Antifibrotic effects of vitamin D3 on human lung fibroblasts derived from patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Up to now, no treatment can stop the progression of IPF. Vitamin D3 (VD) reduces experimental lung fibrosis in murine models and depletion of vitamin D3 might be associated with the reduced survival of patients with IPF. In this context, we determined if VD can prevent the pro-fibrotic functions of human lung fibroblasts (HLFs) isolated from patients with IPF. IPF and control HLFs were derived from surgical lung biopsies collected from patients with IPF or with primary lung cancer, respectively. VD (3-100 nM) markedly reduced the basal and PDGF-induced proliferation of HLFs. VD also altered cell cycle by increasing the percentage of IPF HLFs arrested in the G0/G1 phase, and by downregulating the expression of various cell cycle regulatory proteins. In addition, VD barely prevented the TGF-ß1-induced differentiation in HLFs. At 100 nM, VD slightly reduced the expression of the pro-fibrotic marker α-smooth muscle actin, and had no effect on fibronectin and collagen-1 expression. In contrast, 100 nM VD strongly inhibited the aerobic glycolytic metabolism induced by TGF- ß1. Finally, VD reduced both the secretion of lactate, the levels of lactate deshydrogenase mRNA and the activity of intracellular LDH in IPF HLFs. In conclusion, our study shows that VD reduced pro-fibrotic functions of HLFs. These findings suggest that it might be interesting to assess the potential clinical benefits of vitamin D supplementation in patients with IPF, especially on lung function decline.

Usefulness of Body Composition CT Analysis in Patients with Idiopathic Pulmonary Fibrosis: A Pilot Study.

PURPOSE: To evaluate the feasibility of a chest CT-based body composition analysis in idiopathic pulmonary fibrosis (IPF), and to investigate the respective contribution of lung and muscle CT quantitative analyses to the prognosis of IPF. METHOD: A total of 71 IPF patients were recruited at diagnosis. All patients underwent a standard chest CT-scan and a bioelectrical impedance analysis considered as reference standard for estimating malnutrition through the use of the fat-free mass index (FFMI). The skeletal muscle index (SMI) was measured on chest-CT at the level of the first lumbar vertebra by two radiologists. Lung fibrosis extent was quantified by three radiologists in consensus. The extent of emphysema, the pulmonary artery to aorta (PA/AO) diameter ratio and lymph node enlargement were also reported. Mortality and hospitalization over a 14-month follow-up were recorded. RESULTS: A low FFMI defining malnutrition was identified in 26.8% of patients. SMI was significantly lower in these patients (p<0.001) and was correlated with FFMI (r=0.637, p<0.001). Interobserver agreement of SMI measurement was very good (ICC=0.91). For diagnosing malnutrition, SMI showed a 0.79 sensitivity, a 0.69 specificity, a 0.48 PPV and a 0.90 NPV. In univariate analysis, fibrosis extent was significantly associated with death, while SMI did not reach significance. In multivariate analysis, fibrosis extent and PA/AO ratio were independently associated with hospitalization. CONCLUSIONS: SMI measured on chest CT could be a reliable tool to exclude malnutrition in IPF. A quantitative analysis of both fibrosis and skeletal muscle may allow holistic management of IPF patients.