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.

Metrics

  • 856
    Page views
  • 100
    Downloads
  • 12
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

  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

Further reading

    1. Medicine
    Hong Chen, Lijun Sun ... Yue Yin
    Research Article

    Mechanism underlying the metabolic benefit of intermittent fasting remains largely unknown. Here, we reported that intermittent fasting promoted interleukin-22 (IL-22) production by type 3 innate lymphoid cells (ILC3s) and subsequent beigeing of subcutaneous white adipose tissue. Adoptive transfer of intestinal ILC3s increased beigeing of white adipose tissue in diet-induced-obese mice. Exogenous IL-22 significantly increased the beigeing of subcutaneous white adipose tissue. Deficiency of IL-22 receptor (IL-22R) attenuated the beigeing induced by intermittent fasting. Single-cell sequencing of sorted intestinal immune cells revealed that intermittent fasting increased aryl hydrocarbon receptor signaling in ILC3s. Analysis of cell-cell ligand receptor interactions indicated that intermittent fasting may stimulate the interaction of ILC3s with dendritic cells and macrophages. These results establish the role of intestinal ILC3s in beigeing of white adipose tissue, suggesting that ILC3/IL-22/IL-22R axis contributes to the metabolic benefit of intermittent fasting.

    1. Medicine
    2. Neuroscience
    Marvin Petersen, Felix Hoffstaedter ... Bastian Cheng
    Research Article

    The link between metabolic syndrome (MetS) and neurodegenerative as well as cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, brain morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis, we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.