at increased risk of ILD: pulmonary function tests and high-resolution chest CT (HRCT). Pulmonary function tests should include spirometry, lung volumes, and diffusion capacity. “Office spirometry alone is insufficient,” said Dr. Johnson, who served as lead author of the guidelines. And while a HRCT scan is recommended, “some patients may present to the emergency room with acute onset shortness of breath, and they may receive a CT angiogram to screen for pulmonary embolism,” she said. “It’s important to note that CT angiograms are performed in incomplete inspiration to maximize pulmonary artery enhancement. This may produce atelectasis that may obscure or mimic ILD. As a result, CTA studies are often inadequate to screen for ILD.”

Once a patient is diagnosed with ILD, three tests are recommended for monitoring: pulmonary function testing (every 3-6 months the first year in patients with IIM and SSc, then less frequently once stable, and every 3-12 months in the first year in patients with RA, SjD, and MCTD, then less frequently once stable); ambulatory desaturation testing every 3-12 months; and HRCT as needed. Dr. Johnson noted that while that the screening of ILD lies within the realm of rheumatologists, “once a patient is diagnosed, we are encouraged to comanage these patients with pulmonologists,” she said. “Ambulatory desaturation testing is not an infrequent test in the hands of pulmonologists. This is where co-management can be helpful.” She characterized a 6-minute walk test with continuous oximetry as “insufficient and is not synonymous with ambulatory desaturation testing. Ambulatory desaturation testing includes up titration of oxygen if a patient desaturates.”

The guidelines conditionally recommend against using chest radiography, 6-minute walk test distance, ambulatory desaturation testing, and bronchoscopy for ILD screening, and there is a strong recommendation against surgical lung biopsy. “However, there are unique circumstances where these tests may be considered,” Dr. Johnson said. “For example, ambulatory desaturation testing may be helpful if a patient is unable to perform a pulmonary function test. Bronchoscopy may be used to rule out infection, sarcoidosis, lymphoma, or alveolar hemorrhage, and surgical lung biopsy may be considered if you’re trying to rule out a malignancy.”

Similarly, several tests are conditionally recommended against for the monitoring of ILD, including chest radiography, the 6-minute walk test distance, and bronchoscopy. “But there are unique circumstances where they may be considered,” she said. “The 6-minute walk test may be used if a patient is unable to perform a pulmonary function test or if they’re being assessed for lung transplantation. Bronchoscopy may be used to rule out infection or alveolar hemorrhage.”
 

Preferred treatment options described

First-line treatment recommendations for ILD were based on the best available published evidence, voting panel expertise, and patient preferences. For SSc, the preferred treatment options include mycophenolate (CellCept), tocilizumab (Actemra), or rituximab (Rituxan and biosimilars), while additional options include cyclophosphamide, nintedanib (Ofev), and azathioprine. For myositis, the preferred treatment options include mycophenolate, azathioprine, rituximab, or calcineurin inhibitors, while additional options include a Janus kinase (JAK) inhibitor or cyclophosphamide. For MCTD, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include tocilizumab or cyclophosphamide. For RA and Sjögren’s, the preferred treatment options include mycophenolate, azathioprine, or rituximab, while additional options include cyclophosphamide. Dr. Johnson emphasized that there was low certainty evidence to recommend one treatment over another. “Many situations might lead a provider to choose a different option for ILD treatment, such as the presence of comorbidities or extra-pulmonary disease,” she said. “So, while our guidelines were focused on effectiveness for ILD, providers may choose therapies that will help ILD and other disease manifestations.”

The guidelines conditionally recommend a short course of glucocorticoids as a bridging therapy or for treatment of a flare of ILD in patients with myositis, MCTD, RA, and Sjögren’s. The panel strongly recommends against the use of glucocorticoids in patients with SSc due to the concern for inducing a scleroderma renal crisis. “While this may be common knowledge for rheumatologists, it may not be common knowledge for pulmonologists,” she said. “So here is an opportunity to educate our pulmonology colleagues in our consultation notes.”

The guidelines also include recommendations for progression of ILD, which was defined using the INBUILD trial criteria. Mycophenolate is conditionally recommended to be the first ILD treatment for all SARDs when progression occurs, if it wasn’t the first ILD treatment used. “If it was, then other medications that rheumatologists are used to can be considered as the next ILD treatment in the face of progression: rituximab, nintedanib, tocilizumab, and cyclophosphamide,” she said. The guidelines include a conditional recommendation against long-term glucocorticoid use in myositis, MCTD, RA, and Sjögren’s, plus a strong recommendation against long-term glucocorticoid use in SSc. Finally, there is a conditional recommendation of referral for lung transplant evaluation at the appropriate time at experienced centers.

University of Toronto

A patient panel provided input

For the undertaking, a core team that included six rheumatologists; one pulmonologist; one thoracic radiologist; one expert on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology; and two literature review experts developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. The literature review team included 13 rheumatologists, 8 pulmonologists, and 3 methodologists. Finally, a 21-member patient panel was convened to share their values and preferences regarding screening, monitoring, and treatment of SARD-related ILD. Of these, Dr. Bernstein said that 4 were at risk for ILD and 17 had been diagnosed with ILD. Next, the literature review team conducted a systematic review and used the GRADE methodology to rate the available evidence as high, moderate, low, or very low. Then, a voting panel comprising 13 rheumatologists, 10 pulmonologists, 1 radiologist, and 3 patients from the patient panel cast votes for each PICO question and made final recommendations.

