A rejuvenation effect of the antifibrotic therapy correlates with lung function improvement in IPF patients

Idiopathic pulmonary fibrosis (IPF) is an irreversible and fatal lung disease destined to increase as a sequel of the Severe Acute Respiratory Syndrome Coronavirus-2. Several studies implicate telomere shortening as hallmark in the pathomechanism of IPF. Our understanding of disease pathogenesis remains, however, incomplete, which hampers also the development of more effective drugs. Aims of this study are: 1) to analyze telomere length in blood leukocytes (LTL) in well phenotypically characterized IPF patients at diagnosis, before treatment with antifibrotic drugs, Pirfenidone and Nintedanib (T0); 2) to investigate in follow up (T1) a possible change in the rate of LTL by combining data on clinic, hematochemical tests, respiratory function and occupational exposure. We examined a group of 24 IPF patients that underwent to a therapy follow up (T1) (mean±SD 297±124 days). We observed an increase in LTL at T1 compared to LTL at T0 (mean±SD LTL (T/S), T1 vs T0, 1.29 ± 0.26 vs 1.19 ± 0.27; p=0.051). Multiple linear regression analysis reveals that the LTL increase, at T1, is significantly related to the time of treatment (p=0.002), LTL at T0 (p<0.0001) and to a slowing in lung function decline (FVC%pred) (p=0.054). The other variables considered including occupational exposure, pack-years, occupational risk factor, gender and body mass index are not significantly related. Our research would indicate a rejuvenation effect of the antifibrotic therapy by measuring the LTL that correlates with lung function improvement. This suggests that targeting fundamental mechanisms of cellular aging has the potential to interfere with the severity of the disease.