Biomarkers of Asthma Relapse and Lung Function Decline in Adults with Remitted Asthma: A Population-Based Cohort Study.

Abstract

Introduction. Whether systemic and airway inflammation persist in remitted asthma and whether such inflammation is associated with adverse long-term respiratory outcomes remains unclear. Objective. To determine the prevalence of systemic and airway inflammation in adults with remitted asthma, and to examine their associations with asthma relapse and lung function decline. Methods. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort first studied in 1968 (n = 8,583). In 2004 (age 44), biomarkers of systemic inflammation (serum IL-4, IL-5, IL-6, IL-8, IL10, TNF-) were measured in a subgroup (n = 1,389) and categorised into cytokine profiles using latent profile analysis (LPA). In 2010 (age 50), markers of airway inflammation, methacholine challenge tests (n = 836) and total nitric oxide products in exhaled breath condensate (EBC NOx), were measured. Asthma relapse and lung function decline were assessed at follow-up in 2014. Multivariable linear and Poisson regression were used to examine relevant associations. Results. Of adults with remitted asthma at age 50 years, 20.8% [95% CI 15.9, 26.7] had bronchial hyperresponsiveness (BHR) and 7.1% [95% CI 4.2 ,11.9] had an elevated EBC NOx (>5.05 mumol/L). Asthma relapse was associated with BHR (RR 2.25 [95%CI 1.52, 3.32]), but not with elevated EBC NOx. Three distinct cytokine profiles were identified via LPA: A reference anormala cytokine profile, a aTh2-higha profile associated with accelerated post-BD FEV1/FVC decline (MD-0.18% predicted/year [-0.33,-0.02]), and a aTh2-lowa profile associated with accelerated postBD FEV1 (MD-0.41% predicted/year [-0.75,-0.06]) and post-BD FVC decline (MD-0.31% predicted/year [-0.62, 0.01]). Conclusion. BHR and elevated biomarkers of asthma activity have prognostic value in adults with remitted asthma. At-risk individuals may benefit from closer follow-up, repeat spirometry and potentially antiinflammatory agents.