Pulmonology

CHICAGO – Patients who meet the criteria for interstitial pneumonia with autoimmune features are more than 14 times more likely to progress to a systemic autoimmune rheumatic disease than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.

Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.

The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).

The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.

During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.

In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.

In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.

Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.

CHICAGO – Patients who meet the criteria for interstitial pneumonia with autoimmune features are more than 14 times more likely to progress to a systemic autoimmune rheumatic disease than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.

Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.

The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).

The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.

During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.

In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.

In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.

Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.

CHICAGO – Patients who meet the criteria for interstitial pneumonia with autoimmune features are more than 14 times more likely to progress to a systemic autoimmune rheumatic disease than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.

Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.

The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).

The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.

During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.

In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.

In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.

Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.

Teenage use of vaping devices jumped significantly in the past year, with 37% of 12th-grade students reporting any vaping in 2018, compared with 28% in 2017, data announced Dec. 17 from the 2018 Monitoring the Future survey show.

LiudmylaSupynska/Thinkstock

In particular, nicotine vaping use in the 30 days prior to the survey nearly doubled among high school seniors, from approximately 11% in 2017 to 21% in 2018. Nicotine vaping also increased by 7.9% (from 8.2% to 16.1%) among 10th graders and by 2.6% (from 3.5% to 6.1%) among 8th graders, according to the survey results.

Vaping involves using a device such as an e-cigarette to inhale a heated aerosol product that usually contains nicotine but can be used to administer other types of drugs, said Nora D. Volkow, MD, director of the National Institute on Drug Abuse at the National Institutes of Health, in a press conference announcing the findings.

The increased prevalence of nicotine vaping in 10th and 12th graders is the largest annual increase in use of any substance recorded by Monitoring the Future, said Richard A. Miech, PhD, MPH, of the Institute for Social Research at the University of Michigan, Ann Arbor, and the principal survey investigator. “Something about this delivery device of vaping seems to really appeal to kids,” he said. The flavorings, concealability of the devices (which can be about the size of a flash drive), and ease of use seem to be contributing to the popularity of vaping, Dr. Miech added.

In addition, marijuana vaping increased significantly across all three grade levels in 2018 from 2017. Within 30 days of the survey, marijuana vaping increased from 4.9% to 7.5% in 12th graders, from 4.3% to 7.0% in 10th graders, and from 1.6% to 2.6% in 8th graders.

A take-home message for clinicians is the need to emphasize to teens that “vaping is not innocuous and not harmless,” said Dr. Miech in a question-and-answer session. Of note, data from multiple studies show that children who vape are about five times more likely to smoke cigarettes, he said.

The vaping devices are manufactured to deliver drugs into the lungs and ultimately high concentrations into the brain – which suggests the use of vaping devices to deliver other types of drugs might increase in the future, Dr. Volkow added.

Use of most other substances, including inhalants, heroin, cocaine, ecstasy, overall marijuana use, alcohol use, and extreme binge drinking remained stable, the researchers said. Cigarette smoking declined slightly among 12th graders but did not change significantly among 8th or 10th graders. Use of prescription opioids and tranquilizers declined in 2018 across all age groups.

“Vaping is reversing hard-fought declines in the number of adolescents who use nicotine,” Dr. Miech said in the news release announcing the results. “These results suggest that vaping is leading youth into nicotine use and nicotine addiction, not away from it.”

The data on vaping and nicotine use among American teens were published in a letter (N Engl J Med. 2018 Dec 17. doi: 10.1056/NEJMc1814130) – with a warning. “These results indicate that the policies in place as of the 2017-2018 school year were not sufficient to stop the spread of nicotine vaping among adolescents,” wrote the authors, led by Dr. Miech. “The rapid entry of new vaping devices on the market ... will require continual updates and modification strategies to keep adolescents from vaping and its associated negative health effects.”

The Monitoring the Future survey tracks annual drug use and drug use attitudes in a nationally representative sample of U.S. students in 8th, 10th, and 12th grades. This year’s survey included 44,482 participants. The survey is funded by a government grant to the University of Michigan, Ann Arbor, from the NIH’s NIDA.

Teenage use of vaping devices jumped significantly in the past year, with 37% of 12th-grade students reporting any vaping in 2018, compared with 28% in 2017, data announced Dec. 17 from the 2018 Monitoring the Future survey show.

LiudmylaSupynska/Thinkstock

In particular, nicotine vaping use in the 30 days prior to the survey nearly doubled among high school seniors, from approximately 11% in 2017 to 21% in 2018. Nicotine vaping also increased by 7.9% (from 8.2% to 16.1%) among 10th graders and by 2.6% (from 3.5% to 6.1%) among 8th graders, according to the survey results.

Vaping involves using a device such as an e-cigarette to inhale a heated aerosol product that usually contains nicotine but can be used to administer other types of drugs, said Nora D. Volkow, MD, director of the National Institute on Drug Abuse at the National Institutes of Health, in a press conference announcing the findings.

The increased prevalence of nicotine vaping in 10th and 12th graders is the largest annual increase in use of any substance recorded by Monitoring the Future, said Richard A. Miech, PhD, MPH, of the Institute for Social Research at the University of Michigan, Ann Arbor, and the principal survey investigator. “Something about this delivery device of vaping seems to really appeal to kids,” he said. The flavorings, concealability of the devices (which can be about the size of a flash drive), and ease of use seem to be contributing to the popularity of vaping, Dr. Miech added.

In addition, marijuana vaping increased significantly across all three grade levels in 2018 from 2017. Within 30 days of the survey, marijuana vaping increased from 4.9% to 7.5% in 12th graders, from 4.3% to 7.0% in 10th graders, and from 1.6% to 2.6% in 8th graders.

A take-home message for clinicians is the need to emphasize to teens that “vaping is not innocuous and not harmless,” said Dr. Miech in a question-and-answer session. Of note, data from multiple studies show that children who vape are about five times more likely to smoke cigarettes, he said.

The vaping devices are manufactured to deliver drugs into the lungs and ultimately high concentrations into the brain – which suggests the use of vaping devices to deliver other types of drugs might increase in the future, Dr. Volkow added.

Use of most other substances, including inhalants, heroin, cocaine, ecstasy, overall marijuana use, alcohol use, and extreme binge drinking remained stable, the researchers said. Cigarette smoking declined slightly among 12th graders but did not change significantly among 8th or 10th graders. Use of prescription opioids and tranquilizers declined in 2018 across all age groups.

“Vaping is reversing hard-fought declines in the number of adolescents who use nicotine,” Dr. Miech said in the news release announcing the results. “These results suggest that vaping is leading youth into nicotine use and nicotine addiction, not away from it.”

The data on vaping and nicotine use among American teens were published in a letter (N Engl J Med. 2018 Dec 17. doi: 10.1056/NEJMc1814130) – with a warning. “These results indicate that the policies in place as of the 2017-2018 school year were not sufficient to stop the spread of nicotine vaping among adolescents,” wrote the authors, led by Dr. Miech. “The rapid entry of new vaping devices on the market ... will require continual updates and modification strategies to keep adolescents from vaping and its associated negative health effects.”

The Monitoring the Future survey tracks annual drug use and drug use attitudes in a nationally representative sample of U.S. students in 8th, 10th, and 12th grades. This year’s survey included 44,482 participants. The survey is funded by a government grant to the University of Michigan, Ann Arbor, from the NIH’s NIDA.

Teenage use of vaping devices jumped significantly in the past year, with 37% of 12th-grade students reporting any vaping in 2018, compared with 28% in 2017, data announced Dec. 17 from the 2018 Monitoring the Future survey show.

LiudmylaSupynska/Thinkstock

In particular, nicotine vaping use in the 30 days prior to the survey nearly doubled among high school seniors, from approximately 11% in 2017 to 21% in 2018. Nicotine vaping also increased by 7.9% (from 8.2% to 16.1%) among 10th graders and by 2.6% (from 3.5% to 6.1%) among 8th graders, according to the survey results.

Vaping involves using a device such as an e-cigarette to inhale a heated aerosol product that usually contains nicotine but can be used to administer other types of drugs, said Nora D. Volkow, MD, director of the National Institute on Drug Abuse at the National Institutes of Health, in a press conference announcing the findings.

The increased prevalence of nicotine vaping in 10th and 12th graders is the largest annual increase in use of any substance recorded by Monitoring the Future, said Richard A. Miech, PhD, MPH, of the Institute for Social Research at the University of Michigan, Ann Arbor, and the principal survey investigator. “Something about this delivery device of vaping seems to really appeal to kids,” he said. The flavorings, concealability of the devices (which can be about the size of a flash drive), and ease of use seem to be contributing to the popularity of vaping, Dr. Miech added.

In addition, marijuana vaping increased significantly across all three grade levels in 2018 from 2017. Within 30 days of the survey, marijuana vaping increased from 4.9% to 7.5% in 12th graders, from 4.3% to 7.0% in 10th graders, and from 1.6% to 2.6% in 8th graders.

A take-home message for clinicians is the need to emphasize to teens that “vaping is not innocuous and not harmless,” said Dr. Miech in a question-and-answer session. Of note, data from multiple studies show that children who vape are about five times more likely to smoke cigarettes, he said.

The vaping devices are manufactured to deliver drugs into the lungs and ultimately high concentrations into the brain – which suggests the use of vaping devices to deliver other types of drugs might increase in the future, Dr. Volkow added.

Use of most other substances, including inhalants, heroin, cocaine, ecstasy, overall marijuana use, alcohol use, and extreme binge drinking remained stable, the researchers said. Cigarette smoking declined slightly among 12th graders but did not change significantly among 8th or 10th graders. Use of prescription opioids and tranquilizers declined in 2018 across all age groups.

“Vaping is reversing hard-fought declines in the number of adolescents who use nicotine,” Dr. Miech said in the news release announcing the results. “These results suggest that vaping is leading youth into nicotine use and nicotine addiction, not away from it.”

The data on vaping and nicotine use among American teens were published in a letter (N Engl J Med. 2018 Dec 17. doi: 10.1056/NEJMc1814130) – with a warning. “These results indicate that the policies in place as of the 2017-2018 school year were not sufficient to stop the spread of nicotine vaping among adolescents,” wrote the authors, led by Dr. Miech. “The rapid entry of new vaping devices on the market ... will require continual updates and modification strategies to keep adolescents from vaping and its associated negative health effects.”

The Monitoring the Future survey tracks annual drug use and drug use attitudes in a nationally representative sample of U.S. students in 8th, 10th, and 12th grades. This year’s survey included 44,482 participants. The survey is funded by a government grant to the University of Michigan, Ann Arbor, from the NIH’s NIDA.

The effectiveness of the influenza vaccine declined significantly after 9 months, according to 5 years of data from approximately 15,000 children in Hong Kong.

CAP53/iStockphoto.com

The vaccine is known to last less than a year, but the findings support the need for more vaccine availability in areas where influenza activity occurs year-round, wrote Shuo Feng, PhD, and Susan S. Chiu, MD, of the University of Hong Kong, and their colleagues.

In a study published in the Lancet Respiratory Medicine, the researchers reviewed how vaccine effectiveness changed over time by analyzing data from children aged 6 months to 17 years admitted to a Hong Kong hospital between 2012 and 2017. The study population involved 15,695 children hospitalized for respiratory infections, including 2,500 who were positive for influenza A or B and 13,195 who were negative. Of these, 6.4% of the positive patients and 11% of the negative patients had been vaccinated; 70% to 80% of the vaccinations occurred before the end of December of a given year.

Overall, the vaccination effectiveness rate was 79% for 0.5 to 2 months after vaccination, then dropped to 60% at 2-4 months, 57% at 4-6 months, and 45% at 6-9 months.

The researchers estimated vaccine effectiveness by three time periods: September to December, January to April, and May to August. Across seasons, vaccine effectiveness for all age groups was 79% for September to December, 67% for January to April, and 43% for May to August.

The study results were strengthened by the inclusion of year-round activity, but limited by several factors including lack of data on patients’ vaccination history and the specifics of each year’s flu virus, and lack of generalizability to an adult population, the researchers said.

However, the findings support data from previous studies on the effectiveness of annual vaccination, with the optimal timing from October to December in Hong Kong, they said. “Improved influenza vaccines are needed to provide year-round protection for children, particularly in subtropical and tropical locations,” they added.

The study was supported by the Health and Medical Research Fund and the Research Grants Council, Hong Kong. The lead authors had no financial conflicts to disclose.

SOURCE: Feng S et al. Lancet Respir Med. 2018;6:925-34.

The effectiveness of the influenza vaccine declined significantly after 9 months, according to 5 years of data from approximately 15,000 children in Hong Kong.

CAP53/iStockphoto.com

The vaccine is known to last less than a year, but the findings support the need for more vaccine availability in areas where influenza activity occurs year-round, wrote Shuo Feng, PhD, and Susan S. Chiu, MD, of the University of Hong Kong, and their colleagues.

