TY - JOUR
T1 - Clinical significance of the bronchodilator response in children with severe asthma
AU - Coverstone, Andrea M.
AU - Bacharier, Leonard B.
AU - Wilson, Bradley S.
AU - Fitzpatrick, Anne M.
AU - Teague, William Gerald
AU - Phipatanakul, Wanda
AU - Wenzel, Sally E.
AU - Gaston, Benjamin M.
AU - Bleecker, Eugene R.
AU - Moore, Wendy C.
AU - Ramratnam, Sima
AU - Jarjour, Nizar N.
AU - Ly, Ngoc P.
AU - Fahy, John V.
AU - Mauger, David T.
AU - Schechtman, Kenneth B.
AU - Yin-DeClue, Huiqing
AU - Boomer, Jonathan S.
AU - Castro, Mario
N1 - Funding Information:
In addition, SARP has received support from the following companies: AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Sanofi-Genzyme-Regeneron, and TEVA. LBB reports personal fees from GlaxoSmithKline, Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi/Regeneron, Vectura, and Circassia. WP has received funding from NIH (Institutional), Genentech, Novartis, Alk-Abello, GSK, Monaghan, Lincoln Diagnostics, Thermo Fisher, Regeneron, Sanofi, Merck, Circassia, AstraZeneca; she has consulted for Genentech, Novartis, GSK, Regeneron, Sanofi and has received speaker's fees from Genentech, GSK. SEW has received financial support for SARP operations from Boehringer Ingelheim; she has consulted for AstraZeneca, GSK, Sanofi Genzyme and has been local PI on multicenter trials for AstraZeneca, GSK, Sanofi Genzyme, Novartis. ERB has received funding for clinical trials from AstraZeneca, MedImmune, Boehringer Ingelheim, Genentech, Novartis, Regeneron, and Sanofi Genzyme; he has consulted for ALK-Abello, AstraZeneca, MedImmune, Glaxo Smith Kline, Novartis, Regeneron, Sanofi Genzyme, and TEVA. NPY has received grant support from Vertex, Gilead, CFF, NSF, and NIH. JVH has received grants from NIH/NHLBI and from Boehringer Ingelheim during the conduct of the study; personal fees from Boehringer Ingelheim, Pieris, Arrowhead Pharmaceuticals, Gossamer, outside the submitted work; in addition, he has a patent US20110123530A1 - "Compositions and methods for treating and diagnosing asthma" issued, a patent WO2014153009A2 – “Thiosaccharide mucolytic agents” issued, and a patent WO2017197360 - “CT Mucus Score” - A new scoring system that quantifies airway mucus impaction using CT lung scans. DTM has received grant support for SARP from AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Sanofi-Genzyme-Regeneron, and TEVA. MC has received University Grant Funding from NIH, American Lung Association, PCORI and Pharmaceutical Grant Funding from AstraZeneca, Chiesi, Novartis, GSK, Sanofi-Aventis; he has consulted for Genentech, Theravance, VIDA, Teva, Sanofi-Aventis; he has received speaker's fees for AstraZeneca, Genentech, GSK, Regeneron, Sanofi, Teva and Royalties from Elsevier. Some of this data was previously presented in abstract form as a poster presentation titled “Predictors of response to bronchodilators in children with severe asthma” at the 20142014 American Thoracic Society Conference in San Diego, CA.
Funding Information:
In addition, SARP has received support from the following companies: AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Sanofi‐Genzyme‐Regeneron, and TEVA. LBB reports personal fees from GlaxoSmithKline, Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi/Regeneron, Vectura, and Circassia. WP has received funding from NIH (Institutional), Genentech, Novartis, Alk‐Abello, GSK, Monaghan, Lincoln Diagnostics, Thermo Fisher, Regeneron, Sanofi, Merck, Circassia, AstraZeneca; she has consulted for Genentech, Novartis, GSK, Regeneron, Sanofi and has received speaker's fees from Genentech, GSK. SEW has received financial support for SARP operations from Boehringer Ingelheim; she has consulted for AstraZeneca, GSK, Sanofi Genzyme and has been local PI on multicenter trials for AstraZeneca, GSK, Sanofi Genzyme, Novartis. ERB has received funding for clinical trials from AstraZeneca, MedImmune, Boehringer Ingelheim, Genentech, Novartis, Regeneron, and Sanofi Genzyme; he has consulted for ALK‐Abello, AstraZeneca, MedImmune, Glaxo Smith Kline, Novartis, Regeneron, Sanofi Genzyme, and TEVA. NPY has received grant support from Vertex, Gilead, CFF, NSF, and NIH. JVH has received grants from NIH/NHLBI and from Boehringer Ingelheim during the conduct of the study; personal fees from Boehringer Ingelheim, Pieris, Arrowhead Pharmaceuticals, Gossamer, outside the submitted work; in addition, he has a patent US20110123530A1 ‐ "Compositions and methods for treating and diagnosing asthma" issued, a patent WO2014153009A2 – “Thiosaccharide mucolytic agents” issued, and a patent WO2017197360 ‐ “CT Mucus Score” ‐ A new scoring system that quantifies airway mucus impaction using CT lung scans. DTM has received grant support for SARP from AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Sanofi‐Genzyme‐Regeneron, and TEVA. MC has received University Grant Funding from NIH, American Lung Association, PCORI and Pharmaceutical Grant Funding from AstraZeneca, Chiesi, Novartis, GSK, Sanofi‐Aventis; he has consulted for Genentech, Theravance, VIDA, Teva, Sanofi‐Aventis; he has received speaker's fees for AstraZeneca, Genentech, GSK, Regeneron, Sanofi, Teva and Royalties from Elsevier. Some of this data was previously presented in abstract form as a poster presentation titled “Predictors of response to bronchodilators in children with severe asthma” at the 20142014 American Thoracic Society Conference in San Diego, CA.
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Background: Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP). Methods: We performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility. Results: We evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05-4.13), second-hand smoke exposure (OR, 2.81, 95%CI, 1.23-6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35-2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1% predicted (OR, 0.91, 95%CI, 0.88-0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1% predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1-year follow-up though less decline in lung function over 1 year compared to those without reversibility. Conclusions: Lung function, that is FEV1% predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.
AB - Background: Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP). Methods: We performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility. Results: We evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05-4.13), second-hand smoke exposure (OR, 2.81, 95%CI, 1.23-6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35-2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1% predicted (OR, 0.91, 95%CI, 0.88-0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1% predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1-year follow-up though less decline in lung function over 1 year compared to those without reversibility. Conclusions: Lung function, that is FEV1% predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.
KW - asthma
KW - bronchodilator response
KW - pediatrics
UR - http://www.scopus.com/inward/record.url?scp=85070818146&partnerID=8YFLogxK
U2 - 10.1002/ppul.24473
DO - 10.1002/ppul.24473
M3 - Article
C2 - 31424170
AN - SCOPUS:85070818146
SN - 8755-6863
VL - 54
SP - 1694
EP - 1703
JO - Pediatric Pulmonology
JF - Pediatric Pulmonology
IS - 11
ER -