Loss of adaptive capacity in asthmatics revealed by biomarker fluctuation dynamics on experimental rhinovirus challenge

Abstract

Asthma is a dynamic disease, in which lung mechanical and inflammatory processes often interact in a complex, unpredictable manner. We hypothesize that this may be explained by respiratory disease-related systems instability and loss of adaptability to changing environmental conditions, resulting in highly fluctuating biomarkers and symptoms. Using time series of inflammatory (eosinophils, neutrophils, FeNO), clinical and lung function biomarkers (PEF, FVC, and FEV1), we estimated this loss of adaptive capacity (AC) during an experimental perturbation with a rhinovirus in 24 healthy and asthmatic volunteers. Loss of AC was estimated by comparing similarities between pre- and post-challenge time series. Unlike healthy participants, the asthmatics post-viral-challenge state resembled significantly more other rhinovirus-infected asthmatics than their own pre-viral-challenge state (hypergeometric-test: p=0.029). This reveals loss of AC, and supports the novel concept that not only single physiological mechanisms, but interacting dynamic disease properties are altered in asthma and contribute to a more vulnerable phenotype.