Search

Introduction Chronic Obstructive Pulmonary Disease (COPD) is the third cause of death worldwide. While tobacco smoking is a key risk factor, COPD also occurs in never-smokers (NS). However, available evidence on risk factors, clinical characteristics, and natural history of the disease in NS is scarce. Here, we perform a systematic review of the literature to better describe the characteristics of COPD in NS. Methods We searched different databases following the PRISMA guidelines with explicit inclusion and exclusion criteria. A purpose-designed quality scale was applied to the studies included in the analysis. It was not possible to pool the results due to the high heterogeneity of the studies included. Results A total of 17 studies that met the selection criteria were included, albeit only 2 of them studied NS exclusively. The total number of participants in these studies were 57,146 subjects, 25,047 of whom were NS and 2,655 of the latter had NS-COPD. Compared to COPD in smokers, COPD in NS is more frequent in women and older ages, and is associated with a slightly higher prevalence of comorbidities. There are not enough studies to understand if COPD progression and clinical symptoms in NS are different to that of ever-smokers. Conclusions There is a significant knowledge gap on COPD in NS. Given that COPD in NS account for about a third of all COPD patients in the world, particularly in low-middle income countries, and the decrease in tobacco consumption in high income countries, understanding COPD in NS constitutes a public-health priority This work was supported by the Instituto de Salud Carlos III (ISCIII)/PI20/00476/Cofinanciado Unión Europea (UE-FEDER) and Grupo de referencia competitiva Xunta de Galicia SI

This study sought to ascertain whether there might be an association between radon concentrations and age, gender, histologic type, and tumor stage at diagnosis.Lung cancer cases from different multicenter case-control studies were analyzed, and clinical data were retrieved from electronic health records and personal interviews. A radon device was placed in all dwellings of participants, and we then tested the existence of an association between residential radon and lung cancer characteristics at diagnosis.Of the total of 829 lung cancer cases included, 56.7% were smokers or ex-smokers. There was no association between indoor radon concentrations and age, gender, histologic type or tumor stage at diagnosis. Median indoor radon concentrations increased with age at diagnosis for men, but not for women. When analyzing participants exposed to more than 1000 Bq/mThere seems to be no association between radon and age, gender, histologic type or tumor stage at diagnosis. Higher radon exposure is more frequent in the case of small-cell lung cancer.

RESUMEN Introducción y objetivos: La Organización Mundial de la Salud calificó la enfermedad por coronavirus de 2019 (COVID-19) como una pandemia global. No está claro si el tratamiento previo con inhibidores de la enzima de conversión de la angiotensina (IECA) y antagonistas de los receptores de la angiotensina II (ARA-II) tiene un impacto en el pronóstico de los pacientes infectados con COVID-19. El objetivo es evaluar la implicación clínica del tratamiento previo con IECA/ARA-II en el pronóstico de la COVID-19. Métodos: Estudio observacional, retrospectivo, unicéntrico y de cohortes basado en todos los habitantes del área de salud. El análisis de los resultados principales (mortalidad, insuficiencia cardiaca, hospitalización, ingreso en la unidad de cuidados intensivos [UCI] y eventos cardiovasculares agudos mayores [un compuesto de mortalidad e insuficiencia cardiaca]), se ajustó mediante modelos de regresión logística multivariada y modelos de coincidencia de puntuación de propensión. Resultados: De una población total de 447.979 habitantes, se diagnosticó de infección por COVID-19 a 965 pacientes (0,22%), de los que 210 (21,8%) estaban en tratamiento con IECA o ARA-II en el momento del diagnóstico. El tratamiento con IECA/ARA-II (combinado o individual) no tuvo efecto en la mortalidad (OR = 0,62; IC95%, 0,17-2,26; p = 0,486), la insuficiencia cardiaca (OR = 1,37; IC95%, 0,39-4,77; p = 0,622), la tasa de hospitalizaciones (OR = 0,85; IC95%, 0,45-1,64; p = 0,638), los ingresos en UCI (OR = 0,87; IC95%, 0,30-2,50; p = 0,798) y los eventos cardiovasculares agudos mayores (OR = 1,06; IC95%, 0,39-2,83; p = 0,915). En el análisis del subgrupos de pacientes que requirieron hospitalización, el efecto se mantuvo neutral. Conclusiones: El tratamiento previo con IECA/ARA-II en pacientes con COVID-19 no tuvo efecto en la mortalidad, la aparición de insuficiencia cardiaca o la necesidad de hospitalización o ingreso en UCI. La supresión de los IECA/ARA-II en pacientes con COVID-19 no estaría justificada en ningún caso según las recomendaciones actuales de las sociedades científicas y las agencias gubernamentales.

Background Asthma is heterogeneous disease with different phenotypes, endotypes and severities. Definition of these subgroups requires the identification of biomarkers in biological samples, and serum proteomics is a useful and minimally invasive method for this purpose. Therefore, the aim of this study was to detect serum proteins whose abundance is distinctively associated with different asthma phenotypes (allergic vs nonallergic) or severities. Methods For each group of donors (32 healthy controls, 43 allergic rhinitis patients and 192 asthmatics with different phenotypes and severities), we generated two pools of sera that were analysed by a shotgun MS approach based on combinatorial peptide ligand libraries and iTRAQ-LC-MS/MS. Results MS analyses identified 18 proteins with a differential abundance. Functional/network study of these proteins identified key processes for asthma pathogenesis, such as complement activation, extracellular matrix organization, platelet activation and degranulation, or post-translational protein phosphorylation. Furthermore, our results highlighted an enrichment of the "Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)" route in allergic asthma and the lectin pathway of complement activation in nonallergic asthma. Thus, several proteins (eg IGFALS, HSPG2, FCN2 or MASP1) displayed a differential abundance between the different groups of donors. Particularly, our results revealed IGFALS as a useful biomarker for moderate-severe allergic asthma. Conclusion Our data suggest a set of serum biomarkers, especially IGFALS, capable of differentiating allergic from nonallergic asthma. These proteins reveal different pathophysiological mechanisms and may be useful in the future for diagnosis, prognosis or targeted therapy purposes.

Discriminating between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains difficult. Thus, novel and efficient biomarkers are required for the diagnosis of pleural effusion (PE). The aim of this study was to validate calprotectin as a diagnostic biomarker of PE in clinical settings. A total of 425 patients were recruited, and the pleural fluid samples collected had BPE in 223 cases (53.7%) or MPE in 137 patients (33%). The samples were all analysed following the same previously validated clinical laboratory protocols and methodology. Calprotectin levels ranged from 772.48 to 3,163.8 ng/mL (median: 1,939 ng/mL) in MPE, and 3,216–24,000 ng/mL in BPE (median: 9,209 ng/mL; p

María Estrella López-Pardo,1 Cristina Candal-Pedreira,2 Luis Valdés-Cuadrado,3 Cristina Represas-Represas,4 Alberto Ruano-Ravina,2,5,6 Mónica Pérez-Ríos2,5,6 1Department of Planning and Health Reform, Galician Health Service, Santiago de Compostela, Spain; 2Department of Preventive Medicine and Public Health, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain; 3Department of Pulmonology, University Clinical Teaching Hospital of Santiago de Compostela, Santiago de Compostela, Spain; 4Respiratory Medicine, Alvaro Cunqueiro University Teaching Hospital, Vigo, Spain; 5Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública/CIBERESP), Madrid, Spain; 6Health Research Institute of Santiago de Compostela (Instituto de Investigación Sanitaria de Santiago de Compostela - IDIS), Santiago de Compostela, SpainCorrespondence: Alberto Ruano-Ravina, Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, University of Santiago de Compostela, C/ San Francisco s/n, Santiago de Compostela, 15782, Spain, Tel +34-981-581237, Fax +34-981-572282, Email alberto.ruano@usc.esIntroduction: The rising trend in hospital admissions among patients with chronic obstructive pulmonary disease (COPD) is worrying, not only because of the increasing costs, but also because of the worsening quality of life. We aimed to identify the predictive factors of hospital admission, re-admission and mortality of COPD patients through using information exclusively registered in electronic clinical records.Methods: We conducted a population-based case–control study. All data were sourced from the different information systems comprising the Galician Health Service electronic record database. We included in the study patients diagnosed with COPD (code R95 in the medical record), ≥ 35 years old and with at least one spirometry performed ≤ 3 years prior inclusion. We fitted three logistic regression models, each one to ascertain the factors that influence the probability of admission, re-admission, and mortality, and calculated odds ratios (OR) with their 95% confidence intervals (95% CI).Results: COPD patients were admitted due to respiratory causes a mean of 1.51 times across the period December 2016–December 2017, with 55% requiring re-admission in the next 90 days. The factor most closely associated with the re-admission profile was home oxygen therapy (OR 3.06 95% CI 2.42– 3.87), followed by male gender (OR 2.01 95% CI 1.48– 2.72), a CHA2D-VASc scale score > 2 (OR 1.28 95% CI 1.16– 1.42), and severity by clinical risk group stratification (OR 1.14 95% CI 1.04– 1.26). Male sex (OR 1.47 CI 95% 1.04– 2.09), having been readmitted ≥ 2 times (OR 1.34 CI 95% 1.11– 1.61) and being ≥ 70 years old (OR 1.05 CI 95% 1.03– 1.08) increase the probability of dying from COPD during the study period.Conclusion: These results confirm the complexity of management of COPD exacerbations, and indicate the need to establish strategies that would ensure continuity of care after hospital admission, with the aim of preventing re-admissions and death.Keywords: case–control study, COPD, hospital discharge, mortality

It is not known whether residential radon exposure may be linked to the development of chronic obstructive pulmonary disease (COPD) and/or have an influence on the functional characteristics or exacerbations of COPD. The aim of this study was therefore to ascertain whether there might be an association between residential radon concentrations and certain characteristics of COPD. We analyzed COPD cases drawn from a case–control study conducted in an area of high radon exposure. Data were collected on spirometric pulmonary function variables, hospital admissions, and smoking. Radon measurements were taken using alpha-track-type CR-39 detectors individually placed in patients’ homes. All statistical analyses were performed using the IBM SPSS v22 computer software program. The study included 189 COPD cases (79.4% men; median age 64 years). The median radon concentration was 157 Bq/m3. No differences were found between radon concentration and sex, age or severity of breathing obstruction as measured by FEV1%. It should be noted, however, that 48.1% of patients with FEV1% 600 Bq/m3 exhibited no different characteristics in lung function. Exposure to radon does not appear to have an influence on the clinical characteristics of smokers and ex-smokers with COPD. As exposure to residential radon increases, there is no trend towards a worsening of FEV1%. Further studies are thus needed to analyze this possible association in never-smokers with COPD Spanish Society of Pneumology & Thoracic Surgery (Sociedad Española de Neumología y Cirugía Torácica—SEPAR), competitive Project Number 439, call 2018 SI

Stage III non-small cell lung cancer (NSCLC) includes a highly heterogeneous group of patients with differences in the extent and localization of disease. Many aspects of stage III disease are controversial. The data supporting treatment approaches are often subject to a number of limitations, due to the heterogeneous patient populations involved in the trials. Furthermore, the definition of stage III disease has changed over time, and early studies were frequently inadequately powered to detect small differences in therapeutic outcome, were not randomized, or had a limited follow-up times. Major improvements in therapy, including the use of more active chemotherapy agents and refinements in radiation and surgical techniques, also limit the interpretation of earlier clinical trials. Lastly, improvements in pretreatment staging have led to reclassification of patients with relatively minimal metastatic disease as stage IV rather than stage III, leading to an apparent increase in the overall survival of both stage III and IV patients. Median overall stage III NSCLC survival ranges from 9 to 34 months. Higher survival rates are observed in younger Caucasian women with good performance status, adenocarcinoma, mutations, stage IIIA, and in patients with multidisciplinary-team-based diagnoses.

Currently in developed countries there is an increase in the consumption of roll your own tobacco, which is associated with a higher proportion of users of this form of tobacco who wish to make an attempt to quit. The objective of this study was to analyze the effectiveness of tobacco cessation interventions based on the type of tobacco consumed.Longitudinal study of a cohort of 641 smokers recruited between 2015 and 2018 in a health area of Galicia included in smoking cessation programs, based on psychological counseling and pharmacological treatment. The characteristics and success of the intervention were evaluated in two groups: roll your own tobacco smokers (RYO) and manufactured tobacco smokers (MT). A logistic regression was performed to determine the probability of success in smoking cessation. The risk measure was the odds ratio (OR) with its 95% confidence interval.RYO users started at a younger age and had a lower sociocultural stratum than MT users. Interventions to quit smoking in RYO users were associated with less abstinence at 4 weeks (52% MT vs 38% LT) (OR: 0.5; 95% CI 0.35-0.99; p=0.045;) and at 3 months (42% TM vs 30% TL) (OR:0.6; 95% CI 0.33-0.98; p=0.04).Smoking cessation programs are less effective in short-term RYO users. There are no differences in long-term abstinence between the two groups.Actualmente en los países desarrollados existe un aumento del consumo de tabaco de liar lo que se asocia a una mayor proporción de usuarios de esta forma de tabaco que desean realizar un intento de abandono. El objetivo de este estudio fue analizar la efectividad de las intervenciones de cesación tabáquica en función del tipo de tabaco consumido.Estudio longitudinal de una cohorte de 641 fumadores reclutados entre 2015 y 2018 en un área sanitaria de Galicia incluidos en programas de deshabituación tabáquica, basados en el asesoramiento psicológico y en el tratamiento farmacológico. Se evaluaron las características y el éxito de la intervención en dos grupos: fumadores de tabaco de liar (TL) y fumadores de tabaco manufacturado (TM). Se realizó una regresión logística para determinar la probabilidad de éxito en la cesación tabáquica. La medida de riesgo fue el odds ratio (OR) con su intervalo de confianza al 95%.Los consumidores de TL se iniciaron a una edad más temprana y tenían un estrato sociocultural más bajo que los consumidores de TM. Las intervenciones para abandonar el tabaco en los consumidores de TL se asociaron a una menor abstinencia a las 4 semanas (52%TM vs 38% TL) (OR: 0,5; 95%IC 0,35-0,99; p=0,045;) y a los 3 meses (42%TM vs 30%TL) (OR:0,6; 95%IC 0,33-0,98; p=0,04).Los programas de cesación tabáquica son menos efectivas en los consumidores de TL a corto plazo. No se observan diferencias en la abstinencia a largo plazo entre ambos grupos.

Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients.

Background: COPD is a multifactorial disease which causes considerable mortality and morbidity worldwide. Previous studies assessing the possible relationship between indoor radon exposure and COPD have shown inconclusive results. Methods: A multicentric, hospital-based, case-control study was conducted in a Spanish radon-prone area. COPD cases were confirmed by spirometry and controls were selected due to trivial surgery or procedures not related to tobacco consumption. All participants had to have lived for at least 15 years in the same dwelling. Radon measurements were conducted individually in dwellings using alpha-track detectors. Results were obtained using multivariate logistic regression. Results: 189 cases and 747 controls took part. There was no significant association between residential radon concentrations and COPD onset with a OR of 1.12 (95%CI 0.41–3.06) for individuals exposed to more than 200 Bq/m3 compared to those exposed to less than 50 Bq/m3. Heavy smokers seem to increase their COPD risk if exposed to higher radon concentrations vs those exposed to lower concentrations. There was a statistically significant synergy index between radon exposure and tobacco consumption, S-index 11.60 (95%CI 3.71–36.26). Indoor radon concentration was higher in never/light smokers with COPD compared to controls. Conclusions: No association between indoor radon and COPD has been observed. However, there might be some effect modification on the COPD risk in heavy smokers when high radon exposure is present. This is supported by the additive synergy observed. Also, a possible association between indoor radon and COPD onset in never and light smokers needs to be further studied.

Background: Respiratory rehabilitation (RR) has demonstrated efficacy within the comprehensive treatment of patients with stable COPD. Aim: To determine the clinical impact of RR in patients with stable COPD in our area. Methods: Descriptive analysis of the pre and post-intervention data of patients who during the last 6 years underwent an RR program. Statistical package for the social sciences (SPSS, version 22) software was used for statistical analysis. Results: 88 patients whose characteristics are shown in Table 1 were included. 71 (80.7%) completed the program. Two months after RR, significant differences in the 6-minute walking test (6MWT) with respect to baseline (X +38.4, SD 73.2, p There was a significant decrease in the assistance to the emergency services between the year before and after (0.89, SD 1.43 vs 0.55, SD 1.02; p 0.012). There were no differences in income or in the amount of days of admission. Conclusion: RR achieves a clinical improvement in patients with stable COPD. 6MWT is an useful tool to evaluate the effect of RR. It is important to refer patients with stable COPD to RR programs.

Background Patients with COPD are at higher risk of presenting with atrial fibrillation (AF). Information about clinical outcomes and optimal medical treatment of AF in the setting of COPD remains missing. We aimed to describe the prevalence of COPD in a sizeable cohort of real-world AF patients belonging to the same healthcare area and to examine the relationship between comorbid COPD and AF prognosis. Methods Prospective analysis performed in a specific healthcare area. Data were obtained from several sources within the "data warehouse of the Galician Healthcare Service" using multiple analytical tools. Statistical analyses were completed using SPSS 19 and STATA 14.0. Results A total of 7,990 (2.08%) patients with AF were registered throughout 2013 in our healthcare area (n=348,985). Mean age was 76.83±10.51 years and 937 (11.7%) presented with COPD. COPD patients had a higher mean CHA2DS2-VASc (4.21 vs 3.46; P=0.02) and received less beta-blocker and more digoxin therapy than those without COPD. During a mean follow-up of 707±103 days, 1,361 patients (17%) died. All-cause mortality was close to two fold higher in the COPD group (28.3% vs 15.5%; P

We aimed to evaluate lung cancer survival in never-smokers, both overall and specifically by sex, exposure to residential-radon, age, histological type, and diagnostic stage. We included lung cancer cases diagnosed in a multicentre, hospital-based, case-control-study of never-smoker patients, diagnosed from January-2011 to March-2015 (Lung Cancer Research In Never Smokers study). 369 never-smokers (79% women; median age 71 years; 80% adenocarcinoma; 66% stage IV) were included. Median overall survival, and at one, 3 and 5 years of diagnosis was 18.3 months, 61%, 32% and 22%, respectively. Higher median survival rates were obtained for: younger age, adenocarcinoma, actionable mutations, and earlier-stage at diagnosis. Higher indoor radon showed a higher risk of death in multivariate analysis. Median lung cancer survival in never-smokers seems higher than that in ever-smokers. Patients with actionable mutations have a significantly higher survival. Higher indoor-radon exposure has a negative effect on survival.

Introduction The presence of eosinophils in asthma inflammation is a relevant factor in the pathophysiology of the disease, however the relationship between the blood eosinophil count (BEC) with asthma severity and prognosis is still under debate. The aim of this work is to analyze the relationship between the BEC levels and hospital readmissions in patients with asthma. Material and methods A review was retrospectively carried out on all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. The personal characteristics and the asthma personal history of each patient were recorded. The BEC was determined from the first blood sample taken from the patient after their arrival at the hospital. Hospital early, late and frequent readmissions were analyzed using 4 cut-off points; less than 150 eosinophils/μL vs ≥150/μL, less than 200 vs 200 /μL, less than 300 vs ≥300/μL, and less than 400 vs ≥400/μL. Results We have included 1316 patients, 70% of whom are women, as well as a mean age of 60 years, and a mean FEV1 of 73.5% of the reference value. The mean eosinophil blood count was 201.7 cells/μL. A BEC ≥300 cells/μL showed a reduction of risk of late readmission of 42%, a BEC ≥400 cells/μL showed a reduction in late readmission risk of 41% and decrease in frequent late readmission of 63%. Conclusions Our study appears to support that an elevated BEC is associated with a lower incidence of asthma hospital readmissions.

The relationship between obesity and asthma exacerbations is still under debate. The aim of our work is to analyse the relationship between obesity and hospital re-admissions in asthmatics. A review was retrospectively performed on all hospital admissions of adult patients due to asthma exacerbation occurring in our hospital for 11 years. All those cases with asthma as the first diagnosis in the discharge report were included, or those with asthma as the second diagnosis provided when the first diagnosis was respiratory infection or respiratory failure. Only the first hospital admission of each patient was included in this study. The Odds Ratios of a higher incidence of early/late readmissions due to asthma exacerbation were calculated using a binary logistic regression, using the body mass index (BMI) as independent variable, adjusted for all the variables included in the study. The study included 809 patients with a mean age of 55.6 years, and 65.2% were female. The majority (71.4%) were obese or overweight. No significant relationship was observed in the univariate or multivariate analyses between overweight or obesity and the early or late hospital readmissions due to asthma. Therefore, obesity does not seem to be a determining factor in the risk of asthma exacerbations.

Serum samples are easily obtained and contain proteins released by cells in steady-state or pathological conditions. Therefore, they are ideal for differential proteomics analyses, which can be applied to heterogeneous disorders like asthma to identify biomarkers associated with patient subgroups. In the present study, sera from healthy controls (HC) or patients with rhinitis (R) or different asthma phenotypes (allergic/AA vs. non-allergic/NAA)/severities (intermittent mild/IM vs. moderate-severe/MS) were collected. The resulting groups of sera (MSAA, IMAA, R, MSNAA, IMNAA, HC) were randomly subdivided into 2 sample pools and analysed in triplicate together with an internal reference sample by means of CPLLs and 8 plex-iTRAQ-LC-MS/MS. This method identified 26 potential biomarkers involved in key processes for asthma pathogenesis, such as immune responses. PANTHER overrepresentation test against human plasma proteome also showed a role of pathways related to the Insulin-like Growth Factor (IGF) in AA and complement factors in NAA. Indeed, our results suggest a set of serum biomarkers to differentiate AA from NAA patients: insulin-like growth factor acid-labile subunit (IGF-ALS) (already validated by ELISA), protein AMBP, and heparan sulfate proteoglycan 2 (HSPG2) for MSAA and complement factor I (CFI) and MASP1 for NAA.

Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19, EudraCT number: 2020-001760-29).

The authors regret not having included the following funding in the paper “Spanish Society of Neumology and Thoracic Surgery”. Project number 848. 2019 call. The authors would like to apologise for any inconvenience caused.

In 2003, FDA approved Omalizumab for the treatment of severe allergic asthma. This mAb recognizes IgE and blocks its binding to basophils and mast cells, attenuating FceRI signalling. Nevertheless, its effect on T helper (Th) subsets like regulatory (Tregs) or effector (Teff) cells remains poorly described. To address this issue peripheral blood samples were drawn from three groups of adults (n= 106): Healthy controls (HC; n= 32) and clinically stable allergic asthmatics (n= 74), either on glucocorticoid (Omalizumab-; n= 50) or Omalizumab (Omalizumab+; n= 24) therapy. Due to the higher severity in the Omalizumab+ group and despite the biological, FEV1 (%) and FEV1/FVC (%) were still lower than those in Omalizumab- patients. Asthmatics showed higher eosinophil numbers and total IgE compared to HC, but Omalizumab did not cause their down-modulation. Flow cytometry evidenced a higher activated status (CD26) in Th cells from asthmatics that was not affected by Omalizumab. In contrast, the increment of “terminally differentiated” Teff percentages in Omalizumab- patients compared to HC was almost lost in the Omalizumab+ group. The biological therapy did not alter the percentage of circulating Treg cells or levels of serum TGFβ1 but led to a significant increment in the percentage of GARP+ cells within Treg and “terminally differentiated” Teff compared to HC. GARP is a receptor for latent TGFβ1 and a Treg activation marker. Therefore, apart from the actions of Omalizumab on mast cells and basophils, an additional mechanism could be the generation of lymphocytes with enhanced regulatory function or higher susceptibility to this activity.

Background Asthma remains a major public health concern because of its high prevalence and the costs it generates. Near-fatal asthma (NFA) episodes represent the most severe forms of the disease after fatal asthma with significant variations in their incidence between different populations. Objective To analyze the episodes of NFA over a period of 11 years in the hospital. Methods The authors retrospectively reviewed all admissions due to asthma exacerbation in our hospital between 2000 and 2010 for patients over 18 years of age. Results The study included 400 NFA episodes of 285 patients (74% women; mean age 66 years). Of these patients, 228 (80%) had a single episode of NFA and 57 had more than 1 episode during the study period. The authors observed no clear upward or downward trend during the study period. Readmitted patients had more comorbidities, poorer lung function, more severe forms of asthma and more admissions in the year before the index admission. There was a mortality rate of 3.1%. More than 20% of patients were not given controller treatment and more than 40% of patients were not treated with inhaled corticosteroids (ICS). Conclusions NFA episodes are still prevalent in the population of patients with asthma. Reasons for this could be related to improper management in the stable phase, as suggested by the low rate of patients treated with ICS. It also seems necessary to optimize patient management during hospitalization because stays appear prolonged in comparison with studies in other countries.

Background: The pathogenesis of asthma is dependent on the balance between regulatory and effector T cells, which display differential expression of CD25 and CD26. Therefore, alteration of circulating levels of sCD25 and sCD26 during allergic asthma could be conditioned by changes in leukocyte phenotype. Objectives: To analyze expression of CD25 and CD26 on T lymphocytes and their soluble derivatives (sCD25, sCD26) during stable phases of moderate-severe allergic asthma. Methods: Cross-sectional study with 2 adult cohorts of allergic asthmatics. Clinical, anthropometric, pulmonary, hematological, and biochemical parameters were measured. Phenotyping was performed with flow cytometry in both circulating and cultured leukocytes. Dipeptidyl peptidase 4 (DPP4) activity was assayed in culture supernatants. Results: In vitro studies revealed upregulation of CD26 on human T lymphocytes upon activation, especially under TH17-favoring conditions, and a correlation with soluble DPP4 activity (rs=0.641; P

The role of effector TH cells (Teff; CD25 low CD127 high ) like TH17 lymphocytes in asthma depends on their interplay with regulatory T cells (Treg; CD25 high CD127 low ), which display low levels of CD26 (TH17>>TH1>TH2>>Treg) but high of LRRC32. The Treg-TH17 balance is controlled by IL-6R, an asthma risk locus together with LRRC32. Our aim was to analyse the levels of CD26, CD126, CD127 and LRRC32 in different lymphocyte subsets during non-active stages of allergic (AA)/non-allergic asthma (NAA) and rhinitis (R). Blood/serum samples were obtained from 268 Spanish adults constituted by 32 healthy donors (HC) and 236 patients (43 R, 103 AA, 90 NAA), and surface markers were assessed by flow cytometry. Our results show that Treg percentage is higher in men, but Treg and Teff numbers remain unchanged in patients (AA, NAA, AR) compared to HC. As expected, AA and NAA have higher mean number of CD26 molecules on CD4 + T cells than HC. Moreover, CD26 (and LRRC32) mean fluorescence intensity within the Treg subset allows to differentiate NAA from AA patients. An expansion of a CD25 low CD26 low CD127 low (triple low; TL) TH subset is detected in AA patients, what is inversely related to CD26 levels and is in line with a reduction of soluble CD26. CD26 (%) and CD126 (%) display a strong positive correlation in TL lymphocytes, and CD26 (%) is decreased in NAA patients compared to AA, AR and HC donors; similar results are obtained for CD26 and CD126 in CD4 − lymphocytes. The % of CD127 + cells in Teff, TL and especially Tregs is increased in patients (AA, NAA, AR) compared to HC. In conclusion, our results open a way to differentiate different phenotypes of asthma according to different levels of T cell surface markers.

Hospital admissions account for a significant part of asthma cost, but with significant differences between geographic areas.The aim of our study is to analyse hospital admissions due to asthma, as well as the factors associated with longer hospital stays.A review was retrospectively carried out on all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. The personal characteristics of each patient, the asthma personal history, characteristics of every exacerbation, as well as the treatment before admission and after hospital discharge were recorded.During the study period, there were 2163 hospital admissions in 1316 patients (mean age 62.6 years; mean hospital stay 11.6 days). The admissions mainly occur in winter, in the 56-75-year age group, and in patients with severe asthma. Female sex, higher comorbidity, a greater number of emergencies due to asthma in the previous year, and baseline treatment with theophylline were independently associated to longer hospital stay.The management of asthma in our population seems improvable. There appears to be a need to optimise both the diagnosis and treatment of the disease, and to identify risk factors as important as tobacco habits. As regards exacerbations, the hospital stay and mortality must be significantly reduced.

Although during the last few years there have been several important changes in the diagnostic or therapeutic methods, pleural effusion is still one of the diseases that the respiratory specialist have to evaluate frequently. The aim of this paper is to update the knowledge about pleural effusions, rather than to review the causes of pleural diseases exhaustively. These recommendations have a longer extension for the subjects with a direct clinical usefulness, but a slight update of other pleural diseases has been also included. Among the main scientific advantages are included the thoracic ultrasonography, the intrapleural fibrinolytics, the pleurodesis agents, or the new pleural drainages techniques.

Resumen A pesar de los multiples avances diagnosticos o terapeuticos de la medicina de los ultimos anos, el derrame pleural (DP) continua siendo una de las enfermedades que con frecuencia tiene que abordar el especialista de aparato respiratorio o el cirujano toracico. El presente texto no tiene como objetivo realizar una revision exhaustiva sobre las enfermedades que pueden producir DP, su diagnostico o su tratamiento, sino constituir una actualizacion de los conocimientos publicados en los ultimos anos. Teniendo en cuenta la vocacion eminentemente practica de esta normativa, se ha concedido mas extension a las enfermedades que presentan una mayor incidencia o prevalencia, aunque no hemos renunciado a un ligero recordatorio de otras menos frecuentes. Entre los mayores avances destacan los conocimientos sobre la utilidad de la ecografia toracica, los fibrinoliticos y los agentes pleurodesicos, o la utilizacion de nuevas tecnicas de drenaje pleural, como los tubos toracicos finos o los cateteres tunelizados. La actualizacion periodica de las normativas favorece la potencial incorporacion de nuevas tecnicas en el estudio de la enfermedad pleural.

The effect of pollen level on asthma hospitalizations is still under debate. The aim of this study was to analyze hospital admissions due to asthma and its relation with environmental pollen and meteorological factors. During 13 years, we included every patient admitted with asthma as primary or secondary diagnosis. For this purpose, we used a case-crossover analysis to compare pollen concentrations at the time of admission with values of the same variables 2 to 6 days before admission. We included 6,687 hospital admissions. High maximum temperature and low humidity were associated with lower risk of asthma admissions. High mean pollen levels exerted a moderate effect and high maximum pollen levels led to a dramatic increase of hospital admissions due to asthma, especially among females. In conclusion, environmental pollen level increases the risk of asthma hospital admissions.

[Abstract] Objective. Assess the prevalence of rhinitis and exposure to environmental tobacco smoke (ETS) of children in our community and its relationship with symptoms of rhinitis Methods (design, setting, participants, main outcome measures). Cross‐sectional study using questionnaire on rhinitis of the International Study of Asthma and Allergies in Childhood, in children (6‐7 years) and adolescents (13‐14 years). Categories: “rhinitis ever”, “recent rhinitis”, “recent rhinoconjunctivitis”, “severe rhinoconjunctivitis”. Parental smoking: (i) neither parent smokes; (ii) only the mother smokes; (iii) only the father smokes; and (iv) both parents smoke. Odds ratio of the prevalence of symptoms of rhinitis according to ETS exposure was calculated using logistic regression. Results. 10 690 children and 10 730 adolescents. The prevalence of “rhinitis ever” in children: 29.4%, “recent rhinitis” 24%, “recent rhinoconjunctivitis” 11.5% and “severe rhinoconjunctivitis” 0.1%. In adolescents: 46.2%, 34.5%, 16.2% and 0.2%, respectively. Environmental tobacco smoke exposure in the home occurred in 51% of cases. Parental smoking was associated with a higher prevalence of forms of rhinitis in adolescents when only the mother was a smoker. In children when both parents were smokers. Conclusion. Rhinitis is highly prevalent in our community. Environmental tobacco smoke exposure is still very common. The relationship between ETS and rhinitis symptoms in children of this community is not as robust as that found for asthma.

The aim of our study is to analyse hospital readmissions due to asthma, as well as the factors associated with their increase. We carried out a retrospective study including all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. The data were gathered by two members of the research team, by reviewing the clinical records. The first hospital admission of each patient was included for this study. An early readmission (ER) was defined as that which occurred in the following 15 days after hospital discharge and late readmission (LR) to that occurring from 16 days after discharge. This study included 2166 hospital admissions and 1316 patients, with a mean age of 62.6 years. Of the 1316 patients analysed, 36 (2.7%) had one ER and 313 (23.8%) one LR. The only factor independently associated with a higher probability of an ER was poor lung function. A higher probability of LR was associated with a greater severity of the asthma (OR: 17.8, for severe asthma versus intermittent asthma), to have had any hospital admission in the previous year (OR: 3.5) and the use of a combination of ICS-LABA as maintenance treatment. About 25% of the patients in our area admitted to hospital due to asthma exacerbation had repeat episodes of hospitalisation.

Introduction: Endobronchial ultrasound (EBUS) has been a major breakthrough in the staging of lung cancer, but its usefulness in the diagnosis of other diseases is limited by the size of the needles available. Objectives: Analyze the diagnostic yield of EBUS without ROSE, and the influence of the use of the cell block in the diagnosis of sarcoidosis. Methods: From August 2010 through November 2015, 804 EBUS were performed without ROSE. Until June 2012 a smear of the material obtained in puncture was subsequently referred to the pathology department. Thereafter the samples were prepared as cell block. Results: Among the 804 EBUS performed, we found 44 (5.4%) sarcoidosis [30 men (68.2%; mean age 51.5 ± 16.2 years) and 14 women (31.8%; 55 7 ± 18.2 years)]. In 13/44 patients (29.5%) had previously undergone another diagnostic procedure with negative results. EBUS was diagnostic in 35 patients (79.5 %). In the remaining 9 patients, the diagnosis was established by mediastinoscopy (7 patients) peripheral lymph node biopsy and transbronchial biopsy. EBUS diagnostic yield increased to 88% (32/36) when cell block was used. On the other hand it fell to 37.5% (3/8) when a conventional smear was used. An average of 1.84 lymph nodes per patient were punctured. Stations most frequently punctured were 7, 4R and 11R (in 38, 16 and 11 cases, respectively). No significant differences were found in diagnostic yield in relation with the number of stations punctured (p=0.259). Conclusions: EBUS is an useful technique for the diagnosis of sarcoidosis. The use of the cell block technique for processing EBUS samples ,improves the diagnostic yield in sarcoidosis and should be the method of choice.

The effect on survival of delays in the consultation, diagnostic and treatment processes of lung cancer (LC) is still under debate. The objective of our study was to analyse these time delays and their possible effect on survival. A retrospective study has been performed on all patients in our health area diagnosed with LC (confirmed by cytohistology) over 3 years. The delay in specialist consultation (time between start of symptoms and the first consultation with a specialist), hospital delay (time between first consultation and start of treatment) and overall delay (the sum of the previous two delays) were analysed. The influence of each of these delays was calculated using Cox regression, adjusted for other factors. A total of 415 patients were included. Of these, 92.5% were male and 75.4% were in stages III-B or IV. The overall delay gave a mean of 123.6 days, the delay in consulting a specialist 82.1 days and the delay in hospitalisation was 41.4 days. A greater overall delay or greater hospital delay was associated with longer survival. No relationship was observed between the specialist consultation delay and survival. Globally analysing all the cases and all the stages with LC, it is seen that longer delays are associated with longer survival. This probably reflects the fact that patients with more symptoms are treated more rapidly.

Lung cancer (LC) is now the leading cause of cancer mortality in the world, therefore it would be useful to identify prognostic factors to determine patient outcome. The objective of this study is to evaluate the usefulness of platelet counts at the time of diagnosis as a prognostic factor. A retrospective study of patients with histological diagnostic evidence of LC was carried in our catchment area over a 3-year period. Survival adjusted for other factors was assessed according to the platelet count at the time of diagnosis. Patients with platelet levels within the reference range (RR) (135000-381000/microl) were divided into two groups, between 135000-258000/microl and 258000-381000/microl. A third group was made up of patients with platelet counts over 381000/microl. Adjusted survival was analysed using Cox regression models. Patients with high platelets have a 37% worse survival than those with a platelet level within the RR, but lower than 258000/microl. When tumour stage is included in the covariates, platelet levels are no longer an independent survival factor. In conclusion, platelet levels at the time of diagnosis could be a useful prognostic factor in LC.

Fundamento y objetivo La anemia es un hallazgo frecuente en pacientes con cancer de pulmon (CP). Los valores de hemoglobina en el momento del diagnostico del CP podrian permitirnos una mas precisa clasificacion pronostica inicial de estos pacientes. El objetivo de nuestro estudio ha sido analizar el valor de la hemoglobina en el momento del diagnostico como factor pronostico en pacientes con CP. Pacientes y metodo Se ha realizado un estudio retrospectivo de todos los pacientes diagnosticados de CP (con confirmacion citohistologica) durante 3 anos en nuestra area sanitaria. Se evaluo la supervivencia en funcion de la hemoglobina en el momento del diagnostico, ajustada por otros factores. Segun el valor de hemoglobina, los pacientes se clasificaron en 2 grupos: uno con hemoglobina baja ( Resultados Se incluyo finalmente a 421 pacientes, de los que el 52,3% presentaron anemia al diagnostico. La edad media fue de 65,8 anos y el 92,7% fueron varones. Presentar una hemoglobina inferior al percentil 25 supone una posibilidad de supervivencia un 41% inferior. Conclusiones La hemoglobina baja se asocia con disminucion de la supervivencia. La evaluacion de este parametro podria permitir una mayor precision en el pronostico del CP y una major adecuacion de las indicaciones terapeuticas.

Objetivo Son conocidas las diferencias entre distintas poblaciones en cuanto a los valores de referencia de la funcion respiratoria, por lo cual parece importante establecerlos. El objetivo del estudio ha sido establecer las ecuaciones de prediccion de parametros espirometricos en ninos y adolescentes sanos de Galicia. Poblacion y metodos Hemos estudiado a ninos y adolescentes sanos de 6 a 18 anos de edad, de colegios seleccionados aleatoriamente en 14 municipios de Galicia. Las maniobras espirometricas se realizaron de acuerdo con los protocolos de la American Thoracic Society de 1987, con evaluacion continua de los espirogramas. Se obtuvieron las ecuaciones de prediccion mediante regresion lineal multivariante. Resultados Con este estudio se obtuvieron las ecuaciones de prediccion de los principales parametros espirometricos en este grupo de edad, en funcion de la edad, el sexo, la talla y el peso. Los valores medios de los parametros espirometricos, en funcion de la estatura, son superiores en la poblacion masculina comparada con la femenina, excepto en el rango entre 140 y 160 cm de altura, donde las mujeres superan a los varones. Para un varon medio de nuestra poblacion, los parametros de funcion pulmonar obtenidos con las ecuaciones de prediccion referidas por otros autores en poblaciones similares difieren de los nuestros, desde una infraestimacion de un 16% para el flujo mesoespiratorio forzado hasta una sobreestimacion de un 15% para el pico de flujo espiratorio; para una mujer, las discrepancias van desde la infraestimacion del flujo mesoespiratorio forzado del 17% hasta la sobreestimacion del pico de flujo espiratorio de un 19%. Conclusiones Estos resultados refuerzan la importancia de utilizar ecuaciones de prediccion especificas para cada poblacion.

Pleural fluid originates in the pleural capillaries (mainly those of the parietal pleura), lymphatics, intrathoracic blood vessels, the interstitial pulmonary space, and the peritoneal cavity. It is reabsorbed mainly through the lymphatics of the parietal pleura. The mechanisms that cause pleural effusion all result in an increase in the production or a decrease in the removal of pleural fluid and may be related to changes in hydrostatic capillary, intravascular or extravascular colloid osmotic, and negative intrathoracic pressures (Table 1). The prevalence of pleural effusion is slightly in excess of 400/100 000 population. Congestive heart failure is the most common cause of pleural effusions overall. However, the predominant etiologies among the exudates are pneumonia, malignancy, and pulmonary embolism. Table 2 shows the most common causes of pleural effusion.

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder, characterized by repeated disruptions of breathing during sleep. This disease has many potential consequences including excessive daytime sleepiness, neurocognitive deterioration, endocrinologic and metabolic effects, and decreased quality of life. Patients with OSAS experience repetitive episodes of hypoxia and reoxygenation during transient cessation of breathing that provoke systemic effects. Furthermore, there may be increased levels of biomarkers linked to endocrine-metabolic and cardiovascular alterations. Epidemiological studies have identified OSAS as an independent comorbid factor in cardiovascular and cerebrovascular diseases, and physiopathological linksmay existwith onset and progression of heart failure. In addition, OSAS is associated with other disorders and comorbidities which worsen cardiovascular consequences, such as obesity, diabetes, and metabolic syndrome. Metabolic syndrome is an emerging public health problem that represents a constellation of cardiovascular risk factors. Both OSAS and metabolic syndrome may exert negative synergistic effects on the cardiovascular system throughmultiplemechanisms (e.g., hypoxemia, sleep disruption, activation of the sympathetic nervous system, and inflammatory activation). It has been found that CPAP therapy for OSAS provides an objective improvement in symptoms and cardiac function, decreases cardiovascular risk, improves insulin sensitivity, and normalises biomarkers. OSAS contributes to the pathogenesis of cardiovascular disease independently and by interaction with comorbidities.The present review focuses on indirect and direct evidence regarding mechanisms implicated in cardiovascular disease among OSAS patients

OBJETIVO: Avaliar a exposição da população infantil à FCA em nossa comunidade e sua relação com os sintomas de asma. MÉTODOS: Foi realizado um estudo transversal usando o questionário de estudo ISAAC em crianças e adolescentes da nossa comunidade. Pelo questionário, fez-se a definição por "já ocorreu sibilância", "asma atual", "asma grave" e "asma induzida pelo exercício". O tabagismo parental foi classificado em quatro categorias mutuamente excludentes: 1) nenhum dos pais fuma; 2) somente a mãe fuma; 3) somente o pai fuma; e 4) ambos os pais fumam. Calculou-se a odds ratio da prevalência de sintomas de asma, de acordo com a exposição à FCA, usando regressão logística. RESULTADOS: Foram incluídas, no total, 10.314 crianças e 10.453 adolescentes. Mais de 51% das crianças e adolescentes foram expostos à FCA em casa. A FCA se associa a uma prevalência mais alta de sintomas de asma, particularmente se a mãe ou ambos os pais fumam. CONCLUSÕES: A prevalência da FCA continua a ser alta em nossa comunidade, embora com uma tendência para diminuição nos últimos 15 anos. A FCA se associa a uma prevalência mais alta de asma.

[Abstract] Background. Some studies indicate some causal relationship between obesity and asthma, while others show inconsistent results. Our objective was to evaluate the prevalence of asthma according to obesity in children. Methods. A cross-sectional study, following the ISAAC study methodology, was conducted on two randomly selected groups consisting of 6–7 year-old children (n = 7485) and 13–14 year-old adolescents (n = 8496). The asthma symptoms and potential risk factors were determined from the questionnaire. Overweight and obesity were defined based on the body mass index. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) and 95% confidence intervals. Results. Obesity was associated with an increase in wheezing ever (OR: 1.35) and exercise-induced asthma (OR: 1.62) in the 6–7 year-old group. No significant relationship was observed in the adolescent population. Conclusion. Obesity was associated with a higher prevalence of asthma in young children, but not in adolescents.

Asthma is a very common chronic disease that occurs in all age groups. Its high prevalence has significant health costs, which are even higher in the most severe disease forms. Lung cancer has the highest incidence of all cancers in the developed world and is an important cause of mortality. Patients with lung cancer are a big economic burden on health services, both in direct and indirect costs. Different authors suggest that atopic constitution, including different manifestations of allergy and asthma, are possible risk factors for lung cancer, above all in never-smokers. Given the high asthma prevalence and lung cancer incidence and mortality in developed countries, this association would have important public health implications. Uncertainties about the association and the underlying physiopathological mechanisms, however, seem to require further studies.

Resumen No esta bien definida el tipo de asistencia especializada que deben dar los hospitales comarcales. Para evaluar diferentes opciones, se analizo retrospectivamente la atencion neumologica en el ano 2008 en dos areas comarcales de Galicia: Barbanza y Cee, con caracteristicas poblacionales similares. El hospital de Barbanza dispone de consulta de neumologia atendida por especialistas del hospital de referencia 3 dias/semana, mientras que en Cee la atienden internistas del propio centro. En ambos casos, la hospitalizacion esta a cargo del servicio de Medicina Interna. Los datos fueron proporcionados por los servicios administrativos de los hospitales y autonomicos. Las estancias medias para el agrupador CDM4 fueron similares en los dos comarcales, pero inferiores a las de los centros de referencia. No hubo diferencias en comorbilidad (Charlson) ni en reingresos al mes de alta. Se realizaron mas exploraciones funcionales en pacientes del Barbanza, tanto en el propio centro (957 espirometrias vs 21; p Estos datos sugieren que en un modelo de hospital comarcal con neumologos consultores, la consulta ambulatoria facilita el acceso a una asistencia mas especializada, mas completa y, probablemente, de mas calidad, que los comarcales sin este tipo de consultoria.

Resumen La fibrosis pulmonar idiopatica (FPI) es una enfermedad cronica y progresiva. En su evolucion puede presentar episodios de exacerbacion aguda, cuya definicion mas aceptada seria aquel episodio de deterioro agudo, con significado clinico, de causa no identificada, en un paciente con una FPI subyacente. La incidencia de la FPI con exacerbacion aguda oscila entre un 5–19% de pacientes por ano, y se estima que un 47% de los pacientes con FPI presentara un deterioro clinico agudo antes del fallecimiento. El signo que invariablemente esta presente es la disnea, acompanada de tos, fiebre y sintomas seudogripales. La presencia de leucocitosis en el hemograma, neutrofilia en el lavado broncoalveolar y opacidades difusas en vidrio deslustrado superpuestas a las habituales de la FPI en la radiogafia de torax orientan el diagnostico. El hallazgo histologico tipico es el dano alveolar difuso. La respuesta al tratamiento es pobre, aunque la metilprednisolona parece ser la mejor opcion terapeutica.