Exhaled breath hydrogen cyanide as a marker of earlyPseudomonas aeruginosainfection 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.

Breath concentration of acetic acid vapour is elevated in patients with cystic fibrosis

“…Most recently, a multi-centre study involving 8 UK hospitals has quantified HCN in the exhaled breath of 233 children with CF and demonstrates that HCN is indeed a discreet specific (albeit not yet entirely sensitive) biomarker of PA. The exciting results of this SPACE study are reported recently in ERJ Open Research [10].…”

SERS detection of the biomarker hydrogen cyanide from Pseudomonas aeruginosa cultures isolated from cystic fibrosis patients

“…The technique was employed in the study by Enderby et al 2,. where median values of 13.5 ppb HCN were detected directly in the breath of CF children with a newly discovered P. aeruginosa lung colonization2, whereas in the more recent study by Gilchrist et al 10,. HCN concentrations at or below 7.5 ppb were detected from breath samples collected in bags and measured within 24 hours10.…”

“…where median values of 13.5 ppb HCN were detected directly in the breath of CF children with a newly discovered P. aeruginosa lung colonization2, whereas in the more recent study by Gilchrist et al 10,. HCN concentrations at or below 7.5 ppb were detected from breath samples collected in bags and measured within 24 hours10. An optimal sensor would be a cheap and simple point-of-care device, allowing for measurements to be carried out directly on human breath, without pre-handling of the samples.…”

“…The drawbacks of all the applied methods are that they need extensive sample handling before measurements can be obtained, and that it can only be done in solution. To the best of our knowledge, selected ion flow tube – mass spectroscopy (SIFT-MS) is the current state-of-the-art method in terms of sensitivity and specificity10. However, it is also an expensive and complex procedure.…”

SERS spectroscopy for detection of hydrogen cyanide in breath from children colonised with P. aeruginosa

“…HCN is considered a potential P. aeruginosa biomarker, and it was detected at median values of 13.5 ppb in children's breath using selected ion flow tube mass spectroscopy (SIFT-MS) 4 . In the SPACE study, Gilchrist and co-workers measured HCN in exhaled breath of CF children, also using SIFT-MS 6 . At present time, SIFT-MS has not been optimized to meet the need for fast detection of bacteria, and the measurements were made after up to 24 hours, whereby some of the exhaled HCN may have been lost.…”