The review of evidence left the guidelines authors with 241 PICO questions, “which is a lot,” Dr. Bernstein said. “To put this in perspective, some guidelines address only 10 or 15 PICO questions. Fortunately, we had a dedicated group of experts who were up to the challenge.” Dr. Johnson emphasized that the forthcoming guidelines should not be used by insurers to mandate a specific order of prescribing. “Clinicians must retain the latitude to prescribe medications based on individual patient factors and preferences,” she said.

Dr. Bernstein disclosed that she is an adviser to, a consultant for, and has received grant or research support from Boehringer Ingelheim and has also received grant or research support from Kadmon and Pfizer. Dr. Johnson disclosed that she has received research support from the American College of Rheumatology to develop these guidelines. She has also been an investigator for trials sponsored by Bristol-Myers Squibb, Roche, and Boehringer Ingelheim and has mitigated these relevant conflicts of interest 1 year prior to the development of these guidelines, and will continue to do so for the foreseeable future.

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Can too much of a healthy habit become bad? 

Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, very vigorous exercise may lead to these infections by triggering immune changes that increase risk, according to a new study.

The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be). 

Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.

But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.

“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”

That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel. 

The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear. 

After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts. 

“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
 

An adaptive mechanism gone awry

During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.

Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”

The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.

But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
 

Advice for patients

More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said. 

As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.  

“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.

And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
 

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

Can too much of a healthy habit become bad? 

Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, very vigorous exercise may lead to these infections by triggering immune changes that increase risk, according to a new study.

The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be). 

Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.

But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.

“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”

That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel. 

The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear. 

After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts. 

“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
 

An adaptive mechanism gone awry

During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.

Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”

The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.

But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
 

Advice for patients

More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said. 

As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.  

“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.

And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
 

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

Can too much of a healthy habit become bad? 

Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, very vigorous exercise may lead to these infections by triggering immune changes that increase risk, according to a new study.

The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be). 

Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.

But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.

“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”

That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel. 

The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear. 

After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts. 

“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
 

An adaptive mechanism gone awry

During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.

Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”

The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.

But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
 

Advice for patients

More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said. 

As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.  

“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.

And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
 

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

Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction, the author commented on the discordance in practice among his peers at his hospital. It seemed that there was no consensus on whether fludrocortisone was necessary.

I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.

It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.

Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
 

Rethinking hydro/fludro

The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.

In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
 

Key takeaways

The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.

The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.

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

Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction, the author commented on the discordance in practice among his peers at his hospital. It seemed that there was no consensus on whether fludrocortisone was necessary.

I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.

It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.

Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
 

Rethinking hydro/fludro

The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.

In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
 

Key takeaways

The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.

The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.

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

Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction, the author commented on the discordance in practice among his peers at his hospital. It seemed that there was no consensus on whether fludrocortisone was necessary.

I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.

It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.

Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
 

Rethinking hydro/fludro

The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.

In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
 

Key takeaways

The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.

The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.

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

TOPLINE:

Tobacco users who quit smoking reduce their risk of developing type 2 diabetes by as much as 30% to 40%, and quitting even after one has developed type 2 diabetes is important in preventing a worsening of the disease’s many serious comorbidities, according to a new policy brief jointly issued by the World Health Organization, the International Diabetes Federation (IDF), and the University of Newcastle, Callaghan, Australia.

With type 2 diabetes representing one of the most prevalent chronic diseases worldwide and the ninth cause of death globally, the potential to reduce the risk and worsening of the disease by quitting smoking adds to the urgency of smoking cessation as a public health interest.
 

METHODOLOGY:

• The policy brief summarizes the evidence on the health impacts of type 2 diabetes, tobacco smoking, and the pathophysiology of tobacco use and its role in the development of type 2 diabetes.
• The brief also describes the latest data on newer products that target smokers or potential smokers, including smokeless tobacco, new nicotine and tobacco products, and their relationship with type 2 diabetes. For instance, evidence suggests that even with smokeless tobacco, heavy use or high consumption increases the risk of developing type 2 diabetes, as the products often contain nicotine, known to contribute to the development of type 2 diabetes and related health conditions.
• Evidence on the effectiveness of tobacco control interventions among those with type 2 diabetes is also summarized, including discussion of a systematic review of six studies suggesting that interventions focusing on education and the involvement of health care professionals and pharmacists can be beneficial for people with type 2 diabetes.

TAKEAWAY:

• Smoking exacerbates the known serious complications of diabetic neuropathy and foot ulcers with type 2 diabetes, while further impeding wound healing.
• Smoking also causes damage to retinal blood vessels already at risk with type 2 diabetes, increasing the risk of diabetic retinopathy and vision loss.
• Quitting tobacco use can help prevent those and other major health complications already linked to diabetes, including kidney failure and cardiovascular events.
• Studies show that key misconceptions among smokers with type 2 diabetes that can prevent cessation include concerns about post-cessation weight gain, the influence of peers who smoke, and the psychological aspect of addiction.
• Clinicians are urged to provide advice on how to stop smoking to all tobacco users during the course of a routine consultation or interaction, which can be accomplished in only a few minutes.

IN PRACTICE:

“Health professionals play a vital role in motivating and guiding individuals with type 2 diabetes in their journey to quit tobacco,” Ruediger Krech, MD, director of the Department of Health Promotion at the World Health Organization in Geneva, Switzerland, said in a press statement on the policy brief.

