Electronic nose breathprints are independent of acute changes in airway caliber in asthma

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 (PC(20)) causing 20% fall in forced expiratory volume in 1 second (FEV(1)) 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 FEV(1) and was followed by a significant change in breathprint (p = 0.04). Saline inhalation did not induce a significant change in FEV(1), 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.

Keywords: airway caliber; bronchial asthma; bronchial provocation; electronic nose; exhaled breathprint; pattern recognition; volatile organic compounds.

Figure 1.

(a) FEV₁ measurements at baseline, after methacholine (Post-MCh) inhalation and post-salbutamol (Post-salb). (b) Breathprints at baseline, after methacholine inhalation and post-salbutamol are presented by plotting Factor 2 (red line) and 3 (blue line). *p < 0.05, **p < 0.01, *** p < 0.001 vs. baseline; ^###p < 0.001 vs. post-methacholine. The data are shown in the table below the figure.

Figure 2.

(a) FEV₁ measurements at baseline, after saline inhalation and post-salbutamol (post-salb). (b) Breathprints at baseline, after saline inhalation and post-salbutamol are presented by plotting Factor 2 (red line) and 3 (blue line). *p < 0.05, **p < 0.01 vs. baseline; ^#p < 0.05, ^###p < 0.001 vs. post-saline. The data are shown in the table below the figure.

Figure 3.

(a) Changes in FEV₁ after the inhalation of methacholine (MCh; orange line) or isotonic saline (black line). (b) Changes in breathprints induced by methacholine or saline inhalation as the change (delta) in Factor 2 (red line) and 3 (blue line); for all deltas: p > 0.05. ^§§§p < 0.001 post-methacholine vs. post-saline.

Figure 4.

Baseline breathprints are unchanged in asthmatic patients. Pre-challenge baseline breathprints at the two visits are shown by plotting Factor 2 (red line) and Factor 3 (blue line); for all factors: p > 0.05. The attached table shows the data.