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Victoria Federico Paly,1 Laura Amanda Vallejo-Aparicio,2 Alan Martin,3 José Luis Izquierdo,4 Juan Antonio Riesco,5 Juan José Soler-Cataluña,6 Catarina Abreu,7 Chandroday Biswas,8 Afisi S Ismaila9,10 1ICON plc, Philadelphia, PA, USA; 2GSK, Madrid, Spain; 3GSK, Brentford, UK; 4Hospital Universitario de Guadalajara, Guadalajara, Spain; 5Hospital San Pedro de Alcántara, Cáceres, Spain; 6Hospital Arnau de Vilanova, Valencia, Spain; 7ICON Plc, New York, NY, USA; 8ICON Plc, Bengaluru, Karnataka, India; 9Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 10Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, CanadaCorrespondence: Afisi S Ismaila, Value Evidence and Outcomes, GSK, 1250 South Collegeville Road, Collegeville, PA, 19426-0989, USA, Tel +1 919 315 8229, Email afisi.s.ismaila@gsk.comPurpose: Given between-country differences in healthcare systems, treatment costs, and disease management guidelines, country-specific cost-effectiveness analyses are important. This study evaluated the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI among patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations from a Spanish healthcare system perspective.Patients and Methods: Baseline data and treatment effects from the IMPACT trial were populated into the validated GALAXY COPD progression model. Utilities were estimated using Spanish observational data. Direct healthcare costs (2019 €) were informed by Spanish public sources. A 3% discount rate for costs and benefits was applied. The time horizon and treatment duration were 3 years (base case). One-way sensitivity, scenario, and probabilistic sensitivity analyses were performed.Results: FF/UMEC/VI treatment resulted in fewer exacerbations over 3 years (4.130 vs 3.648) versus FF/VI, with a mean (95% confidence interval [CI]) incremental cost of € 444 (€ 149, € 713) per patient and benefit of 0.064 (0.053, 0.076) quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of € 6887 per QALY gained. FF/UMEC/VI was a dominant treatment strategy versus UMEC/VI, resulting in fewer exacerbations (4.130 vs 3.360), with a mean (95% CI) incremental cost of –€ 450 (–€ 844, –€ 149) and benefit of 0.054 (0.043, 0.064) QALYs. FF/UMEC/VI was cost-effective versus FF/VI and UMEC/VI across all analyses.Conclusion: FF/UMEC/VI was predicted to be a cost-effective treatment option versus FF/VI or UMEC/VI in symptomatic COPD patients at risk of exacerbations in Spain, across all scenarios and sensitivity analyses.Keywords: chronic obstructive pulmonary disease, cost-effectiveness, single-inhaler triple therapy, Spain, triple inhaled therapy

Objective The aim of this study was to evaluate the quality of diagnosis and treatment of COPD using Big Data methodology on the Savana Manager 2.1 clinical platform. Materials and methods A total of 59,369 patients with a diagnosis of COPD were included from a population of 1,219,749 adults over 40 years of age. Results In total, 78% were men. Spirometry data were available for only 26,453 (43.5%) subjects. Disease severity was classified in 18,172 patients: 4396 mild, 7100 moderate, and 6676 severe, although only 27%, 34%, and 28%, respectively, presented obstructive spirometry. The clinical management of COPD is mainly the responsibility of the primary care and pulmonology departments, while internal medicine and, to a lesser extent, geriatrics also participate. Drug treatment was based on bronchodilators and inhaled corticosteroids (ICS). A marked decline in the use of long-acting beta-2 agonists (LABA) in monotherapy and a slight reduction in ICS/LABA combinations, associated with a long-acting anticholinergic (LAMA) in 74% of cases, were observed. All-cause in-hospital mortality among the overall population was 5.6% compared to 1% of the general population older than 40 years. In total, 35% were admitted to hospital, with an average stay of 6.6 days and an in-hospital mortality rate in this group of 10.74%. Discussion This study identifies the main features of an unselected COPD population and the main errors made in the management of the disease.

Asma eosinofílica greu; Comparació indirecta del tractament; Mepolizumab Severe eosinophilic asthma; Indirect treatment comparison; Mepolizumab Asma eosinofílica severa; Comparación de tratamiento indirecto; Mepolizumab Aim To analyse the cost-effectiveness of MEP with standard of care (SoC) versus other anti-IL-5 therapies approved for the treatment of severe eosinophilic asthma (SEA) patients, within the Spanish National Health System (NHS) perspective. Methods A Markov model with a 4-week cycle length was used to compare MEP with BEN and RES as therapies added to SoC in the management of SEA, in terms of cost per QALY gained and incremental cost-effectiveness ratio (ICER). Costs (€2019) were obtained from public sources, while utilities and transition probabilities were retrieved from literature, e.g. network meta-analysis. Continuation criteria for biological treatment and reduction of oral corticosteroids (OCS) was set at 50% minimum reduction of exacerbation rate. Adverse events related to chronic OCS use included diabetes, osteoporosis, cataracts, acute myocardial infarct, and peptic ulcer. The analysis was performed over a 5-year time horizon from the National Healthcare System (NHCS) perspective, with a yearly discount rate of 3% applied to both costs and QALYs. Probabilistic sensitivity analysis and univariate deterministic sensitivity analysis were performed to address uncertainty around the cost-effectiveness results. Results On top of SoC, the model indicates that MEP is dominant (lower cost, higher benefit) compared to BEN and RES: For BEN and RES, respectively, treatment with MEP had a point estimate of 0.076 and 0.075 additional QALYs, and savings of €3,173.47 and €7,772.95 per patient. The findings were robust to variation as estimated using sensitivity analysis. Conclusions MEP is a cost-effective treatment in comparison with BEN and RES added to SoC for patients with SEA in the Spanish setting. This study was funded by GlaxoSmithKline [Study code: HO-19-19968].

Melanie Schroeder,1 Nicole Benjamin,2 Laura Atienza,3 Chandroday Biswas,4 Alan Martin,5 John D Whalen,6 José Luis Izquierdo Alonso,7 Juan Antonio Riesco Miranda,8 Juan José Soler-Cataluña,9 Alicia Huerta,3 Afisi S Ismaila10,11 1Value Evidence and Outcomes, GlaxoSmithKline plc., Brentford, UK; 2Global Health Economics, ICON plc., Boston, MA, USA; 3Market Access, GlaxoSmithKline SA, Madrid, Spain; 4Global Health Economics, ICON plc., Bengaluru, Karnataka, India; 5Value Evidence and Outcomes, GlaxoSmithKline plc., Uxbridge, UK; 6Global Health Economics, ICON plc., Abingdon, UK; 7Pneumology, Hospital Universitario de Guadalajara, Guadalajara, Spain; 8Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Servicio de Neumología, Hospital San Pedro de Alcántara, Cáceres, Spain; 9Pneumology Department, Hospital Arnau de Vilanova-Lliria (Valencia), Valencia, Spain; 10Value Evidence and Outcomes, GlaxoSmithKline plc., Collegeville, PA, USA; 11Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Afisi S IsmailaGlaxoSmithKline Plc., 1250 South Collegeville Road, Collegeville, PA 19426-0989, USATel +1 (919) 315 8229Email afisi.s.ismaila@gsk.comPurpose: To evaluate the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) vs twice-daily budesonide/formoterol (BUD/FOR) in patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations, from the Spanish National Healthcare System perspective.Patients and Methods: The validated GALAXY-COPD model was used to simulate disease progression and predict healthcare costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) over a 3-year time horizon for a Spanish population. Patient characteristics from published literature were supplemented by data from FULFIL (NCT02345161), which compared FF/UMEC/VI vs BUD/FOR in patients with symptomatic COPD at risk of exacerbations. Treatment effects, extrapolated to 3 years, were based on Week 24 results in the FULFIL intent-to-treat population, including change in forced expiratory volume in 1 second, St. George’s Respiratory Questionnaire score, and exacerbation rates. Treatment, exacerbations, and COPD management costs (2019€) were informed by Spanish public sources and published literature. A 3% discount rate for costs and benefits was applied. One-way sensitivity and scenario analyses, and probabilistic sensitivity analysis (PSA), were performed.Results: FF/UMEC/VI treatment led to fewer moderate and severe exacerbations (2.126 and 0.306, respectively) vs BUD/FOR (2.608 and 0.515, respectively), with a mean incremental cost of € 69 and gain of 0.107 QALYs, which resulted in an ICER of € 642 per QALY gained. In sensitivity analyses, the ICER was most sensitive to treatment effect variations in exacerbations and healthcare resource utilization/event costs. Overall, 95% of 1000 PSA simulations resulted in an ICER less than € 11,000 per QALY gained for FF/UMEC/VI vs BUD/FOR, confirming robustness of the results. The probability of FF/UMEC/VI being cost-effective vs BUD/FOR was 100% at a willingness-to-pay threshold of € 30,000 per QALY gained.Conclusion: At the accepted Spanish ICER threshold of € 30,000, FF/UMEC/VI represents a cost-effective treatment option vs BUD/FOR in patients with symptomatic COPD at risk of exacerbations.Keywords: cost-utility analysis, health-related quality of life, incremental cost-effectiveness ratio, fluticasone furoate, vilanterol, umeclidinium

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19) and can be associated with serious complications, including acute respiratory distress syndrome. This condition is accompanied by a massive release of cytokines, also denominated cytokine storm, development of systemic oxidative stress and a prothrombotic state. In this context, it has been proposed a role for acetylcysteine (NAC) in the management of patients with COVID-19. NAC is a molecule classically known for its mucolytic effect, but it also has direct and indirect antioxidant activity as a precursor of reduced glutathione. Other effects of NAC have also been described, such as modulating the immune and inflammatory response, counteracting the thrombotic state, and having an antiviral effect. The pharmacological activities of NAC and its effects on the mechanisms of disease progression make it a potential therapeutic agent for COVID-19. NAC is safe, tolerable, affordable, and easily available. Moreover, the antioxidant effects of the molecule may even prevent infection and play an important role as a complement to vaccination. Although the clinical efficacy and dosing regimens of NAC have been evaluated in the clinical setting with small series of patients, the results are promising. In this article, we review the pathogenesis of SARS-CoV-2 infection and the current knowledge of the mechanisms of action of NAC across disease stages. We also propose NAC posology strategies to manage COVID-19 patients in different clinical scenarios.

On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Till now, it affected 452.4 million (Spain, 11.18 million) persons all over the world with a total of 6.04 million of deaths (Spain, 100,992). It is observed that 75% of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. It was shown that people with underlying chronic illnesses are more likely to get it and grow seriously ill. Individuals with COVID-19 who have a past medical history of cardiovascular disorder, cancer, obesity, chronic lung disease, diabetes, or neurological disease had the worst prognosis and are more likely to develop acute respiratory distress syndrome or pneumonia. COVID-19 can affect the respiratory system in a variety of ways and across a spectrum of levels of disease severity, depending on a person's immune system, age and comorbidities. Symptoms can range from mild, such as cough, shortness of breath and fever, to critical disease, including respiratory failure, shock and multi-organ system failure. So, COVID-19 infection can cause overall worsening of these previous respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc. This review aims to provide information on the impact of the COVID-19 disease on pre-existing lung comorbidities.

Infection by SARS-CoV-2 causing coronavirus disease 2019 (COVID-19) can be associated with serious and life-threatening conditions, including acute respiratory distress syndrome (ARDS). Severity and mortality have been related to a cytokine storm, an imbalance of oxidative stress, and a pro-thrombotic state. We conducted an observational retrospective cohort study from a community-based large population of hospitalized COVID-19 PCR + patients admitted from March 01, 2020, to January 24, 2021, with integrated primary to tertiary care information in Castilla la Mancha, Spain. We explored the potential benefits of the antioxidant, anti-inflammatory and anti-thrombotic drug N-acetylcysteine (NAC) administered orally in high doses (600 mg every 8 h), added to standard of care in COVID-19 patients by using the free text information contained in their electronic health records (EHRs). Out of 19,208 patients with a diagnosis of COVID-19 hospitalized, we studied 2071 (10.8%) users of oral NAC at high doses. COVID-19 patients treated with NAC were older, predominantly male, and with more comorbidities such as hypertension, dyslipidemia, diabetes, and COPD when compared with those not on NAC (all p

Chronic obstructive pulmonary disease (COPD) is a public health problem due to its high prevalence (11% in the adult population in Spain), increasing incidence, and great social and economic impact. Despite this, it is underdiagnosed (and, therefore, undertreated) at a rate of around 80%. In this paper, a group of respiratory physicians specializing in COPD discuss 7 fundamental problems ("cardinal sins") that contribute to this situation, with the explicit aim of proposing specific solutions that may help to improve this unfavorable state of affairs.

