Breath volatile organic compounds and inflammatory markers in adult asthma patients: negative results from the ALLIANCE cohort

Abstract

Despite recent publications, we are not close to finding a clinically valuable breath VOC biomarker for asthma or asthma phenotypes https://bit.ly/3heTgtK

Trial registration: ClinicalTrials.gov NCT02419274.

Conflict of interest statement

Conflict of interest: O. Holz has nothing to disclose. Conflict of interest: B. Waschki has nothing to disclose. Conflict of interest: H. Watz has nothing to disclose. Conflict of interest: A. Kirsten has nothing to disclose. Conflict of interest: M. Abdo has nothing to disclose. Conflict of interest: F. Pedersen has nothing to disclose. Conflict of interest: M. Weckmann has nothing to disclose. Conflict of interest: O. Fuchs has nothing to disclose. Conflict of interest: A-M. Dittrich has nothing to disclose. Conflict of interest: G. Hansen reports grants from the German Federal Ministry for Education and Research (BMBF) for the German Center for Lung Research (DZL), during the conduct of the study. Conflict of interest: M.V. Kopp reports grants from the German Federal Ministry for Education and Research (BMBF) for the German Center for Lung Research (DZL), during the conduct of the study; personal fees for lectures and consultancy from ALK-Abello, Allergopharma, Chiesi, Meda, Novartis Pharma, Vertex, Abbvie and Infectopharm, grants from Allergopharma and Vertex, outside the submitted work. Conflict of interest: E. von Mutius reports grants from the German Federal Ministry for Education and Research (BMBF) for the German Center for Lung Research (DZL), during the conduct of the study; authorship fees from Springer-Verlag GmbH, Georg Thieme Verlag and Elsevier Ltd, personal fees for consultancy from HiPP GmbH & Co. KG, OM Pharma SA and Peptinnovate Ltd, personal fees for lectures from Boehringer Ingelheim International GmbH, outside the submitted work; and has a patent LU101064, “Barn dust extract for the prevention and treatment of diseases” pending, a patent EP2361632, “Specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders” with royalties paid to ProtectImmun GmbH, a patent number EP 1411977, “Composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases” licensed to ProtectImmun GmbH, a patent EP1637147, “Stable dust extract for allergy protection” licensed to ProtectImmun GmbH, and a patent EP 1964570, “Pharmaceutical compound to protect against allergies and inflammatory diseases” licensed to ProtectImmun GmbH. Conflict of interest: K.F. Rabe reports grants and personal fees from Boehringer Ingelheim and AstraZeneca, personal fees from Novartis, Sanofi, Regeneron, Roche and Chiesi Pharmaceuticals outside the submitted work. Conflict of interest: J.M. Hohlfeld reports grants from German Ministry for Education and Research (BMBF; grant DZL 2016-2020/82DZL002A2), during the conduct of the study; personal fees for consultancy from Boehringer Ingelheim and Merck & Co., Inc., personal fees for lectures from Novartis and HAL, grants from AstraZeneca AB, Novartis, Janssen Pharmaceutica NV, ALK, Boehringer Ingelheim, LETI, GlaxoSmithKline, Sanofi-Aventis, Astellas Pharma and Allergopharma, outside the submitted work. Conflict of interest: T. Bahmer reports grants from BMBF (unrestricted research grant for the German Center for Lung Research, DZL), during the conduct of the study; personal fees lectures and consultancy, and compensation of travel expenses from AstraZeneca, GlaxoSmithKline, Novartis and Roche, outside the submitted work.

Figures

FIGURE 1

a) Patient demographics according to asthma phenotypes. Data are presented as median (interquartile range). Statistics: Kruskal–Wallis ANOVA. ICS: inhaled corticosteroids; OCS: oral corticosteroids; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; RV: residual volume; TLC: total lung capacity; sRtot: specific total airway resistance; R5Hz: resistance at 5 Hz; FDRabs: frequency dependence of resistance (resistance at 5 Hz minus resistance at 20 Hz). #: omalizumab or mepolizumab; ¶: missing values. b) Gas chromatography/mass spectrometry chromatogram of one representative patient with inserts and arrows indicating the retention time (RT) for propanol-1, hexane, 2-hexanone and nonanal [3]. The black line indicates the total ion content (TIC), the insert coloured plots show specific masses of the respective volatile organic compounds (VOCs). c–e) Correlation between VOCs and sputum neutrophils (%). All patients and subgroup correlations not significant (unadjusted p-value >0.05). f) Correlation between hexane and sputum eosinophils (%). All patients and subgroup correlations not significant (unadjusted p-value >0.05), except for smokers (r=−0.45, unadjusted p-value 0.02, adjusted p-value 0.48). Selection of VOCs based on published data [3]. As shown in (b), 2-hexanone was not detectable in our samples. g) Histograms of unadjusted p-values for the correlation between all detected VOCs and sputum neutrophils and eosinophils (%), exhaled nitric oxide fraction (FENO) and blood eosinophils (%). a.u.: arbitrary units.