“Simultaneously, governments must take the crucial step of ensuring all indoor public places, workplaces, and public transport are completely smoke-free. These interventions are essential safeguards against the onset and progression of this and many other chronic diseases,” he emphasized.
 

SOURCE:

The policy brief was jointly developed by the World Health Organization, the International Diabetes Federation, and the University of Newcastle.

The detailed policy brief can be downloaded on the IDF website.
 

LIMITATIONS:

Research remains limited on some issues, including the effectiveness of tobacco control interventions and smoking cessation methods for people with type 2 diabetes.

Likewise, specific guidelines for smoking cessation in the type 2 diabetes population are lacking.  However, the general approaches of building patient motivation, behavioral interventions, and pharmacological treatments are advised.

“These interventions should be at least as intensive as those for the general population, while considering the unique characteristics of the disease and the individual,” the authors asserted.
 

DISCLOSURES:

The authors reported no relevant financial relationships.

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

TOPLINE:

Tobacco users who quit smoking reduce their risk of developing type 2 diabetes by as much as 30% to 40%, and quitting even after one has developed type 2 diabetes is important in preventing a worsening of the disease’s many serious comorbidities, according to a new policy brief jointly issued by the World Health Organization, the International Diabetes Federation (IDF), and the University of Newcastle, Callaghan, Australia.

With type 2 diabetes representing one of the most prevalent chronic diseases worldwide and the ninth cause of death globally, the potential to reduce the risk and worsening of the disease by quitting smoking adds to the urgency of smoking cessation as a public health interest.
 

METHODOLOGY:

• The policy brief summarizes the evidence on the health impacts of type 2 diabetes, tobacco smoking, and the pathophysiology of tobacco use and its role in the development of type 2 diabetes.
• The brief also describes the latest data on newer products that target smokers or potential smokers, including smokeless tobacco, new nicotine and tobacco products, and their relationship with type 2 diabetes. For instance, evidence suggests that even with smokeless tobacco, heavy use or high consumption increases the risk of developing type 2 diabetes, as the products often contain nicotine, known to contribute to the development of type 2 diabetes and related health conditions.
• Evidence on the effectiveness of tobacco control interventions among those with type 2 diabetes is also summarized, including discussion of a systematic review of six studies suggesting that interventions focusing on education and the involvement of health care professionals and pharmacists can be beneficial for people with type 2 diabetes.

TAKEAWAY:

• Smoking exacerbates the known serious complications of diabetic neuropathy and foot ulcers with type 2 diabetes, while further impeding wound healing.
• Smoking also causes damage to retinal blood vessels already at risk with type 2 diabetes, increasing the risk of diabetic retinopathy and vision loss.
• Quitting tobacco use can help prevent those and other major health complications already linked to diabetes, including kidney failure and cardiovascular events.
• Studies show that key misconceptions among smokers with type 2 diabetes that can prevent cessation include concerns about post-cessation weight gain, the influence of peers who smoke, and the psychological aspect of addiction.
• Clinicians are urged to provide advice on how to stop smoking to all tobacco users during the course of a routine consultation or interaction, which can be accomplished in only a few minutes.

IN PRACTICE:

“Health professionals play a vital role in motivating and guiding individuals with type 2 diabetes in their journey to quit tobacco,” Ruediger Krech, MD, director of the Department of Health Promotion at the World Health Organization in Geneva, Switzerland, said in a press statement on the policy brief.

“Simultaneously, governments must take the crucial step of ensuring all indoor public places, workplaces, and public transport are completely smoke-free. These interventions are essential safeguards against the onset and progression of this and many other chronic diseases,” he emphasized.
 

SOURCE:

The policy brief was jointly developed by the World Health Organization, the International Diabetes Federation, and the University of Newcastle.

The detailed policy brief can be downloaded on the IDF website.
 

LIMITATIONS:

Research remains limited on some issues, including the effectiveness of tobacco control interventions and smoking cessation methods for people with type 2 diabetes.

Likewise, specific guidelines for smoking cessation in the type 2 diabetes population are lacking.  However, the general approaches of building patient motivation, behavioral interventions, and pharmacological treatments are advised.

“These interventions should be at least as intensive as those for the general population, while considering the unique characteristics of the disease and the individual,” the authors asserted.
 

DISCLOSURES:

The authors reported no relevant financial relationships.

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

TOPLINE:

Tobacco users who quit smoking reduce their risk of developing type 2 diabetes by as much as 30% to 40%, and quitting even after one has developed type 2 diabetes is important in preventing a worsening of the disease’s many serious comorbidities, according to a new policy brief jointly issued by the World Health Organization, the International Diabetes Federation (IDF), and the University of Newcastle, Callaghan, Australia.

With type 2 diabetes representing one of the most prevalent chronic diseases worldwide and the ninth cause of death globally, the potential to reduce the risk and worsening of the disease by quitting smoking adds to the urgency of smoking cessation as a public health interest.
 

METHODOLOGY:

• The policy brief summarizes the evidence on the health impacts of type 2 diabetes, tobacco smoking, and the pathophysiology of tobacco use and its role in the development of type 2 diabetes.
• The brief also describes the latest data on newer products that target smokers or potential smokers, including smokeless tobacco, new nicotine and tobacco products, and their relationship with type 2 diabetes. For instance, evidence suggests that even with smokeless tobacco, heavy use or high consumption increases the risk of developing type 2 diabetes, as the products often contain nicotine, known to contribute to the development of type 2 diabetes and related health conditions.
• Evidence on the effectiveness of tobacco control interventions among those with type 2 diabetes is also summarized, including discussion of a systematic review of six studies suggesting that interventions focusing on education and the involvement of health care professionals and pharmacists can be beneficial for people with type 2 diabetes.