Background: The impact of sex and gender in the incidence and severity of coronavirus disease 2019 (COVID-19) remains controversial. Here, we aim to describe the characteristics of COVID-19 patients at disease onset, with special focus on the diagnosis and management of female patients with COVID-19. Methods: We explored the unstructured free text in the electronic health records (EHRs) within the SESCAM Healthcare Network (Castilla La-Mancha, Spain). The study sample comprised the entire population with available EHRs (1,446,452 patients) from January 1st to May 1st, 2020. We extracted patients' clinical information upon diagnosis, progression, and outcome for all COVID-19 cases. Results: A total of 4,780 patients with a confirmed diagnosis of COVID-19 were identified. Of these, 2,443 (51%) were female, who were on average 1.5 years younger than male patients (61.7 ± 19.4 vs. 63.3 ± 18.3, p = 0.0025). There were more female COVID-19 cases in the 15-59-year-old interval, with the greatest sex ratio (95% confidence interval) observed in the 30-39-year-old range (1.69; 1.35-2.11). Upon diagnosis, headache, anosmia, and ageusia were significantly more frequent in females than males. Imaging by chest X-ray or blood tests were performed less frequently in females (65.5% vs. 78.3% and 49.5% vs. 63.7%, respectively), all p < 0.001. Regarding hospital resource use, females showed less frequency of hospitalization (44.3% vs. 62.0%) and intensive care unit admission (2.8% vs. 6.3%) than males, all p < 0.001. Conclusion: Our results indicate important sex-dependent differences in the diagnosis, clinical manifestation, and treatment of patients with COVID-19. These results warrant further research to identify and close the gender gap in the ongoing pandemic.

ObjectivesThe aim is to systematically describe the findings of lung ultrasound in patients with COVID-19 pneumonia and to analyze its prognostic value.MethodsLung ultrasound was performed to 63 patients with COVID-19 pneumonia admitted to a University Hospital. Lung involvement was evaluated using a 4-point scale with a 12-area pulmonary division (lung score -LS-). Ultrasound findings, along with clinical characteristics, were recorded.ResultsAll patients showed ultrasound involvement in at least 1 area (mean 8 ± 3.5). Total LS was 15.3 ± 8.1, without differences between left and right lung. Most affected regions were the lower one (95.2%) and the posterior one (73.8%). Total LS showed a strong correlation (r = -0.765) with PaO2/FiO2; by lung regions, those with a higher correlation were the LS of the anterior one (r = -0.823) and the LS of the upper one (r = -0.731). 22.2% of patients required non-invasive respiratory support (NIRS). Multivariate analysis shows that anterior region LS, adjusted for age and sex, is significant (odds ratio 2.159, 95% confidence interval 1.309 to 3.561) for the risk of requiring NIRS. Anterior region LS ≥ 4 and total LS ≥19 have similar characteristics to predict the need for NIRS.ConclusionsUltrasound involvement in COVID-19 pneumonia is bilateral and heterogeneous. Most affected regions are the posterior and the lower ones. The anterior region has prognostic value, because its involvement strongly correlates with the risk of requiring NIRS, and an anterior region LS ≥ 4 has high sensitivity and specificity for predicting the need for NIRS.

COPD is often not diagnosed, or is diagnosed too late. It is time for a change that anticipates both diagnosis and treatment.https://bit.ly/2BrDSv1

Background: The use of inhaled corticosteroids (ICS) in combination with bronchodilators in patients with COPD has been shown to decrease the rate of disease exacerbations and to improve the lung function and patients' quality of life. However, their use has also been associated with an increased risk of pneumonia. Materials and methods: We have reviewed existing clinical evidence on the risks and benefits of ICS in COPD, including large randomized clinical trials, meta-analyses, and clinical reviews. Results: A large body of evidence supports the clinical benefits of ICS in patients with COPD in terms of exacerbations, symptoms, lung function, and quality of life. The incidence of adverse events related to ICS, including pneumonia, varies strongly among the studies and seems to be dose dependent, with recent well-designed, large studies on low-dose ICS reporting similar safety profiles in ICS and non-ICS groups. Conclusion: The benefits of ICS in COPD continue to outweigh the risks, especially when lower ICS doses are employed. Given that the data on ICS withdrawal in COPD are scarce and conflicting, we argue that using reduced doses of ICS could be an optimal strategy to manage patients with COPD., Jose Luis Izquierdo reports speaker fees, travel grants, and advisory board fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Chiesi, Glaxo Smith Kline, Menarini, Novartis, Pfizer, Sandoz, and Teva. Borja G. Cosio reports speaker fees, travel grants, and advisory board fees from AstraZeneca, Boehringer-Ingelheim, Chiesi, Menarini, Mundipharma, Novartis, Sanofi, and Teva.

[EN] The wide diversity of irrigation water sources (i.e., drinking water, groundwater, reservoir water, river water) includes reclaimed water as a requested measure for increasing water availability, but it is also a challenge as pathogen exposure may increase. This study evaluates the level of microbial contamination in different irrigation waters to improve the knowledge and analyses management measures for safety irrigation. Over a one-year period, the occurrence of a set of viruses, bacteria and protozoa, was quantified and the performance of a wetland system, producing reclaimed water intended for irrigation, was characterized. Human fecal pollution (HAdV) was found in most of the irrigation water types analysed. Hepatitis E virus (HEV), an emerging zoonotic pathogen, was present in groundwater where porcine contamination was identified (PAdV). The skin-carcinoma associated Merkel cell polyomavirus (MCPyV), was found occasionally in river water. Noroviruses were detected, as expected, in winter, in river water and reclaimed water. Groundwater, river water and reservoir water also harboured potential bacterial pathogens, like Helicobacter pylori, Legionella spp. and Aeromonas spp. that could be internalized and viable inside amoebas like Acanthamoeba castellanii, which was also detected. Neither Giardia cysts, nor any Cryptosporidium oocysts were detected. The wetland system removed 3 Log(10) of viruses and 5 Log(10) of bacteria, which resembled the river water quality. Irrigation waters were prone to variable contamination levels and according to the European guidance documents, the E. coli (EC) levels were not always acceptable. Sporadic detection of viral pathogens as NoV GII and HAdV was identified in water samples presenting lower EC than the established limit (100MNP/100 mL). When dealing with reclaimed water as a source of irrigation the analysis of some viral parameters, like HAdV during the peak irrigation period (summer and spring) or NoV during the coldest months, could complement existing water management tools based on bacterial indicators., Thiswork was partially funded by a grant fromthe Spanish Ministry of Economy and Competitiveness (MINECO) in the frame of the collaborative international consortium JPIW2013-095-C03-01, JPIW2013095-C03-02 and JPIW2013-095-C03-03 of the Water Challenges for a Changing World Joint Programming Initiative (Water JPI) Pilot Call and partially by AGL2017-86797-C2-1-R. Silvia Bofill-Mas is a SerraHunter fellow at the University of Barcelona. Special thanks to E. Fores, E. Anfruns, and X. Romero from Granollers city council, for the valuable information and help during the sampling campaign.

