Effect of changes in tidal volume on multiple breath washout outcomes

The lung clearance index (LCI), measured by multiple breath washout (MBW), reflects global ventilation inhomogeneity and is a sensitive marker of early obstructive airway disease. For the MBW test to accurately reflect a subject’s gas mixing within the lungs, the breathing pattern should represent physiologically appropriate tidal volumes (V_T) and respiratory rate (RR). We aimed to assess whether changes in V_T impact MBW outcome measures with a series of prospective and retrospective studies. MBW testing was performed using the Exhalyzer ^® D (EcoMedics AG, Switzerland). Healthy adult subjects performed MBW with uninstructed tidal breathing and a series of instructed tidal breathing tests, designed to isolate specific features of the breathing pattern. In addition, we retrospectively analyzed MBW data from two pediatric multi-centre interventional studies of cystic fibrosis (CF) subjects to determine the range of V_T observed during uninstructed breathing, and whether breathing outside this range impacted results. The LCI was lower, but not significantly different between deep breathing at 20 ml/kg body weight and uninstructed tidal breathing; whereas LCI was significantly higher during shallow breathing compared with normal tidal breathing. For the majority of subjects with CF (80%), V_T ranged from 9-15mL/kg. Within the observed V_T range, LCI was similar in trials with mean V_{T /}kg below this range compared to trials with V_T /kg within the range. If subjects breathe naturally and are not instructed to use specific targets, the range of V_T is within physiologically appropriate limits and normal variations observed do not impact MBW outcomes.