Non-invasive phenotyping using exhaled volatile organic compounds in asthma

Abstract

Background Breath volatile organic compounds (VOCs) may be useful for asthma diagnosis and phenotyping, identifying patients who could benefit from personalised therapeutic strategies. The authors aimed to identify specific patterns of breath VOCs in patients with asthma and in clinically relevant disease phenotypes. Methods Breath samples were analysed by gas chromatographyemass spectrometry. The Asthma Control Questionnaire was completed, together with lung function and induced sputum cell counts. Breath data were reduced to principal components, and these principal components were used in multiple logistic regression to identify discriminatory models for diagnosis, sputum inflammatory cell profile and asthma control. Results The authors recruited 35 patients with asthma and 23 matched controls. A model derived from 15 VOCs classified patients with asthma with an accuracy of 86%, and positive and negative predictive values of 0.85 and 0.89, respectively. Models also classified patients with asthma based on the following phenotypes: sputum (obtained in 18 patients with asthma) eosinophilia $2% area under the receiver operating characteristics (AUROC) curve 0.98, neutrophilia $40% AUROC 0.90 and uncontrolled asthma (Asthma Control Questionnaire $1) AUROC 0.96. Conclusions Detection of characteristic breath VOC profiles could classify patients with asthma versus controls, and clinically relevant disease phenotypes based on sputum inflammatory profile and asthma control. Prospective validation of these models may lead to clinical application of non-invasive breath profiling in asthma.

Allergic asthma exhaled breath metabolome: A challenge for comprehensive two-dimensional gas chromatography

“…A relevant aspect brought by the results is that from the 67 identified alkanes 19 are methylated, which corresponds to 28% of this chemical family and from these, two methylated compounds, as for example 2,2,4,6,6-pentamethylheptane and 3,6-dimethyldecane have a major contribution in the observed distinction. The methylated alkanes family have also been previously reported as these may well be important in asthma characterization [2,64]. These compounds also have an important role in diseases, in which oxidative stress apparently may be involved, but to other extents, and with different consequences than asthma, such as lung and breast cancer, as well as in lung cancer cell lines [65][66][67].…”

Improving the diagnosis of eosinophilic asthma

“…The current hypothesis is that pulmonary diseases are characterized by a diseasespecific breath-print, as distinct profiles were found in patients with different lung diseases [75]. Exhaled breath has been used in the detection of lung diseases such as lung cancer, tuberculosis, and cystic fibrosis [74], but its most promising application lies in stratification of inflammatory airways disease into different subphenotypes [76]. In asthma, specific exhaled VOCs profiles defined by GC-MS appear to be associated with the eosinophilic phenotype and are associated with disease activity [76].…”

“…Exhaled breath has been used in the detection of lung diseases such as lung cancer, tuberculosis, and cystic fibrosis [74], but its most promising application lies in stratification of inflammatory airways disease into different subphenotypes [76]. In asthma, specific exhaled VOCs profiles defined by GC-MS appear to be associated with the eosinophilic phenotype and are associated with disease activity [76]. The distinctiveness of breath prints for inflammatory subtypes was also confirmed in a study with an electronic nose [77].…”

Fevipiprant, a prostaglandin D 2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial

“…Subjects wear a tight-fitting mask supplied with air and with a sample tube attached, and breathe normally until 2.5 L of exhaled breath are collected through the sample tube. Sample tubes are sent to Loughborough University for analysis (Ibrahim et al, 2011). …”