TAKEAWAY:

• Smoking exacerbates the known serious complications of diabetic neuropathy and foot ulcers with type 2 diabetes, while further impeding wound healing.
• Smoking also causes damage to retinal blood vessels already at risk with type 2 diabetes, increasing the risk of diabetic retinopathy and vision loss.
• Quitting tobacco use can help prevent those and other major health complications already linked to diabetes, including kidney failure and cardiovascular events.
• Studies show that key misconceptions among smokers with type 2 diabetes that can prevent cessation include concerns about post-cessation weight gain, the influence of peers who smoke, and the psychological aspect of addiction.
• Clinicians are urged to provide advice on how to stop smoking to all tobacco users during the course of a routine consultation or interaction, which can be accomplished in only a few minutes.

IN PRACTICE:

“Health professionals play a vital role in motivating and guiding individuals with type 2 diabetes in their journey to quit tobacco,” Ruediger Krech, MD, director of the Department of Health Promotion at the World Health Organization in Geneva, Switzerland, said in a press statement on the policy brief.

“Simultaneously, governments must take the crucial step of ensuring all indoor public places, workplaces, and public transport are completely smoke-free. These interventions are essential safeguards against the onset and progression of this and many other chronic diseases,” he emphasized.
 

SOURCE:

The policy brief was jointly developed by the World Health Organization, the International Diabetes Federation, and the University of Newcastle.

The detailed policy brief can be downloaded on the IDF website.
 

LIMITATIONS:

Research remains limited on some issues, including the effectiveness of tobacco control interventions and smoking cessation methods for people with type 2 diabetes.

Likewise, specific guidelines for smoking cessation in the type 2 diabetes population are lacking.  However, the general approaches of building patient motivation, behavioral interventions, and pharmacological treatments are advised.

“These interventions should be at least as intensive as those for the general population, while considering the unique characteristics of the disease and the individual,” the authors asserted.
 

DISCLOSURES:

The authors reported no relevant financial relationships.

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

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

ANAHEIM, CALIF. – Gargling and nasal rinsing with saltwater several times a day appeared to be associated with significantly lower COVID-19 hospitalization rates in a small, randomized, double-blind, controlled study.

“The hypothesis was that interventions that target the upper respiratory tract may reduce the frequency and duration of upper respiratory symptoms associated with COVID-19,” said Sebastian Espinoza, first author of the study; he is with Trinity University, San Antonio.

Adults aged 18-65 years who tested positive for SARS-CoV-2 on polymerase chain reaction (PCR) testing between 2020 and 2022 were randomly selected to use low- or high-dose saltwater regimens for 14 days at the Harris Health System, Houston. For patients to be included in the study, 14 days had to have elapsed since the onset of any symptoms associated with COVID.

The low dose was 2.13 grams of salt dissolved in 8 ounces of warm water, and the high dose was 6 grams. Participants gargled the saltwater and used it as a nasal rinse for 5 minutes four times a day.

Primary outcomes included frequency and duration of symptoms associated with SARS-CoV-2 infection; secondary outcomes included admission to the hospital or the intensive care unit, mechanical ventilatory support, or death.

The findings were presented in a poster at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Fifty-eight people were randomly assigned to either the low-saline (n = 27) or the high-saline (n = 28) group; three patients were lost to follow-up in both these groups. The reference control population consisted of 9,398 people with confirmed SARS-CoV-2 infection. Rates of vaccination were similar for all participants.

Hospitalization rates in the low- (18.5%) and high- (21.4%) saline groups were significantly lower than in the reference control population (58.8%; P < .001). No significant differences were noted in other outcomes among these groups.

The average age of patients in the control population (n = 9,398) was 45 years. The average age was similar in the low- and high-saline groups. In the low-saline group (n = 27), the average age was 39, and in the high-saline group, the average age was 41.

In all three groups, body mass index was between 29.6 and 31.7.

Exclusion criteria included chronic hypertension or participation in another interventional study.
 

‘Low risk, small potential benefit’

Allergist Zach Rubin, MD, a spokesperson for the ACAAI, said in an interview that the findings are in line with other small studies that previously reported some benefit in using nasal saline irrigation and gargling to treat a SARS-CoV-2 infection.

“This is a type of intervention that is low risk with some small potential benefit,” he said.

The researchers did not evaluate the potential reason for the saline regimen’s association with fewer hospitalizations, but Dr. Rubin said, “It may be possible that nasal saline irrigation and gargling help improve viral clearance and reduce the risk of microaspiration into the lungs, so it may be possible that this intervention could reduce the risk of pneumonia, which is a major cause of hospitalization.”

Dr. Rubin, who is an allergist at Oak Brook Allergists, Ill., said, “I generally recommend nasal saline irrigation to my patients for allergic rhinitis and viral upper respiratory infections already. It can help reduce symptoms such as nasal congestion, rhinorrhea, postnasal drip, and sinus pain and pressure.”

The intervention may be reasonable beyond an adult population, he said.

“This could be used for pediatric patients as well, if they are developmentally ready to try this intervention,” he said.

Mr. Espinoza said further study is warranted, but he said that if confirmed in later trials, the simple intervention may be particularly helpful in low-resource settings.

