Lower Respiratory Tract Pathogens Analyzed by Breath Test

Healthcare associated infections, including ventilator associated pneumonia, are difficult to diagnose and treat, and are associated with significant morbidity, mortality and cost.

Chemically analyzing breath volatile profiles that were associated with the presence of clinically relevant pathogens in the lower respiratory tract from patients in intensive care can reveal bacterial infection in ventilated patients at risk of developing pneumonia.

Scientists at the University of Manchester (UK) and their colleagues recruited patients undergoing invasive mechanical ventilation in an intensive care unit. Clinical details related to the patient diagnoses and investigations were recorded, including data related to physiology, radiology, microbiology as well as blood biochemistry and hematology. In addition serum was analyzed for the inflammatory cytokines interleukin (IL)-6, IL-10 and procalcitonin. Samples were collected from 54 patients and assent obtained for 46 consultees between January and July 2010.

A novel sampling apparatus was developed for the specific purpose of capturing volatiles from the distal intratracheal air of mechanically ventilated patients. Analysis of breath samples was performed by thermal desorption/gas chromatography/time-of-flight mass spectrometry (TD/GC-MS, Markes International; Llantrisant, UK), and the GCT Premier mass spectrometer, (Waters Corp; Manchester, UK). Samples were also cultured for pathogens.

The dominant factors affecting breath sample analysis were the individual breath profile and duration of intubation. When these were taken into account, clear separation was seen between breath profiles at each time point by the presence/absence of pathogens. The most commonly isolated pathogens were Haemophilus influenzae found in 12 samples from 10 patients and Staphylococcus aureus found in 18 samples from 10 patients. Thirty-one (67%) patients had negative respiratory and blood culture samples at baseline, and 20 (43%) remained culture-negative for the duration of the study, although only two of these were sampled on more than two occasions.

Compounds found to be lower in concentration in the breath of infected versus non-infected patients included ethanol, 2-methyl cyclopentanone, heptane, and N-cyclohexyl-N′(2-hydroxyethyl)thiourea, while those found in higher concentration included 3-carene, n-butyric acid 2-ethylhexyl ester , nonanal and 2,6,11,15-tetramethyl-hexadecane. Multivariate analysis showed none of the blood inflammatory biomarkers measured, procalcitonin, IL10, IL6, IL10/6 ratio, total white cell count, predicted the presence of lower respiratory tract pathogens.

The authors concluded that volatile metabolites in the breath of ventilated patients at high risk of developing ventilator associated pneumonia (VAP) show distinct patterns that enable the differentiation of patients with and without pathogens in the airway. The study was published in the April 2015 issue of the journal Thorax.

Related Links:
University of Manchester 
Markes International
Waters Corp.