Soluble interleukin-2 receptor in exhaled breath condensate in pulmonary sarcoidosis: a cross-sectional pilot study.

INTRODUCTION: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is an urgent need to identify new and novel biomarkers to help differentiate between clinical phenotypes and guide clinical decisions with respect to commencing and monitoring treatment. Across the spectrum of respiratory disease there has been a growing interest in the role of breath-based biomarkers given their non-invasive nature and ability to repeat sampling with ease for serial monitoring. Soluble interleukin-2 receptor (sIL2R) in bronchoalveolar lavage and serum correlates with disease activity in sarcoidosis; however, no previous study has evaluated sIL2R in exhaled breath. OBJECTIVES: The main aim of this cross-sectional case-controlled pilot study was to determine the concentration of sIL2R in exhaled breath condensate (EBC) from patients with recently diagnosed sarcoidosis compared to healthy volunteers and to establish, if present, if this correlated with markers of disease activity, pulmonary function tests and serological markers used in current clinical practice. METHODS: Paired serum and EBC samples were collected from twelve treatment naïve patients with histologically proven sarcoidosis diagnosed during the previous six months and compared to twelve healthy volunteers matched for age and gender. RESULTS: Mean concentration of serum sIL2R was significantly elevated in participants with sarcoidosis compared to healthy controls (1584.3 ± 489.1 versus 874.2 ± 235.7 pg mL-1; p = 0.001). Soluble interleukin-2 receptor in EBC was detectable in only five subjects including three participants with sarcoidosis. The range of sIL2R across all five samples was 148.0-288.2 pg mL-1 with the two highest concentrations observed in two participants with sarcoidosis. There was no significant difference observed in EBC sIL2R between sarcoidosis and healthy controls (p = 0.71). No apparent correlations were observed between EBC sIL2R and radiological stage, pulmonary function tests or serological markers. CONCLUSION: Soluble interleukin-2 receptor is detectable in EBC; however, the findings from our study do not support its role as a diagnostic marker in sarcoidosis. Further research is required to evaluate its prognostic utility.

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

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-ß1, 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.