Mr. Espinoza and Dr. Rubin have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

ANAHEIM, CALIF. – Gargling and nasal rinsing with saltwater several times a day appeared to be associated with significantly lower COVID-19 hospitalization rates in a small, randomized, double-blind, controlled study.

“The hypothesis was that interventions that target the upper respiratory tract may reduce the frequency and duration of upper respiratory symptoms associated with COVID-19,” said Sebastian Espinoza, first author of the study; he is with Trinity University, San Antonio.

Adults aged 18-65 years who tested positive for SARS-CoV-2 on polymerase chain reaction (PCR) testing between 2020 and 2022 were randomly selected to use low- or high-dose saltwater regimens for 14 days at the Harris Health System, Houston. For patients to be included in the study, 14 days had to have elapsed since the onset of any symptoms associated with COVID.

The low dose was 2.13 grams of salt dissolved in 8 ounces of warm water, and the high dose was 6 grams. Participants gargled the saltwater and used it as a nasal rinse for 5 minutes four times a day.

Primary outcomes included frequency and duration of symptoms associated with SARS-CoV-2 infection; secondary outcomes included admission to the hospital or the intensive care unit, mechanical ventilatory support, or death.

The findings were presented in a poster at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Fifty-eight people were randomly assigned to either the low-saline (n = 27) or the high-saline (n = 28) group; three patients were lost to follow-up in both these groups. The reference control population consisted of 9,398 people with confirmed SARS-CoV-2 infection. Rates of vaccination were similar for all participants.

Hospitalization rates in the low- (18.5%) and high- (21.4%) saline groups were significantly lower than in the reference control population (58.8%; P < .001). No significant differences were noted in other outcomes among these groups.

The average age of patients in the control population (n = 9,398) was 45 years. The average age was similar in the low- and high-saline groups. In the low-saline group (n = 27), the average age was 39, and in the high-saline group, the average age was 41.

In all three groups, body mass index was between 29.6 and 31.7.

Exclusion criteria included chronic hypertension or participation in another interventional study.
 

‘Low risk, small potential benefit’

Allergist Zach Rubin, MD, a spokesperson for the ACAAI, said in an interview that the findings are in line with other small studies that previously reported some benefit in using nasal saline irrigation and gargling to treat a SARS-CoV-2 infection.

“This is a type of intervention that is low risk with some small potential benefit,” he said.

The researchers did not evaluate the potential reason for the saline regimen’s association with fewer hospitalizations, but Dr. Rubin said, “It may be possible that nasal saline irrigation and gargling help improve viral clearance and reduce the risk of microaspiration into the lungs, so it may be possible that this intervention could reduce the risk of pneumonia, which is a major cause of hospitalization.”

Dr. Rubin, who is an allergist at Oak Brook Allergists, Ill., said, “I generally recommend nasal saline irrigation to my patients for allergic rhinitis and viral upper respiratory infections already. It can help reduce symptoms such as nasal congestion, rhinorrhea, postnasal drip, and sinus pain and pressure.”

The intervention may be reasonable beyond an adult population, he said.

“This could be used for pediatric patients as well, if they are developmentally ready to try this intervention,” he said.

Mr. Espinoza said further study is warranted, but he said that if confirmed in later trials, the simple intervention may be particularly helpful in low-resource settings.

Mr. Espinoza and Dr. Rubin have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

ANAHEIM, CALIF. – Gargling and nasal rinsing with saltwater several times a day appeared to be associated with significantly lower COVID-19 hospitalization rates in a small, randomized, double-blind, controlled study.

“The hypothesis was that interventions that target the upper respiratory tract may reduce the frequency and duration of upper respiratory symptoms associated with COVID-19,” said Sebastian Espinoza, first author of the study; he is with Trinity University, San Antonio.

Adults aged 18-65 years who tested positive for SARS-CoV-2 on polymerase chain reaction (PCR) testing between 2020 and 2022 were randomly selected to use low- or high-dose saltwater regimens for 14 days at the Harris Health System, Houston. For patients to be included in the study, 14 days had to have elapsed since the onset of any symptoms associated with COVID.

The low dose was 2.13 grams of salt dissolved in 8 ounces of warm water, and the high dose was 6 grams. Participants gargled the saltwater and used it as a nasal rinse for 5 minutes four times a day.

Primary outcomes included frequency and duration of symptoms associated with SARS-CoV-2 infection; secondary outcomes included admission to the hospital or the intensive care unit, mechanical ventilatory support, or death.

The findings were presented in a poster at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Fifty-eight people were randomly assigned to either the low-saline (n = 27) or the high-saline (n = 28) group; three patients were lost to follow-up in both these groups. The reference control population consisted of 9,398 people with confirmed SARS-CoV-2 infection. Rates of vaccination were similar for all participants.

Hospitalization rates in the low- (18.5%) and high- (21.4%) saline groups were significantly lower than in the reference control population (58.8%; P < .001). No significant differences were noted in other outcomes among these groups.

The average age of patients in the control population (n = 9,398) was 45 years. The average age was similar in the low- and high-saline groups. In the low-saline group (n = 27), the average age was 39, and in the high-saline group, the average age was 41.

In all three groups, body mass index was between 29.6 and 31.7.

Exclusion criteria included chronic hypertension or participation in another interventional study.
 

‘Low risk, small potential benefit’

Allergist Zach Rubin, MD, a spokesperson for the ACAAI, said in an interview that the findings are in line with other small studies that previously reported some benefit in using nasal saline irrigation and gargling to treat a SARS-CoV-2 infection.

