Title: Can elevated hydrogen cyanide levels in exhaled breath be used to detect pseudomonas aeruginosa infection in children with cystic fibrosis?
Funder: Department of Health (England)

Abstract: Background In cystic fibrosis (CF), Pseudomonas aeruginosa (PA) infection causes increased morbidity and mortality. Diagnosis of the infection in children is made using microbiological methods which are unreliable, unpleasant or invasive. We urgently require a child-friendly technology for accurate, early diagnosis, preferably at a preclinical stage. Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) is an exciting, new, non-invasive diagnostic technology that detects volatile compounds in exhaled breath down to a concentration of one part per billion. We have shown that hydrogen cyanide (HCN) levels are elevated in the breath of CF children with PA infection but are very low or undetectable in healthy children. We plan a 2.5 year study to determine if HCN is an early predictor of PA infection. Aims The main aim of this project is to show that in children with CF, an elevated breath HCN level is an early indicator of PA infection. If PA infection can be accurately diagnosed using this technique then it will become an alternative to the current methods of diagnosing PA infection in children. These techniques are unreliable (cough swab), unpleasent (induced sputum) or invasive (bronchoscopy samples). Early diagnosis of PA infection will allow early treatment. Studies have shown this can reduce the symptoms associated with acute PA infection and limit the development of chronic PA infection (1). Chronic PA infection has significant associated morbidity and mortality. Plan of Investigation Children aged 3-17 years attending a specialist CF clinic in the Midlands who have not isolated PA over the previous year or have never isolated PA will be invited to participate. At each routine 2 monthly CF clinic appointment a breath sample will be collected in a Tedlar bag, in addition to their normal microbiology culture (cough swab or sputum sample). Data of recent symptoms, antibiotic use and culture results will be recorded. The bags containing exhaled breath will be transported to Stoke for measurement of HCN using the SIFT-MS instrument. Samples will be collected for 2 years (12 per patient). At the end of the study, HCN levels will be correlated with culture results to see if HCN is a useful marker of early PA infection, prior to the development of symptoms Potential Impact If exhaled breath HCN can be used to diagnose early PA infection then this child-friendly technique could be used as the first line investigation for PA. It would become an alternative to the current methods of diagnosing PA which are unpleasant, unreliable or invasive. Early diagnosis would allow treatment to be commenced quickly. This has been shown in previous studies to prevent the distressing symptoms of acute PA infection and reduce the risk of chronic PA infection, which is associated with permanent lung damage. If breath HCN is a useful diagnostic tool we will work with our industrial partner to build inexpensive, portable breath HCN monitors, allowing widespread, near-patient use.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION;CONGENITAL DISORDERS