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

Severe asthma represents a true challenge for clinicians from two basic perspectives, i.e.: a rational assessment of the underlying endo/phenotype and the subsequent selection of the best fitted (personalized) and effective treatment. Even though asthma is a heterogeneous disease, in the majority of therapy-compliant patients, it is possible to achieve (almost) complete disease control or even remission through conventional and quite uniform step-based pharmacotherapy, even without phenotyping. However, the absence of deeper assessment of individual patients revealed its handicap to its fullest extent during the first years of the new millennium upon the launch of biological therapeutics for patients with the most severe forms of asthma. The introduction of differentially targeted biologics into clinical practice became a challenge in terms of understanding and recognizing the etiopathogenetic heterogeneity of the asthmatic inflammation, pheno/endotyping, and, consequently, to choose the right biologic for the right patient. The answers to the following three questions should lead to correct identification of the dominant pheno/endotype: Is it really (severe) asthma? Is it eosinophilic asthma? If eosinophilic, is it (predominantly) allergen-driven? The identification of the best achievable and relevant alliance between endotypes and phenotypes ("euphenotypes") should be based not only on the assessment of the actual clinical characteristics and laboratory biomarkers, but more importantly, on the evaluation of their development and changes over time. In the current paper, we present a pragmatic three-step approach to severe asthma diagnosis and management.

• MeSH
• antiastmatika terapeutické užití   MeSH
• biologické přípravky terapeutické užití   MeSH
• bronchiální astma * farmakoterapie   MeSH
• fenotyp * MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• individualizovaná medicína * metody   MeSH
• lidé MeSH
• omalizumab terapeutické užití   MeSH
• stupeň závažnosti nemoci * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Chronic effects of noninvasive ventilation on myocardial function in patients with obesity hypoventilation syndrome (OHS) are scarcely understood. The aim of the present study was to evaluate the long-term effects of volume-targeted bilevel positive airway pressure ventilation (BiPAP) on cardiac parameters and myocardial biomarkers in patients with OHS. METHODS: Clinically stable patients with OHS referred to the tertiary center for the initiation of long-term BiPAP therapy were consecutively enrolled. At baseline, all participants underwent overnight cardiorespiratory polygraphy. BiPAP therapy using volume-targeted spontaneous/timed mode delivered via an oro-nasal mask was initiated. Beat-to-beat noninvasive monitoring by impedance cardiography was used to assess heart function at baseline and after 3 and 12 months of BiPAP use. Serum troponin 1, N-Terminal Pro-B-Type Natriuretic Peptide (NT-ProBNP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were monitored. RESULTS: Thirteen patients (10 men; mean age, 55.8 ± 9.8 years; mean body mass index of 47.8 ± 5.9 kg/m2) were recruited. From baseline to 3, and to 12 months of BiPAP use, left ventricular stroke volume (SV), ejection time (LVET), and ejection time index significantly increased (P = 0.030; P < 0.001; P = 0.003, respectively), while heart rate and systolic time ratio significantly decreased (P = 0.004; P = 0.034, respectively). Reductions in serum NT-proBNP, IL-6 and TNF-α were observed (P = 0.045; P = 0.018; P = 0.003, respectively). No significant changes in serum troponin were detected throughout the study. CONCLUSIONS: The present findings of increased SV, in association with lengthening of LVET, reductions of NT-proBNP and reductions in circulatory inflammatory markers in patients with stable OHS and chronic moderate-to-severe daytime hypercapnia treated with BiPAP over 1 year support the role of this therapeutic mode in such patients.

• MeSH
• biologické markery * krev   MeSH
• časové faktory MeSH
• hypoventilační syndrom při obezitě * terapie   patofyziologie   MeSH
• interleukin-6 * krev   MeSH
• kardiografie impedanční MeSH
• lidé středního věku MeSH
• lidé MeSH
• natriuretický peptid typu B * krev   MeSH
• neinvazivní ventilace * metody   MeSH
• peptidové fragmenty * krev   MeSH
• senioři MeSH
• TNF-alfa krev   MeSH
• troponin I krev   MeSH
• ventilace umělá s výdechovým přetlakem metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Quality of life and survival in Cystic Fibrosis (CF) have improved dramatically, making family planning a feasible option. Maternal and perinatal outcomes in women with CF (wwCF) are similar to those seen in the general population. However, the effect of undergoing multiple pregnancies is unknown. METHODS: A multinational-multicenter retrospective cohort study. Data was obtained from 18 centers worldwide, anonymously, on wwCF 18-45 years old, including disease severity and outcome, as well as obstetric and newborn complications. Data were analyzed, within each individual patient to compare the outcomes of an initial pregnancy (1st or 2nd) with a multigravid pregnancy (≥3) as well as secondary analysis of grouped data to identify risk factors for disease progression or adverse neonatal outcomes. Three time periods were assessed - before, during, and after pregnancy. RESULTS: The study population included 141 wwCF of whom 41 (29%) had ≥3 pregnancies, "multiparous". Data were collected on 246 pregnancies, between 1973 and 2020, 69 (28%) were multiparous. A greater decline in ppFEV1 was seen in multiparous women, primarily in pancreatic insufficient (PI) wwCF and those with two severe (class I-III) mutations. Multigravid pregnancies were shorter, especially in wwCF over 30 years old, who had high rates of prematurity and newborn complications. There was no effect on pulmonary exacerbations or disease-related complications. CONCLUSIONS: Multiple pregnancies in wwCF are associated with accelerated respiratory deterioration and higher rates of preterm births. Therefore, strict follow-up by a multidisciplinary CF and obstetric team is needed in women who desire to carry multiple pregnancies.

