Survival benefit of lung transplantation compared with medical management and pulmonary rehabilitation for patients with end-stage COPD

Irina Timofte¹, Marniker Wijesinha², Roumen Vesselinov², June Kim¹, Robert Reed¹, Pablo G Sanchez³, Nicholas Ladikos⁴, Si Pham⁵, Zachary Kon⁶, Keshava Rajagopal⁷, Steven M Scharf¹, Robert Wise⁸, Alice L Sternberg⁹, David Kaczorowski¹⁰, Bartley Griffith¹⁰, Michael Terrin², Aldo Iacono¹¹

Affiliations

¹ Dept of Medicine, University of Maryland Medical Center, Baltimore, MD, USA.
² Dept of Epidemiology and Public Health, University of Maryland Medical Center, Baltimore, MD, USA.
³ Dept of Cardio Thoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Dept of Pharmacy, Suburban Hospital/Johns Hopkins Medicine, Bethesda, MD, USA.
⁵ Dept of Cardio Thoracic Surgery, Mayo Clinic Florida, Jacksonville, FL, USA.
⁶ Dept of Thoracic Surgery, New York University, New York, NY, USA.
⁷ Dept of Cardio Thoracic Surgery, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁸ Dept of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Dept of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁰ Dept of Cardio Thoracic Surgery, University of Maryland Medical Center, Baltimore, MD, USA.
¹¹ R. Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, MD, USA.

PMID: 32363207
PMCID: PMC7184114
DOI: 10.1183/23120541.00177-2019

Survival benefit of lung transplantation compared with medical management and pulmonary rehabilitation for patients with end-stage COPD

Irina Timofte et al. ERJ Open Res. 2020.

. 2020 Apr 27;6(2):00177-2019.

doi: 10.1183/23120541.00177-2019. eCollection 2020 Apr.

Authors

Affiliations

¹ Dept of Medicine, University of Maryland Medical Center, Baltimore, MD, USA.
² Dept of Epidemiology and Public Health, University of Maryland Medical Center, Baltimore, MD, USA.
³ Dept of Cardio Thoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Dept of Pharmacy, Suburban Hospital/Johns Hopkins Medicine, Bethesda, MD, USA.
⁵ Dept of Cardio Thoracic Surgery, Mayo Clinic Florida, Jacksonville, FL, USA.
⁶ Dept of Thoracic Surgery, New York University, New York, NY, USA.
⁷ Dept of Cardio Thoracic Surgery, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁸ Dept of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Dept of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁰ Dept of Cardio Thoracic Surgery, University of Maryland Medical Center, Baltimore, MD, USA.
¹¹ R. Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, MD, USA.

PMID: 32363207
PMCID: PMC7184114
DOI: 10.1183/23120541.00177-2019

Abstract

Background: COPD patients account for a large proportion of lung transplants; lung transplantation survival benefit for COPD patients is not well established.

Methods: We identified 4521 COPD patients in the United Network for Organ Sharing (UNOS) dataset transplanted from May 2005 to August 2016, and 604 patients assigned to receive pulmonary rehabilitation and medical management in the National Emphysema Treatment Trial (NETT). After trimming the populations for NETT eligibility criteria and data completeness, 1337 UNOS and 596 NETT patients remained. Kaplan-Meier estimates of transplant-free survival from transplantation for UNOS, and NETT randomisation, were compared between propensity score-matched UNOS (n=401) and NETT (n=262) patients.

Results: In propensity-matched analyses, transplanted patients had better survival compared to medically managed patients in NETT (p=0.003). Stratifying on 6 min walk distance (6 MWD) and FEV₁, UNOS patients with 6 MWD <1000 ft (∼300 m) or FEV₁ <20% of predicted had better survival than NETT counterparts (median survival 5.0 years UNOS versus 3.4 years NETT; log-rank p<0.0001), while UNOS patients with 6 MWD ≥1000 ft (∼300 m) and FEV₁ ≥20% had similar survival to NETT counterparts (median survival, 5.4 years UNOS versus 4.9 years NETT; log-rank p=0.73), interaction p=0.01.

