Pulmonary vascular morphology in cystic fibrosis.

BACKGROUND

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

METHODS

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 1st generation modulators and those that received Trikafta). The relationship between BV5/TBV% and age in healthy controls was examined.

RESULTS

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%.

CONCLUSIONS

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 1st generation modulator use, but not with Trikafta.