Abstract
BACKGROUND: Methods used to assess ventilation heterogeneity through inert gas washout have been standardised and showed high sensitivity in diagnosing many respiratory diseases. We hypothesised that nitrogen single or multiple breath washout tests, respectively nitrogen single breath washout (N(2)SBW) and nitrogen multiple breath washout (N(2)MBW), may be pathological in patients with clinical suspicion of asthma but normal spirometry. Our aim was to assess whether N(2)SBW and N(2)MBW are associated with methacholine challenge test (MCT) results in this population. We also postulated that an alteration in S(III) at N(2)SBW could be detected before the 20% fall of forced expiratory volume in the first second (FEV(1)) in MCT. STUDY DESIGN AND METHODS: This prospective, observational, single-centre study included patients with suspicion of asthma with normal spirometry. Patients completed questionnaires on symptoms and health-related quality-of-life and underwent the following lung function tests: N(2)SBW (S(III)), N(2)MBW (Lung clearance index (LCI), S(cond), S(acin)), MCT (FEV(1) and sGeff) as well as N(2)SBW between each methacholine dose. RESULTS: 182 patients were screened and 106 were included in the study, with mean age of 41.8±14 years. The majority were never-smokers (58%) and women (61%). MCT was abnormal in 48% of participants, N(2)SBW was pathological in 10.6% at baseline and N(2)MBW abnormality ranged widely (LCI 81%, S(cond) 18%, S(acin) 43%). The dose response rate of the MCT showed weak to moderate correlation with the subsequent N(2)SBW measurements during the provocation phases (ρ 0.34-0.50) but no correlation with N(2)MBW. CONCLUSIONS: Both MCT and N(2) washout tests are frequently pathological in patients with suspicion of asthma with normal spirometry. The weak association and lack of concordance across the tests highlight that they reflect different but not interchangeable pathological pathways of the disease.