Search

Background: The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF. Methods: MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients ( n = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals ( n = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment. Results: We confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p CO (diffuse lung capacity) at the IPF diagnosis were associated with survival. Conclusion: Our real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort.

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 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. 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 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). 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., Boehringer IngelheimBoehringer Ingelheim, The EMPIRE registry is supported by a grant from Boehringer Ingelheim (since 2014). the sponsor did not have any involvement in the collection, analysis, and interpretation of the data or in the writing of or commenting on this manuscript

Key feature of IPF is decline in forced vital capacity (FVC) and CO diffusion (DLco), but data on clinical determinants of this change in patients who have established disease are scarce. For a given patient it is unknown if different natural histories represent distinct phenotypes of IPF or if geographic, ethnic or other factors might have influence on progression. The EMPIRE (European Multipartner IPF Registry) is a multicountry IPF register in the CEE region. Out of 1229 patients from the registry 324 with available data on FVC and DLco at inclusion and at 6 months rapid decliners (RD: FVC >10% or DLco >10% in 6 months) and controls (C) were included into the analysis. Clinical characteristics at inclusion were analyzed between groups to find clinical determinants of RD. Average age was 67,4±9.7 years, more males were affected than females (male:female 221:103) most patients had classic signs of UIP on HRCT. Most common comorbidity was hypertension (50.9%), coronary heart disease (20.5%), diabetes (20.1%) and hyperlipidaemia (20.1%). RD of FVC was present in 33.7%, while RD of DLco in 53.3% of patients. Comparison of RD and C patients for smoking status, dyspnoe severity, comorbidities, HRCT pattern, lung function parameters at inclusion, 6 minute walk distance or the presence of pulmonary hypertension did not show any difference between groups. The rate of change in FVC or DLco among IPF patients is highly variable, with 34-53 % of patients showing increased rates of decline in FVC and/or DLco. No clinical characteristics could be identified which can predict rapid decline using the data of EMPIRE registry.

Aims: Many patients with idiopathic pulmonary fibrosis (IPF) have a delay in diagnosis and thus also in treatment. We investigated whether such delay influenced survival and treatment response to pirfenidone and nitedanib. Methods: The retrospective study used data from European Multipartner IPF registry (EMPIRE). 1170 IPF patients were divided to the 2 groups: 1) patients diagnosed within (824) and 2) patients diagnosed after 12 months (346) from initiation of symptoms. The groups did not differ in demographic data, and in proportion of the patients treated with antifibrotic drugs. Survival from diagnosis up to 120 months was evaluated by Kaplan-Meier curve. The vital capacity (VC) initial values (% PV) and VC decline (l) in 6, 12, and 18 months of follow-up were evaluated and compared between both groups using t-test. Results: VC at the time of diagnosis was higher in earlier diagnosed group (2.72 l (2.63; 2.80) versus 2.49 l (2.37; 2.61); p=0.002). The Kaplan-Meier survival curve showed longer median survival in the earlier diagnosed patients (74.4 vs. 50.9 months (P=0.001)). The patients treated with pirfenidone showed longer median survival versus those without antifibrotic treatment (46.9 vs. 39.6 months; p=0.014), nintedanib showed similar tendency. Treatment with antifibrotic drugs similarly reduced decline of VC and TLCO in both early and later diagnosed patients. Conclusion: The patients with IPF diagnosed within 1 year from symptoms have longer survival than those diagnosed later. Antifibrotic treatment in real-world prolongs survival in IPF and slows down decline of lung function irrespective of timeliness of diagnosis.

Prognostic factors of idiopathic pulmonary fibrosis (IPF) currently recognized include changes in vital capacity and radiologic findings. However, most of the prognostic studies in IPF are based on clinical studies with preselected IPF populations. Therefore, we decided to analyze the factors influencing IPF prognosis based on the real-practice data from our IPF registry.Data of 514 subjects consecutively entered since 2012 into Czech EMPIRE IPF registry were analyzed.Median age of our patient cohort was 67 years (50-82). Median overall survival (OS) of the cohort was 63.1 months. The clinical course of IPF according to FVC (forced vital capacity) changes was stabilized in 32.8% of patients (29.7% according to DLDL

AIMS: Idiopathic pulmonary fibrosis (IPF) is characterized by radiologic pattern of usual interstitial pneumonia (UIP) with honey-combing reflecting end-stage of the disease. Nevertheless significant part of patients with IPF does not present with typical UIP pattern. In our study we investigated whether HRCT pattern can influence course of the disease and prognosis of IPF patients. CONCLUSIONS: Our results show that IPF patients with atypical HRCT pattern have the same prognosis as those with typical UIP pattern. It does mean that these patients should be treated the same way as the cases with typical HRCT UIP pattern.

