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Original research
Changes in exhaled volatile organic compounds following indirect bronchial challenge in suspected asthma
  1. Adam Peel1,
  2. Ran Wang2,3,
  3. Waqar Ahmed2,
  4. Iain White2,4,
  5. Maxim Wilkinson2,
  6. Yoon K Loke5,6,
  7. Andrew M Wilson5,6,
  8. Stephen J Fowler2,3
  1. 1 Respiratory medicine, Norfolk Community Health and Care NHS Trust, Norwich, Norfolk, UK
  2. 2 Division of Immunology, Immunity to infection & Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, UK
  3. 3 Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK
  4. 4 Laboratory for Environmental and Life Sciences, University of Nova Gorica, Nova Gorica, Slovenia
  5. 5 Norwich Medical School, University of East Anglia, Norwich, Norfolk, UK
  6. 6 Department of Respiratory Medicine, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK
  1. Correspondence to Dr Stephen J Fowler, Division of Immunology, Immunity to infection & Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester M23 9LT, UK; stephen.fowler{at}


Background Inhaled mannitol provokes bronchoconstriction via mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that the mannitol challenge would trigger changes in exhaled volatile organic compounds (VOCs), generating both candidate biomarkers and novel insights into their origin.

Methods Participants with a clinical diagnosis of asthma, or undergoing investigation for suspected asthma, were recruited. Inhaled mannitol challenges were performed, followed by a sham challenge after 2 weeks in participants with bronchial hyper-responsiveness (BHR). VOCs were collected before and after challenges and analysed using gas chromatography–mass spectrometry.

Results Forty-six patients (mean (SD) age 52 (16) years) completed a mannitol challenge, of which 16 (35%) were positive, and 15 of these completed a sham challenge. Quantities of 16 of 51 identified VOCs changed following mannitol challenge (p<0.05), of which 11 contributed to a multivariate sparse partial least square discriminative analysis model, with a classification error rate of 13.8%. Five of these 16 VOCs also changed (p<0.05) in quantity following the sham challenge, along with four further VOCs. In patients with BHR to mannitol distinct postchallenge VOC signatures were observed compared with post-sham challenge.

Conclusion Inhalation of mannitol was associated with changes in breath VOCs, and in people with BHR resulted in a distinct exhaled breath profile when compared with a sham challenge. These differentially expressed VOCs are likely associated with acute airway inflammation and/or bronchoconstriction and merit further investigation as potential biomarkers in asthma.

  • asthma

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • AMW and SJF are joint senior authors.

  • Twitter @Ran_Wang_UoM, @StephenJ_Fowler

  • AP and RW contributed equally.

  • Contributors AP contributed to the planning, study set up, data acquisition and reviewing of the submitted article. RW conducted the statistical analysis and writing of the article. WA, IW and AMW contributed to sample analysis, data pre-processing, data quality check and reviewing of the submitted article. YKL contributed critical review to the study design and writing of the manuscript. AMW and SJF contributed to the conception, planning, study design and writing of this article. SJF is responsible for the overall content as the guarantor.

  • Funding We would like to acknowledge the support provided by Asthma UK Centre for Applied Research (AUK-AC-2018-01). SJF, WA and RW are supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC) (Grant Number: IS-BRC-1215-20007). IW is supported by the Slovenian research agency (ARRS) through program P1-0034: Analytics and Chemical Characterization of Materials and Processes.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.