Journal article
Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations
American journal of respiratory and critical care medicine, Vol.195(3), pp.302-313
02/01/2017
DOI: 10.1164/rccm.201602-0419OC
PMCID: PMC5328178
PMID: 27556234
Abstract
Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.
To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.
Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (≥3). Replication of a multivariable model was performed with data from the SARP-1 + 2 cohort.
Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval], 1.6 [1.2-2.1] for every log unit of eosinophils, 1.3 [1.1-1.4] for every 10 body mass index units, and 1.2 [1.1-1.4] for every 10% increase in bronchodilatory responsiveness). Chronic sinusitis and gastroesophageal reflux were also associated with exacerbation frequency (1.7 [1.4-2.1] and 1.6 [1.3-2.0]), even after adjustment for multiple factors. These effects were replicated in the SARP-1 + 2 multivariable model.
EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).
Details
- Title: Subtitle
- Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations
- Creators
- Loren C Denlinger - University of Wisconsin–MadisonBrenda R Phillips - Pennsylvania State UniversitySima Ramratnam - University of Wisconsin–MadisonKristie Ross - Case Western Reserve UniversityNirav R Bhakta - University of California, San FranciscoJuan Carlos Cardet - Harvard UniversityMario Castro - Washington University in St. LouisStephen P Peters - Wake Forest UniversityWanda Phipatanakul - Harvard UniversityShean Aujla - University of PittsburghLeonard B Bacharier - Washington University in St. LouisEugene R Bleecker - Wake Forest UniversitySuzy A A Comhair - Cleveland ClinicAndrea Coverstone - Washington University in St. LouisMark DeBoer - University of VirginiaSerpil C Erzurum - Cleveland ClinicSean B Fain - University of Wisconsin–MadisonMerritt Fajt - University of PittsburghAnne M Fitzpatrick - Emory UniversityJonathan Gaffin - Harvard UniversityBenjamin Gaston - Case Western Reserve UniversityAnnette T Hastie - Wake Forest UniversityGregory A Hawkins - Wake Forest UniversityFernando Holguin - University of PittsburghAnne-Marie Irani - Virginia Commonwealth UniversityElliot Israel - Harvard UniversityBruce D Levy - Harvard UniversityNgoc Ly - University of California, San FranciscoDeborah A Meyers - Wake Forest UniversityWendy C Moore - Wake Forest UniversityRoss Myers - Case Western Reserve UniversityMaria Theresa D Opina - Wake Forest UniversityMichael C Peters - University of California, San FranciscoMark L Schiebler - University of Wisconsin–MadisonRonald L Sorkness - University of Wisconsin–MadisonW Gerald Teague - University of VirginiaSally E Wenzel - University of PittsburghPrescott G Woodruff - University of California, San FranciscoDavid T Mauger - Pennsylvania State UniversityJohn V Fahy - University of California, San FranciscoNizar N Jarjour - University of Wisconsin–MadisonNational Heart, Lung, and Blood Institute’s Severe Asthma Research Program-3 Investigators
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.195(3), pp.302-313
- DOI
- 10.1164/rccm.201602-0419OC
- PMID
- 27556234
- PMCID
- PMC5328178
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Grant note
- K23 HL116657 / NHLBI NIH HHS R01 HL115118 / NHLBI NIH HHS U10 HL109146 / NHLBI NIH HHS UL1 TR001102 / NCATS NIH HHS UL1 TR000454 / NCATS NIH HHS U10 HL109250 / NHLBI NIH HHS UL1 RR025011 / NCRR NIH HHS U10 HL109086 / NHLBI NIH HHS U10 HL109257 / NHLBI NIH HHS U10 HL109168 / NHLBI NIH HHS U10 HL109164 / NHLBI NIH HHS UL1 TR000427 / NCATS NIH HHS K23 AI106945 / NIAID NIH HHS U10 HL109152 / NHLBI NIH HHS U10 HL109172 / NHLBI NIH HHS K12 HL119997 / NHLBI NIH HHS UL1 TR001420 / NCATS NIH HHS
- Language
- English
- Date published
- 02/01/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Health, Sport, and Human Physiology
- Record Identifier
- 9984274954002771
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