The Impact of Switching to a Second Antifibrotic in Patients With Idiopathic Pulmonary Fibrosis: A Retrospective Multicentre Study From the EMPIRE Registry.

INTRODUCTION: Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE). METHODS: The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF - "lack of efficacy" (LE) and "intolerance" (INT). RESULTS: While 263 (43%) of 612 patients received no second AF ("non-switched"), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: -98ml/y in switched and -172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001). CONCLUSION: The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy.

News in respiratory medicine.

Pneumology and phthisiology (respiratory medicine) has undergone dynamic development in the last two decades. The main focus of pulmonology in the past was care for patients with tuberculosis and pneumonia. Since then, respiratory medicine evolved and the current focus is on chronic pulmonary diseases, including chronic obstructive pulmonary disease, bronchial asthma, interstitial lung diseases, but also on acute lung conditions (e.g., pneumonia, pleural diseases, respiratory failure), pneumooncology or highly specialized care for rare lung diseases (e.g., cystic fibrosis, rare interstitial diseases). Bronchology, interventional pneumology and pulmonary function testing are also important components of respiratory medicine. The importance of respiratory medicine was apparent during the COVID-19 pandemic. In this article, we provide a brief overview of the most important news to the field of respiratory medicine in the year 2022, addressing the thematic areas of bronchology, cystic fibrosis, chronic obstructive pulmonary disease, asthma, interstitial lung diseases, pleural diseases, pneumooncology, tuberculosis and non-tuberculous mycobacteria.

Germline variant of CTC1 gene in a patient with pulmonary fibrosis and myelodysplastic syndrome.

Introduction: Telomeropathies are associated with a wide range of diseases and less common combinations of various pulmonary and extrapulmonary disorders. Case presentation: In proband with high-risk myelodysplastic syndrome and interstitial pulmonary fibrosis, whole exome sequencing revealed a germline heterozygous variant of CTC1 gene (c.1360delG). This "frameshift" variant results in a premature stop codon and is classified as likely pathogenic/pathogenic. So far, this gene variant has been described in a heterozygous state in adult patients with hematological diseases such as idiopathic aplastic anemia or paroxysmal nocturnal hemoglobinuria, but also in interstitial pulmonary fibrosis. Described CTC1 gene variant affects telomere length and leads to telomeropathies. Conclusions: In our case report, we describe a rare case of coincidence of pulmonary fibrosis and hematological malignancy caused by a germline gene mutation in CTC1. Lung diseases and hematologic malignancies associated with short telomeres do not respond well to standard treatment.

The effect of nintedanib on lung functions and survival in idiopathic pulmonary fibrosis: real-life analysis of the Czech EMPIRE registry.

INTRODUCTION: The antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry. PATIENTS/METHODS: Data of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated. RESULTS: During 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN). CONCLUSION: Our real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI.

Antifibrotic therapy and its indications for interstitial pulmonary fibrosis.

Idiopathic pulmonary fibrosis and chronic fibrotic interstitial lung disease with progressive phenotype are characterized by fibrotic lung parenchyma. Current antifibrotic treatment does not affect pre-existing lung parenchyma fibrosis, but prevents fibrosis progression and reduces mortality by reducing fibrotization. This work summarizes fibrotic lung processes and their treatment options.

Langerhans cell histiocytosis (LCH). Overview of symptoms of LCH, which may lead the patients to any of these medical specialists.

Langerhans cell histiocytosis (LCH) is a rare condition with incidence in adults 1-2/1 million, wherein Langerhans cells proliferate abnormally, adversely impacting organs including most frequently bones, skin, lungs, pituitary gland, lymph nodes, gums and other organs. The LCH course varies widely among patients from a self-limiting condition, to one that progresses. But LCH only very rarely culminates in death. To aim of this text is to review all possible symptoms and manifestations of this disease.

A novel temperature-controlled open source microcontroller based sampler for collection of exhaled breath condensate in point-of-care diagnostics.