“This is a type of intervention that is low risk with some small potential benefit,” he said.

The researchers did not evaluate the potential reason for the saline regimen’s association with fewer hospitalizations, but Dr. Rubin said, “It may be possible that nasal saline irrigation and gargling help improve viral clearance and reduce the risk of microaspiration into the lungs, so it may be possible that this intervention could reduce the risk of pneumonia, which is a major cause of hospitalization.”

Dr. Rubin, who is an allergist at Oak Brook Allergists, Ill., said, “I generally recommend nasal saline irrigation to my patients for allergic rhinitis and viral upper respiratory infections already. It can help reduce symptoms such as nasal congestion, rhinorrhea, postnasal drip, and sinus pain and pressure.”

The intervention may be reasonable beyond an adult population, he said.

“This could be used for pediatric patients as well, if they are developmentally ready to try this intervention,” he said.

Mr. Espinoza said further study is warranted, but he said that if confirmed in later trials, the simple intervention may be particularly helpful in low-resource settings.

Mr. Espinoza and Dr. Rubin have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) who start a tumor necrosis factor inhibitor (TNFi) appear to have rates of survival and respiratory-related hospitalization similar to those initiating a non-TNFi biologic disease-modifying antirheumatic drug (bDMARD) or Janus kinase inhibitor (JAKi), results from a large pharmacoepidemiologic study show.

“These results challenge some of the findings in prior literature that perhaps TNFi should be avoided in RA-ILD,” lead study investigator Bryant R. England, MD, PhD,  said in an interview. The findings were presented during a plenary session at the American College of Rheumatology annual meeting.

Dr. England, associate professor of rheumatology and immunology at the University of Nebraska Medical Center, Omaha, said that while RA-ILD carries a poor prognosis, a paucity of evidence exists on the effectiveness and safety of disease-modifying therapies in this population.

It’s a pleasant surprise “to see that the investigators were unable to demonstrate a significant difference in the risk of respiratory hospitalization or death between people with RA-ILD initiating non-TNFi/JAKi versus TNFi. Here is a unique situation where a so called ‘negative’ study contributes important information. This study provides needed safety data, as they were unable to show that TNFi results in worsening of severe RA-ILD outcomes,” Sindhu R. Johnson, MD, PhD, professor of medicine at the University of Toronto, said when asked for comment on the study.

University of Toronto

“While this study does not address the use of these medications for the treatment of RA-ILD, these data suggest that TNFi may remain a treatment option for articular disease in people with RA-ILD,” said Dr. Johnson, who was not involved with the study.

For the study, Dr. England and colleagues drew from Veterans Health Administration data between 2006 and 2018 to identify patients with RA-ILD initiating TNFi or non-TNFi biologic/JAKi for the first time. Those who received ILD-focused therapies such as mycophenolate and antifibrotics were excluded from the analysis.

The researchers used validated administrative algorithms requiring multiple RA and ILD diagnostic codes to identify RA-ILD and used 1:1 propensity score matching to compare TNFi and non-TNFi biologic/JAKi factors such as health care use, comorbidities, and several RA-ILD factors, such as pretreatment forced vital capacity, obtained from electronic health records and administrative data. The primary outcome was a composite of time to respiratory-related hospitalization or death using Cox regression models.

Dr. England reported findings from 237 TNFi initiators and 237 non-TNFi/JAKi initiators. Their mean age was 68 years and 92% were male. After matching, the mean standardized differences of variables in the propensity score model improved, but a few variables remained slightly imbalanced, such as two markers of inflammation, inhaled corticosteroid use, and body mass index. The most frequently prescribed TNFi drugs were adalimumab (51%) and etanercept (37%), and the most frequently prescribed non-TNFi/JAKi drugs were rituximab (53%) and abatacept (28%).

The researchers observed no significant difference in the primary outcome between non-TNFi/JAKi and TNFi initiators (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.92-1.60). They also observed no significant differences in respiratory hospitalization, all-cause mortality, or respiratory-related death at 1 and 3 years. In sensitivity analyses with modified cohort eligibility requirements, no significant differences in outcomes were observed between non-TNFi/JAKi and TNFi initiators.

During his presentation at the meeting, Dr. England posed the question: Are TNFi drugs safe to be used in RA-ILD?

“The answer is: It’s complex,” he said. “Our findings don’t suggest that we should be systematically avoiding TNFis with every single person with RA-ILD. But that’s different than whether there are specific subpopulations of RA-ILD for which the choice of these therapies may differ. Unfortunately, we could not address that in this study. We also could not address whether TNFis have efficacy at stopping, slowing, or reversing progression of the ILD itself. This calls for us as a field to gather together and pursue clinical trials to try to generate robust evidence that can guide these important clinical decisions that we’re making with our patients.”

He acknowledged certain limitations of the analysis, including its observational design. “So, despite best efforts to minimize bias with pharmacoepidemiologic designs and approaches, there could still be confounding and selection,” he said. “Additionally, RA-ILD is a heterogeneous disease characterized by different patterns and trajectories. While we did account for several RA- and ILD-related factors, we could not account for all heterogeneity in RA-ILD.”

When asked for comment on the study, session moderator Janet Pope, MD, MPH, professor of medicine in the division of rheumatology at the University of Western Ontario, London, said that the study findings surprised her.

