Single-Breath Washout Tests to Assess Small Airway Disease in COPD

Background: Current functional assessments do not allow a reliable assessment of small airways, which are a major site of disease in COPD. Single-breath washout (SBW) tests are feasible and reproducible methods for evaluating small airway disease. Their relevance in COPD remains unknown.

Methods: We performed a cross-sectional study in 65 patients with moderate to severe COPD. Phase III slope of nitrogen (SIII_N2) and double tracer gas (SIII_DTG) SBW tests were used as a measure of ventilation inhomogeneity. The association of both markers with established physiological and clinical features of COPD was assessed.

Results: Ventilation inhomogeneity as measured by SIII_N2 and SIII_DTG was increased in patients with COPD compared with healthy subjects (P < .001 and P < .001, respectively). SIII_N2 was associated with FEV₁ predicted, residual volume (RV)/total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (Dlco) (all P < .001). Furthermore, SIII_N2 was related to dyspnea, exercise-induced desaturation, and exercise capacity (P = .001, P < .001, and P = .047, respectively). SIII_DTG was associated with TLC, Dlco, and cough (P < .001, P = .001, and P = .009, respectively). In multivariate regression models, we demonstrated that these associations are largely independent of FEV₁ and mostly stronger than associations with FEV₁. In contrast, FEV₁ was superior in predicting emphysema severity.

Conclusions: SIII_N2 and SIII_DTG, two fast and clinically applicable measures of small airway disease, reflect different physiological and clinical aspects of COPD, largely independent of spirometry.

Trial registry: ISRCTN99586989, Ethics committee Beider Basel (approval number 295/07).