Quality control for multiple breath washout tests in multicentre bronchiectasis studies:Experiences from the BRONCH-UK clinimetrics study

Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or “over-reading” is resource intensive and the impact is unclear. Objectives: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading. Methods: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared. Results: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity. Conclusion: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW

Multiple Breath Washout Outcome Measures in Adults with Bronchiectasis

RATIONALE: Lung Clearance index (LCI) has good intra-visit repeatability with better sensitivity in detecting lung disease on CT scan compared to Forced Expiratory Volume in 1 second (FEV1) in adults with bronchiectasis. Alternative multiple breath washout (MBW) parameters have not been systematically studied in bronchiectasis. OBJECTIVES: To determine the validity, repeatability, sensitivity, specificity and feasibility of standard LCI (LCI2.5), shortened LCI (LCI5.0), ScondVT and SacinVT in a cross-sectional observational cohort of adults with bronchiectasis. METHODS: Cross-sectional MBN2W data (Exhalyzer® D) from 132 patients with bronchiectasis across 5 UK centres (Bronch-UK Clinimetrics study) and 88 healthy controls were analysed. RESULTS: Within test repeatability (mean CV%) was 2 z-score) but normal FEV1 (<-2 z-score) was 42% (LCI2.5) and 36% (LCI5.0). Overall results from the receiver operator characteristic curve (AUCROC) indicated that LCI2.5 had greatest combined sensitivity and specificity to discriminate between bronchiectasis and control subjects, followed by LCI5.0, FEV1 and ScondVT z-scores. There was a 57% time saving with LCI5.0. CONCLUSIONS: LCI2.5 and LCI5.0 had good within test repeatability and superior sensitivity compared with spirometry measures, in differentiating between health and bronchiectasis disease. LCI5.0 is shorter and more feasible than LCI2.5. Clinical trial registered with ClinicalTrials.gov (NCT02468271)

Multiple Breath Washout Outcome Measures in Adults with Bronchiectasis

RATIONALE: Lung Clearance index (LCI) has good intra-visit repeatability with better sensitivity in detecting lung disease on CT scan compared to Forced Expiratory Volume in 1 second (FEV1) in adults with bronchiectasis. Alternative multiple breath washout (MBW) parameters have not been systematically studied in bronchiectasis. OBJECTIVES: To determine the validity, repeatability, sensitivity, specificity and feasibility of standard LCI (LCI2.5), shortened LCI (LCI5.0), ScondVT and SacinVT in a cross-sectional observational cohort of adults with bronchiectasis. METHODS: Cross-sectional MBN2W data (Exhalyzer® D) from 132 patients with bronchiectasis across 5 UK centres (Bronch-UK Clinimetrics study) and 88 healthy controls were analysed. RESULTS: Within test repeatability (mean CV%) was 2 z-score) but normal FEV1 (<-2 z-score) was 42% (LCI2.5) and 36% (LCI5.0). Overall results from the receiver operator characteristic curve (AUCROC) indicated that LCI2.5 had greatest combined sensitivity and specificity to discriminate between bronchiectasis and control subjects, followed by LCI5.0, FEV1 and ScondVT z-scores. There was a 57% time saving with LCI5.0. CONCLUSIONS: LCI2.5 and LCI5.0 had good within test repeatability and superior sensitivity compared with spirometry measures, in differentiating between health and bronchiectasis disease. LCI5.0 is shorter and more feasible than LCI2.5. Clinical trial registered with ClinicalTrials.gov (NCT02468271)