In a study published in the Lancet Respiratory Medicine, the researchers reviewed how vaccine effectiveness changed over time by analyzing data from children aged 6 months to 17 years admitted to a Hong Kong hospital between 2012 and 2017. The study population involved 15,695 children hospitalized for respiratory infections, including 2,500 who were positive for influenza A or B and 13,195 who were negative. Of these, 6.4% of the positive patients and 11% of the negative patients had been vaccinated; 70% to 80% of the vaccinations occurred before the end of December of a given year.

Overall, the vaccination effectiveness rate was 79% for 0.5 to 2 months after vaccination, then dropped to 60% at 2-4 months, 57% at 4-6 months, and 45% at 6-9 months.

The researchers estimated vaccine effectiveness by three time periods: September to December, January to April, and May to August. Across seasons, vaccine effectiveness for all age groups was 79% for September to December, 67% for January to April, and 43% for May to August.

The study results were strengthened by the inclusion of year-round activity, but limited by several factors including lack of data on patients’ vaccination history and the specifics of each year’s flu virus, and lack of generalizability to an adult population, the researchers said.

However, the findings support data from previous studies on the effectiveness of annual vaccination, with the optimal timing from October to December in Hong Kong, they said. “Improved influenza vaccines are needed to provide year-round protection for children, particularly in subtropical and tropical locations,” they added.

The study was supported by the Health and Medical Research Fund and the Research Grants Council, Hong Kong. The lead authors had no financial conflicts to disclose.

SOURCE: Feng S et al. Lancet Respir Med. 2018;6:925-34.

The effectiveness of the influenza vaccine declined significantly after 9 months, according to 5 years of data from approximately 15,000 children in Hong Kong.

CAP53/iStockphoto.com

The vaccine is known to last less than a year, but the findings support the need for more vaccine availability in areas where influenza activity occurs year-round, wrote Shuo Feng, PhD, and Susan S. Chiu, MD, of the University of Hong Kong, and their colleagues.

In a study published in the Lancet Respiratory Medicine, the researchers reviewed how vaccine effectiveness changed over time by analyzing data from children aged 6 months to 17 years admitted to a Hong Kong hospital between 2012 and 2017. The study population involved 15,695 children hospitalized for respiratory infections, including 2,500 who were positive for influenza A or B and 13,195 who were negative. Of these, 6.4% of the positive patients and 11% of the negative patients had been vaccinated; 70% to 80% of the vaccinations occurred before the end of December of a given year.

Overall, the vaccination effectiveness rate was 79% for 0.5 to 2 months after vaccination, then dropped to 60% at 2-4 months, 57% at 4-6 months, and 45% at 6-9 months.

The researchers estimated vaccine effectiveness by three time periods: September to December, January to April, and May to August. Across seasons, vaccine effectiveness for all age groups was 79% for September to December, 67% for January to April, and 43% for May to August.

The study results were strengthened by the inclusion of year-round activity, but limited by several factors including lack of data on patients’ vaccination history and the specifics of each year’s flu virus, and lack of generalizability to an adult population, the researchers said.

However, the findings support data from previous studies on the effectiveness of annual vaccination, with the optimal timing from October to December in Hong Kong, they said. “Improved influenza vaccines are needed to provide year-round protection for children, particularly in subtropical and tropical locations,” they added.

The study was supported by the Health and Medical Research Fund and the Research Grants Council, Hong Kong. The lead authors had no financial conflicts to disclose.

SOURCE: Feng S et al. Lancet Respir Med. 2018;6:925-34.

Only 15% of U.S. physician practices report using telemedicine for patient care. Also today, you ought to be judicious with empiric antibiotics for febrile neutropenia, home-based exercise is better than supervised treadmill exercise for peripheral arterial disease, and brain injury in sickle cell merits more attention.
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Only 15% of U.S. physician practices report using telemedicine for patient care. Also today, you ought to be judicious with empiric antibiotics for febrile neutropenia, home-based exercise is better than supervised treadmill exercise for peripheral arterial disease, and brain injury in sickle cell merits more attention.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Only 15% of U.S. physician practices report using telemedicine for patient care. Also today, you ought to be judicious with empiric antibiotics for febrile neutropenia, home-based exercise is better than supervised treadmill exercise for peripheral arterial disease, and brain injury in sickle cell merits more attention.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

sworcester@mdedge.com

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

sworcester@mdedge.com

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

sworcester@mdedge.com

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

The Food and Drug Administration has issued an alert regarding two e-liquids sold by HelloCig Electronic Technology that contain undeclared prescription drugs. E-liquid is the flavored mixture used in electronic cigarettes.

