Katherine O'Neill1, Gokul R Lakshmipathy1, Curtis Neely1, Denise Cosgrove2, Kathryn Ferguson2, Rebecca McLeese1, Adam T Hill3,4, Michael R Loebinger5,6, Mary Carroll7, James D Chalmers8, Timothy Gatheral9, Chris Johnson10, Anthony De Soyza11, John R Hurst12, Ian Bradbury13, Joseph S Elborn1, Judy M Bradley1. 1. Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom. 2. Belfast Health and Social Care Trust, Belfast, United Kingdom. 3. Royal Infirmary of Edinburgh, Edinburgh, United Kingdom. 4. University of Edinburgh, Edinburgh, United Kingdom. 5. Royal Brompton Hospital, London, United Kingdom. 6. Imperial College London, London, United Kingdom. 7. University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. 8. College of Medicine, University of Dundee, Dundee, United Kingdom. 9. Department of Respiratory Medicine, University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster, United Kingdom. 10. Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, United Kingdom. 11. Institute of Cellular Medicine, Newcastle University, National Institute of Health Research Biomedical Research Centre, Newcastle, United Kingdom. 12. Department of Respiratory Medicine, University College London, London, United Kingdom; and. 13. Frontier Science (Scotland) Ltd., Kincraig, United Kingdom.
Abstract
Rationale: Lung clearance index (LCI) has good intravisit repeatability with better sensitivity in detecting lung disease on computed tomography scan compared with forced expiratory volume in 1 second (FEV1) in adults with bronchiectasis. Alternative multiple-breath washout 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), ventilation heterogeneity arising within proximal conducting airways (ScondVT), and ventilation heterogeneity arising within the acinar airways (SacinVT) in a cross-sectional observational cohort of adults with bronchiectasis. Methods: Cross-sectional multiple-breath nitrogen washout data (Exhalyzer D; Eco Medics AG) from 132 patients with bronchiectasis across five United Kingdom centers (BronchUK Clinimetrics study) and 88 healthy control subjects were analyzed. Results: Within-test repeatability (mean coefficient of variation) was <5% for both LCI2.5 and LCI5.0 in patients with bronchiectasis, and there was no difference in mean coefficient of variation for LCI2.5 and LCI5.0 in patients with bronchiectasis compared with healthy volunteers. Moderate-strength correlations were seen between FEV1 and LCI2.5 (r = -0.54), LCI5.0 (r = -0.53), ScondVT (r = -0.35), and SacinVT (r = -0.38) z-scores. The proportion of subjects with abnormal multiple-breath washout (z-score > 2) but in normal FEV1 (z-score < -2) was 42% (LCI2.5) and 36% (LCI5.0). Overall results from the receiver operating characteristic curve analysis indicated that LCI2.5 had the 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 quicker and more feasible than LCI2.5. Clinical trial registered with www.clinicaltrials.gov (NCT02468271).
Rationale: Lung clearance index (LCI) has good intravisit repeatability with better sensitivity in detecting lung disease on computed tomography scan compared with forced expiratory volume in 1 second (FEV1) in adults with bronchiectasis. Alternative multiple-breath washout 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), ventilation heterogeneity arising within proximal conducting airways (ScondVT), and ventilation heterogeneity arising within the acinar airways (SacinVT) in a cross-sectional observational cohort of adults with bronchiectasis. Methods: Cross-sectional multiple-breath nitrogen washout data (Exhalyzer D; Eco Medics AG) from 132 patients with bronchiectasis across five United Kingdom centers (BronchUK Clinimetrics study) and 88 healthy control subjects were analyzed. Results: Within-test repeatability (mean coefficient of variation) was <5% for both LCI2.5 and LCI5.0 in patients with bronchiectasis, and there was no difference in mean coefficient of variation for LCI2.5 and LCI5.0 in patients with bronchiectasis compared with healthy volunteers. Moderate-strength correlations were seen between FEV1 and LCI2.5 (r = -0.54), LCI5.0 (r = -0.53), ScondVT (r = -0.35), and SacinVT (r = -0.38) z-scores. The proportion of subjects with abnormal multiple-breath washout (z-score > 2) but in normal FEV1 (z-score < -2) was 42% (LCI2.5) and 36% (LCI5.0). Overall results from the receiver operating characteristic curve analysis indicated that LCI2.5 had the 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 quicker and more feasible than LCI2.5. Clinical trial registered with www.clinicaltrials.gov (NCT02468271).
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