Single and multiple breath nitrogen washout compared with the methacholine test in patients with suspected asthma and normal spirometry.

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 (NSBW) and nitrogen multiple breath washout (NMBW), may be pathological in patients with clinical suspicion of asthma but normal spirometry. Our aim was to assess whether NSBW and NMBW are associated with methacholine challenge test (MCT) results in this population. We also postulated that an alteration in S at NSBW could be detected before the 20% fall of forced expiratory volume in the first second (FEV) 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: NSBW (S), NMBW (Lung clearance index (LCI), S, S), MCT (FEV and sGeff) as well as NSBW 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, NSBW was pathological in 10.6% at baseline and NMBW abnormality ranged widely (LCI 81%, S 18%, S 43%). The dose response rate of the MCT showed weak to moderate correlation with the subsequent NSBW measurements during the provocation phases (ρ 0.34-0.50) but no correlation with NMBW.

Conclusions: Both MCT and N 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.