Diffusing capacity of the lung for carbon monoxide: association with long-term outcomes after lung transplantation in a 20-year longitudinal study

David Ross Darley; Jin Ma; Ella Huszti; Rasheed Ghany; Michael Hutcheon; Chung-Wai Chow; Jussi Tikkanen; Shaf Keshavjee; Lianne Gail Singer; Tereza Martinu

doi:10.1183/13993003.03639-2020

Diffusing capacity of the lung for carbon monoxide: association with long-term outcomes after lung transplantation in a 20-year longitudinal study

Eur Respir J. 2022 Jan 27;59(1):2003639. doi: 10.1183/13993003.03639-2020. Print 2022 Jan.

Authors

David Ross Darley^{1

2}, Jin Ma³, Ella Huszti³, Rasheed Ghany¹, Michael Hutcheon¹, Chung-Wai Chow^{1

4}, Jussi Tikkanen¹, Shaf Keshavjee¹, Lianne Gail Singer^{1

4}, Tereza Martinu^{5

4}

Affiliations

¹ Toronto Lung Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
² UNSW Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
³ Biostatistics Research Unit, University Health Network, Toronto, ON, Canada.
⁴ Dept of Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Toronto Lung Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada Tereza.Martinu@uhn.ca.

PMID: 34172463
DOI: 10.1183/13993003.03639-2020

Abstract

Rationale: The diffusing capacity of the lung for carbon monoxide corrected for haemoglobin (D _LCOcor) measures gas movement across the alveolar-capillary interface. We hypothesised that D _LCOcor is a sensitive measure of injurious allograft processes disrupting this interface.

Objectives: To determine the prognostic significance of the D _LCOcor trajectory on chronic lung allograft dysfunction (CLAD) and survival.

Methods: A retrospective analysis was conducted of all bilateral lung transplant recipients at a single centre, between January 1998 and January 2018, with one or more D _LCOcor measurements. Low baseline D _LCOcor was defined as the failure to achieve a D _LCOcor >75% predicted. Drops in D _LCOcor were defined as >15% below recent baseline.

Results: 1259 out of 1492 lung transplant recipients were included. The median (range) time to peak D _LCOcor was 354 (181-737) days and the mean±sd D _LCOcor was 80.2±21.2% pred. Multivariable analysis demonstrated that low baseline D _LCOcor was significantly associated with death (hazrd ratio (HR) 1.68, 95% CI 1.27-2.20; p<0.001). Low baseline D _LCOcor was not independently associated with CLAD after adjustment for low baseline forced expiratory volume in 1 s or forced vital capacity. Any D _LCOcor declines ≥15% were significantly associated with death, independent of concurrent spirometric decline. Lower percentage predicted D _LCOcor values at CLAD onset were associated with shorter post-CLAD survival (HR 0.75 per 10%-unit change, p<0.01).

Conclusion: Low baseline D _LCOcor and post-transplant declines in D _LCOcor were significantly associated with survival, independent of spirometric measurements. We propose that D _LCOcor testing may allow identification of a subphenotype of baseline and chronic allograft dysfunction not captured by spirometry. There may be benefit in routine monitoring of D _LCOcor after lung transplantation to identify patients at risk of poor outcomes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbon Monoxide
Humans
Longitudinal Studies
Lung
Lung Transplantation*
Primary Graft Dysfunction*
Retrospective Studies

Substances

Carbon Monoxide