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

Loren C. Denlinger(University of Wisconsin–Madison), Brenda R. Phillips(Pennsylvania State University), Sima Ramratnam(University of Wisconsin–Madison), Kristie Ross(Clinical Trial Investigators), Nirav R. Bhakta(University of California, San Francisco), Juan Carlos Cardet(Harvard University), Mario Castro(Washington University in St. Louis), Stephen P. Peters(Wake Forest University), Wanda Phipatanakul(Harvard University), Shean Aujla(University of Pittsburgh), Leonard B. Bacharier(Washington University in St. Louis), Eugene R. Bleecker(Wake Forest University), Suzy Comhair(Cleveland Clinic), Andrea M. Coverstone(Washington University in St. Louis), Mark D. DeBoer(University of Virginia), Serpil C. Erzurum(Cleveland Clinic), Sean B. Fain(University of Wisconsin–Madison), Merritt L. Fajt(University of Pittsburgh), Anne M. Fitzpatrick(Emory University), Jonathan M. Gaffin(Harvard University), Benjamin Gaston(Clinical Trial Investigators), Annette T. Hastie(Wake Forest University), Gregory A. Hawkins(Wake Forest University), Fernando Holguín(University of Pittsburgh), Anne-Marie Irani(Virginia Commonwealth University), Elliot Israel(Harvard University), Bruce D. Levy(Harvard University), Ngoc P. Ly(University of California, San Francisco), Deborah A. Meyers(Wake Forest University), Wendy C. Moore(Wake Forest University), Ross Myers(Clinical Trial Investigators), Maria Theresa D. Opina(Wake Forest University), Michael C. Peters(University of California, San Francisco), Mark L. Schiebler(University of Wisconsin–Madison), Ronald L. Sorkness(University of Wisconsin–Madison), W. Gerald Teague(University of Virginia), Sally E. Wenzel(University of Pittsburgh), Prescott G. Woodruff(University of California, San Francisco), David T. Mauger(Pennsylvania State University), John V. Fahy(University of California, San Francisco), Nizar N. Jarjour(University of Wisconsin–Madison)
American Journal of Respiratory and Critical Care Medicine
August 24, 2016
10.1164/rccm.201602-0419oc
Cited by 444Open Access
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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-1 + 2 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-1 + 2 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).

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