BackgroundSince 2009, IPF patients across Europe are recruited into the eurIPFreg, providing epidemiological data and biomaterials for translational research.MethodsThe registry data are based on patient and physician baseline and follow-up questionnaires, comprising 1700 parameters. The mid- to long-term objectives of the registry are to provide clues for a better understanding of IPF phenotype sub-clusters, triggering factors and aggravating conditions, regional and environmental characteristics, and of disease behavior and management.ResultsThis paper describes baseline data of 525 IPF subjects recruited from 11/2009 until 10/2016. IPF patients had a mean age of 68.1 years, and seeked medical advice due to insidious dyspnea (90.1%), fatigue (69.2%), and dry coughing (53.2%). A surgical lung biopsy was performed in 32% in 2009, but in only 8% of the cases in 2016, possibly due to increased numbers of cryobiopsy. At the time of inclusion in the eurIPFreg, FVC was 68.4% ± 22.6% of predicted value, DLco ranged at 42.1% ± 17.8% of predicted value (mean value ± SD). Signs of pulmonary hypertension were found in 16.8%. Steroids, immunosuppressants and N-Acetylcysteine declined since 2009, and were replaced by antifibrotics, under which patients showed improved survival (p = 0.001).ConclusionsOur data provide important insights into baseline characteristics, diagnostic and management changes as well as outcome data in European IPF patients over time.Trial registrationThe eurIPFreg and eurIPFbank are listed in ClinicalTrials.gov(NCT02951416).

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: (1) Aim of the study: In spite of extensive research, up to 20% of interstitial lung diseases (ILD) patients cannot be safely classified. We analyzed clinical features, progression factors, and outcomes of unclassifiable ILD (uILD). (2) Methods: A total of 140 uILD subjects from the University of Giessen and Marburg Lung Center (UGMLC) were recruited between 11/2009 and 01/2019 into the European Registry for idiopathic pulmonary fibrosis (eurIPFreg) and followed until 01/2020. The diagnosis of uILD was applied only when a conclusive diagnosis could not be reached with certainty. (3) Results: In 46.4% of the patients, the uILD diagnosis was due to conflicting clinical, radiological, and pathological data. By applying the diagnostic criteria of usual interstitial pneumonia (UIP) based on computed tomography (CT), published by the Fleischner Society, 22.2% of the patients displayed a typical UIP pattern. We also showed that forced vital capacity (FVC) at baseline (p = 0.008), annual FVC decline ≥10% (p < 0.0001), smoking (p = 0.033), and a diffusing capacity of the lung for carbon monoxide (DLco) ≤55% of predicted value at baseline (p < 0.0001) were significantly associated with progressive disease. (4) Conclusions: The most important prognostic factors in uILD are baseline level and decline in lung function and smoking. The use of Fleischner diagnostic criteria allows further differentiation and accurate diagnosis.

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Background The aim of this study was to analyze the relative frequency, clinical characteristics, disease onset and progression in f-IPF vs. sporadic IPF (s-IPF). Methods Familial IPF index patients and their family members were recruited into the European IPF registry/biobank (eurIPFreg) at the Universities of Giessen and Marburg (UGMLC). Initially, we employed wide range criteria of f-IPF (e.g. relatives who presumably died of some kind of parenchymal lung disease). After narrowing down the search to occurrence of idiopathic interstitial pneumonia (IIP) in at least one first grade relative, 28 index patients were finally identified, prospectively interviewed and examined. Their family members were phenotyped with establishment of pedigree charts. Results Within the 28 IPF families, overall 79 patients with f-IPF were identified. In the same observation period, 286 f-IIP and s-IIP patients were recruited into the eurIPFreg at our UGMLC sites, corresponding to a familial versus s-IPF of 9.8%. The both groups showed no difference in demographics (61 vs. 79% males), smoking history, and exposure to any environmental triggers known to cause lung fibrosis. The f-IPF group differed by an earlier age at the onset of the disease (55.4 vs. 63.2 years; p < 0.001). On average, the f-IPF patients presented a significantly milder extent of functional impairment at the time point of inclusion vs. the s-IPF group (FVC 75% pred. vs. FVC 62% pred., p = 0.011). In contrast, the decline in FVC was found to be faster in the f-IPF vs. the s-IPF group (4.94% decline in 6 months in f-IPF vs. 2.48% in s-IPF, p = 0.12). The average age of death in f-IPF group was 67 years vs. 71.8 years in s-IPF group ( p = 0.059). The f-IIP group displayed diverse inheritance patterns, mostly autosomal-dominant with variable penetrance. In the f-IPF, the younger generations showed a tendency for earlier manifestation of IPF vs. the older generation (58 vs. 66 years, p = 0.013). Conclusions The 28 f-IPF index patients presented an earlier onset and more aggressive natural course of the disease. The disease seems to affect consecutive generations at a younger age. Trial registration Nr. NCT02951416 http://www.www.clinicaltrials.gov

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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic pulmonary disease with rising incidence. In this study the effectiveness of pirfenidone, as measured by longitudinal change in individual slope of forced vital capacity (FVC) prior to and after initiating pirfenidone treatment, was evaluated in IPF patients recruited into the European registry for idiopathic pulmonary fibrosis (eurIPFreg). Secondary variables were the evaluation of the change in individual slope of diffusion capacity of the lungs for carbon monoxide (DLco), the Borg dyspnea scale, and six-minute walking distance (6MWD), as well as survival analyses. Results: Data of 122 eurIPFreg patients, who had at least two pulmonary function tests (PFTs) prior to or under treatment with pirfenidone, were analyzed by calculating slope-changes. The global analysis revealed an average slope change of +1.48 ± 0.28 (% per annum (p.a)) after start of treatment (p < 0.001), reflecting a reduction in annual FVC decline of approx. 50% under pirfenidone; it also showed a reduction in DLco, and increase in 6MWD (both p < 0.0001), as well as a flattening of the Borg dyspnea scale (p = 0.02). The median survival under treatment was 4.82 years. Patients with a more restrictive disease (FVC < 80% pred.), with a rapid progression (FVC decline >10% pred. p.a.), previous smokers and patients > 60 years of age seemed to profit more from pirfenidone treatment. Conclusions: We report the effectiveness of pirfenidone in a European “real world” IPF cohort with outcome data extending up to 9 years. Global analyses demonstrated a positive effect of pirfenidone on the decline of the lung function over time. Survival was dependent on Gender–Age–Physiology (GAP) score and age prior to therapy.

Objectives: In idiopathic pulmonary fibrosis (IPF), alterations in the pulmonary surfactant system result in an increased alveolar surface tension and favor repetitive alveolar collapse. This study aimed to assess the usefulness of electrical impedance tomography (EIT) in characterization of regional ventilation in IPF. Materials and methods: We investigated 17 patients with IPF and 15 healthy controls from the University of Giessen and Marburg Lung Center (UGMLC), Germany, for differences in the following EIT parameters: distribution of ventilation (TID), global inhomogeneity index (GI), regional impedance differences through the delta of end-expiratory lung impedance (dEELI), differences in surface of ventilated area (SURF), as well as center of ventilation (CG) and intratidal gas distribution (ITV). These parameters were assessed under spontaneous breathing and following a predefined escalation protocol of the positive end-expiratory pressure (PEEP), applied through a face mask by an intensive care respirator (EVITA, Draeger, Germany). Results: Individual slopes of dEELI over the PEEP increment protocol were found to be highly significantly increased in both groups (p < 0.001) but were not found to be significantly different between groups. Similarly, dTID slopes were increasing in response to PEEP, but this did not reach statistical significance within or between groups. Individual breathing patterns were very heterogeneous. There were no relevant differences of SURF, GI or CGVD over the PEEP escalation range. A correlation of dEELI to FVC, BMI, age, or weight did not forward significant results. Conclusions: In this study, we did see a significant increase in dEELI and a non-significant increase in dTID in IPF patients as well as in healthy controls in response to an increase of PEEP under spontaneous breathing. We propose the combined measurements of EIT and lung function to assess regional lung ventilation in spontaneously breathing subjects.