RT Journal Article
SR Electronic
T1 Loss of adaptive capacity in asthmatics revealed by biomarker fluctuation dynamics upon experimental rhinovirus challenge
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 684910
DO 10.1101/684910
A1 Sinha, Anirban
A1 Lutter, René
A1 Xu, Binbin
A1 Dekker, Tamara
A1 Dierdorp, Barbara
A1 Sterk, Peter J.
A1 Frey, Urs
A1 Delgado-Eckert, Edgar
YR 2019
UL http://biorxiv.org/content/early/2019/07/02/684910.abstract
AB 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 asthmatic’s 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.