Prognostic Properties of the GOLD 2023 Classification System.

Introduction: Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published an update on the Global Strategy for Prevention, Diagnosis and Management of COPD, introducing a new classification of chronic obstructive pulmonary disease (COPD). Our aim was to assess the prognostic value of the new GOLD classification system in comparison with the previous GOLD classification systems (GOLD stages I-IV and GOLD groups A-D) and the BODE index. Methods: We used the data of 784 patients with COPD from the Czech Multicenter Research Database of COPD. Patient survival was analyzed with the use of Kaplan-Meier estimate and Cox model of proportional risks. ROC analysis and area under curve (AUC) were used for comparison of GOLD classifications and BODE index. The analyses were performed with the use of software R (version 4.2.0). Results: We analyzed data of 782 patients with complete data on GOLD classifications. The study population comprised 72.9% of men, 89.1% current or former smokers, with a mean age of 66.6 years, a mean BMI of 27.4 and a mean FEV1 44.9% of predicted. Probability of 5-year survival differed by GOLD classification. Application of the 2023 GOLD classification showed increased risk of death in group B (HR 1.82, 95% CI 1.14-2.92; p = 0.013) and in group E (HR 2.48, 95% CI 1.54-3.99; p˂0.001). The ROC analysis showed that the overall prognostic value of the 2023 GOLD classification was similarly weak to previous A-D GOLD classification schemes (AUCs 0.557-0.576) and was lower compared to the GOLD 1-4 system (AUC 0.614) and even lower when compared to the BODE index (AUC 0.715). Conclusion: We concluded that the new GOLD classification system has poor prognostic properties and that specific prediction tools (eg, the BODE index) should be used for mortality risk assessment.

The expression of selected fibrotic factors in COPD and asthma.

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). Text in PDF www.elis.sk Keywords: TGFB signalling pathway, COPD, asthma, chronic bronchitis, bronchoalveolar lavage.

Self-Reported Overall Adherence and Correct Inhalation Technique Discordance in Chronic Obstructive Pulmonary Disease Population.

Background: Adherence to inhaled medication constitutes a major problem in patients with chronic obstructive pulmonary disease (COPD) globally. However, large studies evaluating adherence in its entirety and capturing a large variety of potentially associated factors are still lacking. Objective: To study both elementary types of adherence to chronic inhaled COPD medication in "real-life" COPD patients and to assess relationships with a wide-ranging spectrum of clinical parameters. Methods: Data from the Czech Multicentre Research Database (CMRD) of COPD, an observational prospective study, were used. Overall adherence (OA) was evaluated with Morisky Medication Adherence Scale (©MMAS-4) and adherence to an application technique (A-ApplT) with the Five Steps Assessment. Mann-Whitney U test, Spearman's correlation, and logistic regression were used to explore relationships between variables. Results: Data of 546 participants (69.6% of all patients from the CMRD) were analyzed. Two-thirds self-reported optimal OA, but only less than one-third demonstrated A-ApplT without any error. OA did not correlate with A-ApplT. Next, better OA was associated with higher education, a higher number of inhalers, a lower rate of exacerbations, poorer lung function, higher degree of upper respiratory tract symptoms (SNOT-22), absence of depressive symptoms, ex-smoking status, regular mouthwash after inhaled corticosteroids (ICS), and flu vaccination. By contrast, better A-ApplT was associated with a lower number of inhalers, better lung function, and regular mouthwash after ICS. Independent predictors of nonoptimal OA included lower degree of education, absence of flu vaccination, anemia, depression, and peptic ulcer history, whereas independent predictors of lower A-ApplT were lower education, absence of regular mouthwash after ICS, and higher COPD Assessment Test score. Conclusions: Parameters associated with OA and A-ApplT differ, and those associated with both adherence domains are sometimes associated inversely. Based on this finding, we understand these as two separate constructs with an overlap.

