Idiopatická plicní fibróza (IPF) je progresivní a obvykle fatální forma idiopatické intersticiální pneumonie (IIP). IPF je charakterizována selháním alveolární reepitelizace, perzistencí fibroblastů, depozicí extracelulární matrix a poruchou alveolární architektoniky, která vede k respiračnímu selhání. Cílem naší práce bylo zjistit klinické charakteristiky, průběh nemoci a prognostické faktory u pacientů s IPF v běžné klinické praxi. Analyzovali jsme 202 pacientů, kteří byli pro IPF sledování v síti center pro diagnostiku a léčbu intersticiálních plicních procesů v České republice. Diagnostika IPF vycházela z doporučení American Thoracic Society (ATS)/European Respiratory Society (ERS). Naším cílem bylo ověřit prognostické faktory nemoci a osud našich pacientů. Do analýzy bylo zahrnuto 73 mužů a 129 žen, s mediánem věku 67 let. IPF byla histologicky ověřena u 66 (33 %) pacientů. Medián času od prvních klinických příznaků do stanovení diagnózy byl 12 měsíců. U 57 nemocných (28,3 %) byla diagnóza stanovena do 6 měsíců od začátku symptomů. Osm (4 %) pacientů mělo akutní exacerbaci. V jednorozměrné analýze byly zjištěny následující faktory, negativně ovlivňující přežití v době diagnózy: vyšší věk, paličkovité prsty, vyšší stupeň dušnosti dle NYHA (New York Heart Association), průkaz neutrofilní alveolitidy v bronchoalveolární tekutině (BALT), vyšší věk bez histologické verifikace, kardiovaskulární komorbidity, diabetes a osteoporóza. Jako příznivé prognostické faktory byly zjištěny: lepší hodnoty vitální kapacity (VC), celkové plicní kapacity (TLC) a plicní difuze (DLCO, KCO). Vícerozměrná analýza ukázala, že nepříznivá prognóza nemoci je asociována s vyšším věkem a vyšším stupněm dušnosti. Průkaz lymfocytární alveolitidy v BALT a lepší hodnoty vstupních parametrů VC a DLCO byly spojeny s lepším přežitím. Nebyl zjištěn žádný rozdíl v přežití mezi pohlavími a mezi kuřáky a nekuřáky. Přítomnost emfyzému neměla vliv na mortalitu a ani na rozsah plicní fibrózy na HRCT hrudníku.Medián přežití dosahoval 51,6 měsíce od diagnózy a nejčastější příčinou smrti bylo respirační selhání.

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.

• MeSH
• bronchoalveolární laváž MeSH
• fenotyp MeSH
• idiopatická plicní fibróza * diagnóza   mortalita   terapie   MeSH
• index tělesné hmotnosti MeSH
• Kaplanův-Meierův odhad MeSH
• komorbidita MeSH
• kouření MeSH
• lidé MeSH
• longitudinální studie MeSH
• počítačová rentgenová tomografie MeSH
• příčina smrti MeSH
• prognóza * MeSH
• respirační funkční testy MeSH
• rizikové faktory * MeSH
• senioři MeSH
• statistika jako téma MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH

V léčbě idiopatické plicní fibrózy mají antifibrotika nezastupitelnou úlohu již desátým rokem. Postupem času se ukazuje, že účinek této skupiny léčiv není omezen jen na idiopatickou plicní fibrózu, ale vztahuje se i na jiná onemocnění charakterizovaná v čase progredující fibrotickou přestavbou plicní tkáně. Nintedanib je v České republice registrován pro léčbu dospělých se systémovou sklerodermií a intersticiálním plicním postižením a pro léčbu dospělých s chronickými fibrotickými intersticiálními plicními procesy s progresivním fenotypem. Pirfenidon je testován v rámci klinických studií v podobných indikacích, včetně neklasifikovatelné plicní fibrózy. Předmětem klinických studií je také možné využití obou antifibrotik v léčbě plicního postižení vzniklého v souvislosti s nemocí covid-19. Sdělení shrnuje informace o probíhajících výzkumech a možném dalším využití antifibrotik.

Antifibrotics have played an irreplaceable role in the treatment of idiopathic pulmonary fibrosis for ten years. Over time, it has been shown that the effect of this group of drugs is not limited to idiopathic pulmonary fibrosis, but also applies to other diseases characterized by time-progressive fibrotic remodeling of lung tissue. Nintedanib is registered in the Czech Republic for the treatment of adults with systemic scleroderma and interstitial lung disease and for the treatment of adults with chronic fibrotic interstitial lung diseases with a progressive phenotype. Pirfenidone is being tested in clinical trials in similar indications, including unclassifiable pulmonary fibrosis. The subject of clinical studies is also the possible use of both antifibrotics in the treatment of pulmonary involvement caused by COVID-19. The manuscript summarizes information on ongoing research and possible further uses of antifibrotics.

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.