“Sometimes RA patients on TNFis were thought to have more new or worsening ILD vs. [those on] non-TNFi bDMARDs, but most [data were] from older studies where TNFis were used as initial bDMARD in sicker patients,” she told this news organization. “So, data were confounded previously. Even in this study, there may have been channeling bias as it was not a randomized controlled trial. We need a definitive randomized controlled trial to answer this question of what the most optimal therapy for RA-ILD is.”

Dr. England reports receiving consulting fees and research support from Boehringer Ingelheim, and several coauthors reported financial relationships from various pharmaceutical companies and medical publishers. Dr. Johnson reports no relevant financial relationships. Dr. Pope reports being a consultant for several pharmaceutical companies. She has received grant/research support from AbbVie/Abbott and Eli Lilly and is an adviser for Boehringer Ingelheim.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) who start a tumor necrosis factor inhibitor (TNFi) appear to have rates of survival and respiratory-related hospitalization similar to those initiating a non-TNFi biologic disease-modifying antirheumatic drug (bDMARD) or Janus kinase inhibitor (JAKi), results from a large pharmacoepidemiologic study show.

“These results challenge some of the findings in prior literature that perhaps TNFi should be avoided in RA-ILD,” lead study investigator Bryant R. England, MD, PhD,  said in an interview. The findings were presented during a plenary session at the American College of Rheumatology annual meeting.

Dr. England, associate professor of rheumatology and immunology at the University of Nebraska Medical Center, Omaha, said that while RA-ILD carries a poor prognosis, a paucity of evidence exists on the effectiveness and safety of disease-modifying therapies in this population.

It’s a pleasant surprise “to see that the investigators were unable to demonstrate a significant difference in the risk of respiratory hospitalization or death between people with RA-ILD initiating non-TNFi/JAKi versus TNFi. Here is a unique situation where a so called ‘negative’ study contributes important information. This study provides needed safety data, as they were unable to show that TNFi results in worsening of severe RA-ILD outcomes,” Sindhu R. Johnson, MD, PhD, professor of medicine at the University of Toronto, said when asked for comment on the study.

University of Toronto

“While this study does not address the use of these medications for the treatment of RA-ILD, these data suggest that TNFi may remain a treatment option for articular disease in people with RA-ILD,” said Dr. Johnson, who was not involved with the study.

For the study, Dr. England and colleagues drew from Veterans Health Administration data between 2006 and 2018 to identify patients with RA-ILD initiating TNFi or non-TNFi biologic/JAKi for the first time. Those who received ILD-focused therapies such as mycophenolate and antifibrotics were excluded from the analysis.

The researchers used validated administrative algorithms requiring multiple RA and ILD diagnostic codes to identify RA-ILD and used 1:1 propensity score matching to compare TNFi and non-TNFi biologic/JAKi factors such as health care use, comorbidities, and several RA-ILD factors, such as pretreatment forced vital capacity, obtained from electronic health records and administrative data. The primary outcome was a composite of time to respiratory-related hospitalization or death using Cox regression models.

Dr. England reported findings from 237 TNFi initiators and 237 non-TNFi/JAKi initiators. Their mean age was 68 years and 92% were male. After matching, the mean standardized differences of variables in the propensity score model improved, but a few variables remained slightly imbalanced, such as two markers of inflammation, inhaled corticosteroid use, and body mass index. The most frequently prescribed TNFi drugs were adalimumab (51%) and etanercept (37%), and the most frequently prescribed non-TNFi/JAKi drugs were rituximab (53%) and abatacept (28%).

The researchers observed no significant difference in the primary outcome between non-TNFi/JAKi and TNFi initiators (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.92-1.60). They also observed no significant differences in respiratory hospitalization, all-cause mortality, or respiratory-related death at 1 and 3 years. In sensitivity analyses with modified cohort eligibility requirements, no significant differences in outcomes were observed between non-TNFi/JAKi and TNFi initiators.

During his presentation at the meeting, Dr. England posed the question: Are TNFi drugs safe to be used in RA-ILD?

“The answer is: It’s complex,” he said. “Our findings don’t suggest that we should be systematically avoiding TNFis with every single person with RA-ILD. But that’s different than whether there are specific subpopulations of RA-ILD for which the choice of these therapies may differ. Unfortunately, we could not address that in this study. We also could not address whether TNFis have efficacy at stopping, slowing, or reversing progression of the ILD itself. This calls for us as a field to gather together and pursue clinical trials to try to generate robust evidence that can guide these important clinical decisions that we’re making with our patients.”

He acknowledged certain limitations of the analysis, including its observational design. “So, despite best efforts to minimize bias with pharmacoepidemiologic designs and approaches, there could still be confounding and selection,” he said. “Additionally, RA-ILD is a heterogeneous disease characterized by different patterns and trajectories. While we did account for several RA- and ILD-related factors, we could not account for all heterogeneity in RA-ILD.”

When asked for comment on the study, session moderator Janet Pope, MD, MPH, professor of medicine in the division of rheumatology at the University of Western Ontario, London, said that the study findings surprised her.

“Sometimes RA patients on TNFis were thought to have more new or worsening ILD vs. [those on] non-TNFi bDMARDs, but most [data were] from older studies where TNFis were used as initial bDMARD in sicker patients,” she told this news organization. “So, data were confounded previously. Even in this study, there may have been channeling bias as it was not a randomized controlled trial. We need a definitive randomized controlled trial to answer this question of what the most optimal therapy for RA-ILD is.”

