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.
Article and author information
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.
Metrics
-
- 881
- views
-
- 101
- downloads
-
- 14
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
Further reading
-
- Medicine
- Neuroscience
Background:
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy.
Methods:
High-resolution mass spectrometry lipidomics was applied to quantify d=255 different lipid mediators in the blood of n=31 patients drawn before and after paclitaxel therapy for breast cancer treatment. A variety of supervised statistical and machine-learning methods was applied to identify lipids that were regulated during paclitaxel therapy or differed among patients with and without post-therapeutic neuropathy.
Results:
Twenty-seven lipids were identified that carried relevant information to train machine learning algorithms to identify, in new cases, whether a blood sample was drawn before or after paclitaxel therapy with a median balanced accuracy of up to 90%. One of the top hits, sphinganine-1-phosphate (SA1P), was found to induce calcium transients in sensory neurons via the transient receptor potential vanilloid 1 (TRPV1) channel and sphingosine-1-phosphate receptors.SA1P also showed different blood concentrations between patients with and without neuropathy.
Conclusions:
Present findings suggest a role for sphinganine-1-phosphate in paclitaxel-induced biological changes associated with neuropathic side effects. The identified SA1P, through its receptors, may provide a potential drug target for co-therapy with paclitaxel to reduce one of its major and therapy-limiting side effects.
Funding:
This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG, Grants SFB1039 A09 and Z01) and by the Fraunhofer Foundation Project: Neuropathic Pain as well as the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD). This work was also supported by the Leistungszentrum Innovative Therapeutics (TheraNova) funded by the Fraunhofer Society and the Hessian Ministry of Science and Arts. Jörn Lötsch was supported by the Deutsche Forschungsgemeinschaft (DFG LO 612/16-1).
-
- Medicine
- Neuroscience
A complex extracted from the amniotic membrane in humans reduces post-surgical pain in mice by directly inhibiting pain-sensing neurons.