Chronic obstructive pulmonary disease: diagnosis and treatment of stable phase of disease; personalized treatment approach using phenotype features of the disease Summary of the 2020-2021 Czech Pneumological and Phthiseological Society position paper.

Chronic obstructive pulmonary disease (COPD) is a heterogenous condition affecting hundreds of millions of people worldwide. COPD is a major health problem associated with significant morbidity and mortality. In this review, the authors present the current concept of care for patients with COPD in the Czech Republic, along with a summary of treatment recommendations formulated by the expert group of the Czech Pneumological and Phthisiological Society. A more detailed version of the position paper was published in 2020. The aim of this work was to transform the most recent scientific knowledge into the context of daily practice in the Czech Republic. Our concept of care for patients with COPD uses a complex approach with special emphasis on individual phenotypic features of the disease. Maximal effort has been put into individualization of treatment according to the presence of certain clinical phenotypes/treatable traits with respect to current scientific knowledge.

The Relation Between Clinical Phenotypes, GOLD Groups/Stages and Mortality in COPD Patients - A Prospective Multicenter Study.

INTRODUCTION: The concept of phenotyping emerged, reflecting specific clinical, pulmonary and extrapulmonary features of each particular chronic obstructive pulmonary disease (COPD) case. Our aim was to analyze prognostic utility of: "Czech" COPD phenotypes and their most frequent combinations, "Spanish" phenotypes and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages + groups in relation to long-term mortality risk. METHODS: Data were extracted from the Czech Multicenter Research Database (CMRD) of COPD. Kaplan-Meier (KM) estimates (at 60 months from inclusion) were used for mortality assessment. Survival rates were calculated for the six elementary "Czech" phenotypes and their most frequent and relevant combinations, "Spanish" phenotypes, GOLD grades and groups. Statistically significant differences were tested by Log Rank test. An analysis of factors underlying mortality risk (the role of confounders) has been assessed with the use of classification and regression tree (CART) analysis. Basic factors showing significant differences between deceased and living patients were entered into the CART model. This showed six different risk groups, the differences in risk were tested by a Log Rank test. RESULTS: The cohort (n=720) was 73.1% men, with a mean age of 66.6 years and mean FEV1 44.4% pred. KM estimates showed bronchiectases/COPD overlap (HR 1.425, p=0.045), frequent exacerbator (HR 1.58, p<0.001), cachexia (HR 2.262, p<0.001) and emphysematous (HR 1.786, p=0.015) phenotypes associated with higher mortality risk. Co-presence of multiple phenotypes in a single patient had additive effect on risk; combination of emphysema, cachexia and frequent exacerbations translated into poorest prognosis (HR 3.075; p<0.001). Of the "Spanish" phenotypes, AE CB and AE non-CB were associated with greater risk of mortality (HR 1.787 and 2.001; both p=0.001). FEV1% pred., cachexia and chronic heart failure in patient history were the major underlying factors determining mortality risk in our cohort. CONCLUSION: Certain phenotypes ("Czech" or "Spanish") of COPD are associated with higher risk of death. Co-presence of multiple phenotypes (emphysematous plus cachectic plus frequent exacerbator) in a single individual was associated with amplified risk of mortality.

Introducing a new prognostic instrument for long-term mortality prediction in COPD patients: the CADOT index.

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).

Chronic obstructive pulmonary disease - diagnosis and management of stable disease; a personalized approach to care, using the treatable traits concept based on clinical phenotypes. Position paper of the Czech Pneumological and Phthisiological Society.

