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.

Background: The non-invasive assessment of pulmonary haemodynamics during exercise provides complementary data for the evaluation of exercise tolerance in patients with COPD. Methods: Exercise echocardiography in the semi-supine position was performed in 27 patients with COPD (C) with a forced expiratory volume in one second (FEV1) of 36±12% predicted and 13 age and gender-matched non-COPD subjects (NC). COPD patients also underwent cardiopulmonary exercise testing with gas exchange detection (CPET). Furthermore, serum high sensitive C-reactive protein (hsCRP), a marker of systemic inflammation, was also measured. Results: The maximal work rate (WRmax) and aerobic capacity (VO2peak) were significantly reduced (WRmax: 77±33 Watt, VO2peak: 50±14 %pred) in COPD. Pulmonary arterial systolic pressure (PAPs) was higher in COPD versus controls both at rest (39±5 vs. 31±2 mmHg, p<0.001), and at peak exercise (72±12 vs. 52±8 mmHg, p<0.001). In 19 (70%) COPD patients, the increase in PAPs was above 22 mmHg. The change in pressure (dPAPs) correlated with hsCRP (r2=0.53, p<0.0001) and forced vital capacity (FVC) (r2=0.18, p<0.001). Conclusion:PAPs at rest and during exercise were significantly higher in COPD patients and correlated with higher hsCRP. This may indicate a role for systemic inflammation and hyperinflation in the pulmonary vasculature in COPD. The study was registered at ClinicalTrials.gov webpage with NCT00949195 registration number.

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Background Patients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry. Methods For this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient’s past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan–Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment. Results A population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths. Conclusions The majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.

Background:CPET is a widely used examination to predict the prognosis of chronic obstructive pulmonary disease or post-transplant lung function, and it has also been examined in the context of respiratory tract involvement and pulmonary hypertension in systemic slerosis (SSc).Objectives:As CPET provides a general overview of the aerobic metabolism, influenced by pulmonary, cardiac and vascular function, the purpose of this investigation was to assess if development of poor overall disease outcome could be predicted by CPET.Methods:Twenty-nine SSc patients (M/F=5/24 DcSSc/LcSSc=16/13) were investigated repeatedly with CPET and followed for a mean of 3.7 (range 1-7) years. The clinical features of the patients were the following: alveolitis (n=15), pulmonary fibrosis (n=16), digital ulcers (n=13), 5 of them required bosentan therapy, macroangiopathy (n=8), GERD (n=26), Barrett metaplasia (n=19), gastrintestinal angiopathy (n=5), motility disorder (n=10), pulmonary artery hypertension (pPulm >40 mmHg) (n=4). The average disease duration was 8.9 years. A composite end point was set up: death or digital ulceration necessitating bosentan therapy or pulmonary hypertension (Ppulm>40mmHg) or the decrease of carbon-monoxide diffusion capacity (δDLCO) > 2%/year, or increase in pulmonary artery pressure (δPpulm) >3mmHg/year). Paralell with the CPET, conventional disease activity check-ups have been performed too (echocardiography, chest CT, resting lung function tests, clinical examinations). The correlations between the CPET mesurements and conventional findings and the predictive value of CPET parameters at the first visit to the future development of the composite end-point have been examined.Results:Various CPET results (anaerobic threshold (AT), work rate (WR), desaturation) have significantly correlated with worsening DLCO (p<0,05; Pearson’s correlation). The change of aT per year (δAT/yr) and the degree of desaturation during exercise predicted the development of poor prognostic end-point (p<0.05 with logistic regression), and the detection of desaturation at the first CPET test was associated with a higher risk of poor prognosis (OR: 5,265 [95% CI 1,077-29,38] p=0.057). In contrast, none of the standard pulmonary or cardiac parameters have proved to be predictive to the end-point in this cohort.Conclusion:CPET parameters correlate well with the standard assessment tools, indicating that this test is feasible in SSc patients too. The changes of aT during follow-up and desaturation are predictive to the appearence of the end point designed to comprise multiple features of the disease. This makes CPET a promising non-invasive examination method to estimate the progression of disease in patients suffering from systemic sclerosis.Disclosure of interests: None declared

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Objective. Cardiopulmonary exercise test (CPET) is a widely used examination to predict the prognosis of many chronic pulmonary diseases, and it has also been tested in systemic sclerosis (SSc) with a focus on the development of pulmonary hypertension. CPET is a highly informative non-invasive tool that provides a more complex information than conventional lung function tests to predict the course of cardiopulmonary diseases, as it provides a general overview of the aerobic metabolism, influenced by pulmonary, cardiovascular and peripheral muscle function. The purpose of this investigation was to assess if the progression and the development of poor overall disease outcome in SSc can be predicted by this method. Methods. Twenty-nine SSc patients were investigated prospectively with standard follow-up plus CPET for a mean of 3.7 years to match the results of conventional evaluation modalities and CPET. A composite end-point of several serious outcomes reflecting SSc-related vascular and cardiopulmonary damage was set up, and the predictive value of and correlations between the CPET parameters and resting lung function and echocardiography variables were assessed. Results. None of the clinical parameters, resting lung function or echocardiographic test results proved to be predictive of the development of the endpoint of poor prognosis in this cohort.In contrast, several CPET parameters were found to discriminate between SSc patients with or without adverse outcome. The detection of desaturation (at any CPET test) was associated with a higher risk of poor prognosis (OR: 5.265). VO 2 and VE/VCO 2 at baseline correlated with the annual decrease in FVC, anaerobic threshold with the development of digital ulcers, and VE/ VO 2 with the increase in pulmonary arterial pressure. Conclusion. Several CPET parameters obtained at the beginning of follow-up are informative of the appearance of various adverse end-points. CPET is a feasible examination in the care of SSc patients and provides excess information to current standard follow-up examinations.