Multiple breath nitrogen washout

Ventilation heterogeneity was assessed by the MBNW technique. Instrumentation consisted of a bag in box system where flow was measured using a precalibrated pneumotachograph (Fleish type, flow range 0–5 L sec⁻¹) and N₂ measured continuously at the patient's mouth (AU9240‐4032, Medgraphics Corporation, Minnesota).

Overall, lung ventilation heterogeneity was assessed by the LCI, defined as the number of FRC turnovers (calculated as the ratio of the cumulative expired volume to the FRC volume) required to reduce alveolar nitrogen concentration to less than 2% (Robinson et al. 2013). Ventilation heterogeneity was also measured for the small conductive regions (S_cond) and distal acinar regions (S_acin) of the lungs.

Analysis and underlying theory of the MBNW test have been documented elsewhere (Crawford et al. 1985; Verbanck et al. 1997, 1998, 2004; Stuart‐Andrews et al. 2011; Robinson et al. 2013). Briefly, the MBNW measures the change in slope of the nitrogen alveolar plateau (Sn) following consecutive 100% O₂ breathing using a 1 L tidal volume, until nitrogen was washed out to below 2%. The rate of rise of Sn versus lung turnover plot between turnovers 1.5 and 6 is a measure of conductive ventilation heterogeneity (S_cond) proximal to the acinar entrance. As the slope of the alveolar plateau has a contribution of both acinar and conductive components of ventilatory heterogeneity, S_acin is calculated as the normalized slope of the first breath minus the contribution of S_cond to the first breath. MBNW data were analyzed using an automated process previously described by our group (Stuart‐Andrews et al. 2011). Each MBNW comprised of three successive washout maneuvers with rest of 4 min between assessments to enable normalization of respiratory gas concentrations.