A75-21 Environmental Exposures and Telomere Lengths in Patients With Chronic Hypersensitivity Pneumonitis

Rationale

Antigenic exposure is a hallmark of chronic hypersensitivity pneumonitis (cHP), but many cHP patients do not have an identified exposure. Genetic risk, including telomere shortening, has also been implicated in the causal pathway for cHP and influences clinical outcomes. Previous studies have shown that cHP patients without an identified exposure suffer worse outcomes, especially after prednisone use. Whether telomere shortening is enriched in cHP patients by exposure status is unknown.

Methods

We conducted a retrospective observational cohort study of patients evaluated at the Columbia University interstitial lung disease (ILD) clinic from 2019-2025. We abstracted medical records including clinical demographics, family history of pulmonary fibrosis, and patient-reported exposures linked to cHP. We performed quantitative PCR (qPCR) leukocyte telomere length (LTL) measurements from banked blood biospecimens. We compared telomere length by exposure status in cHP patients using chi-square test (for dichotomous LTL <10th percentile) and t-test (for continuous age-adjusted LTL), and logistic regression to determine adjusted effect of exposure status on age-adjusted LTL. We also compared family history of pulmonary fibrosis in cHP patients by exposure status using chi-squared test.

Results

In total, we included 76 patients with cHP with available telomere length measurements. We stratified cHP patients by self-reported exposure to avian only (n = 9), mold only (n = 23), mold and avian (n = 8), other exposure (n = 7), or no exposure identified (n = 25). Age-adjusted LTL varied by specific exposure to avian only (median -0.18, IQR -0.05 to -0.27]), mold only (-0.12, -0.06 to -0.24), mold and avian (-0.06, -0.03 to -0.24), other (-0.19, 0.09 to -0.40), and no exposure (-0.23, -0.10 to -0.46). cHP patients with no exposures identified had significantly shorter age-adjusted telomere lengths compared to those with any exposure (p = 0.03). Exposure status (exposure vs no exposure) remained significantly associated with age-adjusted telomere length (p = 0.05) in adjusted analyses (for age, sex, and non-Hispanic White race/ethnicity) Amongst cHP patients without an identified exposure, there was a trend towards greater proportion of familial cases (chi-squared p = 0.09).

Conclusions

We find that telomere length varies by exposure status in cHP patients. In cases without an identified exposure, we find significantly shorter telomere length and a trend towards greater proportion of familial cases, suggesting that genetic risk is enriched in the absence of overt environmental risk in cHP.

This abstract is funded by: NIH