M. Basanta, B. Ibrahim, H. Sumner, D. Singh, J. Smith, #J. Goshawk, #D. Douce, #M. Morris, A. Woodcock, S.J. Fowler.
University of Manchester, UK
#Waters Corporation, Manchester, UK. |
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Introduction: Breath analysis is non-invasive and highly sensitive, and could lead to the future development of miniaturised, inexpensive point-of-care monitors for a variety of diseases. Exhaled compounds arise not only from metabolic processes in the lungs, but also from other regions of the body due to diffusion across the alveolar-capillary interface (1). Our initial clinical investigations have focused on chronic respiratory diseases such asthma and chronic obstructive pulmonary disease (COPD). In our institution we are investigating the use of inhaled capsaicin as an experimental model to investigate the pathophysiology of cough (2). We here describe the effects of this challenge on the breath profile of patients with COPD. An experimental design was carefully developed to account for variability that could compromise breath analysis in clinical settings.
Experimental: Data were initially evaluated by analysing all the samples using the MassLynxTM application manager, MarkerLynxTM XS, to select markers that were significantly different between the comparison groups. Baseline correction, deconvolution and peak areas were performed with AMDIS (Automated Mass Spectral Deconvolution and Identification System), and a library consisting of approximately 500 compounds created. Breath samples were collected from 16 patients (11 male, 8 smokers, mean age 63 yrs) at baseline and following sequential inhalation of nebulised capsaicin solution in a stepwise fashion, until either cough was induced or all doses had been given
Discussion: Principal component analysis was performed and relative peak areas of compounds were used to visualise any intra- and inter-variability across COPD ex-smokers and smokers. This clearly demonstrated that breath analysis could distinguish four separate groups based on the first three principal components: smokers pre- and post-challenge, and ex-smokers pre- and post-challenge. Twenty six individual compounds showed significant changes after the challenge. For example, indole and dodecanoic ac methylester decreased in both groups following challenge, whereas benzene, 1, 2, 3, 4, tetramethyl increased.
Conclusions: We have used a clinical model to study serial changes in breath profile, showing clear discrimination of groups by smoking status and following inhalation of capsaicin. We have identified many compound of interest that merit future investigation as biomarkers of the disease process. This model can also be used in future to study other longitudinal effects of clinical relevance, such as the impact of exacerbations or treatments.
References
1. Basanta, M., et al. Analyst, 2007, 132, 153-163
2. Morice, AH., et al. Eur Respir J. 2007 Jun; 29(6):1256-76 |
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