Inflammatory Biomarkers in Exhaled Breath Condensate: A Systematic Review

Abstract

Inflammation is a comprehensive set of physiological processes that an organism undertakes in response to a wide variety of foreign stimuli, such as viruses, bacteria, and inorganic particles. A key role is played by cytokines, protein-based chemical mediators produced by a broad range of cells, including the immune cells recruited in the inflammation site. The aim of this systematic review is to compare baseline values of pro/anti-inflammatory biomarkers measured in Exhaled Breath Condensate (EBC) in healthy, non-smoking adults to provide a summary of the concentrations reported in the literature. We focused on: interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), and C reactive protein (CRP). Eligible articles were identified in PubMed, Embase, and Cochrane CENTRAL. Due to the wide differences in methodologies employed in the included articles concerning EBC sampling, storage, and analyses, research protocols were assessed specifically to test their adherence to the ATS/ERS Task Force guidelines on EBC. The development of reference intervals for these biomarkers can result in their introduction and use in both research and clinical settings, not only for monitoring purposes but also, in the perspective of future longitudinal studies, as predictive parameters for the onset and development of chronic diseases with inflammatory aetiology.

Keywords: cytokines; exhaled breath condensate; inflammation; non-invasive; non-smoking healthy adults; reference values.

Figure A1

Quality Assessment for cross-sectional studies, according to JBI critical appraisal tool and to the ATS/ERS Task Force guidelines on EBC [20,21]. (+) means “yes”; (-) means “no”; (?) means “unclear”; (n.a.) means “not applicable”.

Figure A2

Quality Assessment for quasi-experimental studies, according to JBI critical appraisal tool and to the ATS/ERS Task Force guidelines on EBC [20,21]. (+) means “yes”; (-) means “no”; (?) means “unclear”; (n.a.) means “not applicable”.

Figure A3

Quality Assessment for randomised-control trial studies, according to JBI critical appraisal tool and to the ATS/ERS Task Force guidelines on EBC [20,21]. (+) means “yes”; (-) means “no”; (?) means “unclear”; (n.a.) means “not applicable”.

Figure 1

PRISMA flow chart summarising the study selection process.

Figure 2

Forest plot summarising the concentration of the selected biomarkers in the articles where the sensitivity of the employed assays, and the measurements above the LOD were reported. † More subjects groups were analysed in the same article. The “a” and “b” following the indication of articles with the same first author and year are referred to the order of the articles in the bibliography paragraph [7,27,28,29,30,31,32,33,34,35,36,37,41,44,45,54,58].