Loss of adaptive capacity in asthmatic patients revealed by biomarker fluctuation dynamics after rhinovirus challenge
- Amsterdam University Medical Center, University of Amsterdam, Netherlands
- University of Bordeaux, France
- University Children's Hospital, University of Basel, Switzerland
Abstract
Asthma is a dynamic disease, in which lung mechanical and inflammatory processes interact in a complex manner, often resulting in exaggerated physiological, in particular, inflammatory responses to exogenous triggers. We hypothesize that this may be explained by respiratory disease-related systems instability and loss of adaptability to changing environmental conditions, manifested in highly fluctuating biomarkers and symptoms. Using time series of inflammatory (eosinophils, neutrophils, FeNO), clinical and lung function biomarkers (PEF, FVC,FEV1), we estimated this loss of adaptive capacity (AC) during an experimental rhinovirus infection in 24 healthy and asthmatic human 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 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 concept that in asthma, biological processes underlying inflammatory and physiological responses are unstable, contributing to loss of control.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
European Respiratory Society-Maria Sklodowska Curie actions Cofund Respire 2 (MCF-7077-2014)
- Anirban Sinha
Chiesi Pharmaceuticals
- Anirban Sinha
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study protocol along with the viral dose used and its safety have been approved by the institutional Medical Ethics Committee in Amsterdam University Medical Centre (Protocol No. NL54293.018.15). The trial has been registered at the Netherlands Trial Register (Netherlands Trial Register (NTR5426/NL5317).Proper Informed Consent was taken from every participant.
Copyright
© 2019, Sinha et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Loss of adaptive capacity in asthmatic patients revealed by biomarker fluctuation dynamics after rhinovirus challenge
eLife 8:e47969.
https://doi.org/10.7554/eLife.47969
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