PURPOSE Diabetes mellitus (DM) is associated with long-term cardiovascular complications, including ischemic heart disease (IHD). Nonetheless, DM may directly impair myocardial and lung structure and function. The aim of this study was to assess the impact of type 2 DM (T2DM) and glycemic control on cardiopulmonary exercise capacity in patients with IHD. METHODS The study involved a cross-sectional analysis of 91 consecutive patients (57 ± 10 yr, 90% men) who underwent a cardiopulmonary exercise test at the beginning of an exercise-based standard phase-II cardiac rehabilitation program, 2 to 3 mo after an acute coronary syndrome. Association of T2DM with cardiopulmonary exercise test parameters was assessed using multiple linear regression analysis controlling for prespecified potential confounders. RESULTS There were 26 (29%) diabetic subjects among IHD patients included in the study. After adjustment, T2DM was an independent predictor of a reduced peak oxygen uptake ((Equation is included in full-text article.)O2peak) (P = .005), a reduced pulse O2 trajectory (P = .001), a steeper minute ventilation to carbon dioxide output (VE/(Equation is included in full-text article.)CO2) slope (P = .046), and an increased dead space-to-tidal volume ratio (VD/VT) at peak exercise (P = .049). Glycated hemoglobin (HbA1c) levels were significantly associated with a reduced forced expiratory volume in the first second of expiration (FEV1) (P = .013), VE (P = .001), and VT (P = .007). (Equation is included in full-text article.)O2peak (P trend < .001), (Equation is included in full-text article.)O2 at anaerobic threshold (P trend < .001), and pulse O2 trajectory (P trend < .001) decreased among HbA1c tertiles. CONCLUSIONS Patients with IHD and a previous diagnosis of T2DM had a reduced aerobic capacity and a ventilation- perfusion mismatch compared with nondiabetic patients. Poor glycemic control in men further deteriorates aerobic capacity probably due to ventilatory inefficiency.

Objective: To describe an evidence- and experience-based expert consensus on the most relevant issues of patients with COPD exacerbations. Methods: The Delphi technique was used. Evidence was reviewed by a scientific committee and 60 experts. A questionnaire was prepared containing 3 sections: diagnosis of the exacerbator; treatment, and healthcare processes. The survey was answered in 2 rounds by 60 pneumologists on an online platform. Statements were scored on a Likert scale from 1 (total disagreement) to 9 (total agreement). Agreement and disagreement were defined as a score of 7-9 or 1-3, respectively, given by more than two thirds of the participants. Results: A total of 48 statements were included, one of which was added in the second round. Consensus was reached in 37 items (78.7%) after the first round (agreement), and in 43 (89.5%) after the second round (42 agreement, 1 disagreement). The statements with the highest proportion of experts agreeing were as follows: in exacerbators, chronic bronchial infection favors lung function decline (93.1%); long-acting bronchodilators should not be withdrawn (93.1%); treatment must be personalized if new exacerbations occur despite optimal bronchodilator treatment (96.6%); management must be coordinated between primary care and the respiratory medicine department (93.1%), and patients must be followed up in specific integrated multicomponent programs (94.8%). Conclusions: The findings of this study could assist in the diagnosis and treatment of COPD exacerbators in our area. (C) 2019 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.

Inhalable medications for patients with asthma and chronic obstructive pulmonary disease (COPD) can be confusing even for health care professionals because of the multitude of available devices each with different operating principles. Dry powder inhalers (DPI) are a valuable option for almost all of the patients with asthma or COPD. Based on recorded patient inspiratory profiles, the peak inspiratory flow requirement of 30 L min−1 of high-resistance devices does not usually pose any practical limitations for the patients. Suboptimal adherence and errors in device handling are common and require continuous checking and patient education in order to avoid these pitfalls of all inhalation therapy. The aim of this opinion paper is to describe the working principles of DPIs and to summarise their key properties in order to help prescribing the correct inhaler for each patient. Funding: Orion Pharma.

The main complaint of patients with chronic obstructive pulmonary disease (COPD) is shortness of breath with exercise, that is usually progressive. The principal mechanism that explains this symptom is the development of lung hyperinflation (LH) which is defined by an increase of functional residual capacity (FRC) above predicted values. Patients with COPD may develop static LH (sLH) because of destruction of pulmonary parenchyma and loss of elastic recoil. In addition, dynamic LH (dLH) develops when patients with COPD breathe in before achieving a full exhalation and, as a consequence, air is trapped within the lungs with each further breath. Dynamic LH may also occur at rest but it becomes clinically relevant during exercise and exacerbation. Lung hyperinflation may have an impact beyond the lungs and the effects of LH on cardiovascular function have been extensively analysed. The importance of LH makes its identification and measurement crucial. The demonstration of LH in COPD leads to the adoption of strategies to minimise its impact on the daily activities of patients. Several strategies reduce the impact of LH; the use of long-acting bronchodilators has been shown to reduce LH and improve exercise capacity. Non pharmacologic interventions have also been demonstrated to be useful. This article describes the pathophysiology of LH, its impact on the lungs and beyond and reviews the strategies that improve LH in COPD.

[Introduction] The objective of this study was to analyze the clinical characteristics of COPD patients attending general respiratory clinics, adherence to clinical guidelines, classification accuracy, and therapeutic management., [Method] Multicenter, cross-sectional study, with the primary objective of describing the number, intensity, and variability of symptoms in COPD patients. Data were collected in 2015 by 300 pulmonologists who evaluated a total of 3,010 patients, of which 2,669 (88.6%) were eligible for analysis., [Results] A total of 22% were active smokers, notably 21% and 17% of GOLD groups C and D, and 17% and 19% of exacerbators in the GesEPOC classification; 62.3% had associated comorbidities. The diagnostic process was characterized by limited use of tests such as diffusion capacity or lung volumes, even in the more severe GOLD groups or the GesEPOC exacerbator phenotypes. The use of multidimensional scales, such as BODE (12%), and specific rehabilitation protocols was also rare. Treatment was based on different combinations of bronchodilators and inhaled corticosteroids. Methylxanthines were used in very few patients (7%)., [Conclusions] A large proportion of COPD patients seen in respiratory clinics have non-complex disease and pulmonology tests are rarely performed. Our study confirms a slight change in treatments and the frequent association with comorbidities that can modify the clinical presentation of the patient., [ntroducción] El objetivo de este estudio ha sido analizar las características clínicas de los pacientes con EPOC vistos en las consultas generales de neumología, el seguimiento de las guías clínicas y la adecuación en la categorización y en el manejo terapéutico., [Método] Estudio multicéntrico, transversal, cuyo objetivo primario es describir el número, intensidad y variabilidad de los síntomas en los pacientes con EPOC. La recogida de los datos fue realizada en 2015 por 300 neumólogos que evaluaron un total de 3.010 pacientes, de los cuales 2.669 (88,6%) fueron válidos para el análisis., [Resultados] El 22% eran fumadores activos, destacando un 21 y 17% en los grupos C y D de GOLD y un 17 y 19% en los pacientes exacerbadores de GesEPOC. El 62,3% presentaba comorbilidades asociadas. En el proceso diagnóstico destaca el bajo uso de pruebas como el test de difusión o la medición de volúmenes pulmonares, incluso en los grupos más graves de GOLD o en los fenotipos exacerbadores de GesEPOC. También es minoritario el uso de escalas multidimensionales como BODE (12%) o programas específicos de rehabilitación. El tratamiento se basa en el uso de broncodilatadores y corticoides inhalados, en diferentes combinaciones. El uso de metilxantinas fue minoritario (7%)., [Conclusiones] En consultas de neumología existe una elevada proporción de pacientes EPOC con baja complejidad y un escaso uso de pruebas neumológicas. Se constata un leve cambio en las pautas terapéuticas y la frecuente asociación con comorbilidades que pueden modificar la presentación clínica del paciente.