Aims and objectives: The aim of the study was to compare the annual declineof lung functions during treatment with pirfenidone in comparison to triple-combination and other treatment modalities in Czech patients with IPF. Methods: Currently, the Czech IPF registry consists of 517 patients diagnosed with IPF-UIP. Our retrospective study included 72 patients treated with pirfenidone, 27 with triple-combination and 97 received other treatment modalities. To estimate the annual change of FVC and TLCO, a linear regression model with mixed effects was used. p -value Results: The comparison of changes in lung function over a 1-year follow-up showed lower decrease in the predicted value (PV) of FVC in pirfenidon group than in triple-combination (-0.093 vs -0.222, p -value=0.026) and trend to lower decrease in comparison to other treatment modalities (-0.093 vs -0.162, p -value=0.082). Also, a 1-year decrease in the PV of a TLCO was smaller in pirfenidon group than in triple-combination (0.221 vs -0.453, p -value=0.096) and other modalities group (-0.221 vs -0.389, p -value=0.082); however the decrease did reach significancy between studied groups. Conclusion: In Czech IPF patients, pirfenidone administration was associated with the lower decrease in lung function (FVC, TLCO) comparing with other treatment modalities. Our observation supports current recommendation of pirferidon for mild and moderate IPF. Supported by IGA_LF_2016_011.

AIMS: Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with mean survival of 2.5 years. Delay in diagnosis and treatment probably decreases a survival in IPF. Our study aims to investigate influence of time from the first symptoms to diagnosis on the survival. CONCLUSIONS: Our results show that earlier diagnosis and treatment may increase survival in IPF. Early diagnosis and treatment does matter in prognosis of IPF patients and thus maximal effort should be generated to get the patients diagnosed and treated as early as possible.

Idiopathic pulmonary fibrosis (IPF) is a rare, progressive and usually fatal form of idiopathic interstitial pneumonia. IPF is characterized by failure of alveolar re-epithelization, persistence of fibroblasts, deposition of extracellular matrix, and distortion of lung architecture, which ultimately results in respiratory failure.We analysed 202 consecutive patients with IPF diagnosed at the Departments of Pulmonary Diseases and Tuberculosis in the Czech Republic, who they were included in the nationwide Czech IPF registry. Our aim was to determine prognostic factors of IPF and outcome of the disease.There were 129 males and 73 females who were the median age 67 years. IPF was biopsy-proven in 66 (33 %) of patients. Median time from the first symptom to diagnosis was 12 months. Diagnosis was made in 57 patients (28.3 %) within 6 months from the onset of respiratory symptoms. 8 (4 %) patients had an acute exacerbation during the course of the disease.In uniparametric (univariate) analysis as prognostic factors associated with poorer survival were found: higher age, higher degree dyspnea scores, clubbing fingers, comorbidities (arterial hypertension, osteoporosis), patients without histology biopsy, and bronchoalveolar increased neutrophil count. We found these positive prognostic factors: higher levels of VC (vital capacity), TLC (total lung capacity) and DLCO (diffusing capacity for carbon monooxide).In multiparametric (multivariate) analysis as prognostic factors associated with mortality were found: higher age, higher degree of dyspnoe score. Increased lymphocytes in bronchoalveolar fluid, higher level of VC a DLCO were associated with better survival. There was no difference in survival of patients by sex, by smoking status. No significant difference in survival rates was found between IPF with and without emphysema, between the extent of fibrosis on HRCT (high resolution computed tomography) of thorax and mortality. Median survival was 51.6 months. 58 (28.7 %) patients died. The most frequent reason of dead was IPF progression with respiratory failure.Idiopathic pulmonary fibrosis; prognosis; treatment.