Wojciech J. Piotrowski et al., Diagnosis and treatment of idiopathic pulmonary fibrosis 43 www.journals.viamedica.pl

Background: 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. Methods: 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 lefttruncation. 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. Results: 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 cutoffs , 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). Conclusions: 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.

N-acetylcysteine (NAC), owing to its antioxidant, mucolytic and anti-inflammatory properties, is used in the treatment of various pulmonary disorders. However, the direct effects of NAC on bronchoalveolar lavage (BAL) cells from patients suffering from interstitial lung diseases have not yet been studied. Therefore, the aim of the present work was to evaluate the effect of NAC on interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) production as well as intercellular cell adhesion molecule-1 (ICAM-1) expression by BAL cells from interstitial lung diseases. The study was performed on BAL cells from nine patients with interstitial lung disease: four patients with idiopathic pulmonary fibrosis (IPF) and five patients with sarcoidosis. Cultured unstimulated BAL cells were treated with increasing doses of NAC (1-30 mM). Production of IL-8 and MMP-9 was evaluated by specific enzyme-linked immuno-sorbent assays and ICAM-1 expression was studied by immunohistochemistry. NAC exerted a dose-dependent inhibitory effect on IL-8 and MMP-9 release and ICAM- expression by BAL macrophages and lymphocytes from patients with IPF and sarcoidosis. In conclusion, NAC inhibits production of factors playing a key role in the etiopathogenesis of interstitial lung diseases, thus suggesting its possible therapeutic potency in the treatment of these disorders.

Serum VEGF-D is the useful biomarker of LAM extension, and might also prove predictive towards therapeutic decision.

Introduction Pulmonary hypertension (PH) is a well-recognised complication of interstitial lung diseases (ILD), which worsens prognosis and impairs exercise capacity. Echocardiography is the most widely used, non-invasive method for PH assessment. The aim of our study was to identify the factors predictive for echocardiographic signs of PH in newly recognised ILD patients. Methods Ninety-three consecutive patients (28F/65M) with different ILD were prospectively evaluated from January 2009 to March 2014. Pulmonary function testing, 6-min walk distance (6MWD), initial and sixth minute room air oxygen saturation, NT-proBNP and echocardiography were assessed in each patient. Echocardiographic PH probability was determined according to the 2009 ESC/ERS guidelines. Results In 41 patients (Group B) increased PH possibility has been diagnosed on echocardiography, in 52 patients (Group A)-low PH probability. Most pronounced differences (p ≤ 0.0005) between groups B and A concerned: age, 6MWD, room air oxygen saturation at 6 min, DLCO and TLC/DLCO index (57.6 vs 43.8 years; 478 vs 583 m; 89.1% vs 93.4%; 54.8% predicted vs 70.5% predicted and 1.86 vs 1.44; respectively). Univariate analysis showed four-fold increased probability of PH when TLC/DLCO exceeded 1.67. A scoring system incorporating age, TLC/DLCO index, 6MWD and room air oxygen saturation at 6 min provided high diagnostic utility, AUC 0.867 (95% CI 0.792-0.867). Conclusion ILD patients with TLC/DLCO index > 1.67 have a high likelihood of PH and should undergo further evaluation. The composite model of PH prediction, including age, 6-min walk test and TLC/DLCO was highly specific for recognition of PH on echocardiography.