Exhaled volatile organic compounds in adult asthma: a systematic review

Abstract

The search for biomarkers that can guide precision medicine in asthma, particularly those that can be translated to the clinic, has seen recent interest in exhaled volatile organic compounds (VOCs). Given the number of studies reporting “breathomics” findings and its growing integration in clinical trials, we performed a systematic review of the literature to summarise current evidence and understanding of breathomics technology in asthma.A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-oriented systematic search was performed (CRD42017084145) of MEDLINE, Embase and the Cochrane databases to search for any reports that assessed exhaled VOCs in adult asthma patients, using the following terms (asthma AND (volatile organic compounds AND exhaled) OR breathomics).Two authors independently determined the eligibility of 2957 unique records, of which 66 underwent full-text review. Data extraction and risk of bias assessment was performed on the 22 studies deemed to fulfil the search criteria. The studies are described in terms of methodology and the evidence narratively summarised under the following clinical headings: diagnostics, phenotyping, treatment stratification, treatment monitoring and exacerbation prediction/assessment.Our review found that most studies were designed to assess diagnostic potential rather than focus on underlying biology or treatable traits. Results are generally limited by a lack of methodological standardisation and external validation and by insufficiently powered studies, but there is consistency across the literature that exhaled VOCs are sensitive to underlying inflammation. Modern studies are applying robust breath analysis workflows to large multi-centre study designs, which should unlock the full potential of measurement of exhaled volatile organic compounds in airways diseases such as asthma.

Breath volatile organic compounds and inflammatory markers in adult asthma patients: negative results from the ALLIANCE cohort

“…Breathomics in asthma is a rapidly growing area of significant scientific interest, as indicated by a recently published review, two research articles, and their accompanying editorials in high impact pneumology journals [1][2][3][4][5]. The repeatedly observed associations between breath volatile organic compounds (VOCs) and sputum or blood inflammatory cells [2,3] suggest that breathomics are on the brink of introduction as a valuable clinically tool.…”

“…However, there are also major concerns about unresolved methodological issues and a general paucity of high-quality data [1,6]. In this letter we detail our concerns with breathomics based on data from a cohort of adult asthma patients with a broad spectrum of clinical phenotypes.…”

Breath biomarkers in asthma: we're getting answers, but what are the important questions?

“…In this issue of the European Respiratory Journal, AZIM et al [7] report a new systematic review covering breathomics in adult asthma. They found that reports of high quality remain relatively few, with only 22 studies meeting the fairly broad inclusion criteria.…”

“…As reported by AZIM et al [7], sufficiently detailed description of technical methods, especially analytical parameters and data pre-processing, are rarely given to allow comparison between studies. Given the sensitivity of the instruments used, and variability between them, it is not surprising that few studies have validated others' findings.…”

“…AZIM et al [7] do not provide an analysis of specific VOCs that have been found to be discriminatory between disease characteristics of interest. This was beyond the scope of their already extensive work, but of interest to both clinicians and researchers.…”