Targeted exhaled breath analysis for detection of Pseudomonas aeruginosa in cystic fibrosis patients

Amsterdam Mucociliary Clearance Disease (AMCD) Research Group and the Amsterdam UMC Breath Research Group

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Pseudomonas aeruginosa (PA) is an important respiratory pathogen for cystic fibrosis (CF) patients. Routine microbiology surveillance is time-consuming, and is best performed on expectorated sputum. As alternative, volatile organic compounds (VOCs) may be indicative of PA colonisation. In this study, we aimed to identify VOCs associated with PA in literature and perform targeted exhaled breath analysis to recognize PA positive CF patients non-invasively. Methods: This study consisted of 1) a literature review to select VOCs of interest, and 2) a cross-sectional CF study. Definitions used: A) PA positive, PA culture at visit/chronically; B) PA free, no PA culture in ≥12 months. Exhaled VOCs were identified via quadrupole MS. The primary endpoint was the area under the receiver operating characteristics curve (AUROCC) of individual VOCs as well as combined VOCs against PA culture. Results: 241 VOCs were identified in literature, of which 56 were further evaluated, and 13 could be detected in exhaled breath in our cohort. Exhaled breath of 25 pediatric and 28 adult CF patients, PA positive (n=16) and free (n=28) was available. 3/13 VOCs were significantly (p<0.05) different between PA groups in children; none were in adults. Notably, a composite model based on 5 or 1 VOC(s) showed an AUROCC of 0.86 (CI 0.71–1.0) and 0.87 (CI 0.72–1.0) for adults and children, respectively. Conclusions: Targeted VOC analysis appears to discriminate children and adults with and without PA positive cultures with clinically acceptable sensitivity values.

Original languageEnglish
Pages (from-to)E28-E34
JournalJournal of Cystic Fibrosis
Volume21
Issue number1
Early online date17 May 2021
DOIs
Publication statusPublished - Jan 2022

Bibliographical note

Funding Information:
AHM and PB are supported by an innovation grant from Vertex Pharmaceuticals B.V.

Funding Information:
AHM reports grants and personal fees from GSK, Boehringer Ingelheim, and AstraZeneca, and grants from Chiesi, outside the submitted work.

Funding Information:
We would like to acknowledge and thank all patients and parents for their time and effort put into this study. We are grateful for a research grant provided by Institut Merieux Annecy France that supported parts of this study.

Funding Information:
This research has been supported by a research grant of the Institut Merieux. We also thank the UK Cystic Fibrosis Trust for funding this research as part of a Strategic Research Centre entitled ‘Personalised Approach to Pseudomonas aeruginosa (PAPA)’ via grant SRC014.

Publisher Copyright:
© 2021

Keywords

  • Cystic fibrosis
  • Exhaled biomarkers
  • Pseudomonas aeruginosa
  • VOC

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