Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post–lung transplantation survival
Open accessAbstract
Background Prior studies have shown that patients with pulmonary fibrosis with mutations in the telomerase genes have a high rate of certain complications after lung transplantation. However, few studies have investigated clinical outcomes by leukocyte telomere length. Methods We conducted an observational cohort study of all pulmonary fibrosis patients who underwent lung transplantation at a single center between January 1, 2007 and December 31, 2014. Leukocyte telomere length was measured from a sample of blood collected prior to lung transplantation and subjects were stratified into two groups (telomere length <10th versus ≥10th percentile). The primary outcome was post-lung transplant survival. Secondary outcomes included incidence of allograft dysfunction, non-pulmonary organ dysfunction and infection. Results Approximately one-third (32%) of subjects had a telomere length below the 10th percentile. Telomere length <10th percentile was independently associated with worse survival (HR 10.9, 95% CI 2.7–44.8, p=0.001). Telomere length <10th percentile was also independently associated with a shorter time to the onset of chronic lung allograft dysfunction (CLAD) (HR 6.3, 95% CI 2.0–20.0, p=0.002). Grade 3 primary graft dysfunction occurred more frequently in the <10th percentile group compared to the ≥10th percentile group (28% vs 7%, p=0.034). There was no difference in the incidence of acute cellular rejection, cytopenias, infection or renal dysfunction in the two groups. Conclusions Telomere length <10th percentile was associated with worse survival and shorter time to onset of CLAD, and thus represents a biomarker that may aid in the risk stratification of pulmonary fibrosis patients prior to lung transplantation.
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In independent cohorts, shorter telomere length is a robust independent predictor of disease progression, response to therapy and death in IPF, and is associated with shorter time to allograft dysfunction after lung transplant.
“In independent cohorts, a shorter telomere length was demonstrated to be a robust independent predictor of disease progression, response to therapy and death55, and to be associated with a shorter time to allograft dysfunction following lung transplant56.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [56]
Experimental — accuracy not yet measuredIn interstitial lung diseases needing special consideration, possible extrapulmonary involvement can complicate transplant assessment and acceptance.
“Transplant challenges in these patients relate to potential extrapulmonary involvement which may complicate assessment and acceptance for transplant.(38, 238, 239)”
From Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. (2021) · cites this paper as [238]
The Introduction mentions rigorous pre-transplant evaluation and selection, and the Results section on other manifestations of organ dysfunction reports non-pulmonary problems after transplantation. Neither passage says that potential extrapulmonary involvement complicates assessment or acceptance for transplantation. Searches for extrapulmonary involvement, transplant candidacy, and pre-transplant evaluation found no passage addressing that link. (LLM, conf=0.74)
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- Authors
- Newton, C. A., Kozlitina, J., Lines, J. R., Kaza, V., Torres, F., & Garcia, C. K.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Garcia, Christine Kim
- Venue
- The Journal of Heart and Lung Transplantation
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 36
- Issue
- 8
- Pages
- 845-853
- ISSN
- 1053-2498 (ISSN-L)
- PMC
- PMC5515686
- OpenAlex
- W2585224414
- Semantic Scholar
- c9f617952dc6fa392316c51853e24f067769e454
- Cited by
- 132
- References
- 49
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 10 · 2023: 15 · 2022: 16 · 2021: 17 · 2020: 12 · 2019: 15 · 2018: 14 · 2017: 2
- FWCI
- 12.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Heart and Lung Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001105)
- National Heart, Lung, and Blood Institute (R01HL093096, T32HL098040)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Keywords
- telomere length, pulmonary fibrosis, lung transplantation, chronic lung allograft dysfunction, post-transplant survival, leukocyte telomere length, telomerase mutations, primary graft dysfunction, acute cellular rejection, risk stratification, biomarkers
- MeSH terms
- Chronic Disease, DNA, Female, Follow-Up Studies, Graft Survival, Humans, Male, Middle Aged, Postoperative Complications, Postoperative Period, Prospective Studies, Pulmonary Fibrosis, Risk Factors, Texas, Incidence, Survival Rate, Lung Transplantation, Polymerase Chain Reaction, Telomere, Primary Graft Dysfunction, Telomere Homeostasis
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