Exhaled breath condensate (EBC) is an attractive, non-invasive sample for clinical diagnostics. During EBC collection, its composition is influenced by the collection temperature, a factor that is often not thoroughly monitored and controlled. In this study, we assembled a novel, simple, portable, and inexpensive device for EBC collection, able to maintain a stable temperature at any value between -7 °C and +12 °C. The temperature was controlled using a microcontroller and a thermoelectric cooler that was employed to cool the aluminum block holding the glass tube or the polypropylene syringe. The performance of the novel sampler was compared with the passively cooled RTube™ and a simple EBC sampler, in which the temperature was steadily increasing during sampling. The developed sampler was able to maintain a stable temperature within ±1 °C. To investigate the influence of different sampling temperatures (i.e., +12, -7, -80 °C) on the analyte content in EBC, inorganic ions and organic acids were analyzed by capillary electrophoresis with a capacitively coupled contactless conductivity detector. It was shown that the concentration of metabolites decreased significantly with decreasing temperature. The portability and the ability to keep a stable temperature during EBC sampling makes the developed sampler suitable for point-of-care diagnostics.

Left ventricular myocardial deformation assessment in asymptomatic patients with recently diagnosed sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease affecting different organs including the heart. Myocardial strain analysis could potentially detect the early stages of cardiac dysfunction in sarcoidosis patients. The present study aims to assess the use of cardiac magnetic resonance (CMR) strain analysis using feature tracking (FT) in the detection of early cardiac involvement in asymptomatic patients with sarcoidosis. METHODS: One hundred and thirteen CMR studies of patients with sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis without pre-existing known cardiovascular disease were included in the study and analysed using FT and compared to 22 age and gender-matched controls. Global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) of the left ventricle (LV) were measured. RESULTS: The sarcoidosis patients did not significantly differ from the controls in basic demographic data and had normal global and regional systolic LV function-LV ejection fraction (EF) 66 ± 7% vs 65 ± 5% in the controls (p = NS). No statistically significant differences were found in all strain parameters between patients and controls: GLS (- 13.9 ± 3.1 vs. - 14.2 ± 2.5), GCS (- 23.4 ± 4.0 vs. - 22.2 ± 2.9) and GRS (53.4 ± 13.5 vs. 51.2 ± 13.6%) (p = NS). CONCLUSION: Patients with sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis had normal myocardial deformation measured by CMR-FT derived global strain.

DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study.

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 < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele (p = 0.016) and MUC5B T* allele (p = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56-40.90; p = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68-43.14; p = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS (p = 0.040; HR = 0.35; 95% CI = 0.13-0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone (p = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DLCO (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.

Myocardial T1 mapping using SMART1 Map and MOLLI mapping in asymptomatic patients with recent extracardiac sarcoidosis.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease affecting in particular the respiratory tract. Cardiac magnetic resonance (CMR), including a measurement of T1 relaxation time, could potentially detect early stadia of sarcoidosis of the heart. The study aims to assess T1 mapping in the detection of early cardiac involvement in asymptomatic patients with sarcoidosis. METHODS: One hundred and twenty patients with extracardiac sarcoidosis and without any heart disease history were included. One hundred and thirteen of them underwent a CMR examination. The mean time from the diagnosis of sarcoidosis was 0.8 (0.2-3.3) years. Cine images for the assessment of left ventricular (LV) functional parameters and pre- and post-contrast saturation method using adaptive recovery times for cardiac T1 mapping (SMART1 Map) and modified Look-Locker inversion recovery (MOLLI) images were acquired for the assessment of native T1 relaxation time and extracellular volume (ECV). The measured parameters were compared between sarcoidosis patients and 22 controls. RESULTS: The sarcoidosis patients had normal global and regional systolic LV function-LV ejection fraction 65 ± 5% versus 66 ± 7% (p NS). The mean native T1 relaxation times were not prolonged-1465 ± 93 ms versus 1480 ± 88 ms (p NS) measured by SMART1 Map and 1317 ± 60 ms versus 1313 ± 83 ms (p NS) measured using a MOLLI sequence. Similarly, the mean ECV values did not increase-16.9 ± 3.9% versus 17.9 ± 3.7% (p NS) measured by SMART1 Map and 30.9 ± 2.9% versus 31.6 ± 8.3% (p NS) measured using a MOLLI sequence. CONCLUSION: Myocardial native T1 relaxation times were not prolonged and ECV was not increased in asymptomatic patients with extracardiac sarcoidosis.