Asthma-COPD ovelap (ACO) is an umbrella term that encompasses patients with COPD and eosinophilic inflammation (e-COPD) and smoking asthmatics with non-fully reversible airflow obstruction (SA). We compared the clinical characteristics and the inflammatory profile of e-COPD and SA. Patients classified as e-COPD were older and more often male and showed significantly impaired pulmonary function (likely explained by a heavier smoking habit). On the contrary, SA had more atopic features, more reversibility of airflow obstruction and higher IgE levels. The concentrations of IL-5, IL-13, IL-8, IL-6, TNF-alpha, IL17 in serum were similar between the 2 groups. However, Th2-related biomarkers (periostin, FeNO and blood eosinophils) shower higher median values in e-COPD patients. Our findings reinforce the notion that ACO is a heterogeneous disorder and, as a consequence, it might be unacceptable to offer the same treatment for two related but different conditions., The project was endorsed by the COPD and Asthma Research Board (PII de EPOC y asma) of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). The project was partially funded by the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Economia y Competitividad (FIS 15/01263) and by an unrestricted grant from Chiesi Espana S.A.U.

Few studies have investigated the variability of COPD-related symptoms or factors related to symptom variability. This observational, prospective, multicentre study was conducted to describe the number and intensity of morning and night-time respiratory symptoms and their variability over one week using the Night-time and Early Morning Symptoms of COPD Instruments (NiSCI and EMSCI) to evaluate stable COPD patients. Logistic regression analyses were performed to investigate factors associated with symptom variability. A total of 2669 patients were evaluated (mean age, 67.7 years; 80.9% men; mean FEV1 50.6%). Of these, 48% reported night-time symptoms and 71% reported morning symptoms. Of the 2293 patients who completed the NiSCI and EMSCI, 90% showed variability in either symptom number (89.6%) or symptom intensity (15.8%). More severe dyspnoea, more exacerbations during the previous year and the exacerbator or mixed COPD-asthma phenotypes were associated with variability in symptom number or intensity. Anxiety was significantly associated with variability in symptom number and intensity. Most COPD patients showed symptom variability over a weeklong period, especially in terms of symptom number. Several COPD-related factors, mainly factors related to more severe disease and more frequent exacerbations, were associated with increased symptom variability.

Pollution of water by sewage and run-off from farms produces a serious public health problem in many countries. Viruses, along with bacteria and protozoa in the intestine or in urine are shed and transported through the sewer system. Even in highly industrialized countries, pathogens, including viruses, are prevalent throughout the environment. Molecular methods are used to monitor viral, bacterial, and protozoan pathogens, and to track pathogen- and source-specific markers in the environment. Molecular techniques, specifically polymerase chain reaction-based methods, provide sensitive, rapid, and quantitative analytical tools with which to study such pathogens, including new or emerging strains. These techniques are used to evaluate the microbiological quality of food and water, and to assess the efficiency of virus removal in drinking and wastewater treatment plants. The range of methods available for the application of molecular techniques has increased, and the costs involved have fallen. These developments have allowed the potential standardization and automation of certain techniques. In some cases they facilitate the identification, genotyping, enumeration, viability assessment, and source-tracking of human and animal contamination. Additionally, recent improvements in detection technologies have allowed the simultaneous detection of multiple targets in a single assay. However, the molecular techniques available today and those under development require further refinement in order to be standardized and applicable to a diversity of matrices. Water disinfection treatments may have an effect on the viability of pathogens and the numbers obtained by molecular techniques may overestimate the quantification of infectious microorganisms. The pros and cons of molecular techniques for the detection and quantification of pathogens in water are discussed.

José Luis Izquierdo,1 José Manuel Paredero,2 Raul Piedra3 1Department of Pneumology, Hospital Universitario de Guadalajara, 2Department of Pharmacy, 3Department of Primary Care, Guadalajara Integrated Care Management, Guadalajara, Spain Introduction: The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence.Methods: We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014.Results: During 2013, the medication collected was 7.4%–10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014.Conclusion: The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence. Keywords: COPD, treatment, adherence, LABAs, LAMAs, PDC, asthma

Lung cancer, a steadily growing problem, ranks as the first cause of tumor-related deaths in developed countries. The relation between lung cancer and smoking makes it a potentially avoidable disease. Found mainly in men, it has made alarming gains among women. The main prognostic factor is the possibility of receiving curative surgery; however, in real practice the diagnosis usually comes when the disease has reached an advanced stage, when only 20% can be treated surgically. Nonsurgical treatments based on chemo- and radiotherapy have not advanced appreciably in recent years, and 5-year survival is poor, estimated at only around 7% to 12% in Spain. Attempts must be made to improve preventive measures and early diagnosis in order to improve the prognosis for lung cancer patients.

To study whether patients with chronic obstructive pulmonary disease (COPD) at the same level of flow limitation but with different clinical phenotypes present different degrees of systemic and/or pulmonary inflammation.We studied 15 male smokers without COPD (control group) and 39 males with COPD in stable clinical condition. The COPD patients were assigned to 2 groups based on the ratio of carbon monoxide diffusing capacity (DLCO) to alveolar volume (DLCO/VA) expressed as a percentage as follows: a) mainly emphysema (n = 15) and b) mainly chronic bronchitis (n = 24). Classification was determined by comparing both clinical features and diagnostic images.Mean (SD) concentrations of interleukin 8 (IL-8) and 8-isoprostane in exhaled breath condensate (EBC) were significantly lower in patients with mainly emphysema (IL-8, 0.34 [0.70] pg/mL; 8-isoprostane, 0.07 [0.26] pg/mL) than in patients with chronic bronchitis (IL-8, 2.32 [3.10] pg/mL; 8-isoprostane, 1.77 [2.98] pg/mL) or in the controls (IL-8, 3.14 [4.59] pg/mL; 8-isoprostane, 1.92 [2.84] pg/mL); P.05 for IL-8 comparisons and P.01 for 8-isoprostane. IL-8, leukotriene B4, and 8-isoprostano in EBC correlated significantly with DLCO/VA (% of predicted) (r = 0.30, P.05; r = 0.29, Por = .05; and r = 0.46, P.01, respectively) but not with forced expiratory volume in 1 second. There was a negative correlation between EBC and serum levels of both IL-8 (r = -0.31; P.05) and 8-isoprostane (r = -0.51; P.001). The correlation between leukotriene B4 concentrations in EBC and serum was not significant, however. No significant differences were found between smokers' and ex-smokers' serum levels of IL-8, leukotriene B4, 8-isoprostane in serum or EBC.The results indicate that COPD patients with an emphysematous phenotype have a less intense inflammatory response and less oxidative stress in the lung.

