Rationale: Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced sputum is indeed not widely available and markers of neutrophilic asthma are still lacking. Objectives: To determine whether analysis of exhaled breath using endogenously generated VOCs can be a surrogate marker for recognition of sputum inflammatory phenotypes. Methods: We conducted a prospective study on 521 patients with asthma recruited from the University Asthma Clinic of Liege. Patients underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction, and gave a blood sample. Subjects with asthma were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.Measurements and Main Results: In the discovery study, seven potential biomarkers were highlighted by gas chromatography-mass spectrometry in a training cohort of 276 patients with asthma. In the replication study (n = 245), we confirmed four VOCs of interest to discriminate among asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry. Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to that of blood eosinophils and FeNO. Moreover, the combination of FeNO, blood eosinophils, and VOCs gave a very good prediction of eosinophilic asthma (area under the receiver operating characteristic curve, 0.9). For neutrophilic asthma, the combination of nonanal, 1-propanol, and hexane had a classification performance similar to FeNO or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma.Conclusions: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of patients with asthma and provide surrogate markers for neutrophilic asthma.
Rationale: Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced sputum is indeed not widely available and markers of neutrophilic asthma are still lacking. Objectives: To determine whether analysis of exhaled breath using endogenously generated VOCs can be a surrogate marker for recognition of sputum inflammatory phenotypes. Methods: We conducted a prospective study on 521 patients with asthma recruited from the University Asthma Clinic of Liege. Patients underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction, and gave a blood sample. Subjects with asthma were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.Measurements and Main Results: In the discovery study, seven potential biomarkers were highlighted by gas chromatography-mass spectrometry in a training cohort of 276 patients with asthma. In the replication study (n = 245), we confirmed four VOCs of interest to discriminate among asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry. Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to that of blood eosinophils and FeNO. Moreover, the combination of FeNO, blood eosinophils, and VOCs gave a very good prediction of eosinophilic asthma (area under the receiver operating characteristic curve, 0.9). For neutrophilic asthma, the combination of nonanal, 1-propanol, and hexane had a classification performance similar to FeNO or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma.Conclusions: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of patients with asthma and provide surrogate markers for neutrophilic asthma.
Authors: Wadah Ibrahim; Liesl Carr; Rebecca Cordell; Michael J Wilde; Dahlia Salman; Paul S Monks; Paul Thomas; Chris E Brightling; Salman Siddiqui; Neil J Greening Journal: Thorax Date: 2021-01-07 Impact factor: 9.139
Authors: Roy Meys; Anouk A F Stoffels; Jana de Brandt; Hieronymus W H van Hees; Frits M E Franssen; Maurice J H Sillen; Emiel F M Wouters; Chris Burtin; Peter Klijn; Eline Bij de Vaate; Bram van den Borst; Jacqueline M Otker; Jos Donkers; Florence N Schleich; Maurice Hayot; Pascal Pomiès; Inge Everaert; Wim Derave; Martijn A Spruit Journal: BMJ Open Date: 2020-09-13 Impact factor: 2.692
Authors: Tesfaye B Mersha; Yashira Afanador; Elisabet Johansson; Steven P Proper; Jonathan A Bernstein; Marc E Rothenberg; Gurjit K Khurana Hershey Journal: Clin Rev Allergy Immunol Date: 2021-04 Impact factor: 8.667
Authors: Wadah Ibrahim; Rebecca L Cordell; Michael J Wilde; Matthew Richardson; Liesl Carr; Ananga Sundari Devi Dasi; Beverley Hargadon; Robert C Free; Paul S Monks; Christopher E Brightling; Neil J Greening; Salman Siddiqui Journal: ERJ Open Res Date: 2021-07-05
Authors: Rosa A Sola-Martínez; Gema Lozano-Terol; Julia Gallego-Jara; Eva Morales; Esther Cantero-Cano; Manuel Sanchez-Solis; Luis García-Marcos; Pedro Jiménez-Guerrero; José A Noguera-Velasco; Manuel Cánovas Díaz; Teresa de Diego Puente Journal: Sci Rep Date: 2021-07-05 Impact factor: 4.379