Vladimir Koblizek

Pharmacological strategies to reduce exacerbation risk in COPD: a narrative review

Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge. Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype. Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype. Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA). For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype. Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents. For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered. In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.

European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency

α1-antitrypsin deficiency (AATD) is the most common hereditary disorder in adults. It is associated with an increased risk of developing pulmonary emphysema and liver disease. The pulmonary emphysema in AATD is strongly linked to smoking, but even a proportion of never-smokers develop progressive lung disease. A large proportion of individuals affected remain undiagnosed and therefore without access to appropriate care and treatment. The most recent international statement on AATD was published by the American Thoracic Society and the European Respiratory Society in 2003. Since then there has been a continuous development of novel, more accurate and less expensive genetic diagnostic methods. Furthermore, new outcome parameters have been developed and validated for use in clinical trials and a new series of observational and randomised clinical trials have provided more evidence concerning the efficacy and safety of augmentation therapy, the only specific treatment available for the pulmonary disease associated with AATD. As AATD is a rare disease, it is crucial to organise national and international registries and collect information prospectively about the natural history of the disease. Management of AATD patients must be supervised by national or regional expert centres and inequalities in access to therapies across Europe should be addressed. Description of the best practice in diagnosis and treatment of pulmonary disease in alpha-1 antitrypsin deficiency http://ow.ly/fD3S30fuy4H

Cytomegalovirus disease in patients with common variable immunodeficiency: three case reports.

Common variable immunodeficiency (CVID) is the most frequent clinically relevant primary immunodeficiency and shows enormous heterogeneity in clinical presentation. Despite clinical immunodeficiency, opportunistic infections are not a typical manifestation of CVID. A retrospective study of 32 patients followed up for 335 patient-years was performed to determine the frequency of cytomegalovirus (CMV) disease. Symptomatic CMV infection was documented in 3 CVID patients. Patients No. 1 and 2 suffered from CMV pneumonia, with complications due to atypical mycobacteriosis in patient No. 1. Patient No. 3 suffered from CMV enteritis. A history of cancer and chronic hepatitis C infection (patient No. 1), immunosuppressive therapy for interstitial lung disease (patient No. 2) and serious enteropathy complicated with malnutrition (patient No. 3) may have contributed to the complications despite only mild abnormalities in T-cell subpopulations. The direct detection of CMV in bronchoalveolar lavage, stool or tissue samples was the most beneficial diagnostic laboratory method, whereas the detection of CMV DNA in blood did not produce positive results. Adequate treatment of CMV disease led to significant clinical improvement in all 3 patients. The frequency of CMV disease appears to be higher than previously described. In our experience, the probability of opportunistic infections in CVID patients increases with secondary comorbidities and their management.

Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region. Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment. 3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma–COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma–COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes. The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes. Distinct phenotypes of COPD in Central and Eastern Europe have differences in symptoms, comorbidities and treatment http://ow.ly/oMZI307ndr5

Skinfold Anthropometry –The Accurate Method for Fat Free Mass Measurement in COPD

Abstract Purpose: Fat free mass index (FFMI) is an independent predictor of metabolic and functional consequences in COPD. For its measurement dual energy X-ray absorptiometry (DEXA), skin-fold anthropometry (SFA), bioelectrical impedance analysis (BIA) and bioimpedance spectroscopy (BIS) are used in clinical practice. The aim of our pilot study was to analyse precisely and critically which method is most accurate and available for common use in clinical practice for measurement of FFM by assessment against relevant DEXA in patients with COPD. Methods: This was an observational cross-sectional study of consecutive COPD subjects. FFM by methods of SFA, two versions of BIA, and BIS was compared with that from clinically relevant DEXA in 41 outpatients (mean age 66.5 ± 7.7 yrs) with stable COPD, 34 men and 7 women, with mean BMI 28.2 ± 6.1 kg.m−2. Results: All methods underestimate FFM in comparison with DEXA. In the general evaluation non-significant differences with the smallest mean bias were demonstrated for SFA (1.2 kg) and BIA (3.8 kg), but there was a difference of more than 9 kg using BIS and BIA COPD methods (p < 0.0001). The best agreement between DEXA and SFA was demonstrated via Lins concordance coefficient and Bland–Altman test. Conclusions: SFA has been demonstrated as an accurate, available and cheap method for determination of FFM and FM with application of the Durnin Womersley equation for body density and with the Siri equation for FM in patients with COPD. SFA can be easily applied in routine clinical practice.

