Aims: Data on differences in clinical characteristics and management of COPD in different countries and settings are limited. We aimed to characterize the profi le of patients with COPD in a number of countries and their treatment in order to evaluate adherence to recommendations of international guidelines. Method: This was an observational, international, cross-sectional study on patients with physician-diagnosed COPD. Demographic and clinical characteristics, risk factors, and treatment were collected by their physician via an internet web-based questionnaire developed for the study. Results: A total of 77 investigators from 17 countries provided data on 833 patients. The countries with the highest number of patients included were: Argentina (128), Ecuador (134), Spain (162), and Hong Kong (153). Overall, 79.3% were men and 81% former smokers, with a mean FEV 1 = 42.7%, ranging from 34.3% in Hong Kong to 58.8% in Ecuador. Patients reported a mean of 1.6 exacerbations the previous year, with this frequency being signifi cantly and negatively correlated with FEV 1 (%) (r = -0.256; p Ͻ 0.0001). Treatment with short-acting bronchodilators and theophyllines was more frequent in Ecuador and Hong Kong compared with Spain and Argentina, and in patients belonging to lower socioeconomic levels (p Ͻ 0.0001 for all comparisons). Inadequacy of treatment with inhaled corticosteroids and theophyllines was high, with signifi cant differences among countries. Conclusions: Differences in the clinical characteristics and management of COPD were signifi cant across countries. Adherence to international guidelines appears to be low. Efforts should be made to disseminate and adapt guidelines to the socioeconomic reality of different settings.

COPD patients who incur higher healthcare resource utilisation show reduced physical activity, increased respiratory failure and increased systemic inflammation.

Nearly one-quarter of the patients with COPD in this study presented clinically significant depression associated with worse quality of life, reduced exercise capacity, greater dyspnea, and a higher score in the BODE index.

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Abstract:Objective: Primary care provides the main route for access to health care for patients with common chronic illnesses such as chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin (AAT) deficiency is an underdiagnosed pathology associated with COPD risk which has a very low prevalence. The Information and Detection of the Deficiency of AAT (IDDEA) project was developed to identify AAT-deficient patients at primary care centres by providing adequate diagnostic tools to family doctors. Methods: Patients with COPD were identified and registered on a specially designed website. Dried blood samples were collected on filter papers and sent to the laboratory for AAT levels and AAT deficiency-related genotype determinations. Results were uploaded to the website and analysed. Results: Between January 2008 and April 2009, 596 patients were identified by 90 participating physicians. The number of patients who did not have AAT deficiency (serum concentrations 60 mg AAT/dl) was 549 (98.9%). Nineteen patients (3.2%) were carriers of the allelic variant Pi*Z among which two were homozygous PiZZ (one of them was an index case) and one was heterozygous PiSZ. These three newly detected cases were registered in the Spanish Registry of Patients with AAT Deficiency. An estimate of the gene frequency of the S allele was 7.65% and the severe deficiency Z allele was 1.76%. Conclusions: Results confirm that ATT deficiency is still underdiagnosed. The IDDEA system appears to be a useful tool for the detection of AAT deficiency in the primary care setting.

The SERPINA1 gene is highly polymorphic, with more than 100 variants described in databases. SERPINA1 encodes the alpha-1 antitrypsin (AAT) protein, and severe deficiency of AAT is a major contributor to pulmonary emphysema and liver diseases. In Spanish patients with AAT deficiency, we identified seven new variants of the SERPINA1 gene involving amino acid substitutions in different exons: PiSDonosti (S+Ser14Phe), PiTijarafe (Ile50Asn), PiSevilla (Ala58Asp), PiCadiz (Glu151Lys), PiTarragona (Phe227Cys), PiPuerto Real (Thr249Ala), and PiValencia (Lys328Glu). We examined the characteristics of these variants and the putative association with the disease. Mutant proteins were overexpressed in HEK293T cells, and AAT expression, polymerization, degradation, and secretion, as well as antielastase activity, were analyzed by periodic acid-Schiff staining, Western blotting, pulse-chase, and elastase inhibition assays. When overexpressed, S+S14F, I50N, A58D, F227C, and T249A variants formed intracellular polymers and did not secrete AAT protein. Both the E151K and K328E variants secreted AAT protein and did not form polymers, although K328E showed intracellular retention and reduced antielastase activity. We conclude that deficient variants may be more frequent than previously thought and that their discovery is possible only by the complete sequencing of the gene and subsequent functional characterization. Better knowledge of SERPINA1 variants would improve diagnosis and management of individuals with AAT deficiency.

Chronic obstructive pulmonary disease (COPD) is frequently associated with chronic heart failure (CHF) or coronary artery disease (CAD). In spite of the recommendation to use beta-blockers (BB) they are likely under-prescribed to patients with concurrent COPD and heart diseases. To find out the prevalence of use of BB, 256 COPD patients were consecutively recruited by pulmonary physicians from 14 hospitals in 7 regions of Spain in their outpatient offices if they had a diagnosis of COPD, were not on long-term oxygen therapy, had CHF or CAD, and met the criteria for BB treatment. In patients with indication 58% (95%CI, 52-64%) of the COPD patients and 97% of the non-COPD patients were on BB (p < 0.001). In patients with COPD, several factors were independently related to at least one visit to the emergency room in the previous year such as use of BB, adjusted OR = 0.27 (95% CI 0.15-0.50), GOLD stage D, OR = 2.52 (1.40-4.53), baseline heart rate >70, OR 2.19 (1.24-3.86) use of long-acting beta2-agonists OR = 2.18 (1.29-3.68), previous episodes of left ventricular failure OR 2.27 (1.19-4.33) and diabetes, OR = 1.82 (1.08-3.38). We conclude that, according to what is recommended by current guidelines, BB are still under-prescribed in COPD patients. COPD patients with CHF or CAD using BB suffer fewer exacerbations and visits to the ER. GOLD stage, use of long-acting beta2-agonists, baseline heart rate and comorbidities are also risk factors for exacerbations in this population.

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