Effect of telomere length on survival in patients with idiopathic pulmonary fibrosis: an observational cohort study with independent validation
Open accessAbstract
Background Short telomere lengths are found in a subset of patients with idiopathic pulmonary fibrosis, but their clinical significance is unknown. Our aim was to investigate whether patients with various blood leucocyte telomere lengths had different overall survival.Methods In this observational cohort study, we enrolled patients with interstitial lung disease from Dallas, TX (primary cohort), and from Chicago, IL, and San Francisco, CA (replication cohorts). We obtained genomic DNA samples from unrelated healthy controls in Dallas, TX, and spouses of patients were also enrolled as an independent control group. Telomere lengths were measured in genomic DNA samples isolated from peripheral blood obtained at the time of the initial enrolment assessment. The primary endpoint was transplant-free survival (ie, time to death or lung transplantation) in the Dallas cohort. Findings were validated in the two independent idiopathic pulmonary fibrosis cohorts (Chicago and San Francisco).Findings 370 patients were enrolled into the Dallas cohort between June 17, 2003, and Aug 25, 2011. The 149 patients with idiopathic pulmonary fibrosis had shorter telomere lengths than did the 195 healthy controls (mean age-adjusted log-transformed ratio of telomere to single copy gene was -0.16 [SD 0.23] vs 0.00 [0.18]; p<0.0001); however, telomere lengths of the Dallas patients with idiopathic pulmonary fibrosis (1.33 [SD 0.25]) were similar to the 221 patients with other interstitial lung disease diagnoses (1.46 [0.24]) after adjusting for age, sex, and ethnicity (p=0.47). Telomere length was independently associated with transplant-free survival time for patients with idiopathic pulmonary fibrosis (HR 0.22 [95% CI 0.08-0.63]; p=0.0048), but not for patients with interstitial lung disease diagnoses other than idiopathic pulmonary fibrosis (HR 0.73 [0.16-3.41]; p=0.69). The association between telomere length and survival in patients with idiopathic pulmonary fibrosis was independent of age, sex, forced vital capacity, or diffusing capacity of carbon monoxide, and was replicated in the two independent idiopathic pulmonary fibrosis replication cohorts (Chicago cohort, HR 0.11 [0.03-0.39], p=0.00066; San Francisco cohort, HR 0.25 [0.07-0.87], p=0.029).Interpretation Shorter leucocyte telomere lengths are associated with worse survival in idiopathic pulmonary fibrosis. Additional studies will be needed to establish clinically relevant thresholds for telomere length and how this biomarker might affect risk stratification of patients with idiopathic pulmonary fibrosis.Funding US National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, Harroun Family Foundation, and Nina Ireland Lung Disease Program.
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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 [55]
The Results (Association between telomere length and survival time in ILD; Replication Cohorts) show that shorter telomere length independently predicted shorter transplant-free survival in three IPF cohorts. The Discussion says future studies are needed to determine whether telomere-based subgroups predict responsiveness to therapy. This source therefore supports the survival finding, but not the attributed prediction of treatment response or a separately measured disease-progression outcome. The lung-transplant allograft claim is attached to a different citation. (LLM, conf=0.90)
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- Authors
- Stuart, B. D., Lee, J. S., Kozlitina, J., Noth, I., Devine, M. S., Glazer, C. S., Torres, F., Kaza, V., Girod, C. E., Jones, K. D., Elicker, B. M., Ma, S.-F., Vij, R., Collard, H. R., Wolters, P. J., & Garcia, C. K.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of California, San Francisco (US)
- University of Chicago (US)
- Corresponding author
- Garcia, Christine Kim
- ORCID
- Venue
- The Lancet Respiratory Medicine
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 2
- Issue
- 7
- Pages
- 557-565
- ISSN
- 2213-2600 (ISSN-L)
- PMC
- PMC4136521
- OpenAlex
- W2116521677
- Cited by
- 310
- References
- 29
- Citations by year
- 2026: 25 · 2025: 29 · 2024: 27 · 2023: 27 · 2022: 31 · 2021: 25 · 2020: 27 · 2019: 25 · 2018: 24 · 2017: 28 · 2016: 18 · 2015: 21 · 2014: 3
- FWCI
- 18.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Respiratory Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (K12 HD-068369, P01 HL108794, UCSF-CTI KL2TR000143)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- idiopathic pulmonary fibrosis, telomere length, short telomeres, overall survival, transplant-free survival, interstitial lung disease, lung transplantation, peripheral blood leukocytes, prognostic factors, replication cohort, mortality risk stratification, lung fibrosis progression, telomere shortening
- MeSH terms
- Adult, Aged, Chicago, DNA, Female, Humans, Leukocytes, Male, Middle Aged, San Francisco, Texas, Cohort Studies, Biomarkers, Survival Rate, Risk Assessment, Idiopathic Pulmonary Fibrosis, Telomere Shortening
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