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.

Academic Department of Child Health University Hospital of North Staffordshire Stoke on Trent UK; Institute of Science and Technology in Medicine Keele University Keele UK

Division of Child Health Obstetrics and Gynaecology School of Medicine University of Nottingham UK

Institute of Child Health Alder Hey Children's Hospital Liverpool UK

Institute of Science and Technology in Medicine Keele University Keele UK

J Heyrovský Institute of Physical Chemistry Academy of Sciences of the Czech Republic Prague Czech Republic

Manchester Adult Cystic Fibrosis Centre University Hospital of South Manchester Manchester UK

School of Computing and Mathematics Keele University Keele UK

Zobrazit více v PubMed

Emerson J, Rosenfeld M, McNamara S, et al. PubMed

Nixon GM, Armstrong DS, Carzino R, et al. Clinical outcome after early PubMed

Valerius NH, Koch C, Høiby N. Prevention of chronic PubMed

Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating PubMed

Douglas TA, Brennan S, Gard S, et al. Acquisition and eradication of PubMed

Rosenfeld M, Emerson J, Accurso F, et al. Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. Pediatr Pulmonol 1999; 28: 321–328. PubMed

Armstrong DS, Grimwood K, Carlin JB, et al. Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis. Pediatr Pulmonol 1996; 21: 267–275. PubMed

De Boeck K, Alifier M, Vandeputte S. Sputum induction in young cystic fibrosis patients. Eur Respir J 2000; 16: 91–94. PubMed

Al-Saleh S, Dell SD, Grasemann H, et al. Sputum induction in routine clinical care of children with cystic fibrosis. J Pediatr 2010; 157: 1006–1011.e1. PubMed

Brennan S, Gangell C, Wainwright C, et al. Disease surveillance using bronchoalveolar lavage. Paediatr Respir Rev 2008; 9: 151–159. PubMed

Clawson BJ, Young CC. Preliminary report on the production of hydrocyanic acid by bacteria. J Biol Chem 1913; 15: 419–422.

Carroll W, Lenney W, Wang T, et al. Detection of volatile compounds emitted by PubMed

Gilchrist FJ, Alcock A, Belcher J, et al. Variation in hydrogen cyanide production between different strains of PubMed

Gilchrist FJ, Sims H, Alcock A, et al. Quantification of hydrogen cyanide and 2-aminoacetophenone in the headspace of

Williams HD, Zlosnik JEA, Ryall B. Oxygen, cyanide and energy generation in the cystic fibrosis pathogen PubMed

Gilchrist FJ, Sims H, Alcock A, et al. Is hydrogen cyanide a marker of PubMed PMC

Enderby B, Smith D, Carroll W, et al. Hydrogen cyanide as a biomarker for PubMed

Gilchrist FJ, Bright-Thomas RJ, Jones AM, et al. Hydrogen cyanide concentrations in the breath of adult cystic fibrosis patients with and without PubMed

Spaněl P, Smith D. Progress in SIFT-MS: breath analysis and other applications. Mass Spectrom Rev 2011; 30: 236–267. PubMed

Spanel P, Dryahina K, Smith D. A general method for the calculation of absolute trace gas concentrations in air and breath from selected ion flow tube mass spectrometry data. Int J Mass Spectrom 2006; 249: 230–239.

Španěl PSD. Selected Ion Flow Tube mass Spectrometry (SIFT-MS) for on-line trace gas analysis of breath. Clin Diagn Ther Monit. 2005; 3–34. PubMed

Gilchrist FJ, Razavi C, Webb AK, et al. An investigation of suitable bag materials for the collection and storage of breath samples containing hydrogen cyanide. J Breath Res 2012; 6: 036004. PubMed

Spanĕl P, Wang T, Smith D. Quantification of hydrogen cyanide in humid air by selected ion flow tube mass spectrometry. Rapid Commun Mass Spectrom 2004; 18: 1869–1873. PubMed

Genders TSS, Spronk S, Stijnen T, et al. Methods for calculating sensitivity and specificity of clustered data: a tutorial. Radiology 2012; 265: 910–916. PubMed

Lee TWR, Brownlee KG, Conway SP, et al. Evaluation of a new definition for chronic PubMed

Schmidt FM, Metsälä M, Vaittinen O, et al. Background levels and diurnal variations of hydrogen cyanide in breath and emitted from skin. J Breath Res 2011; 5: 046004. PubMed

Wang T, Pysanenko A, Dryahina K, et al. Analysis of breath, exhaled via the mouth and nose, and the air in the oral cavity. J Breath Res 2008; 2: 037013. PubMed

Lee TWR. Eradication of early PubMed

Recent developments and applications of selected ion flow tube mass spectrometry (SIFT-MS)

Quantification of volatile metabolites in exhaled breath by selected ion flow tube mass spectrometry, SIFT-MS