The role of measuring exhaled breath biomarkers in sarcoidosis: a systematic review

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The role of measuring exhaled breath biomarkers in sarcoidosis: a systematic review

Terrington et al., 2019 | J Breath Res | Meta Analysis

Citation

Terrington Dayle L, Hayton Conal, ... Wilson Andrew M. The role of measuring exhaled breath biomarkers in sarcoidosis: a systematic review. J Breath Res. 2019-Jun-24;13(3):036015. doi:10.1088/1752-7163/ab1284

Abstract

INTRODUCTION: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is a growing need to identify non-invasive biomarkers to differentiate between clinical phenotypes, identify those at risk of disease progression and monitor response to treatment. OBJECTIVES: We undertook a systematic review and meta-analysis to evaluate the utility of breath-based biomarkers in discriminating sarcoidosis from healthy controls, alongside correlation with existing non breath-based biomarkers used in clinical practice, radiological stage, markers of disease activity and response to treatment. METHODS: Electronic searches were undertaken during November 2017 using PubMed, Ebsco, Embase and Web of Science to capture relevant studies evaluating breath-based biomarkers in adult patients with sarcoidosis. RESULTS: 353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-β1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to distinguish sarcoidosis from controls. Meta-analysis of four studies assessing alveolar nitric oxide showed no significant difference between sarcoidosis and healthy controls (2.22 ppb; 95% CI -0.83, 5.27) however, a high degree of heterogeneity was observed with an I 2 of 93.4% (p < 0.001). Inconsistent or statistically insignificant results were observed for correlations between several biomarkers and radiological stage, markers of disease activity or treatment. CONCLUSIONS: The evidence for using breath biomarkers to diagnose and monitor sarcoidosis remains inconclusive with many studies limited by small sample sizes and lack of standardisation. VOCs have shown promising potential but further research is required to evaluate their prognostic role.

Key Findings

353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-β1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to disting

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population adult patients
Sample Size 8
Age Range See abstract
Condition See abstract

MeSH Terms

  • Adult
  • Aged
  • Biomarkers
  • Breath Tests
  • Cytokines
  • Exhalation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide
  • Oxidative Stress
  • Publication Bias
  • Sarcoidosis
  • Volatile Organic Compounds
  • Young Adult

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: chromium

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09