Diagnosis of Bloom Syndrome in a Patient with Short Stature, Recurrence of Malignant Lymphoma, and Consanguineous Origin.

Bloom syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early-onset cancer and development of multiple malignancies. Loss-of-function variants of the BLM gene, which codes for a RecQ helicase, cause Bloom syndrome. We report a consanguineous family, with 2 siblings showing clinical signs of suspected chromosome breakage disorder. One of them developed recurrent malignant lymphoma during lifetime. We performed next-generation sequencing analysis, focusing on cancer predisposition syndromes. We identified a homozygous pathogenic nonsense variant c.1642C>T (p.Gln548*) in the BLM gene in the proband, associated with Bloom syndrome. Sanger sequencing validated the presence of a homozygous pathogenic variant in the proband and also in the brother with short stature. In this article, we will focus on the clinical presentation of the syndrome in this particular family as well as the characteristics of malignancies found in the proband.

Heat treatment dependent cytotoxicity of silicalite-1 films deposited on Ti-6Al-4V alloy evaluated by bone-derived cells.

A silicalite-1 film (SF) deposited on Ti-6Al-4V alloy was investigated in this study as a promising coating for metallic implants. Two forms of SFs were prepared: as-synthesized SFs (SF-RT), and SFs heated up to 500 °C (SF-500) to remove the excess of template species from the SF surface. The SFs were characterized in detail by X-ray photoelectron spectroscopy (XPS), by Fourier transform infrared spectroscopy (FTIR), by scanning electron microscopy (SEM) and water contact angle measurements (WCA). Two types of bone-derived cells (hFOB 1.19 non-tumor fetal osteoblast cell line and U-2 OS osteosarcoma cell line) were used for a biocompatibility assessment. The initial adhesion of hFOB 1.19 cells, evaluated by cell numbers and cell spreading area, was better supported by SF-500 than by SF-RT. While no increase in cell membrane damage, in ROS generation and in TNF-alpha secretion of bone-derived cells grown on both SFs was found, gamma H2AX staining revealed an elevated DNA damage response of U-2 OS cells grown on heat-treated samples (SF-500). This study also discusses differences between osteosarcoma cell lines and non-tumor osteoblastic cells, stressing the importance of choosing the right cell type model.

Increased Microvessel and Arteriole Density in the Contracted Side of the Relapsed Clubfoot.

BACKGROUND: Clubfoot deformity (pes equinovarus) is one of the most common birth defects, and its etiology is still unknown. Initial clubfoot treatment is based on the Ponseti method throughout most of the world. Despite the effectiveness of this therapy, clubfoot may relapse. Recent studies confirm the theory of active fibrotic remodeling processes in the extracellular matrix of the affected tissue. The aim of this study was to clarify whether relapses in clubfoot therapy are associated with altered angiogenesis and to suggest possible regulatory pathways of this pathologic process. METHODS: We compared microvessel density, arteriole density, and concentration of angioproliferative-related proteins found between tissues in the contracted, that is, the medial side (M-side), and noncontracted, that is, the lateral side (L-side) of the relapsed clubfeet. Tissue samples from 10 patients were analyzed. Histopathologic analysis consisted of immunohistochemistry and image analysis. Real-time polymerase chain reaction was used to study mRNA expression. RESULTS: An increase in microvessel and arteriole density was noted in contracted, relapsed clubfoot tissue. This was accompanied by a significant increase in the levels of the vascular endothelial growth factor, vascular endothelial growth factor receptor 2, ß catenin and active ß catenin. Vascular endothelial growth factor, vascular endothelial growth factor receptor 2, and CD31 overexpression was also seen with mRNA analysis. CONCLUSIONS: Increased microvessel and arteriole density in the contracted side of the relapsed clubfoot was noted. These processes are mediated by specific proangiogenic proteins that are overexpressed in the contracted tissue. These findings contribute to the etiology and the development of relapses in the treatment of clubfoot. LEVEL OF EVIDENCE: Level II-analytical and prospective.