In a laboratory analysis, the FDA found that “E-Cialis HelloCig E-Liquid” contained both sildenafil and tadalafil, and that “E-Rimonabant HelloCig E-Liquid” contained sildenafil. Sildenafil and tadalafil are approved for the treatment of erectile dysfunction. Unapproved usage of these drugs in over-the-counter e-liquids is therefore illegal.

Both sildenafil and tadalafil can interact with nitrates found in some prescription drugs and can cause a dangerous lowering of blood pressure. Conditions commonly treated with nitrates include diabetes, high blood pressure, high cholesterol, or heart disease.

“FDA recently warned HelloCig of these issues and contacted the company several times to recommend they recall these products due to the risks to consumers. However, HelloCig has not responded to the agency’s recommendation. Therefore, FDA urges consumers to stop using these products and to contact their health care professional with any concerns associated with their use,” the FDA said in the press release.

Find the full press release on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has issued an alert regarding two e-liquids sold by HelloCig Electronic Technology that contain undeclared prescription drugs. E-liquid is the flavored mixture used in electronic cigarettes.

In a laboratory analysis, the FDA found that “E-Cialis HelloCig E-Liquid” contained both sildenafil and tadalafil, and that “E-Rimonabant HelloCig E-Liquid” contained sildenafil. Sildenafil and tadalafil are approved for the treatment of erectile dysfunction. Unapproved usage of these drugs in over-the-counter e-liquids is therefore illegal.

Both sildenafil and tadalafil can interact with nitrates found in some prescription drugs and can cause a dangerous lowering of blood pressure. Conditions commonly treated with nitrates include diabetes, high blood pressure, high cholesterol, or heart disease.

“FDA recently warned HelloCig of these issues and contacted the company several times to recommend they recall these products due to the risks to consumers. However, HelloCig has not responded to the agency’s recommendation. Therefore, FDA urges consumers to stop using these products and to contact their health care professional with any concerns associated with their use,” the FDA said in the press release.

Find the full press release on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has issued an alert regarding two e-liquids sold by HelloCig Electronic Technology that contain undeclared prescription drugs. E-liquid is the flavored mixture used in electronic cigarettes.

In a laboratory analysis, the FDA found that “E-Cialis HelloCig E-Liquid” contained both sildenafil and tadalafil, and that “E-Rimonabant HelloCig E-Liquid” contained sildenafil. Sildenafil and tadalafil are approved for the treatment of erectile dysfunction. Unapproved usage of these drugs in over-the-counter e-liquids is therefore illegal.

Both sildenafil and tadalafil can interact with nitrates found in some prescription drugs and can cause a dangerous lowering of blood pressure. Conditions commonly treated with nitrates include diabetes, high blood pressure, high cholesterol, or heart disease.

“FDA recently warned HelloCig of these issues and contacted the company several times to recommend they recall these products due to the risks to consumers. However, HelloCig has not responded to the agency’s recommendation. Therefore, FDA urges consumers to stop using these products and to contact their health care professional with any concerns associated with their use,” the FDA said in the press release.

Find the full press release on the FDA website.

lfranki@mdedge.com

Leave policies for residents who become new parents are uneven, often ignored by training boards, and provide less time off than similar policies for faculty physicians. Also today, exercise is important for patients with sickle cell, COPD patients are experiencing a risk in non-TB mycobacteria infections, and how to be an influencer on social media.
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Apple Podcasts
Google Podcasts
Spotify
 

Leave policies for residents who become new parents are uneven, often ignored by training boards, and provide less time off than similar policies for faculty physicians. Also today, exercise is important for patients with sickle cell, COPD patients are experiencing a risk in non-TB mycobacteria infections, and how to be an influencer on social media.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Leave policies for residents who become new parents are uneven, often ignored by training boards, and provide less time off than similar policies for faculty physicians. Also today, exercise is important for patients with sickle cell, COPD patients are experiencing a risk in non-TB mycobacteria infections, and how to be an influencer on social media.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.

Dr. George Kubica/CDC

For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.

Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.

Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.

The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.

Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.

Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.

SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.

Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.

Dr. George Kubica/CDC

For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.

Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.

Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.

The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.

Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.

Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.

SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.

Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.

Dr. George Kubica/CDC

For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.

Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.

Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.

The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.

Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.

Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.

SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.

In patients at risk for pulmonary arterial hypertension (PAH) due to a connective tissue disease, composite novel screening methods are improving early detection when employed in the context of traditional tools, such as transthoracic echocardiography (TTE), according to a systematic review of studies published over the last 5 years.

The review was conducted to prepare for a guideline update, according to the authors of this recently published summary in Seminars in Arthritis and Rheumatism.

In a literature review for 2012-2015, the authors evaluated whether new tools or strategies have improved PAH screening in patients with connective tissue disease since the last review was undertaken (Semin Arthritis Rheum 2014;43:536-41).

The latest review found that although TTE and pulmonary function tests (PFT) remain a mainstay of screening, there is growing evidence that composite measures, such as the DETECT and ASIG algorithms, add sensitivity and specificity, compared with guidelines that rely on TTE and PFT alone.

After a literature search, the systematic review included 16 cohort studies and 6 case-control studies. Most of these evaluated PAH screening strategies for patients with systemic sclerosis specifically despite the potential for other connective tissue disease etiologies to lead to PAH.

“We need more longitudinal observational studies to develop and validate screening algorithms for non–systemic sclerosis connective tissue diseases,” stated the authors, led by senior investigator Dinesh Khanna, MD, medical director of ambulatory and chronic disease in the University of Michigan’s Office of Research, Ann Arbor.

Relative to screening primarily based on TTE and PFT as advocated in 2009 joint guidelines from the European Society of Cardiology and the European Respiratory Society (ESC/ERS), the preponderance of data supported the addition of DIRECT and ASIG algorithms to improve the sensitivity and specificity of traditional screening and diagnostic tools, according to the data reviewed.

Several of the studies evaluating DETECT and ASIG compared their sensitivities and specificities to the screening strategy recommended in the 2009 ESC/ERS guidelines because the 2015 ESC/ERS guidelines were not yet available at the time these studies were taking place.

In fact, the advantage of these algorithms has been acknowledged in a set of subsequent ESC/ERS guidelines issued in 2015. These specifically recommend DETECT in selected populations, such as adults with more than a 3-year history of systemic sclerosis and less than 60% diffusing capacity of the lung for carbon monoxide.

Based on the systematic review, the authors did not conclude that there is a single set of optimal tests for PAH screening whether in patients with systemic sclerosis or another connective tissue disease, but the authors did conclude that there has been progress in strategies for early PAH detection.

They also speculated that more progress might be coming. They noted that several newer tests, such as stress TTE to assess cardiopulmonary function during exercise, might further improve PAH detection at early stages.

According to the authors, this work is important, because better screening that results in earlier PAH detection means earlier treatment, which, in turn, “may improve survival.”

SOURCE: Young A et al. Semin Arthritis Rheum. 2018; Oct 14. doi: 10.1016/j.semarthrit.2018.10.010.

In patients at risk for pulmonary arterial hypertension (PAH) due to a connective tissue disease, composite novel screening methods are improving early detection when employed in the context of traditional tools, such as transthoracic echocardiography (TTE), according to a systematic review of studies published over the last 5 years.

The review was conducted to prepare for a guideline update, according to the authors of this recently published summary in Seminars in Arthritis and Rheumatism.

In a literature review for 2012-2015, the authors evaluated whether new tools or strategies have improved PAH screening in patients with connective tissue disease since the last review was undertaken (Semin Arthritis Rheum 2014;43:536-41).

The latest review found that although TTE and pulmonary function tests (PFT) remain a mainstay of screening, there is growing evidence that composite measures, such as the DETECT and ASIG algorithms, add sensitivity and specificity, compared with guidelines that rely on TTE and PFT alone.

After a literature search, the systematic review included 16 cohort studies and 6 case-control studies. Most of these evaluated PAH screening strategies for patients with systemic sclerosis specifically despite the potential for other connective tissue disease etiologies to lead to PAH.

“We need more longitudinal observational studies to develop and validate screening algorithms for non–systemic sclerosis connective tissue diseases,” stated the authors, led by senior investigator Dinesh Khanna, MD, medical director of ambulatory and chronic disease in the University of Michigan’s Office of Research, Ann Arbor.