This position paper has been drafted by experts from the Czech national board of diseases with bronchial obstruction, of the Czech Pneumological and Phthisiological Society. The statements and recommendations are based on both the results of randomized controlled trials and data from cross-sectional and prospective real-life studies to ensure they are as close as possible to the context of daily clinical practice and the current health care system of the Czech Republic. Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable heterogeneous syndrome with a number of pulmonary and extrapulmonary clinical features and concomitant chronic diseases. The disease is associated with significant mortality, morbidity and reduced quality of life. The main characteristics include persistent respiratory symptoms and only partially reversible airflow obstruction developing due to an abnormal inflammatory response of the lungs to noxious particles and gases. Oxidative stress, protease-antiprotease imbalance and increased numbers of pro-inflammatory cells (mainly neutrophils) are the main drivers of primarily non-infectious inflammation in COPD. Besides smoking, household air pollution, occupational exposure, low birth weight, frequent respiratory infections during childhood and also genetic factors are important risk factors of COPD development. Progressive airflow limitation and airway remodelling leads to air trapping, static and dynamic hyperinflation, gas exchange abnormalities and decreased exercise capacity. Various features of the disease are expressed unequally in individual patients, resulting in various types of disease presentation, emerging as the "clinical phenotypes" (for specific clinical characteristics) and "treatable traits" (for treatable characteristics) concept. The estimated prevalence of COPD in Czechia is around 6.7% with 3,200-3,500 deaths reported annually. The elementary requirements for diagnosis of COPD are spirometric confirmation of post-bronchodilator airflow obstruction (post-BD FEV1/VCmax <70%) and respiratory symptoms assessement (dyspnoea, exercise limitation, cough and/or sputum production. In order to establish definite COPD diagnosis, a five-step evaluation should be performed, including: 1/ inhalation risk assessment, 2/ symptoms evaluation, 3/ lung function tests, 4/ laboratory tests and 5/ imaging. At the same time, all alternative diagnoses should be excluded. For disease classification, this position paper uses both GOLD stages (1 to 4), GOLD groups (A to D) and evaluation of clinical phenotype(s). Prognosis assessment should be done in each patient. For this purpose, we recommend the use of the BODE or the CADOT index. Six elementary clinical phenotypes are recognized, including chronic bronchitis, frequent exacerbator, emphysematous, asthma/COPD overlap (ACO), bronchiectases with COPD overlap (BCO) and pulmonary cachexia. In our concept, all of these clinical phenotypes are also considered independent treatable traits. For each treatable trait, specific pharmacological and non-pharmacological therapies are defined in this document. The coincidence of two or more clinical phenotypes (i.e., treatable traits) may occur in a single individual, giving the opportunity of fully individualized, phenotype-specific treatment. Treatment of COPD should reflect the complexity and heterogeneity of the disease and be tailored to individual patients. Major goals of COPD treatment are symptom reduction and decreased exacerbation risk. Treatment strategy is divided into five strata: risk elimination, basic treatment, phenotype-specific treatment, treatment of respiratory failure and palliative care, and treatment of comorbidities. Risk elimination includes interventions against tobacco smoking and environmental/occupational exposures. Basic treatment is based on bronchodilator therapy, pulmonary rehabilitation, vaccination, care for appropriate nutrition, inhalation training, education and psychosocial support. Adequate phenotype-specific treatment varies phenotype by phenotype, including more than ten different pharmacological and non-pharmacological strategies. If more than one clinical phenotype is present, treatment strategy should follow the expression of each phenotypic label separately. In such patients, multicomponental therapeutic regimens are needed, resulting in fully individualized care. In the future, stronger measures against smoking, improvements in occupational and environmental health, early diagnosis strategies, as well as biomarker identification for patients responsive to specific treatments are warranted. New classes of treatment (inhaled PDE3/4 inhibitors, single molecule dual bronchodilators, anti-inflammatory drugs, gene editing molecules or new bronchoscopic procedures) are expected to enter the clinical practice in a very few years.

Performance studies of new optics for the time-of-flight detector of the AFP project.

