1. Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations
- Author
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Denlinger, Loren C, Phillips, Brenda R, Ramratnam, Sima, Ross, Kristie, Bhakta, Nirav R, Cardet, Juan Carlos, Castro, Mario, Peters, Stephen P, Phipatanakul, Wanda, Aujla, Shean, Bacharier, Leonard B, Bleecker, Eugene R, Comhair, Suzy AA, Coverstone, Andrea, DeBoer, Mark, Erzurum, Serpil C, Fain, Sean B, Fajt, Merritt, Fitzpatrick, Anne M, Gaffin, Jonathan, Gaston, Benjamin, Hastie, Annette T, Hawkins, Gregory A, Holguin, Fernando, Irani, Anne-Marie, Israel, Elliot, Levy, Bruce D, Ly, Ngoc, Meyers, Deborah A, Moore, Wendy C, Myers, Ross, Opina, Maria Theresa D, Peters, Michael C, Schiebler, Mark L, Sorkness, Ronald L, Teague, W Gerald, Wenzel, Sally E, Woodruff, Prescott G, Mauger, David T, Fahy, John V, Jarjour, Nizar N, and National Heart, Lung, and Blood Institute’s Severe Asthma Research Program-3 Investigators
- Subjects
Adult ,Male ,Adolescent ,sinusitis ,gastroesophageal reflux ,Respiratory System ,Drug Resistance ,Comorbidity ,Nitric Oxide ,Severity of Illness Index ,Medical and Health Sciences ,Body Mass Index ,Clinical Research ,Humans ,Albuterol ,Sex Distribution ,Child ,Lung ,Inflammation ,Chi-Square Distribution ,Sputum ,National Heart ,Immunoglobulin E ,Middle Aged ,Asthma ,Bronchodilator Agents ,Eosinophils ,bronchodilator reversibility ,Breath Tests ,Disease Progression ,Respiratory ,Female ,Disease Susceptibility ,and Blood Institute’s Severe Asthma Research Program-3 Investigators ,Biomarkers ,exacerbation-prone asthma - Abstract
RationaleReducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.ObjectivesTo describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.MethodsBaseline 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 resultsOf 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.ConclusionsEPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).
- Published
- 2017