Abstract
Background: Disorders of mucociliary clearance, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and bronchiectasis of unknown origin, are characterised by periods with increased respiratory symptoms, referred to as pulmonary exacerbations. These exacerbations are hard to predict and associated with lung function decline and the loss of quality of life. To optimise treatment and preserve lung function, there is a need for non-invasive and reliable methods of detection. Breath analysis might be such a method. Methods: We systematically reviewed the existing literature on breath analysis to detect pulmonary exacerbations in mucociliary clearance disorders. Extracted data included the study design, technique of measurement, definition of an exacerbation, identified compounds and diagnostic accuracy. Results: Out of 244 identified articles, 18 were included in the review. All studies included patients with CF and two also with PCD. Age and the definition of exacerbation differed between the studies. There were five that measured volatile organic compounds (VOCs) in exhaled breath using gas chromatography with mass spectrometry, two using an electronic nose and eleven measured organic compounds in exhaled breath condensate. Most studies showed a significant correlation between pulmonary exacerbations and one or multiple compounds, mainly hydrocarbons and cytokines, but the validation of these results in other studies was lacking. Conclusions: The detection of pulmonary exacerbations by the analysis of compounds in exhaled breath seems possible but is not near clinical application due to major differences in results, study design and the definition of an exacerbation. There is a need for larger studies, with a longitudinal design, international accepted definition of an exacerbation and validation of the results in independent cohorts.