We present the results of performance studies of the upgraded optical part of the time-of-flight subdetector prototype for the AFP (ATLAS Forward Proton) detector obtained during the test campaign in a synchrotron test-beam facility with 5 GeV electrons at the DESY laboratory (Hamburg, Germany) in June 2019. The detection of the particle arrival time is based on generation of Cherenkov light in an L-shaped fused silica bar. In the previous version of the ToF, all bars were made of two pieces (radiator and light guide) glued together with a dedicated glue (Epotek 305). This solution suffers from additional radiation damage of glue. We adopted a new technique of bar production without the need of glue. The new bars have a higher optical throughput by a factor of 1.6, reduced fragility, and better geometrical precision.

Efficacy and analgesic use during the therapy of iatrogenic pneumothorax using Pleuralvent™ and Chest Tube (ASPIRATE): A randomised controlled trial protocol.

BACKGROUND: Iatrogenic pneumothorax is a common complication of various diagnostic and therapeutic procedures such as transbronchial lung biopsies. The classical mode of treatment is chest tube insertion. Pneumothorax devices are now available on the market but there is a dearth of data on their efficacy to treat iatrogenic pneumothorax. It is important to provide such data as the pathophysiology of iatrogenic pneumothorax is different in comparison with spontaneous pneumothorax for which some data is available. METHODS: This is a randomized, non-blinded, actively controlled trial of effectivity of iatrogenic pneumothorax treatment using the Pleuralvent™ device and chest tube insertion (16F). The secondary aim is to compare the overall pain level and the need for analgesic treatment in both treatment arms. We are planning to enrol 126 patients (63 in each treatment arm). DISCUSSION: Preliminary results showed similar effectivity of the Pleuralvent™ system compared to large bore chest tube insertion. This randomized clinical trial should confirm these results and prove that the Pleuralvent™ system is an effective way of treatment of patients with iatrogenic pneumothorax. If Pleuralvent™ proves to have the same level of efficacy, it may become the standard of care of patients with iatrogenic pneumothorax. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03700554.

Comparison of lymphocyte immune phenotypes in bronchoalveolar lavage of non-smoking patients with sarcoidosis and other interstitial lung diseases.

BACKGROUND: Bronchoalveolar lavage (BAL) as complementary method is still used as ancillary tool in diagnosis of interstitial lung diseases. Tobacco smoking has been described to affect the BAL lavage cellular profile. To our knowledge, only few reports have so far investigated CD3+CD4+ and CD3+CD8+ lymphocyte subsets in non-smoking sarcoidosis patients additionally stratified according to CXR stage, and compared them to other non-smoking patients with interstitial lung diseases (ILDs). METHODS: We compared lymphocytes immune phenotypes, subsets, with CD3+, CD3+CD4+ and CD3+CD8+ cell markers, in the non-smoking subjects (n=297) including the patients with pulmonary sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) (n=22), hypersensitivity pneumonitis (HP) (n=15), other interstitial idiopathic pneumonias (OIIPs) (n=39). According to prognosis, the patients with S were divided into four groups: 18 patients with Löfgren's syndrome (LS) in chest X-ray (CXR) ≤1 stage, 64 patients without LS in CXR ≤1 stage, 113 patients in CXR 2 stage and 26 patients with advanced CXR ≥3 stage. RESULTS: After the use of false discovery rate (FDR) correction, relative numbers (%) of CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD4/CD3+CD8 ratio showed the most significant differences between the non-smokers with S (both with/without LS) and the non-smokers with other ILDs (IPF, OIIPs, HP). These lymphocytes subsets were further altered in the non-smokers with CXR stage 2 compared to the non-smokers with other ILDs (IPF, OIIPs, HP). We did not observe any differences in these lymphocyte subsets and CD3+CD4+/CD3+CD8+ ratio between the non-smokers with advanced sarcoidosis stage (CXR ≥3) and the non-smokers with IPF. CONCLUSIONS: Our data on the non-smokers confirmed the presence of the typical BAL cellular profile in sarcoidosis. The BAL cellular profile was helpful namely for differentiation of less advanced sarcoidosis. Its definite diagnostic utility should be the subject of further clinical studies with large numbers of the well characterized patients taking into consideration other clinical factors influencing BAL cellular profile, such as smoking or treatment.

