Abstract
Molecular profiling of exhaled volatile organic compounds (VOC) by electronic nose technology provides breathprints that discriminate between patients with different inflammatory airway diseases, such as asthma and COPD. However, it is unknown whether this is determined by differences in airway caliber. We hypothesized that breathprints obtained by electronic nose are independent of acute changes in airway caliber in asthma. Ten patients with stable asthma underwent methacholine provocation (Visit 1) and sham challenge with isotonic saline (Visit 2). At Visit 1, exhaled air was repetitively collected pre-challenge, after reaching the provocative concentration (PC20) causing 20% fall in forced expiratory volume in 1 second (FEV1) and after subsequent salbutamol inhalation. At Visit 2, breath was collected pre-challenge, post-saline and post-salbutamol. At each occasion, an expiratory vital capacity was collected after 5 min of tidal breathing through an inspiratory VOC-filter in a Tedlar bag and sampled by electronic nose (Cyranose 320). Breathprints were analyzed with principal component analysis and individual factors were compared with mixed model analysis followed by pairwise comparisons. Inhalation of methacholine led to a 30.8 ± 3.3% fall in FEV1 and was followed by a significant change in breathprint (p = 0.04). Saline inhalation did not induce a significant change in FEV1, but altered the breathprint (p = 0.01). However, the breathprint obtained after the methacholine provocation was not significantly different from that after saline challenge (p = 0.27). The molecular profile of exhaled air in patients with asthma is altered by nebulized aerosols, but is not affected by acute changes in airway caliber. Our data demonstrate that breathprints by electronic nose are not confounded by the level of airway obstruction.
Highlights
Asthma is a chronic inflammatory disorder of the airways characterized by recurrent episodes of wheezing and chest tightness that are associated with variable airway obstruction
The associated airway inflammation can be evaluated by validated non-invasive techniques such as sputum eosinophil counts [2] and exhaled nitric oxide level (NO) [3], which have shown to be useful in monitoring asthma
Exhaled air is a mixture of thousands of volatile organic compounds (VOCs) [4], which are generated via metabolic pathways that may be altered by lung diseases
Summary
Asthma is a chronic inflammatory disorder of the airways characterized by recurrent episodes of wheezing and chest tightness that are associated with variable airway obstruction. Asthma diagnosis is established based on symptoms, measurement of lung function and assessment of airway responsiveness [1]. The associated airway inflammation can be evaluated by validated non-invasive techniques such as sputum eosinophil counts [2] and exhaled nitric oxide level (NO) [3], which have shown to be useful in monitoring asthma. Identification and quantification of individual VOCs require laboratory methodologies employing gas chromatography coupled to mass spectrometry (GC-MS). Less laborious peak pattern analysis after spectrometry without direct VOC characterization has recently been successful in recognizing lung cancer patients [7]. The procedure still requires skilled personnel and advanced technical facilities, limiting potential widespread medical applicability
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