PT  - JOURNAL ARTICLE
AU  - Anirban Sinha
AU  - René Lutter
AU  - Binbin Xu
AU  - Tamara Dekker
AU  - Barbara Dierdorp
AU  - Peter J. Sterk
AU  - Urs Frey
AU  - Edgar Delgado-Eckert
TI  - Loss of adaptive capacity in asthmatics revealed by biomarker fluctuation dynamics upon experimental rhinovirus challenge
AID  - 10.1101/684910
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 684910
4099  - http://biorxiv.org/content/early/2019/07/02/684910.short
4100  - http://biorxiv.org/content/early/2019/07/02/684910.full
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.