Background The central role of chronic inflammation of the airways in asthma pathogenesis is supported by the efficacy of corticosteroids in controlling clinical symptoms. However, the search continues for potentially safer anti-inflammatory alternatives. Roflumilast is an oral, once-daily phosphodiesterase type 4 inhibitor with anti-inflammatory activity in preclinical models of asthma and chronic obstructive pulmonary disease. Objective To investigate the dose-ranging efficacy and safety of roflumilast in patients with mild-to-moderate asthma. Methods Patients (N = 693) were randomized in a double-blind, parallel-group, phase 2/3 study. After a 1- to 3-week placebo run-in period, patients (mean forced expiratory volume in 1 second [FEV 1 ], 73% of predicted) were randomized to receive 100, 250, or 500 μg of roflumilast once daily for 12 weeks. The primary end point was change from baseline in FEV 1 ; secondary end points included change from baseline in morning and evening peak expiratory flow. Results Roflumilast use significantly increased FEV 1 ( P 1 at the last visit were 260, 320, and 400 mL for the 100-, 250-, and 500-μg dose groups, respectively. Roflumilast, 500 μg, was superior to roflumilast, 100 μg, by 140 mL in improving FEV 1 ( P = .002). There were also significant improvements from baseline in morning and evening peak expiratory flow in all the dose groups ( P ≤ .006). Roflumilast was well tolerated at all doses tested. Most adverse events were mild to moderate in intensity and transient. Conclusion These results support the emerging role of roflumilast, 500 μg/d, in the treatment of asthma.

To assess the impact of prescribing pulmonary drugs according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines on direct costs in stable chronic obstructive pulmonary disease (COPD).A total of 560 ambulatory COPD patients completed a specific questionnaire that included data regarding drug therapy. Severity was graded according to the British Thoracic Society (BTS) criteria and appropriateness of pharmacological treatment according to GOLD guidelines.Annual direct costs were 1,657 EUR in stage I, 2,425 EUR in stage II, and 3,303 EUR in stage III. The mean direct costs was 2,061 EUR (38% corresponded to drug therapy). Medication accounted for 43%, 37.6%, and 28.4% of total direct costs for stage I, II, and III, respectively. Inhaled steroids and long-acting beta2-agonists accounted for 78%, 76%, and 75% of total drugs costs in stages I, II, and III, respectively. Drug therapy which was not in accordance with guidelines accounted for 78.7% and 54% of total drug costs in stages I and II, respectively. Most patients with severe disease were treated adequately. ANSWER TO THE QUESTION: Pharmacologic treatment has a great impact on direct medical costs in stable COPD. According to GOLD guidelines, patients with mild or moderate COPD are frequently treated with nonrecommended drugs.

The aim of this study was to evaluate PCR and fluorescent in situ hybridization (FISH) techniques for detecting Arcobacter and Campylobacter strains in river water and wastewater samples. Both 16S and 23S rRNA sequence data were used to design specific primers and oligonucleotide probes for PCR and FISH analyses, respectively. In order to assess the suitability of the methods, the assays were performed on naturally and artificially contaminated samples and compared with the isolation of cells on selective media. The detection range of PCR and FISH assays varied between 1 cell/ml (after enrichment) to 10 3 cells/ml (without enrichment). According to our results, both rRNA-based techniques have the potential to be used as quick and sensitive methods for detection of campylobacters in environmental samples.

José Luis Izquierdo, Pilar Resano, Abdulkader El Hachem, Desiré Graziani, Carlos Almonacid, Ignacio M Sánchez Pulmonology Department, Guadalajara University Hospital, Guadalajara, Spain Abstract: While it is relatively well known that the prognosis of patients with lung cancer (LC) treated with surgery is worse in the presence of chronic obstructive pulmonary disease (COPD), it is unknown if this assessment can be extrapolated to patients with advanced disease treated with chemotherapy and/or tyrosine kinase inhibitors. The aim of our study is to analyze the clinical characteristics and survival rates in patients with LC and COPD, and to compare these to the patients without airflow obstruction. From 471 evaluable patients, 324 (69%) were not treated with surgery due to disseminated disease (stages 3B and 4). Of them, 47.7% also had COPD. All patients were treated at the moment of diagnosis according to National Comprehensive Cancer Network guidelines with platinum-based chemotherapy or tyrosine kinase inhibitors. Kaplan–Meier curves showed no significant differences in overall survival between COPD and non-COPD patients (log–rank P=0.65). In the multivariate Cox proportional hazard model adjusting for the most relevant variables, the adjusted hazard ratio (HRadj) was statistically significant for performance status (HRadj =1.33, 95% confidence interval [CI]: 1.11–1.59; P=0.002) and clinical stage (HRadj =0.67, 95% CI: 0.50–0.89; P=0.006), but not for COPD status (HRadj =1.20, 95% CI: 0.83–1.50; P=0.46). Our conclusion is that at present, when using standard care in advanced LC (stages 3B and 4), COPD does not have a significant deleterious impact on overall survival. Keywords: lung cancer, chronic obstructive pulmonary disease, extended disease, chemotherapy, survival

There has been growing interest in recent years in the extraosseous effects of vitamin D. In this article, we review the physiology of vitamin D, the physiopathological effects associated with vitamin D deficit and the available evidence on its etiopathogenic role in respiratory diseases. Given the pleiotropic actions of vitamin D, it is biologically plausible that the deficit of this vitamin could play a pathogenic role of in the development of various respiratory diseases. However, the many epidemiological studies that have shown an association between low vitamin D levels and a higher risk of developing various respiratory diseases or a poorer prognosis if they do appear, were unable to show causality. Post-hoc analyses of some clinical trials, particularly in chronic obstructive pulmonary disease (COPD) and asthma, appear to suggest that some patient subtypes may benefit from correction of a vitamin D deficit. In this respect, it would be interesting to determine if the interindividual differences found in the effect of vitamin D deficit and responses to correcting this deficit could be explained by the genetic variants involved in vitamin D metabolism. Ultimately, only appropriately designed clinical trials will determine whether 25-OHD supplements can prevent or improve the course of the various respiratory diseases in which an epidemiological association between prognosis and vitamin D deficit has been described.

