Loss of adaptive capacity in asthmatic patients revealed by biomarker fluctuation dynamics after rhinovirus challenge

  1. Anirban Sinha  Is a corresponding author
  2. René Lutter
  3. Binbin Xu
  4. Tamara Dekker
  5. Barbara Dierdorp
  6. Peter J Sterk
  7. Urs Frey
  8. Edgar Delgado Eckert
  1. Amsterdam University Medical Center, University of Amsterdam, Netherlands
  2. University of Bordeaux, France
  3. 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

  1. Anirban Sinha

    Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
    For correspondence
    a.sinha@amsterdamumc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4146-9687
  2. René Lutter

    Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Binbin Xu

    Inserm, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Tamara Dekker

    Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Barbara Dierdorp

    Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter J Sterk

    Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Urs Frey

    University Children's Hospital, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  8. Edgar Delgado Eckert

    University Children's Hospital, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.

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.

Reviewing Editor

  1. Jos WM van der Meer, Radboud University Medical Centre, Netherlands

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.

Version history

  1. Received: April 26, 2019
  2. Accepted: November 4, 2019
  3. Accepted Manuscript published: November 5, 2019 (version 1)
  4. Version of Record published: November 25, 2019 (version 2)
  5. Version of Record updated: December 13, 2019 (version 3)
  6. Version of Record updated: October 30, 2020 (version 4)

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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  1. Anirban Sinha
  2. René Lutter
  3. Binbin Xu
  4. Tamara Dekker
  5. Barbara Dierdorp
  6. Peter J Sterk
  7. Urs Frey
  8. Edgar Delgado Eckert
(2019)
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

Share this article

https://doi.org/10.7554/eLife.47969

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