Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations

• Type of Material: Article
• Authors: Loren C. Denlinger, University of Wisconsin; Brenda R. Phillips, Penn State University; Sima Ramratnam, University of Wisconsin; Kristie Ross, Case Western Reserve University; Nirav R. Bhakta, University of California San Francisco; Juan Carlos Cardet, Harvard Medical School; Mario Castro, Washington University; Stephen P. Peters, Wake Forest University; Wanda Phipatanakul, Harvard Medical School; Shean Aujla, University of Pittsburgh; Leonard B. Bacharier, Washington University; Eugene R Bleecker, Wake Forest University; Suzy A. A. Comhair, Cleveland Clinic; Andrea Coverstone, Washington University; Mark DeBoer, University of Virginia; Serpil C. Erzurum, Cleveland Clinic; Sean B. Fain, University of Wisconsin; Merritt Fajt, University of Pittsburgh; Anne M Fitzpatrick, Emory University; Jonathan Gaffin, Harvard Medical School; Benjamin Gaston, Case Western Reserve University; Annette T. Hastie, Wake Forest University; Gregory A. Hawkins, Wake Forest University; Fernando Holguin, University of Pittsburgh; Anne-Marie Irani, Virginia Commonwealth University; Elliot Israel, Harvard Medical School; Bruce D. Levy, Harvard Medical School; Ngoc Ly, University of California San Francisco; Deborah A. Meyers, Wake Forest University; Wendy C. Moore, Wake Forest University; Ross Myers, Case Western Reserve University; Maria Theresa D. Opina, Wake Forest University; Michael C. Peters, University of California San Francisco; Mark L. Schiebler, University of Wisconsin; Ronald L. Sorkness, University of Wisconsin; W. Gerald Teague, University of Virginia; Sally E. Wenzel, University of Pittsburgh; Prescott G. Woodruff, University of California San Francisco; David T. Mauger, The Pennsylvania State University College of Medicine; John V. Fahy, University of California San Francisco; Nizar N. Jarjour, University of Wisconsin
• Language: English
• Date: 2017-02-01
• Publisher: American Thoracic Society
• Publication Version: Final Published Version
• Copyright Statement: © 2017 by the American Thoracic Society
• Final Published Version (URL): http://dx.doi.org/10.1164/rccm.201602-0419OC
• Title of Journal or Parent Work: American Journal of Respiratory and Critical Care Medicine
• ISSN: 1073-449X
• Volume: 195
• Issue: 3
• Start Page: 302
• End Page: 313
• Grant/Funding Information: Supported by NHLBI to the Severe Asthma Research Program (SARP) Principal Investigators, Clinical Centers, and Data Coordinating Center as follows: U10 HL109164 (E.R.B.), U10 HL109257 (M.C.), U10 HL109250 (S.C.E.), U10 HL109146 (J.V.F.), U10 HL109250 (B.G.), U10 HL109172 (E.I. and B.D.L.), U10 HL109168 (N.N.J.), U10 HL109250 (W.G.T.), U10 HL109152 (S.E.W.), and U10 HL109086–04 (D.T.M.).; As an ancillary study to SARP, RO1 HL115118 (L.C.D.) focused on the mechanisms of recovery from virus-induced asthma exacerbations.; In addition, this program is supported through the following National Institutes of Health National Center for Advancing Translational Sciences awards: UL1 TR001420 (Wake Forest University), UL1 TR000427 (University of Wisconsin), UL1 TR001102 (Harvard University), and UL1 TR000454 (Emory University).
• Keywords: REVERSIBILITY; eosinophils; CONTROLLED-TRIAL; RESEARCH-PROGRAM; exacerbation-prone asthma; ALLERGIC-ASTHMA; DISEASE; General & Internal Medicine; Critical Care Medicine; gastroesophageal reflux; bronchodilator reversibility; ADULTS; TO-TREAT ASTHMA; sinusitis; Life Sciences & Biomedicine; RISK; Respiratory System; LUNG; CLUSTER-ANALYSIS; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Biostatistics

Abstract

Rationale: 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. Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA. Methods: 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-112 cohort. Measurements and Main Results: 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-112 multivariable model. Conclusions: 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).