Feasibility and challenges of using multiple breath washout in COPD

Abstract

Background

Lung clearance index (LCI), derived from multiple-breath washout (MBW), is a well-established assessment of ventilation inhomogeneity in cystic fibrosis but has not been widely applied in other conditions characterized by heterogeneous airways disease, such as COPD. The aim of this study was to evaluate the sensitivity, repeatability, and practicality of LCI in patients with COPD.

Methods

Fifty-four COPD patients completed MBW using nitrogen as the washout tracer gas (MBW_N2, measured using an Exhalyzer™ device), spirometry, and plethysmography. Twenty patients repeated MBW_N2, MBW_SF6 (using a separate Innocor™ gas analyzer to measure washout of the exogenous trace sulphur hexafluoride), and spirometry at a second visit ≥24 hours later.

Results

Mean (SD) COPD LCI measured by nitrogen washout (LCI_N2) was 12.1 (2.2); mean (SD) LCI Z-score 5.8 (2.0). LCI_N2 increased across Global Initiative for Obstructive Lung Disease stages 1 to 3 and was abnormal (Z-score >1.65) in all COPD patients, including those with forced expiratory volume in 1 second (FEV₁) ≥80% predicted. LCI was repeatable (median intra-test coefficient of variation 4.1%) and reproducible (limits of agreement −1.8 to 1.6) after mean of 16 days. Functional residual capacity (FRC) measurements were significantly greater using nitrogen than SF₆ or plethysmography: mean FRC measured by nitrogen washout (FRC_N2) 139% predicted versus FRC measured by plethysmography 125% predicted, p<0.0001.

Conclusion

LCI is most suitable as a measure of early airways disease in COPD in those with well-preserved FEV₁, with similar repeatability and limitations to that observed in cystic fibrosis. Using the Exhalyzer system to perform MBW_N2, however, appeared to substantially over-read FRC. This discrepancy needs addressing before FRC_N2 measurements made using this device can be reliably deployed.

Keywords:

• COPD
• multiple breath washout
• lung volumes
• lung physiology
• functional residual capacity
• lung clearance index

Acknowledgments

The authors gratefully thank the patients who kindly took part in this study and acknowledge Paul Hitchen in aiding data collection. This study received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors. AH received funding to support the study from the National Institute of Health Research (NIHRS012-13). This report, therefore, presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Disclosure

ASB and PJL were supported by the Medicines Evaluation Unit, University Hospital of South Manchester, UK. DS reports personal fees from Apellis, Peptinovate, Skyepharma, Cipla, and Genentech, and grants and personal fees from AstraZeneca, Boehringer Ingleheim, Chiesi, Glenmark, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Therevance and Verona, all outside the submitted work. AH reports personal fees from Celtaxys, Vertex, Chiesi, Boehringer Ingelheim, and collaboration agreement with Innovision ApS, outside the submitted work. The authors report no other conflicts of interest in this work.