Dr. England reports receiving consulting fees and research support from Boehringer Ingelheim, and several coauthors reported financial relationships from various pharmaceutical companies and medical publishers. Dr. Johnson reports no relevant financial relationships. Dr. Pope reports being a consultant for several pharmaceutical companies. She has received grant/research support from AbbVie/Abbott and Eli Lilly and is an adviser for Boehringer Ingelheim.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) who start a tumor necrosis factor inhibitor (TNFi) appear to have rates of survival and respiratory-related hospitalization similar to those initiating a non-TNFi biologic disease-modifying antirheumatic drug (bDMARD) or Janus kinase inhibitor (JAKi), results from a large pharmacoepidemiologic study show.

“These results challenge some of the findings in prior literature that perhaps TNFi should be avoided in RA-ILD,” lead study investigator Bryant R. England, MD, PhD,  said in an interview. The findings were presented during a plenary session at the American College of Rheumatology annual meeting.

Dr. England, associate professor of rheumatology and immunology at the University of Nebraska Medical Center, Omaha, said that while RA-ILD carries a poor prognosis, a paucity of evidence exists on the effectiveness and safety of disease-modifying therapies in this population.

It’s a pleasant surprise “to see that the investigators were unable to demonstrate a significant difference in the risk of respiratory hospitalization or death between people with RA-ILD initiating non-TNFi/JAKi versus TNFi. Here is a unique situation where a so called ‘negative’ study contributes important information. This study provides needed safety data, as they were unable to show that TNFi results in worsening of severe RA-ILD outcomes,” Sindhu R. Johnson, MD, PhD, professor of medicine at the University of Toronto, said when asked for comment on the study.

University of Toronto

“While this study does not address the use of these medications for the treatment of RA-ILD, these data suggest that TNFi may remain a treatment option for articular disease in people with RA-ILD,” said Dr. Johnson, who was not involved with the study.

For the study, Dr. England and colleagues drew from Veterans Health Administration data between 2006 and 2018 to identify patients with RA-ILD initiating TNFi or non-TNFi biologic/JAKi for the first time. Those who received ILD-focused therapies such as mycophenolate and antifibrotics were excluded from the analysis.

The researchers used validated administrative algorithms requiring multiple RA and ILD diagnostic codes to identify RA-ILD and used 1:1 propensity score matching to compare TNFi and non-TNFi biologic/JAKi factors such as health care use, comorbidities, and several RA-ILD factors, such as pretreatment forced vital capacity, obtained from electronic health records and administrative data. The primary outcome was a composite of time to respiratory-related hospitalization or death using Cox regression models.

Dr. England reported findings from 237 TNFi initiators and 237 non-TNFi/JAKi initiators. Their mean age was 68 years and 92% were male. After matching, the mean standardized differences of variables in the propensity score model improved, but a few variables remained slightly imbalanced, such as two markers of inflammation, inhaled corticosteroid use, and body mass index. The most frequently prescribed TNFi drugs were adalimumab (51%) and etanercept (37%), and the most frequently prescribed non-TNFi/JAKi drugs were rituximab (53%) and abatacept (28%).

The researchers observed no significant difference in the primary outcome between non-TNFi/JAKi and TNFi initiators (adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.92-1.60). They also observed no significant differences in respiratory hospitalization, all-cause mortality, or respiratory-related death at 1 and 3 years. In sensitivity analyses with modified cohort eligibility requirements, no significant differences in outcomes were observed between non-TNFi/JAKi and TNFi initiators.

During his presentation at the meeting, Dr. England posed the question: Are TNFi drugs safe to be used in RA-ILD?

“The answer is: It’s complex,” he said. “Our findings don’t suggest that we should be systematically avoiding TNFis with every single person with RA-ILD. But that’s different than whether there are specific subpopulations of RA-ILD for which the choice of these therapies may differ. Unfortunately, we could not address that in this study. We also could not address whether TNFis have efficacy at stopping, slowing, or reversing progression of the ILD itself. This calls for us as a field to gather together and pursue clinical trials to try to generate robust evidence that can guide these important clinical decisions that we’re making with our patients.”

He acknowledged certain limitations of the analysis, including its observational design. “So, despite best efforts to minimize bias with pharmacoepidemiologic designs and approaches, there could still be confounding and selection,” he said. “Additionally, RA-ILD is a heterogeneous disease characterized by different patterns and trajectories. While we did account for several RA- and ILD-related factors, we could not account for all heterogeneity in RA-ILD.”

When asked for comment on the study, session moderator Janet Pope, MD, MPH, professor of medicine in the division of rheumatology at the University of Western Ontario, London, said that the study findings surprised her.

“Sometimes RA patients on TNFis were thought to have more new or worsening ILD vs. [those on] non-TNFi bDMARDs, but most [data were] from older studies where TNFis were used as initial bDMARD in sicker patients,” she told this news organization. “So, data were confounded previously. Even in this study, there may have been channeling bias as it was not a randomized controlled trial. We need a definitive randomized controlled trial to answer this question of what the most optimal therapy for RA-ILD is.”

Dr. England reports receiving consulting fees and research support from Boehringer Ingelheim, and several coauthors reported financial relationships from various pharmaceutical companies and medical publishers. Dr. Johnson reports no relevant financial relationships. Dr. Pope reports being a consultant for several pharmaceutical companies. She has received grant/research support from AbbVie/Abbott and Eli Lilly and is an adviser for Boehringer Ingelheim.

A version of this article appeared on Medscape.com.