2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung.
BACKGROUND
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).


METHODS
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).


RESULTS
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).


CONCLUSIONS
Our results report 2-AA as a promising breath biomarker for the detection of Ps. aeruginosa infections in the cystic fibrosis lung.
Christchurch School of Medicine and Health Sciences, Department of Pathology, University of Otago, Christchurch, 8140, New Zealand. amy.scott-thomas@otago.ac.nz
Amy J
AJ
Scott-Thomas
Mona
M
Syhre
Philip K
PK
Pattemore
Michael
M
Epton
Richard
R
Laing
John
J
Pearson
Stephen T
ST
Chambers
D000098:Acetophenones / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008168:Lung / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000150:complications / Q000175:diagnosis*; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000254:growth & development; D012141:Respiratory Tract Infections / Q000150:complications / Q000175:diagnosis; D012680:Sensitivity and Specificity; D055815:Young Adult
D000098:Acetophenones; D015415:Biomarkers; C055495:2-aminoacetophenone