Prognostic Accuracy of Three COPD Classification Systems in Relation to Long-Term Mortality of COPD Patients: A Prospective Multicenter Study.

Recent research showed group B patients express higher mortality compared to group C patients when GOLD A-D grouping is used. We aimed to compare the prognostic accuracy of three GOLD classification systems, I-IV ("pre-2011"), A-D ("2011-2016") and A-D ("2017-present") in relation to mortality, exacerbation risk, quality of life (QoL) assessment and specific treatments use in a real-life COPD cohort. We used the data of 720 patients from the Czech Multicenter Research Database of COPD. Four-year mortality and time-to-exacerbation using the GOLD "pre-2011", "2011-2016" and "2017-present" classification schemes were assessed. Moreover, distribution of specific treatments use and QoL measures were analyzed. The GOLD I-IV classification system showed gradual increase in 4-year mortality across the stages (GOLD II 18.8%, III 28.5%, IV 38.7%) (p = 0.001). Using the A-D "2011-2016" classification scheme, group C patients had lower mortality (16.7%) than group B (18.7%) (p = 0.009). The A-D "2017-present" classification showed higher mortality in group B (25.5%) compared to group C (20%) (p = 0.05). For additional outcomes, the GOLD I-IV scheme showed highest match between the calculated 4-year exacerbation risk and QoL measures and GOLD stage/grouping. In terms of specific treatment distributions, various patterns for each GOLD classification system were observed with best match of GOLD "2017-present" system to the layout of GOLD groups and categories. We conclude the GOLD I-IV classification system had the highest accuracy related to mortality, QoL measures and exacerbation risk prediction, while the A-D "2017-present" scheme was most accurate within severity of symptoms prediction reflected also by more frequent specific treatments use.

Respiratory parameters predict poor outcome in COPD patients, category GOLD 2017 B.

Background: Respiratory parameters are important predictors of prognosis in the COPD population. Global Initiative for Obstructive Lung Disease (GOLD) 2017 Update resulted in a vertical shift of patients across COPD categories, with category B being the most populous and clinically heterogeneous. The aim of our study was to investigate whether respiratory parameters might be associated with increased all-cause mortality within GOLD category B patients. Methods: The data were extracted from the Czech Multicentre Research Database, a prospective, noninterventional multicenter study of COPD patients. Kaplan-Meier survival analyses were performed at different levels of respiratory parameters (partial pressure of oxygen in arterial blood [PaO2], partial pressure of arterial carbon dioxide [PaCO2] and greatest decrease of basal peripheral capillary oxygen saturation during 6-minute walking test [6-MWT]). Univariate analyses using the Cox proportional hazard model and multivariate analyses were used to identify risk factors for mortality in hypoxemic and hypercapnic individuals with COPD. Results: All-cause mortality in the cohort at 3 years of prospective follow-up reached 18.4%. Chronic hypoxemia (PaO2 <7.3 kPa), hypercapnia (PaCO2 >7.0 kPa) and oxygen desaturation during the 6-MWT were predictors of long-term mortality in COPD patients with forced expiratory volume in 1 second ≤60% for the overall cohort and for GOLD B category patients. Univariate analyses confirmed the association among decreased oxemia (<7.3 kPa), increased capnemia (>7.0 kPa), oxygen desaturation during 6-MWT and mortality in the studied groups of COPD subjects. Multivariate analysis identified PaO2 <7.3 kPa as a strong independent risk factor for mortality. Conclusion: Survival analyses showed significantly increased all-cause mortality in hypoxemic and hypercapnic GOLD B subjects. More important, PaO2 <7.3 kPa was the strongest risk factor, especially in category B patients. In contrast, the majority of the tested respiratory parameters did not show a difference in mortality in the GOLD category D cohort.