Diagnosing COPD: advances in training and practice – a systematic review

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung syndrome, caused by long-term inhalation of noxious gases and particles, which leads to gradual airflow limitation. All health care professionals who care for COPD patients should have full access to high-quality spirometry testing, as postbronchodilator spirometry constitutes the principal method of COPD diagnosis. One out of four smokers 45 years or older presenting respiratory symptoms in primary care, have non-fully reversible airflow limitation compatible with COPD and are mostly without a known diagnosis. Approximately 50.0%–98.3% of patients are undiagnosed worldwide. The majority of undiagnosed COPD patients are isolated at home, are in nursing or senior-assisted living facilities, or are present in oncology and cardiology clinics as patients with lung cancers and coronary artery disease. At this time, the prevalence and mortality of COPD subjects is increasing, rapidly among women who are more susceptible to risk factors. Since effective management strategies are currently available for all phenotypes of COPD, correctly performed and well-interpreted postbronchodilator spirometry is still an essential component of all approaches used. Simple educational training can substantially improve physicians’ knowledge relating to COPD diagnosis. Similarly, a physician inhaler education program can improve attitudes toward inhaler teaching and facilitate its implementation in routine clinical practices. Spirometry combined with inhaled technique education improves the ability of predominantly nonrespiratory physicians to correctly diagnose COPD, to adequately assess its severity, and to increase the percentage of correct COPD treatment used in a real-life setting.

POPE study: rationale and methodology of a study to phenotype patients with COPD in Central and Eastern Europe

Introduction Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries. However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown. This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE. Methods/design The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE. Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks. Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded. The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494. Outcomes The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications. Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries. Conclusion There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD. The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE.

GOLD 2017 on the way to a phenotypic approach? Analysis from the Phenotypes of COPD in Central and Eastern Europe (POPE) Cohort

Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) released a revised consensus report (2017 GOLD Report) [1] in which the formerly defined ABCD classification of patients with COPD has been refined. The 2011 GOLD Report and its 2016 Update classified patients on the basis of three variables, i.e. the symptom burden, lung function impairment and exacerbations [2], now the A–D groups are defined solely on the basis of symptoms and history of exacerbations – thus recognising the limitations of the forced expiratory volume in 1 s (FEV1) in influencing therapeutic decisions in COPD [1]. The obvious consequence of the new classification is a shift of a proportion of patients from the C to the A group, and from the D to the B group. Nevertheless, the magnitude of such redistribution remains unknown. The distribution of patients based on exacerbations solely is the most profound consequence of the 2017 GOLD Report http://ow.ly/4UJa309fLbM

Nasal symptomatology, obstruction, and paranasal sinus opacity in patients with chronic obstructive pulmonary disease

Abstract Conclusion: Patients with chronic obstructive pulmonary disease (COPD) more frequently suffer from nasal symptoms as well as upper respiratory tract obstruction compared with the healthy population. Objective: The relationship between chronic rhinosinusitis and bronchial asthma has been studied in detail in the past. In recent years, a limited number of authors have also studied involvement of the nose and paranasal sinuses in patients with COPD. Methods: This was an observational cross-sectional study with subsequent prospective assessment; 42 patients with COPD were included. The control group consisted of 12 healthy subjects. All patients with a history of rhinitis or rhinosinusitis and patients with previous surgery of the nose and sinuses were excluded from the study. Clinical variables evaluated were nasal symptoms (SNAQ-11 questionnaire), nasal endoscopy, nasal patency (active rhinomanometry), and computed tomography of paranasal sinuses. Results: In the COPD group, there was a higher occurrence of nasal symptoms and pathological findings on nasal endoscopy compared with the control group. The overall nasal airflow was higher in the control group (compared with COPD patients) and the overall nasal resistance was higher in the COPD group (compared with controls). Pathological opacity of one or more sinuses was confirmed in 38% of COPD patients.

Hand grip endurance test relates to clinical state and prognosis in COPD patients better than 6-minute walk test distance

Purpose Patients with COPD present peripheral muscle dysfunction and atrophy, expressed as muscle strength and endurance reduction. The goal of this study was direct dynamometric assessment of hand grip endurance and strength in relation to the stage of disease, multidimensional predictors of mortality, and 6-minute walk test (6MWT). To the best of our knowledge, there has been no previous study determining these parameters. Patients and methods In this observational study, 58 consecutive outpatients with stable COPD and 25 volunteers without respiratory problems were compared. All COPD subjects underwent a comprehensive examination to determine COPD severity, prognostic scales, and 6MWT. Body composition, basic spirometric parameters, and hand grip strength and endurance were determined in all study participants. Results Patients in the COPD group had a 15% decrease in maximum strength (P=0.012) and a 28% decrease in area under the force/time curve (AUC) of the endurance test (P<0.001) compared to the control group. Dynamometric parameters were significantly negatively associated with the stage of disease and values of multivariable prediction indexes, and positively associated with the results of 6MWT. In most cases, closer associations were found with AUC than with 6MWT and in the gender-specific groups. Conclusion Both hand grip strength and endurance are impaired in COPD patients in comparison with the control group. In particular, AUC could be considered as an attractive option not only to assess exercise capacity but also as a predictive marker with a better prognostic value than 6MWT in COPD patients. This is the first study to observe the dependence of hand grip endurance on combined COPD assessment.