Silicalite-1 Layers as a Biocompatible Nano- and Micro-Structured Coating: An In Vitro Study on MG-63 Cells.

Silicalite-1 is a purely siliceous form of zeolite, which does not contain potentially harmful aluminum in its structure as opposed to ZSM-5 aluminosilicate types of zeolite. This paper reports on a study of a silicalite-1 film, deposited on a silicon Si(100) substrate, as a potential anti-corrosive and biocompatible coating for orthopaedic implants. Silicalite-1 film was prepared in situ on the surface of Si(100) wafers using a reaction mixture of tetrapropyl-ammonium hydroxide (TPAOH), tetraethyl-orthosilicate (TEOS), and diH2O. The physico-chemical properties of the obtained surface were characterized by means of X-ray photoelectron spectroscopy, water contact angle measurement, atomic force microscopy, and scanning electron microscopy. The biocompatibility was assessed by interaction with the MG-63 cell line (human osteosarcoma) in terms of cell adhesion, morphology, proliferation, and viability. The synthesized silicalite-1 film consisted of two layers (b- and a, b-oriented crystals) creating a combination of micro- and nano-scale surface morphology suitable for cell growth. Despite its hydrophobicity, the silicalite-1 film increased the number of initially adhered human osteoblast-like MG-63 cells and the proliferation rate of these cells. The silicalite-1 film also improved the cell viability in comparison with the reference Si(100) substrate. It is therefore a promising candidate for coating of orthopaedic implants.

Lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare systemic disease that occurs sporadically (S/LAM) or as part of tuberous sclerosis (TS/LAM). LAM is characterized by proliferation of abnormal smooth muscle cells. This disease clinically manifests as dyspnea on exertion and pneumothorax. Lymphadenopathy in the abdominal and pelvic region leading to lymphatic obstruction can also occur. LAM is associated with kidney angiomyolipoma and meningioma. The disease is diagnosed histologically and/or using typical high-resolution computed tomography findings and anamnestic information. In histopathological studies, the diagnosis is supported by detection of characteristic LAM cells. Mammalian target of rapamycin (mTOR) inhibitors are possible treatment options. MATERIAL AND METHODS: Ten consecutive patients diagnosed with LAM and pulmonary manifestation (eight with S/LAM and two with TS/LAM) in 2002-2018 were retrospectively analyzed. Their individual clinical characteristics and our treatment experience are described. RESULTS: The patients varied in terms of disease stage. The best predictors of prognosis were lung function parameters (forced vital capacity, forced expiratory volume in 1 second, and diffusing capacity for carbon monoxide). Four patients are currently being treated with mTOR inhibitors. This treatment stabilized lung functions in all four patients. The median follow-up was 48 months (12-132 months). Median survival was not achieved and only three patients died. CONCLUSION: An interdisciplinary approach is required to care for LAM patients. Cooperation of pneumologists, surgeons, oncologists, and geneticists is needed. Treatment with mTOR inhibitors led to stabilization in our patients. The side effects were well managed.

Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report.

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diathesis, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes. Homozygous or compound heterozygous pathological variants in HPS1, HPS3, HPS4, and several other genes lead to clinical manifestation of the disease. CASE PRESENTATION: A 57-year-old female was admitted with congenital oculocutaneous albinism, thrombocytopathy and late-onset accelerated pulmonary fibrosis (first symptoms from age 50 onwards). Chest high-resolution computed tomography identified thickening of peribronchovascular interstitium, bronchiectasis, reticulations, honeycombing, ground glass opacities and lung parenchyma consolidations. HPS was clinically suspected. We performed whole exome sequencing (WES), a form of massive parallel sequencing, of proband-parents trio. Whole exome libraries were processed using KAPA Hyper Prep Kit, SeqCap EZ MedExome Enrichment Kit and HyperCap Bead Kit according to the SeqCap EZ HyperCap Workflow. The paired-end 2 × 75 bp sequencing was performed on the Illumina NextSeq 500 Sequencer (Illumina Inc., USA). Furthermore, obtained variants by WES were evaluated using a virtual panel of genes: HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, and PLDN. We identified a compound heterozygous genotype in HPS1 gene in the proband. We identified a pathogenic frameshift variant c.1189delC; p.(Gln397Serfs*2), resulting in a premature stop codon. This variant has been previously associated with HPS. Furthermore, we characterized previously undescribed nonsense variant c.1507C > T; p.(Gln503*), resulting in a premature stop codon and mRNA degradation through nonsense-mediated decay. Sanger sequencing validated the presence of both variants and simultaneously confirmed the heterozygous carrier status of parents. Unfortunately, the patient died due to fulminant progression of pulmonary fibrosis 2 months after diagnostics. CONCLUSIONS: Compound heterozygous mutations in HPS1 in the proband lead to disruption of HPS1 gene and clinical manifestation of HPS with severe pulmonary fibrosis. This case illustrates the need to consider HPS in differential diagnostics of pulmonary fibrosis. Pulmonary fibrosis is a common cause of death in HPS patients. Earlier diagnosis may enable better treatment for these patients.

