Abstract
BackgroundPseudomonas 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. MethodsThis 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. Results241 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. ConclusionsTargeted VOC analysis appears to discriminate children and adults with and without PA positive cultures with clinically acceptable sensitivity values.
Highlights
Cystic fibrosis (CF) is a recessively inherited, progressive multiorgan disease that results in infection of the respiratory tract by pathogens such as Pseudomonas aeruginosa (PA)
Eradication of PA should be initiated swiftly, but monitoring of colonisation is based on microbial sputum cultures, which frequently cannot be obtained in young cystic fibrosis (CF) patients
Cultures of Haemophilus influenza and Staphylococcus aureus were more prevalent in children, whereas other cultures were less prevalent in children (Table S11). 13 adults and 15 children were classified as PA
Summary
Cystic fibrosis (CF) is a recessively inherited, progressive multiorgan disease that results in infection of the respiratory tract by pathogens such as Pseudomonas aeruginosa (PA). The result of sputum cultures take one week and lack in sensitivity, delaying prompt treatment of infections [8,9]. Exhaled breath analysis provides a non-invasive alternative for microbial cultures. Volatile organic compounds (VOCs) in exhaled breath originate from different processes: 1) host metabolism in the lung and elsewhere, 2) microbial metabolism and 3) foreign sources such as contamination via inhaled air or the oropharynx [10]. We aimed to identify VOCs associated with PA in literature and perform targeted exhaled breath analysis to recognize PA positive CF patients non-invasively
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