2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung
1 University of Otago, Christchurch School of Medicine and Health Sciences, Department of Pathology, P.O. Box 4345, Christchurch, 8140, New Zealand
2 Leipzig University, Department for Inner Medicine, Neurology and Dermatology, Johannisallee 32, 04103 Leipzig, Germany
3 Canterbury District Health Board, Private Bag 4710, Christchurch, 8140 New Zealand
BMC Pulmonary Medicine 2010, 10:56 doi:10.1186/1471-2466-10-56Published: 7 November 2010
Pseudomonas aeruginosa infections are associated with progressive life threatening decline of lung function in cystic fibrosis sufferers. Growth of Ps. aeruginosa releases a "grape-like" odour that has been identified as the microbial volatile organic compound 2-aminoacetophenone (2-AA).
We investigated 2-AA for its specificity to Ps. aeruginosa and its suitability as a potential breath biomarker of colonisation or infection by Solid Phase Micro Extraction and Gas Chromatography-Mass Spectrometry (GC/MS).
Cultures of 20 clinical strains of Ps. aeruginosa but not other respiratory pathogens had high concentrations of 2-AA in the head space of in vitro cultures when analysed by GC/MS. 2-AA was stable for 6 hours in deactivated glass sampling bulbs but was not stable in Tedlar® bags. Optimisation of GC/MS allowed detection levels of 2-AA to low pico mol/mol range in breath. The 2-AA was detected in a significantly higher proportion of subjects colonised with Ps. aeruginosa 15/16 (93.7%) than both the healthy controls 5/17 (29%) (p < 0.0002) and CF patients not colonised with Ps. aeruginosa 4/13(30.7%) (p < 0.001). The sensitivity and specificity of the 2-AA breath test compared to isolation of Ps. aeruginosa in sputum and/or BALF was 93.8% (95% CI, 67-99) and 69.2% (95% CI, 38-89) respectively. The peak integration values for 2-AA analysis in the breath samples were significantly higher in Ps. aeruginosa colonised subjects (median 242, range 0-1243) than the healthy controls (median 0, range 0-161; p < 0.001) and CF subjects not colonised with Ps. aeruginosa (median 0, range 0-287; p < 0.003)
Our results report 2-AA as a promising breath biomarker for the detection of Ps. aeruginosa infections in the cystic fibrosis lung.