Abstract Rationale Interstitial lung disease (ILD) includes a wide range of heterogenous lung disorders, idiopathic pulmonary fibrosis (IPF) being the most prevalent. Studies have identified that up to 50% of patients with IPF have short telomere length (STL). Telomere length (TL) measurements includes both lymphocyte and granulocyte length, though traditionally “short” telomere length is based upon only lymphocyte telomere length (LTL). We sought to further extrapolate lymphocyte and granulocyte TL (GTL) measurements amongst lung transplant recipients (LTR’s) to examine if there are significant differences in pathology and radiology findings in three groups of individuals: short lymphocytes and granulocytes, long lymphocytes and granulocytes, and long lymphocytes with short granulocytes. Methods Patient characteristics, chest CT scans, and native lung explant pathology reports were extracted on a retrospective cohort of 148 ILD-LTRs that had TL testing. TL was measured via flow cytometry and fluorescent in-situ hybridization (flowFISH). Patients were stratified based on their age-adjusted LTL and GTL percentile (67 with LTL and GTL 10th percentile (classic short), 37 with LTL and GTL 10th percentile (classic long), and 44 with LTL10th percentile and GTL 10th percentile (atypical). Radiograph findings and explant pathology features between groups were compared using Fisher’s exact test. Genetic testing analyzed telomere and/or surfactant related genes. Results Amongst these three cohorts of ILD-LTR’s, IPF was the most common clinical diagnosis (75-82%). Pre-transplant radiology findings identified UIP in a similar percentage of patients with no statistically significant differences (79% classic, 76% long, 68% atypical, p = 0.42). Other pre-transplant radiology findings included: NSIP, emphysema, ILD with groundglass predominance, fibrosing pleuritis, GVHD, sarcoidosis, lymphangiomyomatosis, chronic hypersensitivity pneumonitis, and bronchiectasis; no significant differences were identified. Explant pathology identified most of the cohort had UIP (87% classic, 81% long, 80% atypical, p = 0.61). Statistically significant differences were identified in those with UIP lacking other features (p = 0.0018), giant cells (p = 0.01), cholesterol and lipid granulomas (p = 0.02), and evidence of aspiration (p = 0.0001). No significant differences were identified in presence of non-necrotizing granulomas, lymphoid infiltrates, necrotizing granulomas, acute and/or organizing lung injury or NSIP. Genetic testing was most often completed in the classic group 60% vs 18% atypical and 30% long (p = 0.0001). Conclusions Our findings largely show minimal differences in diagnosis and radiology features, though some pathology features were statistically significant amongst these three cohorts. Further studies are imperative to evaluate outcomes post-transplant in ILD-LTR’s with atypical TL as they may be overlooked for increased risks of extra-pulmonary complications post-transplant. This abstract is funded by: NHLBI R01 HL166265; The Raman Family lung Transplantation Fund
Sutton et al. (Fri,) studied this question.