Relative to screening primarily based on TTE and PFT as advocated in 2009 joint guidelines from the European Society of Cardiology and the European Respiratory Society (ESC/ERS), the preponderance of data supported the addition of DIRECT and ASIG algorithms to improve the sensitivity and specificity of traditional screening and diagnostic tools, according to the data reviewed.

Several of the studies evaluating DETECT and ASIG compared their sensitivities and specificities to the screening strategy recommended in the 2009 ESC/ERS guidelines because the 2015 ESC/ERS guidelines were not yet available at the time these studies were taking place.

In fact, the advantage of these algorithms has been acknowledged in a set of subsequent ESC/ERS guidelines issued in 2015. These specifically recommend DETECT in selected populations, such as adults with more than a 3-year history of systemic sclerosis and less than 60% diffusing capacity of the lung for carbon monoxide.

Based on the systematic review, the authors did not conclude that there is a single set of optimal tests for PAH screening whether in patients with systemic sclerosis or another connective tissue disease, but the authors did conclude that there has been progress in strategies for early PAH detection.

They also speculated that more progress might be coming. They noted that several newer tests, such as stress TTE to assess cardiopulmonary function during exercise, might further improve PAH detection at early stages.

According to the authors, this work is important, because better screening that results in earlier PAH detection means earlier treatment, which, in turn, “may improve survival.”

SOURCE: Young A et al. Semin Arthritis Rheum. 2018; Oct 14. doi: 10.1016/j.semarthrit.2018.10.010.

In patients at risk for pulmonary arterial hypertension (PAH) due to a connective tissue disease, composite novel screening methods are improving early detection when employed in the context of traditional tools, such as transthoracic echocardiography (TTE), according to a systematic review of studies published over the last 5 years.

The review was conducted to prepare for a guideline update, according to the authors of this recently published summary in Seminars in Arthritis and Rheumatism.

In a literature review for 2012-2015, the authors evaluated whether new tools or strategies have improved PAH screening in patients with connective tissue disease since the last review was undertaken (Semin Arthritis Rheum 2014;43:536-41).

The latest review found that although TTE and pulmonary function tests (PFT) remain a mainstay of screening, there is growing evidence that composite measures, such as the DETECT and ASIG algorithms, add sensitivity and specificity, compared with guidelines that rely on TTE and PFT alone.

After a literature search, the systematic review included 16 cohort studies and 6 case-control studies. Most of these evaluated PAH screening strategies for patients with systemic sclerosis specifically despite the potential for other connective tissue disease etiologies to lead to PAH.

“We need more longitudinal observational studies to develop and validate screening algorithms for non–systemic sclerosis connective tissue diseases,” stated the authors, led by senior investigator Dinesh Khanna, MD, medical director of ambulatory and chronic disease in the University of Michigan’s Office of Research, Ann Arbor.

Relative to screening primarily based on TTE and PFT as advocated in 2009 joint guidelines from the European Society of Cardiology and the European Respiratory Society (ESC/ERS), the preponderance of data supported the addition of DIRECT and ASIG algorithms to improve the sensitivity and specificity of traditional screening and diagnostic tools, according to the data reviewed.

Several of the studies evaluating DETECT and ASIG compared their sensitivities and specificities to the screening strategy recommended in the 2009 ESC/ERS guidelines because the 2015 ESC/ERS guidelines were not yet available at the time these studies were taking place.

In fact, the advantage of these algorithms has been acknowledged in a set of subsequent ESC/ERS guidelines issued in 2015. These specifically recommend DETECT in selected populations, such as adults with more than a 3-year history of systemic sclerosis and less than 60% diffusing capacity of the lung for carbon monoxide.

Based on the systematic review, the authors did not conclude that there is a single set of optimal tests for PAH screening whether in patients with systemic sclerosis or another connective tissue disease, but the authors did conclude that there has been progress in strategies for early PAH detection.

They also speculated that more progress might be coming. They noted that several newer tests, such as stress TTE to assess cardiopulmonary function during exercise, might further improve PAH detection at early stages.

According to the authors, this work is important, because better screening that results in earlier PAH detection means earlier treatment, which, in turn, “may improve survival.”

SOURCE: Young A et al. Semin Arthritis Rheum. 2018; Oct 14. doi: 10.1016/j.semarthrit.2018.10.010.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.