Association of Donor and Recipient Telomere Length with Clinical Outcomes following Lung Transplantation

Courtwright, Andrew; Fried, Sabrina; Villalba, Julian A.; Moniodis, Anna; Guleria, Indira; Wood, Isabelle; Milford, Edgar L.; Mallidi, H.; Hunninghake, Gary M.; Raby, Benjamin A.; Agarwal, Suneet; Camp, P.; Rosas, Iván O.; Goldberg, Hilary J.; El–Chemaly, Souheil

doi:10.1371/journal.pone.0162409

Cited by 30 publications

(24 citation statements)

References 26 publications

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“…In contrast to this study, a previous study by Courtwright and colleagues looked at both donor lymphocyte and recipient lung TL and did not find a significant association with survival in their cohort 7. Another study since then examined recipient TL specifically in patients with pulmonary fibrosis and divided the cohort into two groups of <10th percentile and ≥10th percentile TL and showed significantly worse survival in the <10th percentile even when controlling for other factors such as infection rate, ACR and primary graft dysfunction 8.…”

contrasting

confidence: 92%

Do donors matter? Short telomeres and survival after lung transplant

Clausen

Snyder

2017

Thorax

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contrasting

confidence: 92%

Do donors matter? Short telomeres and survival after lung transplant

Clausen

Snyder

2017

Thorax

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“…In CLAD, telomere dysfunction is increasingly appreciated as a research target. A small study in lung transplant patients found no association of donor peripheral blood LTL or recipient tissue RTL with survival [ 36 ]. More recently, Faust et al reported that short donor peripheral blood LTL was associated with worse CLAD-free survival after transplantation.…”

Section: Discussionmentioning

confidence: 99%

The aging lung: tissue telomere shortening in health and disease

et al. 2018

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BackgroundTelomere shortening has been associated with several lung diseases. However, telomere length is generally measured in peripheral blood leucocytes rather than in lung tissue, where disease occurs. Consequently, telomere dynamics have not been established for the normal human lung nor for diseased lung tissue. We hypothesized an age- and disease-dependent shortening of lung tissue telomeres.MethodsAt time of (re-)transplantation or autopsy, 70 explant lungs were collected: from unused donors (normal, n = 13) and patients with cystic fibrosis (CF, n = 12), chronic obstructive pulmonary disease (COPD, n = 11), chronic hypersensitivity pneumonitis (cHP, n = 9), bronchiolitis obliterans syndrome (BOS) after prior transplantation (n = 11) and restrictive allograft syndrome (RAS) after prior transplantation (n = 14). Lungs were inflated, frozen and then scanned using CT. Four tissue cores from distinct lung regions were sampled for analysis. Disease severity was evaluated using CT and micro CT imaging. DNA was extracted from the samples and average relative telomere length (RTL) was determined using real-time qPCR.ResultsThe normal lungs showed a decrease in RTL with age (p < 0.0001). Of the diseased lungs, only BOS and RAS showed significant RTL decrease with increasing lung age (p = 0.0220 and p = 0.0272 respectively). Furthermore, we found that RTL showed considerable variability between samples within both normal and diseased lungs. cHP, BOS and RAS lungs had significant shorter RTL in comparison with normal lungs, after adjustment for lung age, sex and BMI (p < 0.0001, p = 0.0051 and p = 0.0301 respectively). When investigating the relation between RTL and regional disease severity in CF, cHP and RAS, no association was found.ConclusionThese results show a progressive decline in telomere length with age in normal, BOS and RAS lungs. cHP, BOS and RAS lungs demonstrated shorter RTL compared to normal lungs. Lung tissue RTL does not associate with regional disease severity within the lung. Therefore, tissue RTL does not seem to fully reflect peripheral blood telomere length.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0794-z) contains supplementary material, which is available to authorized users.

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“…Only one prior study has investigated the effect of telomere length on transplant outcomes(22). This study is similar in that the cohort was stratified by telomere length, and the group with shorter lengths represented ~1/3 of the total.…”

Section: Discussionmentioning

confidence: 99%

Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post–lung transplantation survival

Newton

Kozlitina

Lines

et al. 2017

The Journal of Heart and Lung Transplantation

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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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Association of Donor and Recipient Telomere Length with Clinical Outcomes following Lung Transplantation

Cited by 30 publications

References 26 publications

Do donors matter? Short telomeres and survival after lung transplant

Do donors matter? Short telomeres and survival after lung transplant

The aging lung: tissue telomere shortening in health and disease

Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post–lung transplantation survival

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