Chemokines and their receptors in pathogenesis of interstitial lung diseases

Sarcoidosis and extrinsic allergic alveolitis (EAA) are granulomatous lung diseases with predominantly Th1 immune response. In this prospective study, we analyzed the expression of chemokine receptors CXCR2, CXCR3 and CCR3 on bronchoalveolar lavage fluid (BALF) CD4 T-cells of patients either with EAA or sarcoidosis. We investigated the correlation of chemokine receptors expression, lymphocyte and neutrophil counts in BALF and high resolution tomography (HRCT) pattern. Thirteen sarcoidosis and 6 EAA patients were enrolled in the study. The expression of chemokine receptors on BALF CD4 T cells were analysed by flow cytometry. HRCT scoring system according to Kazerooni EA. was used for evaluation of the disease extent. We have found positive correlation between BALF CD4 T-cells CXCR3 expression and HRCT alveolar score in EAA patiens (p<0.01). CXCR2 expression on BALF CD4 T-cells and interstitial HRCT score did not show a correlation either in the EAA or the sarcoidosis group. Positive correlation between CCR3 expression on CD4+ T cells and HRCT interstitial score was proven in the EAA group (p<0.05). We conclude, that Th2 predominant immune response may play an important role in chronic EAA pathogenesis. The role of chemokine receptors in the pathogenesis of EAA and sarcoidosis should be presumed and investigated

The European MultiPartner IPF registry (EMPIRE): validating long-term prognostic factors in idiopathic pulmonary fibrosis

Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF.The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for left-truncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors.The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3-3.7) and III (HR 4.0; 95% CI: 2.8-5.7) while, with redefined cut-offs, the corresponding HRs were 2.7 (95% CI: 1.8-4.0) and 5.8 (95% CI: 4.0-8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5-2.9) and lung cancer (HR 2.6; 95% CI: 1.3-4.9).EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients

The effect of nintedanib on lung functions and survival in idiopathic pulmonary fibrosis: real-life analysis of the Czech EMPIRE registry

Abstract Introduction The antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry. Patients/methods Data of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated. Results During 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN). Conclusion Our real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI