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 S(cond) (r=0.18, p=0.36) and significant bias for S(acin) (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 S(cond) during free breathing may limit its clinical utility.