Bronchoprovocation testing in asthma: Effect on exhaled monoxides

Exhaled carbon monoxide and nitric oxide reflect allergic inflammation in asthma and have clinical utility for monitoring disease severity. The effects of allergen challenge and of inflammatory versus non-inflammatory bronchoconstrictive stimuli on the exhalation kinetics of these gases are unclear. The aim of this study is to compare and contrast the effects of methacholine and allergen challenges on the exhaled levels of carbon monoxide and nitric oxide in a cohort of adult subjects with atopic asthma. Eight subjects underwent inhaled allergen testing, nine underwent methacholine testing, and five subjects underwent both tests. Additionally, seven healthy controls underwent a mock challenge. Mixed-expired and end-expiratory carbon monoxide and end-expiratory nitric oxide levels were measured together with spirometry before, during (i.e. after each step of the inhalations), and after the challenges. Decreases in both end-expiratory (-14.4% in 9/11 subjects, p = 0.04) and mixed-expired (-7.5%, 9/11 subjects, p = 0.007) levels of carbon monoxide were noted during the immediate phase of the allergen challenge, with similar reductions after methacholine challenge, but levels were unaffected by repeated forced vital capacity exhalations alone. End-expiratory nitric oxide increased during the immediate phase of allergen challenge in 10/13 subjects (+10.8%, p = 0.05), but decreased after methacholine challenge in 14/14 subjects (-32.2%, p = 0.00009). Bronchospasm negatively modulates exhaled carbon monoxide and nitric oxide, but the inflammatory stimulus of allergen exposure increases exhaled nitric oxide. Measurements of exhaled monoxides may need to be referenced to the FEV₁.