• MeSH
• cystická fibróza * komplikace   MeSH
• dospělí MeSH
• komplikace těhotenství epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• parita MeSH
• předčasný porod epidemiologie   MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• stupeň závažnosti nemoci MeSH
• těhotenství mnohočetné MeSH
• těhotenství MeSH
• výsledek těhotenství * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The development of monoclonal antibody therapies targeting specific components of the pathways relevant to asthma pathophysiology has revolutionized treatment of severe asthma both in adults and children and helped to further unravel the heterogeneity of this disease. However, the availability of multiple agents, often with overlapping eligibility criteria, creates a need for pragmatic guidance for specialists undertaking care of patients with severe asthma. In this review, we provide an overview of the data supporting the clinical efficacy of biologics in distinct asthma phenotypes/endotypes. We also focus on the role of biomarkers and treatable traits, including comorbidities, in the choice of asthma biologics, highlight which treatments have been demonstrated to be steroid sparing in corticosteroid dependent asthma, and provide practical guidance that can drive shared decision making on treatment choice with patients. In addition, we summarize what is known to date regarding long-term safety of these drugs, and lastly, discuss future directions in biologics research.

• MeSH
• antiastmatika * terapeutické užití   MeSH
• biologické markery MeSH
• biologické přípravky * terapeutické užití   MeSH
• bronchiální astma * MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• individualizovaná medicína MeSH
• lidé MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Since its global invasion in 2019, COVID-19 has affected several aspects of patients' lives and posed a significant impact on the health care system. Several patient populations were identified to be at high risk of contracting SARS-CoV-2 infection and/or developing severe COVID-19-related sequelae. Conversely, anyone who has contracted SARS-CoV-2 is at risk to experience symptoms and signs consistent with post-COVID manifestations. Patients with asthma were initially thought to be at increased risk and severity for SARS-CoV-2 infection. However, accumulating evidence demonstrates that asthma endotypes/phenotypes and comorbidities influence the risk stratification in this population. Furthermore, initial concerns about the potentially increased risk of poor outcomes with asthma treatments such as inhaled corticosteroids and biologics have not been substantiated. In this review, we provide an update on COVID-19 and asthma, including risk of susceptibility, clinical manifestations and course in this population as well as discuss recommendations for management.

• MeSH
• bronchiální astma * diagnóza   MeSH
• COVID-19 * epidemiologie   komplikace   MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• komorbidita MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• bronchiální astma * diagnóza   terapie   MeSH
• lidé MeSH
• pacienti MeSH
• praktičtí lékaři * MeSH
• stupeň vzdělání MeSH
• zdravotničtí záchranáři MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Bronchial asthma is a heterogeneous respiratory condition characterized by chronic airway inflammation, airway hyperresponsiveness and airway structural changes (known as remodeling). The clinical symptoms can be evoked by (non)specific triggers, and their intensity varies over time. In the past, treatment was mainly focusing on symptoms' alleviation; in contrast modern treatment strategies target the underlying inflammation, even during asymptomatic periods. Components of airway remodeling include epithelial cell shedding and dysfunction, goblet cell hyperplasia, subepithelial matrix protein deposition, fibrosis, neoangiogenesis, airway smooth muscle cell hypertrophy and hyperplasia. Among the other important, and frequently forgotten aspects of airway remodeling, also loss of epithelial barrier integrity, immune defects in anti-infectious defence and mucociliary clearance (MCC) dysfunction should be pointed out. Mucociliary clearance represents one of the most important defence airway mechanisms. Several studies in asthmatics demonstrated various dysfunctions in MCC - e.g., ciliated cells displaying intracellular disorientation, abnormal cilia and cytoplasmic blebs. Moreover, excessive mucus production and persistent cough are one of the well-recognized features of severe asthma and are also associated with defects in MCC. Damaged airway epithelium and impaired function of the ciliary cells leads to MCC dysfunction resulting in higher susceptibility to infection and inflammation. Therefore, new strategies aimed on restoring the remodeling changes and MCC dysfunction could present a new therapeutic approach for the management of asthma and other chronic respiratory diseases.

• MeSH
• bronchiální astma * farmakoterapie   MeSH
• hyperplazie MeSH
• lidé MeSH
• mukociliární clearance fyziologie   MeSH
• remodelace dýchacích cest * MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• biomedicínský výzkum MeSH
• bronchiální astma * terapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodní články MeSH
• úvodníky MeSH

Allergen specific immunotherapy (AIT) is the only causal therapeutic option for allergic airway diseases including asthma and allergic rhinitis. AIT has been shown to restore the allergen immune tolerance, can modify both the early and late-onset allergen-specific airway hyperreactivity, helps to achieve disease control/remission and prevents new sensitisations. Recent real life data on long-term effectiveness of house dust mite (HDM) AIT in a large group of patients with HDM-driven asthma further underscored its unique therapeutic potential as well as confirmed previous data with pollen AIT. More widespread use of this causal treatment in select patient populations should further move this promising therapeutic field. In this mini-review, we discuss updates on new insights based on real world patient data.

• MeSH
• alergeny MeSH
• alergická rýma * farmakoterapie   MeSH
• antigeny roztočů domácího prachu terapeutické užití   MeSH
• bronchiální astma * etiologie   MeSH
• desenzibilizace imunologická MeSH
• lidé MeSH
• pyl MeSH
• Pyroglyphidae MeSH
• sublinguální imunoterapie * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH