Controlled versus free breathing for multiple breath nitrogen washout in healthy adults

Multiple breath nitrogen washout (MBNW) quantifies ventilation heterogeneity. Two distinct protocols are currently used for MBNW testing: controlled breathing, with targeted tidal volume (V-T) and respiratory rate (RR); and free breathing, with no constraints on breathing pattern. Indices derived from the two protocols (functional residual capacity (FRC), lung clearance index (LCI), S-cond, S-acin) have not been directly compared in adults. We aimed to determine whether MBNW indices are comparable between protocols, to identify factors underlying any between-protocol differences and to determine the between-session variabilities of each protocol. We performed MBNW testing by both protocols in 27 healthy adult volunteers, applying the currently proposed correction for V-T to S-cond and S-acin derived from free breathing. To establish between-session variability, we repeated testing in 15 volunteers within 3 months. While FRC was comparable between controlled versus free breathing (3.17 (0.98) versus 3.18 (0.94) L, p=0.88), indices of ventilation heterogeneity derived from the two protocols were not, with poor correlation for Scond (r=0.18, p=0.36) and significant bias for Sacin (0.057 (0.021) L-1 versus 0.085 (0.038) L-1, p=0.0004). Between-protocol differences in S-acin were related to differences in the breathing pattern, i.e. V-T (p=0.004) and RR (p=0.01), rather than FRC. FRC and LCI showed good between-session repeatability, but S-cond and S-acin from free breathing showed poor repeatability with wide limits of agreement. These findings have implications for the ongoing clinical implementation of MBNW, as they demonstrate that S-cond and S-acin from free breathing, despite V-T correction, are not equivalent to the controlled breathing protocol. The poor between-session repeatability of Scond during free breathing may limit its clinical utility.

Automated summary

Multiple breath nitrogen washout (MBNW) quantifies ventilation heterogeneity using two distinct protocols: controlled breathing and free breathing. While functional residual capacity (FRC) was comparable between the two protocols, indices of ventilation heterogeneity differed, with poor between-session repeatability for Scond and S-acin derived from free breathing. Differences in S-acin were related to differences in breathing patterns rather than FRC, indicating implications for the clinical implementation of MBNW.