A Study to Investigate Breath Biomarkers in Suspected Sarcoidosis

• Research type

  Research Study

• Full title

  Non-invasive Profiling of Breath Volatile Organic Compounds in Sarcoidosis: Relation to the Lung Microbiome and Markers of Disease Progression.

• IRAS ID

  241100

• Contact name

  Stephen Fowler

• Contact email

  Stephen.Fowler@manchester.ac.uk

• Sponsor organisation

  Manchester University NHS Foundation Trust

• Duration of Study in the UK

  3 years, 0 months, 1 days

• Research summary

  Research Summary

  Sarcoidosis is chronic disease which can affect any organ within the body, however frequently involves the lungs. The exact cause of the disease remains uncertain and it thought that the immune system overreacts to something inhaled from the environment. A role has been suggested for triggers such as certain types of infection.
  The clinical course and prognosis of sarcoidosis is extremely variable. Some patients make a full recovery without the need for any specific treatment, however up to a third of patients may develop a more severe form of the disease which can lead to scarring and fibrosis of the lungs. Treatment of sarcoidosis focuses on suppressing the immune system, however the evidence to support this remains weak, and furthermore places the patient at risk of long-term side effects.

  At the present time, there is a lack of useful markers which can not only help diagnose the condition, but also help to predict and identify those patients at risk of developing more severe disease who require treatment.

  The purpose of this study is to use a technique which analyses breath samples to provide a profile of chemicals which are present in the exhaled breath of patients with sarcoidosis. We want to know if this profile differs from healthy people, relates to infections or changes over time, particularly in response to treatment. We hope this technique will provide an accurate way of monitoring the disease or predicting progression.

  We will perform an observational case-control study of patients with suspected sarcoidosis receiving standard care at two NHS hospitals over the course of 12 months. At baseline patients will undergo bronchoscopy (as part of routine clinical care) to collect bronchoalveolar lavage fluid to identify any possible infections. We will see patients at four visits to take breath samples, blood tests and complete questionnaires.

  Summary of Results

  We recruited participants with suspected or known sarcoidosis at hospitals in both Norwich and Manchester, not yet on any treatment that would affect our tests, such as steroids or methotrexate. We collected detailed information from their medical records to form as complete a picture of how the sarcoidosis was affecting them as possible. This included information from blood, breathing and imaging tests. We also collected samples of lung fluid from those having a camera test called a bronchoscopy, to investigate the bacterial changes that may be occurring in the lung. A breath test was then collected from these volunteers and analysed in a laboratory at the University of Manchester so that we could find out what chemicals were being breathed out. We have now analysed all these samples, and investigated whether there are any differences in these breath chemicals between people with and without sarcoidosis, between people with different bacteria in their lungs, and with different severities of the disease.

  Our original target number was 80 patients sampled four times over the course of a year. By the end of the study period we recruited, and collected and analysed samples from 43 patients and 11 healthy people. Recruitment was more difficult than expected, first due to delays in getting approvals for the study from the regulatory authorities, second due to difficulties in identifying patients who could be recruited into the study before they had their diagnostic tests and/or needed to have treatment started, and third due to the suspension of research activities during the COVID pandemic.

  We finished recruitment in March 2021, with that last participant getting a 3-month follow-up visit in June.

  Our preliminary data analysis has demonstrated the following:
  1. Sarcoidosis appears to be associated with key differences in several exhaled breath chemicals
  2. Breath chemicals are closely associated with the diversity of microbes in the lung in sarcoidosis
  3. Levels of some breath chemicals are different in the breath of people with sarcoidosis according to the severity of disease, measured for example by lung function or changes on lung scan

• REC name

  North West - Greater Manchester Central Research Ethics Committee

• REC reference

  18/NW/0345

• Date of REC Opinion

  5 Jul 2018

• REC opinion

  Further Information Favourable Opinion