Exhaled breath hydrogen cyanide as a marker of early Pseudomonas aeruginosa infection in children with cystic fibrosis

Abstract

Hydrogen cyanide is readily detected in the headspace above Pseudomonas aeruginosa cultures and in the breath of cystic fibrosis (CF) patients with chronic (P. aeruginosa) infection. We investigated if exhaled breath HCN is an early marker of P. aeruginosa infection. 233 children with CF who were free from P. aeruginosa infection were followed for 2 years. Their median (interquartile range) age was 8.0 (5.0-12.2) years. At each study visit, an exhaled breath sample was collected for hydrogen cyanide analysis. In total, 2055 breath samples were analysed. At the end of the study, the hydrogen cyanide concentrations were compared to the results of routine microbiology surveillance. P. aeruginosa was isolated from 71 children during the study with an incidence (95% CI) of 0.19 (0.15-0.23) cases per patient-year. Using a random-effects logistic model, the estimated odds ratio (95% CI) was 3.1 (2.6-3.6), which showed that for a 1- ppbv increase in exhaled breath hydrogen cyanide, we expected a 212% increase in the odds of P. aeruginosa infection. The sensitivity and specificity were estimated at 33% and 99%, respectively. Exhaled breath hydrogen cyanide is a specific biomarker of new P. aeruginosa infection in children with CF. Its low sensitivity means that at present, hydrogen cyanide cannot be used as a screening test for this infection.

FIGURE 1

Kaplan–Meier curve showing the proportion of children remaining free from Pseudomonas aeruginosa infection during the study period for each P. aeruginosa status group. FF: Free From; FFT: Free From But Treated.

FIGURE 2

Histogram showing the breath hydrogen cyanide concentrations in samples taken from children who remained free from Pseudomonas aeruginosa throughout the study. The dashed line represents the polynomial trend.

FIGURE 3

Histogram showing the bimodal distribution of breath hydrogen cyanide concentrations taken from children at the time of Pseudomonas aeruginosa isolation. The dashed line represents the polynomial trend.