Conclusions: Overall survival is better for matched lung transplant patients compared with medical management alone. Patients who derive maximum benefit are those with 6 MWD <1000 ft (∼300 m) or FEV₁ <20% of predicted, compared with pulmonary rehabilitation and medical management.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: I. Timofte has nothing to disclose. Conflict of interest: M. Wijesinha has nothing to disclose. Conflict of interest: R. Vesselinov has nothing to disclose. Conflict of interest: J. Kim has nothing to disclose. Conflict of interest: R. Reed reports grants from the Dept of Defense and the Flight Attendant Medical Research Institute during the conduct of the study; and grants from the National Institutes of Health, the COPD Foundation, Janssen Research & Development LLC and the University of Maryland Institute for Clinical and Translational Research outside the submitted work. Conflict of interest: P.G. Sanchez has nothing to disclose. Conflict of interest: N. Ladikos has nothing to disclose. Conflict of interest: S. Pham has nothing to disclose. Conflict of interest: Z. Kon reports consulting and speaking fees from Medtronic, Inc., and consulting fees from Breethe, Inc., outside the submitted work. Conflict of interest: K. Rajagopal has nothing to disclose. Conflict of interest: S.M. Scharf has nothing to disclose. Conflict of interest: R. Wise reports grants, and personal fees for data monitoring committees and consulting from AstraZeneca, Medimmune, Pearl and Boehringer Ingelheim; personal fees for a clinical endpoint committee from Contrafect; personal fees for data safety monitoring committees from Pulmonx, Roche, Merck and AbbVie; personal fees for a steering committee from Spiration; personal fees for a workshop and consulting from Sunovion; research grants from Pearl Therapeutics and Sanofi-Aventis; personal fees for consultancy from Circassia, Pneuma, Verona, Mylan/Theravance and Propelleor Health; grants, and personal fees for a data monitoring committee, consultancy, a scientific advisory board and a clinical endpoint committee from GSK, outside the submitted work. Conflict of interest: A.L. Sternberg reports that the NETT was supported by contracts from the NHLBI during the conduct of the study. Conflict of interest: D. Kaczorowski has nothing to disclose. Conflict of interest: B. Griffith has nothing to disclose. Conflict of interest: M. Terrin has nothing to disclose. Conflict of interest: A. Iacono has nothing to disclose.

Figures

**FIGURE 1**
Kaplan–Meier plot of transplant-free survival for United Network for Organ Sharing (UNOS) listed and National Emphysema Treatment Trial (NETT) patients.

**FIGURE 2**
Kaplan–Meier plot of survival curves for propensity-matched United Network for Organ Sharing (UNOS) transplant patients and National Emphysema Treatment Trial (NETT) patients.

**FIGURE 3**
Kaplan–Meier plot of survival curves for propensity-matched United Network for Organ Sharing (UNOS) transplant patients and National Emphysema Treatment Trial (NETT) patients, within each disease severity stratum. FEV₁: forced expiratory volume in 1 s.

**FIGURE 4**
Kaplan–Meier plot comparing post-transplant survival between pre-operative disease severity strata. 6MWD: 6-min walking distance; FEV₁: forced expiratory volume in 1 s.

See this image and copyright information in PMC

References

1. Chambers DC, Yusen RD, Cherikh WS, et al. . The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung And Heart-Lung Transplantation Report-2017; Focus Theme: Allograft ischemic time. International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2017; 36: 1047–1059, Epub 2017 Jul 19. doi:10.1016/j.healun.2017.07.016 - DOI - PubMed
1. Aziz F, Penupolu S, Xu X, et al. . Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review. J Thorac Dis 2010; 2: 111–116. PMID:22263028. - PMC - PubMed
1. Anthonisen NR. Prognosis in chronic obstructive pulmonary disease: results from multicentre clinical trials. Am Rev Respir Dis 1989; 140: S95–S99. doi:10.1164/ajrccm/140.3_Pt_2.S95 - DOI - PubMed
1. Siddiqui FM, Diamond JM. Lung transplantation for chronic obstructive pulmonary disease: past, present, and future directions. Curr Opin Pulm Med 2018; 24: 199–204. PMID:29227305. doi:10.1097/MCP.0000000000000452 - DOI - PMC - PubMed
1. George MP, Champion HC, Pilewski JM. Lung transplantation for pulmonary hypertension. Pulm Circ 2011; 1: 182–191. PMID:22034605. doi:10.4103/2045-8932.83455 - DOI - PMC - PubMed

Grants and funding

LinkOut - more resources

Full Text Sources
- Europe PubMed Central
- PubMed Central

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Survival benefit of lung transplantation compared with medical management and pulmonary rehabilitation for patients with end-stage COPD

Affiliations

Survival benefit of lung transplantation compared with medical management and pulmonary rehabilitation for patients with end-stage COPD

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources