Airway Complications in Lung Transplant Recipients with Telomere-Related Interstitial Lung Disease

Abstract

PurposePatients with short telomeres and interstitial lung disease (ILD) appear to have increased mortality and bronchiolitis obliterans syndrome after lung transplant. Given the dysfunctional response of short telomere patients to cell damage and stress due to cell senescence, they may be more susceptible to impaired large airway healing. We hypothesized that post-transplant airway complications, including dehiscence and bronchial stenosis, would be more common in the short telomere ILD transplant population.MethodsWe studied 63 recipients transplanted at two centers between 2009 and 2019 with ILD and short telomeres, defined either by telomere length below the 1st percentile for age in any lineage or below the 10th percentile in the lymphocyte lineage by flow-FISH telomere length analysis of peripheral blood lymphocytes, with or without the presence of a known telomere-related mutation. The primary outcomes were the presence of dehiscence or of significant stenosis (i.e. requiring dilation or stenting) after transplant. The control population was 4,359 adult recipients with ILD transplanted over similar years, taken from the Scientific Registry of Transplant Recipients (SRTR).ResultsAmong the short telomere cohort, 6 patients (9.5%) had dehiscence and 9 (14.3%) had stenosis compared to 1.4% and 3.4%, respectively, in the SRTR cohort. When adjusted for age, sex, and bilaterality, the presence of short telomeres was associated with a significantly higher odds of dehiscence (odds ratio (OR)=7.34, 95% confidence interval (CI)=3.01-17.92, p<0.001) and higher odds of stenosis (OR=4.72, 95% CI 2.26-9.85, p<0.001).ConclusionWe identified an association between the presence of short telomeres and post-transplant large airway complications, including dehiscence and significant stenosis. Airway complications may be a contributor to worse outcomes in patients with telomere-related ILD. Patients with short telomeres and interstitial lung disease (ILD) appear to have increased mortality and bronchiolitis obliterans syndrome after lung transplant. Given the dysfunctional response of short telomere patients to cell damage and stress due to cell senescence, they may be more susceptible to impaired large airway healing. We hypothesized that post-transplant airway complications, including dehiscence and bronchial stenosis, would be more common in the short telomere ILD transplant population. We studied 63 recipients transplanted at two centers between 2009 and 2019 with ILD and short telomeres, defined either by telomere length below the 1st percentile for age in any lineage or below the 10th percentile in the lymphocyte lineage by flow-FISH telomere length analysis of peripheral blood lymphocytes, with or without the presence of a known telomere-related mutation. The primary outcomes were the presence of dehiscence or of significant stenosis (i.e. requiring dilation or stenting) after transplant. The control population was 4,359 adult recipients with ILD transplanted over similar years, taken from the Scientific Registry of Transplant Recipients (SRTR). Among the short telomere cohort, 6 patients (9.5%) had dehiscence and 9 (14.3%) had stenosis compared to 1.4% and 3.4%, respectively, in the SRTR cohort. When adjusted for age, sex, and bilaterality, the presence of short telomeres was associated with a significantly higher odds of dehiscence (odds ratio (OR)=7.34, 95% confidence interval (CI)=3.01-17.92, p<0.001) and higher odds of stenosis (OR=4.72, 95% CI 2.26-9.85, p<0.001). We identified an association between the presence of short telomeres and post-transplant large airway complications, including dehiscence and significant stenosis. Airway complications may be a contributor to worse outcomes in patients with telomere-related ILD.