[Non-CF bronchiectasis of adults: short review for clinical practice Position paper of Board of disease with bronchial obstruction Czech Pulmonological and Phthiseological Society Czech Medical Association of J. E. Purkyne]. / Non-CF bronchiektázie dospelých: strucný prehled pro praxi Dokument Sekce chorob s bronchiální obstrukcí Ceské pneumologické a ftizeologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne.

Bronchiectasis is a clinically important, but poorly understood, pulmonary condition characterized by dilated and thick-walled bronchi. Bronchiectasis remains a significant cause of morbidity and mortality around the world. Targeted effort to early high-resolution computed tomography diagnosis and detailed confirmation of causation are in the spotlight of respiratory physicians in the developed countries. The risk population consists of subjects with persistent and/or productive cough, where another clear diagnosis has not been performed. Specific treatment tailored on underlying diseases and non-specific airway clearance techniques are able to improve symptoms, and reduce lung impairment. Evidence-based treatment algorithms for anti-inflammatory, and antibiotic treatment of stable non-CF BE will have to await large-scale, long-term controlled studies. Surgery should be reserved for individuals with highly symptomatic, localized bronchiectasis who have failed medical management. Unfortunately, there have been few well designed longitudinal or cross-sectional studies in the field of bronchiectasis. To give truly meaningful and generalizable results, a longitudinal observational study of bronchiectasis would require to enrol several thousand patients, more than any one center can enrol. The European Bronchiectasis Registry will create an open, pan-European registry of patients with non-CF bronchiectasis. The authors emphatically recommend that all respiratory specialist managed non-CF BE subjects should be actively involved in the European Bronchiectasis Registry.Key words: bronchiectasis - diagnosis - registry - treatment.

NAS agar is more suitable than McKay agar for primary culture of Streptococcus milleri group (SMG) fastidious bacteria, S. intermedius in particular.

Streptococcus milleri group (SMG) is a group of three streptococcal species (S. anginosus, intermedius and constellatus) that act as opportunist pathogens, among others in cystic fibrosis. Due to their fastidious character, they are both difficult to cultivate and to differentiate from less pathogenic streptococcal species, therefore being most probably underdiagnosed. Semi-selective McKay agar and NAS agar were developed to facilitate SMG recovery from clinical samples; however, direct comparison of recovery rates has not been published yet. We tested the performance of both media on 123 patient samples and demonstrated general superiority of NAS agar for SMG recovery during primary cultivation convincingly. This observation was also confirmed by quantitative drop tests during subculture. Despite the undisputed overall superiority of NAS agar over McKay agar, a smaller fraction of strains grew better on McKay agar. Inter-strain differences were the most probable explanation. Therefore, when economic conditions are not limiting and maximum recovery rate is desirable, both plates are advised to be used in parallel for primary cultivation of clinical samples.

McRAPD unlike MALDI-TOF MS is a suitable candidate for routine discrimination of new Haemophilus influenzae strain acquisition in chronic obstructive pulmonary disease (COPD) and cystic fibrosis.

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.

[Prolonged culture in a humid chamber increases the yields of pathogenic bacteria from the respiratory tract samples of patients suffering from cystic fibrosis].

Current standards of care for cystic fibrosis (CF) patients lack unequivocal recommendations concerning the duration of primary culture of bacteriological samples. With the exception of Burkholderia cepacia (5 days), the minimum recommended duration of primary culture varies between 48 and 72 hours. Our aim was to evaluate the effect of an extended 10-day period of primary culture in a humid chamber in samples acquired from the respiratory tract of patients suffering from CF. Compared to standard culture, prolonged culture in a humid chamber yielded 1.85 times more isolates of pathogenic species in pharyngeal swabs (76 versus 41 isolates) and 1.4 times more isolates in sputum samples (116 versus 82), but only 1.14 times more isolates in nasal swabs (25 versus 22). Prolonged culture was most beneficial for Achromobacter spp. (6 versus 0), Stenotrophomonas maltophilia (16 versus 5) and Pseudomonas aeruginosa (69 versus 49), whereas there was little or no benefit at all for Staphylococcus aureus (87 versus 73) and Moraxella catarrhalis (10 versus 10). Therefore, prolonged culture in a humid chamber may definitely be recommended for pharyngeal swabs and sputum samples obtained from patients suffering from CF to achieve the maximum recovery rate of pathogenic bacteria, in particular non-fermenting Gram-negative rods.