SummaryAimTo determine the prevalence and analyze the most relevant clinical characteristics of three clinical phenotypes of COPD: emphysema (type 1), chronic bronchitis (type 2) or COPD-asthma (type 3).MethodObservational, multicenter study performed with 331 COPD patients recruited in pulmonology outpatient services. The stratification in three phenotypes was performed with imaging tests, pulmonary function, and a standardized clinical questionnaire.ResultsThe 43.2% presented an emphysematous phenotype, 44.7% were chronic bronchitic and the other 12.1% presented a phenotype showing mixed characteristics with asthma. There were no significant differences in the smoking level, in the gasometric values or time of disease evolution. Type 1 patients showed lower FEV1 values in comparison with types 2 and 3, 46.6% (21.1), 55.2% (21.2) and 54.4% (21.8), respectively (p

This study involved collaboration between three centres with expertise in viruses, bacteria and protozoa. The focus of the research was the study of the dissemination and removal of pathogens and faecal indicators in two sewage treatment plants (STP1 and STP2) using tertiary treatments. Samples were collected over a period of five months through the sewage treatment processes. Analysis of the samples revealed that the plants were not efficient at removing the faecal indicators and pathogens tested during the study. From entry point (raw sewage) to effluent level (tertiary treatment effluent water), the experimental results showed that the reduction ratios of human adenoviruses were 1.2 log10 in STP1 and 1.9 log10 in STP2. Whereas for Giardia spp. and Cryptosporidium spp. the reduction ratios were 2.3 log10 for both pathogens in STP1, and 3.0 and 1.7 log10 in STP2, respectively. Furthermore, the presence of faecal indicators and pathogens at different sampling points was evaluated revealing that the tested pathogens were present in reclaimed water. Human adenovirus and Arcobacter spp. showed positive results in infectivity assays for most of the tertiary effluent water samples that comply with current legislation in Spain. The pathogens detected must be evaluated using a risk assessment model, which will be essential for the development of improved guidelines for the re-use of reclaimed water.

Objectives To analyse the clinical utility and economic impact of conventional transbronchial needle aspiration (TBNA) in patients with diagnosis of bronchogenic carcinoma (BC) and mediastinal lymphadenopathies in thoracic computed tomography (CT). To assess the predictive factors of valid aspirations. Patients and methods Retrospective observational study between 2006 and 2011 of all TBNA performed in patients with final diagnosis of BC and accessible hilar or mediastinal lymphadenopathies on thoracic CT. Results We performed TBNA on 267 lymphadenopathies of 192 patients. In 34.9% of patients, two or more lymph nodes were biopsied. Valid aspirations were obtained in 153 patients (79.7%) that were diagnostic in 124 patients (64.6%). Multivariate analysis showed that factors associated with valid or diagnostic results are the diameter of the lymph node and the number of lymph nodes explored. TBNA was the only endoscopic technique that provided the diagnosis of BC in 54 patients (28.1%). Staging mediastinoscopy was avoided in 67.6% of patients. The prevalence of mediastinal lymph node involvement was 74.4%, sensitivity of TBNA was 86.2% and negative predictive value was 63.6%. Including mediastinoscopy and other avoided diagnostic techniques, TBNA saved 451.57 € per patient. Conclusions TBNA is a clinically useful, cost-effective technique in patients with BC and mediastinal or hilar lymphadenopathies. It should therefore be performed on a regular basis during diagnostic bronchoscopy of these patients.

Despite the fact that the recommendations of the main clinical guidelines have restricted the indications for inhaled corticosteroids in chronic obstructive pulmonary disease (COPD), currently more than 80% of patients are receiving this treatment in Spain, mostly with high doses. A detailed review of the literature does not justify the use of these high doses, a position that agrees with the recommendations of the FDA. A re-evaluation of their safety, the consistency of the data on their efficacy showing similar results with moderate doses and a better patient selection require the use of this treatment in COPD patients to be reconsidered.

The objective of this study is to analyze the clinical characteristics of two COPD patient populations: one diagnosed using the lower limit of normal (LLN) and another diagnosed by the GOLD criteria. We also compared the population excluded by the LLN criterion with a non-COPD control population. The COPD patients determined with the LLN criterion presented significantly lower levels of FEV1/FVC at 0.55 (0.8) vs. 0.66 (0.2), P=.000; FEV1 44.9% (14) vs. 53.8% (13), P=.000, and FVC 64.7% (17) vs. 70.4% p 0.04. The two COPD groups presented more frequent ER visits in the last year (57% and 52% of the patients, respectively, compared with 11.9% of the control group), without any statistically significant differences between the two. This same pattern was observed in the number of ER visits in the last year: 1.98 (1.6), 1.84 (1.5) and 1.18 (0.7), respectively. When we analyzed the prevalence of the comorbidities that are most frequently associated COPD, there was a clear increase in the percentage of patients who presented associated disorders compared with the control group. Nevertheless, these differences were not very relevant between the two COPD groups. The differences also were not relevant between both COPD groups in the pharmacological prescription profile. In conclusion, the use of the LLN as a criterion for establishing the diagnosis of COPD, compared with the GOLD criteria, excludes a population with important clinical manifestations and with a high consumption of health-care resources. Before its implementation, the relevance of applying this criterion in clinical practice should be analyzed.

Patients with chronic obstructive pulmonary disease (COPD) and associated bronchitis are at higher risk of exacerbations, which are a major cause of morbidity and impaired quality of life. Moreover, exacerbations are associated with more rapid disease progression and higher mortality. The typical symptoms of chronic bronchitis (chronic cough and sputum production) are correlated with inflammatory markers in COPD. Roflumilast is an anti-inflammatory drug belonging to the novel therapeutic class of phosphodiesterase-4 inhibitors and is the first drug to be developed for the treatment of a specific COPD phenotype (COPD associated with chronic bronchitis). The results of clinical trials indicate that, in patients with COPD associated with chronic bronchitis and a history of exacerbations, roflumilast improves pulmonary function and reduces the symptoms and frequency of exacerbations requiring medical intervention. This effect is maintained when regular treatment with a long-acting bronchodilator or an inhaled corticosteroid is added.

Patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis have a reduction in lung function and a higher risk of suffering exacerbations, which result in a deterioration in their quality of life, an accelerated progression of the disease and a greater mortality. COPD is currently considered an inflammatory disease involving airways and lung parenchyma. The symptoms that are typical of chronic bronchitis (chronic cough and sputum production) are markers of underlying inflammation, characteristic of COPD. Roflumilast, an antiinflammatory drug that belongs to the new therapeutic class of phosphodiesterase PDE4 inhibitors, is the first drug developed for the treatment of a specific phenotype of COPD (COPD associated with chronic bronchitis). The results of clinical trials indicated that in patients with COPD associated with chronic bronchitis and a history of exacerbations, roflumilast improves lung function and reduces the frequency of exacerbations that require medical interventions. This effect remained when it was added to a regular treatment with long-acting bronchodilators such as tiotropium or long-acting β₂-adrenoceptor agonists (LABAs) such as salmeterol. Roflumilast has been shown to be generally well tolerated. Side effects were typically mild to moderate and included diarrhea, nausea, weight decrease and headache. Gastrointestinal side effects mainly occurred within the first weeks of therapy and mostly resolved on continued treatment.

[EN] Cryptosporidium and Giardia are major causes of diarrheal disease in humans worldwide and are major causes of protozoan waterborne diseases. Two DNA TaqMan PCR-based Giardia and Cryptosporidium methods targeting a 74-bp sequence of the ß-giardin Giardia gene and a 151-bp sequence of the COWP Cryptosporidium gene, respectively, were used as models to compare two different LNA/DNA TaqMan probes to improve the detection limit in a real-time PCR assay. The LNA probes were the most sensitive resulting in 0.96 to 1.57 lower C t values than a DNA Giardia TaqMan probe and 0.56 to 2.21 lower than a DNA Cryptosporidium TaqMan probe. Evaluation of TaqMan Giardia and Cryptosporidium probes with LNA substitutions resulted in real-time PCR curves with an earlier C t values than conventional DNA TaqMan probes. In conclusion, the LNA probes could be useful for more sensitive detection limits. © 2011 Springer-Verlag., This work was supported by the Spanish Ministerio de Ciencia e Innovacion grants AGL2005-07776-C03-03 and AGL2008-05275-C03-03/ALI). Part of this work was also funded by the Fondo Europeo de Desarrollo Regional (Feder) grant POICV 2000-2006. We thank staff at the wastewater treatment plants and the Entidad de Saneamiento de Aguas for assistance in sample collection.

In the last decade, various studies have suggested that chronic obstructive pulmonary disease (COPD) could favor the development of ischemic heart disease. Several observational and case-control studies have confirmed that patients with COPD have a higher risk of cardiovascular disorders. However, this increased risk could be largely explained by a greater prevalence of classical risk factors. Currently, there are no data to indicate a causal relation between COPD and cardiovascular disease and the concept of systemic inflammation as a common pathogenic mechanism has not been demonstrated. Equally, there is insufficient evidence to conclude that some drugs, such as statins or inhaled corticoids, could decrease cardiovascular risk in patients with COPD by reducing systemic inflammation. Currently, these drugs should only be recommended if patients show specific indications for their use.

A field study in Valencia, Spain, was done to determine the occurrence of Giardia and Cryptosporidium on salad products that are frequently eaten raw, such as lettuces and Chinese cabbage, and in irrigation waters. Four water samples were taken weekly 1 month before harvesting the vegetables. All water samples were analyzed using techniques included in the U.S. Environmental Protection Agency Method 1623. Standard methods for detecting protozoan parasites on salad vegetables are not available. Published techniques for the isolation of parasites from vegetables generally have low and variable recovery efficiencies. In this study, vegetables were analyzed using a recently reported method for detection of Cryptosporidium oocysts and Giardia cysts on salad products. The waters tested were positive for both Cryptosporidium and Giardia. Of 19 salad products studied, we observed Cryptosporidium in 12 samples and Giardia in 10 samples. Recoveries of the Texas Red–stained Cryptosporidium and Giardia, which were used as internal controls, were 24.5% ± 3.5% for Cryptosporidium and 16.7% ± 8.1% for Giardia (n = 8). This study provides data on the occurrence of Cryptosporidium and Giardia in salad products in Spain. The method was useful in the detection of Cryptosporidium oocysts and Giardia cysts on the vegetables tested, and it provides a useful analytical tool for occurrence monitoring.

There is little information regarding the clinical management of hospital inpatients diagnosed with exacerbation of Chronic Obstructive Pulmonary Disease (COPD). AUDIPOC is a clinical audit dealing with the clinical management of COPD in Spain.To examine the adequacy and validity of the instruments used to measure the variables proposed by AUDIPOC Spain (Preliminary Study) and to verify the viability of AUDIPOC in a complex environment with hospitals of different sizes, resources, and organizational layout (Pilot Study).The Preliminary Study took place in 4 hospitals and studied 213 cases. The Pilot Study took place in 30 hospitals of 6 Autonomous Communities (i.e. Regions) and studied 1203 cases.The results of both studies contributed to the improvement of the design, methods and organization of the AUDIPOC work. Some of the improvements include better training of those responsible at a hospital level, a new classification of hospitals, the incorporation of new variables and the creation of a Bureau for the Coordination and Management of the Project.The AUDIPOC study is viable. It aims to recruit 10000 patients across 142 hospitals from all the Regions of Spain.

Almost all clinical practice guidelines have defined chronic obstructive pulmonary disease (COPD) as being characterized by airway obstruction, which is usually progressive. In Spain, COPD is the fifth most common cause of death, behind vascular diseases and cancer. In the last decade, the management of COPD has undergone a marked change, resulting in better disease control by acting on variables other than forced expiratory volume in 1 second, such as exacerbations and symptoms. Clinical experience also indicates favorable effects on functional deterioration and mortality. However, from a scientific point of view, the grade of evidence is still limited. If one of the challenges for the next few years is early diagnosis of COPD, the most upto-date strategies should focus on disease progression and mortality; in the case of the former, to avoid deterioration and reduce the burden of the disease, which is mostly associated with advanced stages, and in the case of the latter, to clarify the role of COPD as a cause of death, since, even in the initial phases, this disease could play an important role in many cases of death associated with cardiovascular disease and lung cancer. The present review aims to put the "classical and new" parameters for the follow-up of COPD into perspective and to evaluate their real importance in the clinical management of these patients today.

Cardiovascular disease is a common cause of death in patients with chronic obstructive pulmonary disease (COPD). It is not clear whether the high cardiovascular comorbidity is due to an increase in traditional risk factors or whether, in contrast, COPD can be considered an independent risk factor. The aim of this study was to analyze the prevalence of risk factors and cardiovascular comorbidity in a community-based population treated for COPD.This was a concurrent multicenter, cross-sectional study that included 572 patients with confirmed diagnosis of COPD. Information on cardiovascular risk factors and comorbidity was collected by extracting data from the medical records of the participating center.The mean (SD) forced expiratory volume in 1 second (FEV1) was 53.7% (16.85%) of predicted and the ratio of FEV1 to forced vital capacity was 57.9% (10.9%). Hypertension was reported in 53%, obesity in 27%, dyslipidemia in 26%, and diabetes in 23% of the patients. The prevalence of risk factors was not related to disease severity, but there was a trend towards an association with age. In the study group, 16.4% had ischemic heart disease, 7% cerebrovascular disease, and 17% peripheral vascular disease. Cardiovascular disease was not associated with COPD severity, but such an association was reported for age and traditional risk factors.Cardiovascular risk factors are highly prevalent in patients with COPD. The prevalence of cardiovascular and cerebrovascular disease exceeds that reported in the general population. No relationship was found between the severity of airflow obstruction and the presence of cardiovascular comorbidity.