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S9 SIFT-MS analysis as a non-invasive determinant of pseudomonas aeruginosa infection in patients with cystic fibrosis
  1. R Pabary1,
  2. S Kumar2,
  3. J Huang2,
  4. EWFW Alton3,
  5. A Bush1,
  6. GB Hanna2,
  7. JC Davies3
  1. 1Royal Brompton and Harefield Hospital Foundation Trust, London, United Kingdom
  2. 2Department of Cancer and Surgery, Imperial College, London, United Kingdom
  3. 3National Heart and Lung Institute, Imperial College, London, United Kingdom

Abstract

Background There is evidence that Pseudomonas aeruginosa (Pa) produces volatile organic compounds (VOCs) such as hydrogen cyanide (HCN) and 2-aminoacetophenone (2-AA). VOCs in exhaled breath are therefore proposed as potential biomarkers of infection. We hypothesised that selective ion-flow mass spectrometry (SIFT-MS) breath analysis might allow discrimination of CF patients with (CF + Pa) and without Pa (CF-Pa).

Methods 79 adults (31 CF + Pa, 22 CF-Pa and 26 healthy controls) provided starved, single tidal exhalation breath samples into NalophanTM bags. Quantification of 15 VOCs was performed within two hours on SIFT-MS. All results are presented as (median parts-per-billion by volume [IQR]).

Results 2-AA was significantly higher in CF + Pa than CF-Pa (5.0 [3.4 7.1] vs. 1.3 [0.0 3.2], p <0.01). However, there was significant overlap and median co-efficient of variation was 35.41%; clinical utility is therefore questionable.

Dimethyl disulphide was also significantly higher in CF + Pa (95.2 [41.3 211.2 vs. 35.5 [22.1 79.8], p < 0.01). When combined with 2-AA, area under ROC curve was 0.867.

Counter to our sputum results, there was no difference in HCN between CF + Pa and CF-Pa (8.1 [5.0 11.9] vs. 6.9 [4.4 11.0], n/s) or between all CF patients and healthy controls (7.8 [4.9 11.5] vs. 7.0 [4.6 11.5], n/s).

Our early in vitro data showed decreased butanol above Pa cultures, suggesting consumption. This was replicated in breath with lower levels in CF + Pa vs. CF-Pa (37.4 [24.3 87.6] vs. 91.7 [46.9 143.7], p < 0.05).

Of VOCs likely to be of host origin, isoprene was increased in CF vs. controls (108.0 [83.4 195.5] vs. 69.6 [46.9 89], p < 0.01) with no difference between CF + Pa vs. CF-Pa. Acetone was reduced in CF (269.9 [161.9 356.4] vs. 324.9 [236.7 598.9], p < 0.01).

Conclusions 2-AA is a potential biomarker of Pa infection but clinical applicability is uncertain. Dimethyl disulphide and butanol also show promise. Mouth-exhaled HCN assessed by SIFT-MS does not appear to fulfil its promise as a Pa biomarker. Other VOCs assessed were either similar between Pa groups or different between healthy controls and CF, but unable to differentiate between Pa status. This study provides proof-of-concept for the development of a non-invasive tool with which to screen for lower airway bacterial infection in CF though a clinically applicable test remains some way off.

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