The Streptococcus milleri group in chronic obstructive pulmonary disease.

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.

A review of national guidelines for management of COPD in Europe.

The quality of care can be improved by the development and implementation of evidence-based treatment guidelines. Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years. Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process. Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden. The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines. There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia. However, there are differences in the definitions of patient subgroups and other recommended treatments.

Performance of pyrosequencing versus MALDI-TOF MS in bacteria identification in chronic lung disease.

Rapid identification of the etiological agent in bacterial infection is necessary for correct diagnosis and appropriate therapy. In general, identification of pure cultures of bacteria using conventional phenotyping techniques requires 4-24 hours. Recently available new molecular technologies offer the potential of same day species identification once pure culture is available. Our aim was to evaluate the performance of rDNA V1 hypervariable region pyrosequencing, and the whole cell MALDI-TOF MS protein profiling in routine species identification. During the period from June 2012 to June 2014, 1.140 pure culture isolates were recovered from 402 samples from 126 patients suffering cystic fibrosis, chronic obstructive pulmonary disease or bronchiectasis. All the isolates were subjected to species identification by both techniques. Unfortunately, pyrosequencing was able to reach the species level in 43.2% of isolates only, whereas MALDI-TOF was clearly superior with 96.8% respectively. The overall sensitivity values also clearly underlined the superiority of MALDI-TOF MS with 96.8% compared to 85.1% achieved by pyrosequencing. Generally, MALDI-TOF MS turned out to be the best suitable technique in routine bacterial identification, whereas pyrosequencing could be recommended as the method of choice particularly in situations where MALDI-TOF MS fails to identify rare species.

Real-life GOLD 2011 implementation: the management of COPD lacks correct classification and adequate treatment.

Chronic obstructive pulmonary disease (COPD) is a serious, yet preventable and treatable, disease. The success of its treatment relies largely on the proper implementation of recommendations, such as the recently released Global Strategy for Diagnosis, Management, and Prevention of COPD (GOLD 2011, of late December 2011). The primary objective of this study was to examine the extent to which GOLD 2011 is being used correctly among Czech respiratory specialists, in particular with regard to the correct classification of patients. The secondary objective was to explore what effect an erroneous classification has on inadequate use of inhaled corticosteroids (ICS). In order to achieve these goals, a multi-center, cross-sectional study was conducted, consisting of a general questionnaire and patient-specific forms. A subjective classification into the GOLD 2011 categories was examined, and then compared with the objectively computed one. Based on 1,355 patient forms, a discrepancy between the subjective and objective classifications was found in 32.8% of cases. The most common reason for incorrect classification was an error in the assessment of symptoms, which resulted in underestimation in 23.9% of cases, and overestimation in 8.9% of the patients' records examined. The specialists seeing more than 120 patients per month were most likely to misclassify their condition, and were found to have done so in 36.7% of all patients seen. While examining the subjectively driven ICS prescription, it was found that 19.5% of patients received ICS not according to guideline recommendations, while in 12.2% of cases the ICS were omitted, contrary to guideline recommendations. Furthermore, with consideration to the objectively-computed classification, it was discovered that 15.4% of patients received ICS unnecessarily, whereas in 15.8% of cases, ICS were erroneously omitted. It was therefore concluded that Czech specialists tend either to under-prescribe or overuse inhaled corticosteroids.