Pulmonary vascular morphology in cystic fibrosis

Morphological changes of the pulmonary vasculature in cystic fibrosis (CF) with advancing age, disease progression and modulator therapy are not fully understood.

Sixty-five subjects with CF and baseline pulmonary function underwent a high-resolution CT scan, exercise testing, diffusion capacity and lung clearance index. The ratio of small blood vessel volume (vessels< 5mm² or ^"BV5") to total blood vessel volume (TBV) was estimated from CT scans (BV5/TBV%). The findings were validated in a second CF cohort with concurrent CT and pulmonary function at baseline. Modulator effects were determined by comparing the changes in BV5/TBV% with age and FEV1 % across groups (subjects who were naïve to modulators, those that received 1^st generation modulators and those that received Trikafta). The relationship between BV5/TBV% and age in healthy controls was examined.

BV5/TBV% began to decline in the first decade of life and below FEV1 % of 113; this decline was associated with a decrease in diffusion and exercise parameters. The decline of BV5/TBV% with age was independent from the decline in FEV1 %. There was no significant decline in BV5/TBV% with advancing age in healthy controls or in those who received Trikafta. Early in CF, there was a relative hypervascularity of the small fraction of the pulmonary circulation which reversed to relative hypovascularity with the steady decline of BV5/TBV%.

The attrition of small blood vessels measured by BV5/TBV% in CF starts during the first decade of life, when lung function is normal, even with 1^st generation modulator use, but not with Trikafta.