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.
CRTH2 (chemoattractant receptor expressed on T-helper (Th) type 2 cells) is a Gprotein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostaglandin (PG)D 2 -driven chemotaxis. We studied the efficacy of the oral CRTH2 antagonist OC000459 in steroid-naïve asthmatic patients.A randomised, double-blind, placebo-controlled, two-way crossover study of 16 days' treatment with OC000459 (200 mg twice daily) on the late (LAR) and early (EAR) asthmatic responses to bronchial allergen challenge was conducted, with 16 subjects completing the study.There was a 25.4% (95% CI 5.1-45.6%) reduction in the LAR area under the curve (AUC) for change in forced expiratory volume in 1 s with OC000459 compared with placebo (p50.018) but no effect on the EAR. Sputum eosinophil counts at 1 day post-allergen challenge were lower after OC000459 treatment (p50.002). PGD 2 -induced blood eosinophil shape change ex vivo was assessed at day 7 (n57). The AUC of eosinophil shift for OC000459 was lower than placebo; the mean difference was -33.6% (95% CI -66.8--0.4%; p50.048).OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils. This CRTH2 antagonist appears to inhibit allergic inflammation in asthma.
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