Bronchial artery hypertrophy: a novel vascular manifestation of telomere biology disorders in pulmonary fibrosis

Abstract

Fibrosing interstitial lung diseases (ILD) associated with telomere-related gene (TRG) mutations exhibit extra-thoracic features suggesting systemic angiogenesis abnormalities. We investigated the bronchial arterial circulation in TRG-mutated ILD patients. We measured right and left bronchial artery diameter at their origin on CT angiography in 86 ILD patients, 42 with TRG mutations (ILD TRG+) and 44 without TRG mutations (ILD TRG-), and in age- and sex-matched control patients without ILD (controls, N = 49). Bronchial artery hypertrophy was defined as a diameter ≥2 mm. Internal and external thoracic arteries were used as control systemic arteries. Median right bronchial artery diameter was larger in ILD patient’s vs. controls (2.00 mm IQR [1.63–2.58] in ILD TRG+, 1.80 mm [1.50–2.10] in ILD TRG-, 1.41 mm [1.23–1.74] in controls; p < 0.001). A similar trend was observed on the left side. Both right and left diameters positively correlated with pulmonary vascular resistance ( p < 0.001), but only left diameter correlated with mean pulmonary arterial pressure ( p = 0.01). Right bronchial artery hypertrophy was more frequent in ILD TRG+ (48%), than in ILD TRG- (25%, p = 0.05) and controls (6%, p < 0.001). In multivariate analysis, bronchial artery hypertrophy was associated with male gender (OR = 7.64, 95% CI [1.36–72.2], p = 0.039 ), pleuroparenchymal fibroelastosis (PPFE) CT pattern (OR = 8.21, 95% CI [1.53–70.7], p = 0.025 ) and increased PaO 2 (OR = 1.05, 95% CI [1.01–1.10], p = 0.018 ). Bronchial artery hypertrophy was not associated with increased risk of death or lung transplant. Bronchial artery hypertrophy is common in patients with fibrotic ILD and may represent a vascular manifestation of telomere biology disorders. Its association with TRG mutations was not independent of the PPFE pattern, and larger cohorts are needed to determine whether PPFE mediates this association.