Novel contribution to clubfoot pathogenesis: The possible role of extracellular matrix proteins.

Idiopathic pes equinovarus (clubfoot) is a congenital deformity of the feet and lower legs. Clubfoot belongs to a group of fibro-proliferative disorders but its origin remains unknown. Our study aimed to achieve the first complex proteomic comparison of clubfoot contracted tissue of the foot (medial side; n = 16), with non-contracted tissue (lateral side; n = 13). We used label-free mass spectrometry quantification and immunohistochemistry. Seven proteins were observed to be significantly upregulated in the medial side (asporin, collagen type III, V, and VI, versican, tenascin-C, and transforming growth factor beta induced protein) and four in the lateral side (collagen types XII and XIV, fibromodulin, and cartilage intermediate layer protein 2) of the clubfoot. Comparison of control samples from cadavers brought only two different protein concentrations (collagen types I and VI). We also revealed pathological calcification and intracellular positivity of transforming growth factor beta only in the contracted tissue of clubfoot. Most of the 11 differently expressed proteins are strongly related to the extracellular matrix architecture and we assume that they may play specific roles in the pathogenesis of this deformity. These proteins seem to be promising targets for future investigations and treatment of this disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Effect of pirfenidone on lung function decline and survival: 5-yr experience from a real-life IPF cohort from the Czech EMPIRE registry.

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.

How to diagnose cardiac sarcoidosis?

Sarcoidosis is a systemic granulomatous disease of unknown etiology that can affect any organ including the heart. Clinical manifestations of heart disease are seen in about 5 % of patients, but histology shows a higher rate of heart involvement by sarcoidosis. Therefore, heart sarcoidosis is underdiagnosed because of clinically non-symptomatic course in some patients or physicians simply do not think about this heart involvement. Echocardiography, Holter monitoring, magnetic resonance imaging, positron emission tomography/computed tomography, thallium scintigraphy, and endomyocardial biopsy are methods of investigation when suspected of heart involvement by sarcoidosis. In particular, magnetic resonance has gained importance recently in the diagnosis of cardiac sarcoidosis. Key words: cardiac sarcoidosis - diagnostics - therapy.

EMPIRE Registry, Czech Part: Impact of demographics, pulmonary function and HRCT on survival and clinical course in idiopathic pulmonary fibrosis.

INTRODUCTION: 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. METHODS: Data of 514 subjects consecutively entered since 2012 into Czech EMPIRE IPF registry were analyzed. RESULTS: 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 DLCO [diffuse lung capacity] changes), slowly progressive in 39.5% (45%), rapidly progressive in 23.5% (20.7%); and 1.7% patients had at least one acute exacerbation during follow-up. Deterioration in FVC of ≥10% at month 12 and in DLCO of ≥15% at months 12, 18, and 24 influenced the OS significantly. The fast progressors defined by the DLCO decline rate had higher risk of death compared to those defined by the FVC change over time. In multivariate analysis, age ≥70 years, interstitial HRCT scores ≥3, and change in DLCO of ≥15% at month 12 were confirmed as factors negatively influencing OS. CONCLUSIONS: DLCO changes over time were shown as a better predictor of mortality compared with FVC changes in our study. In our opinion it is necessary to implement the DLCO analysis into clinical trials and routine practice.