• MeSH
• časové faktory MeSH
• idiopatická plicní fibróza epidemiologie   MeSH
• komorbidita MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• prospektivní studie MeSH
• registrace * MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

• MeSH
• diagnostické techniky a postupy normy   MeSH
• idiopatická plicní fibróza * diagnóza   terapie   MeSH
• kongresy jako téma MeSH
• lidé MeSH
• registrace MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH
• zprávy MeSH

BACKGROUND: Since 2009, IPF patients across Europe are recruited into the eurIPFreg, providing epidemiological data and biomaterials for translational research. METHODS: The 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. RESULTS: This 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). CONCLUSIONS: Our data provide important insights into baseline characteristics, diagnostic and management changes as well as outcome data in European IPF patients over time. TRIAL REGISTRATION: The eurIPFreg and eurIPFbank are listed in ClinicalTrials.gov( NCT02951416 ).

• MeSH
• biopsie mortalita   trendy   MeSH
• idiopatická plicní fibróza diagnóza   mortalita   patofyziologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• longitudinální studie MeSH
• míra přežití trendy   MeSH
• plíce patologie   patofyziologie   MeSH
• registrace * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

• MeSH
• idiopatická plicní fibróza * farmakoterapie   MeSH
• kombinovaná farmakoterapie MeSH
• kongresy jako téma MeSH
• registrace MeSH
• systémy dodávající nikotin elektronicky MeSH
• vaping škodlivé účinky   MeSH
• Publikační typ
• novinové články MeSH
• rozhovory MeSH

BACKGROUND: There is a lack of data on the long-term effect of nintedanib on survival in specific groups of idiopathic pulmonary fibrosis (IPF) patients with different phenotypes. We investigated the outcomes of nintedanib therapy in an observational study of a large multicentre real-world cohort of IPF patients with various initial characteristics. METHODS: The analysis included IPF patients treated with nintedanib (NIN) and IPF patients not receiving antifibrotic treatment (NAF) enrolled for the EMPIRE registry in 2015-2020. The patients were stratified according to their initial FVC predicted, dyspnoea, UIP pattern and age. All-cause mortality and annual rate of FVC decline were the main endpoints. Cox proportional hazards model for survival assessment and linear mixed-effects model for FVC decline modelling were used. RESULTS: A total of 869 NIN patients and 691 NAF patients were eligible for the analysis. The annual FVC decline rate was significantly different (adjusted values -0.053 l/yr vs -0.122 l/yr; p = 0.001). The adjusted hazard ratio (HR) for mortality was 0.40 (95 % CI 0.3 to 0.53, p < 0.001). The most significant effect of nintedanib was demonstrated in patients with impaired lung function, i.e., with an FVC predicted to be less than 80 % and a NYHA II to IV. Nintedanib therapy also reduced the difference in survival between men and women. CONCLUSIONS: Modelling confirmed that NIN therapy reduced differences in OS between patients with better and worse initial conditions and prognosis. Our results indicate that NIN is particularly beneficial for patients with advanced IPF and more severe phenotypes. TRIAL REGISTRATION: EMPIRE was registered as a non-interventional post-registration study at the State Institute for Drug Control of the Czech Republic under ID 1412080000 on December 8, 2014.

• MeSH
• antifibrotické látky terapeutické užití   MeSH
• časové faktory MeSH
• fenotyp MeSH
• idiopatická plicní fibróza * farmakoterapie   mortalita   patofyziologie   MeSH
• indoly * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• proporcionální rizikové modely MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

INTRODUCTION: Oral pirfenidone reduces lung function decline and mortality in patients with idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side effects, including nausea, rash, photosensitivity, weight loss and fatigue. Reduced doses may be suboptimal in slowing disease progression. METHODS: This phase 1b, randomised, open-label, dose-response trial at 25 sites in six countries (Australian New Zealand Clinical Trials Registry (ANZCTR) registration number ACTRN12618001838202) assessed safety, tolerability and efficacy of inhaled pirfenidone (AP01) in IPF. Patients diagnosed within 5 years, with forced vital capacity (FVC) 40%-90% predicted, and intolerant, unwilling or ineligible for oral pirfenidone or nintedanib were randomly assigned 1:1 to nebulised AP01 50 mg once per day or 100 mg two times per day for up to 72 weeks. RESULTS: We present results for week 24, the primary endpoint and week 48 for comparability with published trials of antifibrotics. Week 72 data will be reported as a separate analysis pooled with the ongoing open-label extension study. Ninety-one patients (50 mg once per day: n=46, 100 mg two times per day: n=45) were enrolled from May 2019 to April 2020. The most common treatment-related adverse events (frequency, % of patients) were all mild or moderate and included cough (14, 15.4%), rash (11, 12.1%), nausea (8, 8.8%), throat irritation (5, 5.5%), fatigue (4, 4.4%) and taste disorder, dizziness and dyspnoea (three each, 3.3%). Changes in FVC % predicted over 24 and 48 weeks, respectively, were -2.5 (95% CI -5.3 to 0.4, -88 mL) and -4.9 (-7.5 to -2.3,-188 mL) in the 50 mg once per day and 0.6 (-2.2 to 3.4, 10 mL) and -0.4 (-3.2 to 2.3, -34 mL) in the 100 mg two times per day group. DISCUSSION: Side effects commonly associated with oral pirfenidone in other clinical trials were less frequent with AP01. Mean FVC % predicted remained stable in the 100 mg two times per day group. Further study of AP01 is warranted. TRIAL REGISTRATION NUMBER: ACTRN12618001838202 Australian New Zealand Clinical Trials Registry.

• MeSH
• antiflogistika nesteroidní * škodlivé účinky   MeSH
• idiopatická plicní fibróza * diagnóza   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pyridony * škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Austrálie MeSH

INTRODUCTION: Pirfenidone, an antifibrotic drug, slows-down the disease progression in idiopathic pulmonary fibrosis (IPF) over 12 months, however limited data on the decline of lung function and overall survival (OS) in real-world cohorts on longer follow-up exists. PATIENTS/METHODS: Of the enrolled Czech IPF patients (n = 841) from an EMPIRE registry, 383 (45.5%) received pirfenidone, 218 (25.9%) no-antifibrotic treatment and 240 (28.5%) were excluded (missing data, nintedanib treatment). The 2- and 5-yrs OS and forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO) were investigated at treatment initiation and 6, 12, 18 and 24 months' follow-up. RESULTS: During a 2-yr follow-up, less than a quarter of the patients progressed on pirfenidone as assessed by the decline of ≥10% FVC (17.0%) and ≥ 15% DLCO (14.3%). On pirfenidone, the DLCO (≥10%) declines at 6, 12, 18 and 24 months' and DLCO (≥15%) declines at 6, 18 and 24 months' follow-up were associated with increased mortality. The DLCO decline showed higher predictive value for mortality than FVC decline. In patients with no-antifibrotics, FVC and DLCO declines were not predictive for mortality. Pirfenidone increased 5-yrs OS over no-antifibrotic treatment (55.9% vs 31.5% alive, P = 0.002). CONCLUSION: Our study observed the 2-yrs sustained effect of pirfenidone on the decline of lung function and survival in the real-world patient's IPF cohort. DLCO decline of ≥10% shows a potential as a mortality predictor in IPF patients on pirfenidone, and should be routinely evaluated during follow-up examinations.

• MeSH
• antiflogistika nesteroidní farmakologie   terapeutické užití   MeSH
• idiopatická plicní fibróza diagnóza   farmakoterapie   epidemiologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• progrese nemoci * MeSH
• pyridony farmakologie   terapeutické užití   MeSH
• registrace * MeSH
• respirační funkční testy trendy   MeSH
• senioři MeSH
• vitální kapacita účinky léků   fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

INTRODUCTION: Nintedanib, a tyrosine kinase receptor inhibitor, may be associated with increased bleeding risk. Thus, patients with an inherited predisposition to bleeding, or those receiving therapeutic doses of anticoagulants or high-dose antiplatelet therapy, have been excluded from clinical trials of nintedanib in idiopathic pulmonary fibrosis (IPF). OBJECTIVE: Our objective was to examine real-world bleeding events in patients with IPF treated with antifibrotics, including those receiving anticoagulants and/or antiplatelet therapy. METHODS: The European MultiPartner IPF Registry (EMPIRE) enrolled 2794 patients with IPF: group A (1828: no anticoagulant or antiplatelet treatment), group B (227: anticoagulant treatment), group C (659: antiplatelet treatment), and group D (80: anticoagulant and antiplatelet treatment). Overall, 673 (24.1%) received nintedanib and 933 (33.4%) received pirfenidone. Bleeding events and their relationship to antifibrotic and anticoagulation treatment were characterized. RESULTS: Group A patients, versus those in groups B, C, and D, were typically younger and generally had the lowest comorbidity rates. A higher proportion of patients in groups A and C, versus group B, received nintedanib. Pirfenidone, most common in group D, was more evenly balanced across groups. In patients with reported bleeding events, seven of eight received nintedanib (groups A, C, and D). Bleeding incidence was 3.0, 0, 1.3, and 18.1 per 10,000 patient-years (groups A, B, C, and D, respectively). CONCLUSION: Real-world data from EMPIRE showed that patients on anticoagulant medications received nintedanib less frequently, perhaps based on its mechanism of action. Overall, bleeding incidence was low (0.29%: nintedanib 0.25%; pirfenidone 0.04%) and irrespective of anticoagulant or antiplatelet therapy received (P = 0.072).

• MeSH
• antikoagulancia škodlivé účinky   terapeutické užití   MeSH
• idiopatická plicní fibróza farmakoterapie   MeSH
• incidence MeSH
• indoly škodlivé účinky   terapeutické užití   MeSH
• inhibitory proteinkinas škodlivé účinky   terapeutické užití   MeSH
• krvácení epidemiologie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• registrace MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH