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.
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
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) and asthma are associated with chronic inflammation leading to airway obstruction and remodelling. There is little information on possible differences in the TGFB signalling pathway in the pathologies compared to less severe chronic bronchitis without airway obstruction. AIM: To assess the expression of the selected TGFB signalling pathway-associated genes in the pathologies. METHOD: RT-PCR was used to quantify the mRNAs in bronchoalveolar cells obtained from the Czech patients with chronic bronchitis (n = 26), COPD (n = 22), asthmatic (n = 14) patients. RESULTS: There was no difference in the BAL cell expression of TGFB1-3, TGFBR1-2, SMAD2,4,5, and 7 between our patients with COPD and those with chronic bronchitis. The expressions were also similar in the patients with asthma and chronic bronchitis. There was no difference between the patients with asthma and COPD. CONCLUSION: Although we observed no differences in our patients, other studies should investigate the genes and their possible correlation with advanced airway obstruction and emphysematous changes (Tab. 2, Fig. 3, Ref. 27).
- MeSH
- bronchoalveolární lavážní tekutina MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- obstrukční plicní nemoci * patofyziologie MeSH
- proteiny Smad biosyntéza MeSH
- proteosyntéza * MeSH
- receptory transformujícího růstového faktoru beta biosyntéza MeSH
- senioři MeSH
- signální transdukce MeSH
- statistika jako téma MeSH
- transformující růstový faktor beta biosyntéza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The BODE (BMI, Obstruction - FEV1, Dyspnoea - mMRC, Exercise - 6-MWT) and the ADO (Age, Dyspnoea - mMRC, Obstruction - FEV1) indices are widely used prognosis assessment tools for long-term mortality prediction in COPD patients but subject to limitations for use in daily clinical practice. The aim of this research was to construct a prognostic instrument that prevents these limitations and which would serve as a complementary prognostic tool for clinical use in these patients. METHODS AND PARTICIPANTS: The data of 699 COPD subjects were extracted from the Czech Multicentre Research Database (CMRD) of COPD patients (the derivation cohort) and analysed to identify factors associated with the long-term risk of mortality. These were entered into the ROC analysis and reclassification analysis. Those with the strongest discriminative power were used to construct the new index (CADOT). The new index was validated on 187 patients of the CIROCO+ cohort (Netherlands; the validation cohort). RESULTS: The CADOT was constructed by adding two newly identified prognosis-determining factors, chronic heart failure (CHF) and TLCO, to the ADO index. In a head-to-head comparison, the CADOT index showed highest c-statistic values compared to the BODE and ADO indices (0.701 vs 0.677 vs 0.644, respectively). The prognostic power was more definitive when applied to the Dutch validation (CIROCO+) cohort (0.842 vs 0.799 vs 0.825, respectively). CONCLUSIONS: The CADOT index has comparable prognostic power to the BODE and ADO indices. The CADOT is complementary/an alternative to the BODE (if 6-MWT is not feasible) and ADO (with less dependence on the age factor) indices. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01923051).
- MeSH
- chronická obstrukční plicní nemoc * mortalita MeSH
- dyspnoe MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- prognóza MeSH
- respirační funkční testy MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with Stage IIA, IIB or IIIA non-small cell lung cancer (NSCLC) after complete resection. Results obtained for Stage IB were not conclusive. While vinorelbine plus cisplatin is the preferred choice after resection, combining vinorelbine with carboplatin promises improved compliance and delivery of drugs due to lower toxicity. We evaluated the impact of this option on treatment compliance and survival under real-world conditions. MATERIAL AND METHODS: A prospective, single-arm, multicenter, non-interventional study evaluated the tolerability, dose intensity and survival resulting from adjuvant use of intravenous carboplatin (AUC 5 on day 1) with vinorelbine administered both intravenously (25 mg/m2 on day 1) and orally (60 mg/m2 on day 8) within four cycles of 21 days each. A total of 74 patients with a median age of 64 years were observed. RESULTS: The mean number of accomplished cycles was 3.78, and 62 patients (83.7%) completed all four planned cycles. Relative dose intensity for carboplatin was 88.9%, for intravenous vinorelbine 93.1%, and for oral vinorelbine 83.2%. Median follow-up was 4.73 years. Median disease-specific survival (DSS) was 7.63 years, median overall survival (OS) was 5.90 years, median disease-free survival (DFS0) was 4.43 years, and five-year survival was 56.2%. TNM stage of disease significantly affected DSS and OS. Favorable survival was observed in females, nonsmokers, patients aged over 65 years, patient with prior lobectomy, patients with tumor of squamous histology, and those who finished the planned therapy, but the differences were non-significant. CONCLUSION: Adjuvant carboplatin with vinorelbine switched from intravenous to oral administration was shown to be a favorable regimen with regard to tolerability and safety. Compliance to therapy was high, and survival parameters were promising, showing that applied regimen can be another potential option for adjuvant chemotherapy in patients with NSCLC.
- MeSH
- adjuvantní chemoterapie metody MeSH
- aplikace orální MeSH
- intravenózní podání metody MeSH
- karboplatina aplikace a dávkování MeSH
- lidé MeSH
- nádory plic farmakoterapie mortalita MeSH
- nemalobuněčný karcinom plic farmakoterapie mortalita MeSH
- přežití po terapii bez příznaků nemoci MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie aplikace a dávkování MeSH
- senioři MeSH
- vinblastin aplikace a dávkování analogy a deriváty MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND AND AIMS: Haemophilus influenzae new strain acquisition has been demonstrated to increase the relative risk of acute exacerbation fourfold in contrast to colonisation or chronic infection by the same strain in chronic obstructive pulmonary disease (COPD). Unfortunately, molecular typing techniques are not suitable for routine use due to cost, labour-intensity and need for special expertise. We tested two techniques potentially useful for routine typing, namely the newly available MALDI-TOF MS and the modified McRAPD compared to MLST as the gold standard. METHODS: In 10 patients (10.8%) suffering from COPD or cystic fibrosis, H. influenzae isolates were recovered repeatedly at different timepoints from the same patient during the study period. This allowed for thirteen pairwise comparisons of typing results in isolates recovered consecutively from the same patient to test the ability of the techniques to uncover new strain acquisition. RESULTS: MLST detected 9 cases of new strain acquisition among the 13 pairwise comparisons. However, MALDI-TOF MS reported all 13 pairs as different and thus new. In contrast, McRAPD was able to differentiate all the new strain acquisitions from pre-existing ones, both by visual inspection of melting profiles and by Relative Significant Difference values. CONCLUSIONS: Unlike MALDI-TOF MS, McRAPD appears to be a suitable candidate for routine discrimination of new strain acquisitions because of its accuracy and, rapid, easy and economic performance.
- MeSH
- chronická obstrukční plicní nemoc diagnóza MeSH
- cystická fibróza diagnóza MeSH
- diferenciální diagnóza MeSH
- Haemophilus influenzae izolace a purifikace MeSH
- hemofilové infekce diagnóza MeSH
- lidé MeSH
- senzitivita a specificita MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice metody normy MeSH
- techniky typizace bakterií metody normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
BACKGROUND AND AIMS: S. anginosus, constellatus and intermedius, also known as the Streptococcus milleri group (SMG) are three streptococcal species more frequently detected in cases of invasive disease, abscesses and empyema in particular. Recent research suggests they play a role in exacerbations of cystic fibrosis (CF). Owing to poor recovery on standard culture media and difficult differentiation from non-pathogenic streptococci, SMG may be underdiagnosed in routine settings. We aimed to establish the incidence of SMG in chronic obstructive pulmonary disease (COPD) patients compared to CF patients and to examine possible links of SMG to exacerbations that plays a key role in progression of COPD. METHODS: Altogether, 90 respiratory tract samples of patients suffering from CF or COPD were examined during the period from July 2012 to December 2013. Semi-selective McKay agar was used for primary cultivation of SMG and MALDI TOF MS was used for species identification that was confirmed by biochemical profiling and specific PCR. RESULTS: We confirmed the presence of SMG in CF (17.6% incidence in adult patients) and newly established its presence in COPD (10.3% incidence). In COPD, SMG was detected in 4 cases of acute exacerbations, where no other bacterial pathogen was detected. In 3/4 cases, increased CRP level indicated bacterial infection as a cause of the exacerbation and in all 3 cases, patients recovered during antibiotic treatment. CONCLUSIONS: Our data indicate SMG may act as opportunist pathogens able to cause exacerbations in COPD.
- MeSH
- akutní nemoc MeSH
- chronická obstrukční plicní nemoc MeSH
- cystická fibróza mikrobiologie MeSH
- dospělí MeSH
- infekce dýchací soustavy mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- oportunní infekce mikrobiologie MeSH
- senioři MeSH
- skupina Streptococcus milleri izolace a purifikace MeSH
- sputum mikrobiologie MeSH
- streptokokové infekce mikrobiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
