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Rafael Golpe, María Suárez-Valor, Irene Martín-Robles, Pilar Sanjuán-López, Esteban Cano-Jiménez, Olalla Castro-Añón, Luis A Pérez de Llano Respiratory Medicine Service, University Hospital Lucus Augusti, Lugo, Spain Purpose: Grouping COPD subjects into clinical phenotypes might be useful for the management of the disease, but the clinical implications of such classification are still not totally clear, especially regarding prognosis. The primary objective of this study was to assess whether the mortality rates were different between four predefined clinical phenotypes. Patients and methods: This is a retrospective, observational study carried out at the COPD clinic of a University Hospital. A total of 891 COPD patients were classified, according to the Spanish COPD guidelines, into the following four phenotypes: asthma–COPD overlap (ACO; 75 subjects), nonexacerbator (NONEX; 531 subjects), exacerbator with chronic bronchitis (EXCB; 194 subjects), and exacerbator with emphysema (EXEMPH; 91 subjects). We compared the mortality outcomes between the phenotypes. Results: After a follow-up of 48.4±25.2 months, there were 194 deaths (21.8%). There were significant differences in all-cause mortality between phenotypes. The ACO phenotype had the best long-term prognosis, whereas EXEMPH had the highest risk of death. NONEX and EXCB mortality figures were in between the other two groups. We also found some differences in the causes of death, and patients with EXEMPH were at a higher risk of dying because of COPD itself. The differences in mortality did not seem related to the classification into phenotypes in itself but to disparities in COPD severity and comorbidity load between groups. Conclusion: Classifying COPD patients according to several predefined clinical phenotypes can identify clusters of subjects with different mortality outcomes. Some phenotypes are associated with a specific cause of death. The mechanisms that underlie these differences seem to be related to COPD severity and comorbidities. Keywords: COPD, phenotypes, mortality

Background: The incidence and clinical significance of pulmonary residual thrombosis 6 months after an acute pulmonary embolism (PE) are still not well-known. Purpose: To evaluate the association between residual vascular obstruction and the risk of venous thromboembolism (VTE) recurrence or death. Material and Methods: Computed tomography pulmonary angiography (CTPA) was repeated in 97 consecutive patients 6 months after an acute episode of hemodynamically stable pulmonary embolism. We assessed the long-term consequences of residual thrombosis on vital status and incidence of recurrent VTE. Results: Six patients were lost for follow-up. The remaining 91 patients were classified according to the presence (Group 1: 18 cases) or absence (Group 2: 73 cases) of residual pulmonary vascular obstruction. After a mean ± SD of 2.91 ± 0.99 years, there were eight (8.8%) deaths and 11 (12.1%) VTE recurrences. Groups 1 and 2 did not differ in the incidence of death or VTE recurrence. Conclusion: Persistent pulmonary vascular obstruction on 6-month CTPA did not predict long-term adverse outcome events. [ABSTRACT FROM AUTHOR]

Background: Pneumonias are events of great prognostic significance in COPD, so it is important to identify predictive factors., Objective: To determine whether poor glycemic control is related to an increased risk of pneumonia in COPD., Method: A historical cohort study conducted in a COPD clinic. The first severe exacerbation after the first visit was analyzed. Exacerbations that presented with pulmonary infiltrates were identified. A Cox proportional hazards analysis was performed including the values of glycosylated hemoglobin (Hb1Ac) in patients with diabetes mellitus (DM) and variables that could plausibly be related to the risk of pneumonia. The best Hb1Ac value to predict pneumonia was assessed using receiver-operating characteristics analysis., Results: There were 1124 cases included in the study. A total of 411 patients were admitted to the hospital at least once and 87 were diagnosed with pneumonia. Variables associated with the risk of pneumonia were previous admissions due to COPD and Hb1Ac values (HR: 2.33, 95% CI: 1.06 - 5.08, p = 0.03). A higher body mass index (BMI) was associated with a lower risk of pneumonia. The optimal cutoff point for Hb1Ac to predict pneumonia risk was 7.8 %. The patients were classified into 3 groups: (1) no DM, (2) controlled DM (Hb1AC < 7.8 %), (3) uncontrolled DM (Hb1AC ≥ 7.8 %). The risk of pneumonia for group 2 was not different from group 1, while the risk for group 3 was significantly higher than for groups 1 and 2 (HR: 4.52, 95 % CI: 1.57 - 13.02)., Conclusions: Poor control of DM is a predictor of the risk of pneumonia in COPD. The cutoff point of 7.8 % for this variable seems to be the most useful to identify patients at risk., Competing Interests: Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No funding was received to assist with the preparation of this manuscript or for conducting this study. The authors have no conflicts of interest to declare that are relevant to the content of this article. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 SPLF and Elsevier Masson SAS. All rights reserved.)

Small cell lung cancer (SCLC) comprises approximately 10% of all lung cancer cases. Tobacco is its main risk factor; however, occupation might play a role in this specific lung cancer subtype. The effect of occupation on SCLC risk has been hardly studied and therefore we aim to assess the role of occupation on the risk of SCLC. To do this, we designed a multicentric, hospital-based, case-control study. Cases consisted exclusively in SCLC patients and controls were recruited from patients having minor surgery at the participating hospitals. Face to face interviews emphasizing occupation and tobacco consumption were held and residential radon was also measured. Logistic regression models were adjusted with odds ratios with 95%CI as estimations of the effect. 423 cases and 905 controls were included. Smoking prevalence was higher in cases compared to controls. Those who worked in known-risk occupations for lung cancer showed an OR of 2.17 (95%CI 1.33; 3.52), with a similar risk when men were analysed separately. The results were adjusted by age, sex, smoking and indoor radon exposure. Those who worked in known-risk occupations and were moderate or heavy smokers had a SCLC risk of 12.19 (95%CI 5.68-26.38) compared with never or moderate smokers who had not worked in such occupations. Occupation is a relevant risk factor of SCLC, and it seems that its effect is boosted when tobacco smoking is present., (© 2023. The Author(s).)

Competing Interests: The authors have disclosed no conflicts of interest.

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to disclose., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction and Objectives: Stable chronic obstructive pulmonary disease (COPD) caused by biomass smoke (B-COPD) has some differences from tobacco-induced-COPD (T-COPD), but acute exacerbations (AECOPD) have not been well characterized in B-COPD., Objective: To compare the incidence, characteristics and outcomes of AECOPD in B-COPD with those of T-COPD., Methods: A retrospective observational study that included consecutive patients seen at a specialized COPD clinic (2008-2021). The incidence of severe AECOPD that required hospital admission was studied. For the first AECOPD, the following variables were recorded: fever, coexistence of pneumonia, purulent sputum, eosinophil count, neutrophil to lymphocyte ratio, hypercapnia, and respiratory acidosis. Outcome variables were intensive care unit (ICU) admission, length of hospital stay, and mortality within 1 month of hospital admission., Results: Of 1060 subjects, 195 (18.4%) belonged to the B-COPD group and 865 (81.6%) to the T-COPD group. During a follow-up of 67.9 (37.8-98.8) months, 75 (38.4%) patients in the B-COPD group and 319 (36.8%) in the T-COPD group suffered at least one severe AECOPD. The only difference between groups was in a higher risk of ICU admission for the T-COPD group. The incidence, characteristics, and the rest of the outcomes of AECOPD were similar for both groups., Conclusion: AECOPD are similar events for B-COPD and T-COPD and should be managed similarly., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Thoracic Medicine.)

Introduction: Residential radon is considered the second cause of lung cancer and the first in never smokers. Nevertheless, there is little information regarding the association between elevated radon levels and small cell lung cancer (SCLC). We aimed to assess the effect of residential radon exposure on the risk of SCLC in general population through a multicentric case-control study., Methods: A multicentric hospital-based case-control study was designed including 9 hospitals from Spain and Portugal, mostly including radon-prone areas. Indoor radon was measured using Solid State Nuclear Track Detectors at the Galician Radon Laboratory., Results: A total of 375 cases and 902 controls were included, with 24.5% of cases being women. The median number of years living in the measured dwelling was higher than 25 years for both cases and controls. There was a statistically significant association for those exposed to concentrations higher than the EPA action level of 148Bq/m 3 , with an Odds Ratio of 2.08 (95%CI: 1.03-4.39) compared to those exposed to concentrations lower than 50Bq/m 3 . When using a dose-response model with 100Bq/m 3 as a reference, it can be observed a linear effect for small cell lung cancer risk. Smokers exposed to higher radon concentrations pose a much higher risk of SCLC compared to smokers exposed to lower indoor radon concentrations., Conclusions: Radon exposure seems to increase the risk of small cell lung cancer with a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: The optimal mode of long-term positive airway pressure (PAP) treatment for obesity-hypoventilation syndrome (OHS) is not clear. The objectives of this study were to analyze whether or not patients with severe OHS treated with continuous positive airway pressure (CPAP) remained controlled with this therapy over the long term and to investigate which variables were associated with CPAP failure and the need to switch to non-invasive ventilation (NIV)., Methods: In a retrospective single-center study, patients admitted to the hospital because of severe OHS between 1996 and 2015 were analyzed. A multiple regression analysis was performed in order to determine which variables were associated with either CPAP success or failure to maintain long-term control., Results: Of 126 consecutive patients, 115 accepted long-term PAP treatment. CPAP or NIV treatment was prescribed according to a protocol that included overnight polysomnographic PAP titration. Follow-up time was 8.0 ± 4.8 years. At the end of this period, 29% of CPAP-treated patients had been re-assigned to NIV because of recurrence of global respiratory failure. High levels of obesity, weight gain, lower FEV1/FVC values and the need for nocturnal supplementary oxygen independently predicted CPAP failure., Conclusion: CPAP therapy for severe OHS in patients who have these risk factors should be closely monitored in the long-term for possible treatment failure.

Introduction: Residential radon is considered the second cause of lung cancer and the first in never smokers. Nevertheless, there is little information regarding the association between elevated radon levels and small cell lung cancer (SCLC). We aimed to assess the effect of residential radon exposure on the risk of SCLC in general population through a multicentric case-control study., Methods: A multicentric hospital-based case-control study was designed including 9 hospitals from Spain and Portugal, mostly including radon-prone areas. Indoor radon was measured using Solid State Nuclear Track Detectors at the Galician Radon Laboratory., Results: A total of 375 cases and 902 controls were included, with 24.5% of cases being women. The median number of years living in the measured dwelling was higher than 25 years for both cases and controls. There was a statistically significant association for those exposed to concentrations higher than the EPA action level of 148Bq/m 3 , with an Odds Ratio of 2.08 (95%CI: 1.03-4.39) compared to those exposed to concentrations lower than 50Bq/m 3 . When using a dose-response model with 100Bq/m 3 as a reference, it can be observed a linear effect for small cell lung cancer risk. Smokers exposed to higher radon concentrations pose a much higher risk of SCLC compared to smokers exposed to lower indoor radon concentrations., Conclusions: Radon exposure seems to increase the risk of small cell lung cancer with a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

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., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Current guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a 'real world' population., Methods: A retrospective analysis was conducted of all patients who underwent pleural fluid (PF) sampling, in a single centre, over 3 years to determine the utility of the initial aspiration., Results: A diagnosis of MPE was confirmed in 230/998 (23%) cases, a further 95/998 (9.5%) were presumed to represent MPE. Transudative biochemistry was found in 3% of cases of confirmed MPE. Positive PF cytology was only sufficient to guide management in 45/140 (32%) cases. Evidence of pleural thickening on CT was associated with both negative cytology (χ 2 1df=26.27, p<0.001) and insufficient samples (χ 2 1df=10.39, p=0.001). In NEL 44.4% of patients did not require further procedures after pleurodesis compared with 72.7% of those with expansile lung (χ 2 1df=5.49, p=0.019). In patients who required a combined diagnostic and therapeutic aspiration 106/113 (93.8%) required further pleural procedures., Conclusions: An initial pleural aspiration does not achieve either definitive diagnosis or therapy in the majority of patients. A new pathway prioritising symptom management while reducing procedures should be considered., Competing Interests: Competing interests: NMR reports grants and personal fees from Rocket Medical UK, grants from BD USA, personal fees from Lung therapeutics USA, outside the submitted work. VG reports personal fees from Teva UK Ltd/Haymarket Media Group, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Hospitalized patients with acute-on-chronic hypercapnic respiratory failure due to obesity hypoventilation syndrome (OHS) have increased short-term mortality. It is unknown whether prescribing empiric positive airway pressure (PAP) at the time of hospital discharge reduces mortality compared with waiting for an outpatient evaluation (i.e., outpatient sleep study and outpatient PAP titration). Objectives: An international, multidisciplinary panel of experts developed clinical practice guidelines on OHS for the American Thoracic Society. The guideline panel asked whether hospitalized adult patients with acute-on-chronic hypercapnic respiratory failure suspected of having OHS, in whom the diagnosis has not yet been made, should be discharged from the hospital with or without empiric PAP treatment until the diagnosis of OHS is either confirmed or ruled out. Methods: A systematic review with individual patient data meta-analyses was performed to inform the guideline panel's recommendation. Grading of Recommendations, Assessment, Development, and Evaluation was used to summarize evidence and appraise quality. Results: The literature search identified 2,994 articles. There were no randomized trials. Ten studies met a priori study selection criteria, including two nonrandomized comparative studies and eight nonrandomized noncomparative studies. Individual patient data on hospitalized patients who survived to hospital discharge were obtained from nine of the studies and included a total of 1,162 patients (1,043 discharged with PAP and 119 discharged without PAP). Empiric noninvasive ventilation was prescribed in 91.5% of patients discharged on PAP, and the remainder received empiric continuous PAP. Discharge with PAP reduced mortality at 3 months (relative risk 0.12, 95% confidence interval 0.05-0.30, risk difference -14.5%). Certainty in the estimated effects was very low. Conclusions: Hospital discharge with PAP reduces mortality following acute-on-chronic hypercapnic respiratory failure in patients with OHS or suspected of having OHS. Well-designed clinical trials are needed to confirm this finding.

Background: The aim of this study was to assess the relationship between do-it-yourself activities entailing the exposure to carcinogenic substances and the risk of lung cancer., Methods: We pooled individual data from different case-control studies conducted in Northwestern Spain which investigated residential radon and lung cancer. Cases had an anatomopathologically confirmed primary lung cancer and controls were selected at the pre-surgery unit with uncomplicated surgeries. Both cases and controls were older than 30 years with no previous cancer history. All participants were interviewed face-to-face using a specific questionnaire. Painting, model building, furniture refinishing and woodworking or home carpentry were the do-it-yourself activities considered risky due to exposure to carcinogenic agents., Results: We included 1528 cases and 1457 controls. Practicing do-it-yourself risk activities was more frequent among cases: 16.0% were exposed to carcinogenic exposures during leisure time, compared to 11.8% for controls. The overall adjusted OR for lung cancer risk among individuals who practiced do-it-yourself risk activities, was 1.77 (95% CI: 1.36-2.31); this was 2.17 (95% CI: 1.51-3.11) when the analysis was restricted to individuals who performed these activities for at least 10 years. These risks were greater when the analyses were carried out exclusively among never-smokers, with the respective ORs being 2.04 (95% CI: 1.38-3.01) and 3.10 (95% CI: 1.78-5.40)., Conclusion: These results support the hypothesis that do-it-yourself activities involving exposure to certain carcinogens are associated with an increased risk of lung cancer, both in ever and never-smokers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To analyze the relationship of GSTT1, GSTM1, XRCC1 (rs25487), ERCC1 (rs11615, rs3212986), ERCC2 (rs13181), XRCC3 (rs861539), OGG1 (rs1052133), and Alpha-1-Antitrypsin mutations (AAT) with the risk of lung cancer in never-smokers, and ascertain if there is an effect modification between these polymorphisms and residential radon exposure., Material and Methods: We designed a multicenter hospital-based case-control study in a radon-prone area. 322 cases and 338 controls, all never-smokers, were included. They were selected using a frequency sampling based on sex and age distribution of the cases. Participants donated 3 ml. of whole blood used to determine genotype for polymorphisms. They placed a radon detector to measure residential radon exposure in their dwelling., Results: The OR for deleted GSTM1 patients was 3.46 (95% CI = 1.52-7.89) at residential radon exposures above 200 Bq/m 3 . The ERCC1 rs3212986 polymorphism was the most associated with the risk of developing lung cancer, both for low and high radon exposures. The ERCC1 rs321986 GT and TT genotypes (at radon concentrations >200 Bq/m 3 ) were more significantly associated with higher lung cancer risk (OR = 2.40, 95% CI = 1.29-4.45; OR = 4.45, 95% CI = 1.26-15.7, respectively)., Conclusions: These findings support the hypothesis that certain polymorphisms in genes involved in DNA-repair and carriers of GSTM1 deletion have an increased risk of lung cancer in never-smokers exposed to residential radon., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Comorbidities are a major cause of death in chronic obstructive pulmonary disease (COPD). The COPD-comorbidity test (COTE) index was designed to measure comorbidity burden in this disease. The objective of this study was to compare the capability of COTE and the non-COPD specific Charlson comorbidity index (CCI) to predict all-cause mortality in real-life conditions., Methods: Retrospective observational study, carried out in two different series of consecutive COPD patients including, respectively, 790 and 439 subjects. The COTE and non-age-adjusted CCI indices were calculated and the values of the C-statistic for predicting all-cause mortality were compared for both indices., Results: Median follow-up was 54 months and there were 321 deaths within this period of time. The value of the C-statistic for the CCI was significantly higher than for the COTE index in both groups., Conclusion: When used in real-life clinical practice, the value of the CCI to predict all-cause mortality in COPD seems higher than that of the COTE index., (© 2019 John Wiley & Sons Ltd.)

Background: Using a pooled case-control study design, including only never-smokers, we have assessed the association of residential radon exposure with the subsequent occurrence of lung cancer. We also investigated whether residential radon poses a different risk specifically for adenocarcinoma., Methods: We pooled individual data from different case-control studies conducted in recent years in Northwestern Spain which investigated residential radon and lung cancer. All participants were never-smokers. Cases had a confirmed biopsy of primary lung cancer. Hospital controls were selected at pre-surgery units, presenting for non-complex surgical procedures. They were interviewed using a standardized instrument. Residential radon was measured using alpha track detectors at the Galician Radon Laboratory at the University of Santiago de Compostela., Results: A total of 1415 individuals, 523 cases and 892 controls were included. We observed an odds ratio of 1.73 (95%CI: 1.27-2.35) for individuals exposed to ≥ 200 Bq/m 3 compared with those exposed to ≤100 Bq/m 3 . Lung cancer risk for adenocarcinoma was 1.52 (95%CI: 1.14-2.02) using the same categories for radon exposure., Conclusions: Residential radon is a clear risk factor for lung cancer in never-smokers. Our data suggest that radon exposure is associated with all histological types of lung cancer and also with adenocarcinoma, which is currently the most frequent histological type for this disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Lung cancer is the deadliest cancer in developed countries but the etiology of lung cancer risk in never smokers (LCRINS) is largely unknown. We aim to assess the effects of alcohol consumption, in its different forms, on LCRINS., Methods: We pooled six multi-center case-control studies developed in the northwest of Spain. Cases and controls groups were composed of never smokers. We selected incident cases with anatomopathologically confirmed lung cancer diagnoses. All participants were personally interviewed. We performed two groups of statistical models, applying unconditional logistic regression with generalized additive models. One considered the effect of alcohol type consumption and the other considered the quantity of each alcoholic beverage consumed., Results: A total of 438 cases and 863 controls were included. Median age was 71 and 66, years, respectively. Adenocarcinoma was the predominant histological type, comprising 66% of all cases. We found that any type of wine consumption posed an OR of 2.20 OR 95%CI 1.12-4.35), and spirits consumption had an OR of 1.90 (95%CI 1.13-3.23). Beer consumption had an OR of 1.33 (95%CI 0.82-2.14). These results were similar when women were analyzed separately, but for men there was no apparent risk for any alcoholic beverage. The dose-response analysis for each alcoholic beverage revealed no clear pattern., Conclusions: Wine and spirits consumption might increase the risk of LCRINSs, particularly in females. These results have to be taken with caution given the limitations of the present study.

Environmental tobacco smoke (ETS) exposure is a main risk factor of lung cancer in never smokers. Epidermal Growth Factor Receptor (EGFR) mutations and ALK translocations are more frequent in never smokers' lung cancer than in ever-smokers. We performed a multicenter case-control study to assess if ETS exposure is associated with the presence of EGFR mutations and its types and if ALK translocations were related with ETS exposure. All patients were never smokers and had confirmed lung cancer diagnosis. ETS exposure during childhood showed a negative association on the probability of EGRF mutation though not significant. Exposure during adulthood, at home or at workplace, did not show any association with EGFR mutation. The mutation type L858R seemed the most associated with a lower probability of EGFR alterations for ETS exposure at home in adult life. There is no apparent association between ETS exposure and ALK translocation. These results might suggest that ETS exposure during childhood or at home in adult life could influence the EGFR mutations profile in lung cancer in never smokers, reducing the probability of presenting EFGR mutation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Small cell lung cancer (SCLC) is the most aggressive histologic type of lung cancer, and accounts for approximately 10%-15% of all cases. Few studies have analyzed the effect of residential radon. Our aim is to determine the risk factors of SCLC., Methods: We designed a multicenter, hospital-based case-control study with the participation of 11 hospitals in 4 autonomous communities., Results: Results of the first 113 cases have been analyzed, 63 of which included residential radon measurements. Median age at diagnosis was 63 years; 11% of cases were younger than 50 years of age; 22% were women; 57% had extended disease; and 95% were smokers or former smokers. Median residential radon concentration was 128Bq/m 3 . Concentrations higher than 400Bq/m 3 were found in 8% of cases. The only remarkable difference by gender was the percentage of never smokers, which was higher in women compared to men (P<.001). Radon concentration was higher in patients with stageIV disease (non-significant difference) and in individuals diagnosed at 63 years of age or older (P=.032)., Conclusions: A high percentage of SCLC cases are diagnosed early and there is a predominance of disseminated disease at diagnosis. Residential radon seems to play an important role on the onset of this disease, with some cases having very high indoor radon concentrations., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Farmer's lung disease (FLD) is a common form of hypersensitivity pneumonitis possibly underdiagnosed in our midst. The aim of this study was to describe clinical characteristics, evolution and factors that influence the prognosis of patients with FLD., Patients and Methods: A retrospective study that included all patients diagnosed with FLD presenting an environmental exposure risk, a clinic, lung function and a compatible radiology, in which antigen sensitisation was demonstrated and/or a concordant pathology., Results: We selected 75 patients with FLD, 50 with acute or subacute form (ASF) and 25 with chronic form (CF). Forty-four percent of patients (n=33) were diagnosed during the months of March and April, especially those with ASF compared to CF (52 vs. 28%; P=.0018). In the ASF group, DLco showed an improvement during follow-up (P=.047). The determination of specific IgG antibodies was positive in 39 patients (78%) with ASF (44% of them against Aspergillus) and CF 12 (48%). The realisation of antigenic avoidance (OR 9.26, 95% CI 1.3-66.7, P=.026) and the administration of immunosuppressive therapy (OR 16.13, 95% CI 1.26-200, P=.033) were predictors of better disease progression., Conclusions: FLD is predominantly seasonal in our environment. CF usually has a negative specific IgG antibodies unlike ASF, where antibodies against Aspergillus are the most common. The realisation of antigenic avoidance and immunosuppressive treatment are possible predictors of better disease progression., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

The aim of this study was to assess if residential radon exposure might cause EGFR mutations or ALK rearrangements in never-smokers.We designed a multicentre case-control study in a radon-prone area (Galicia, Spain); only lung cancer cases were included in the study. We obtained residential radon measurements and clinical information for all the participants. We compared the median values of residential radon between patients with EGFR mutations or ALK rearrangements versus those without them.323 patients were included. Median age was 70 years and 19.5% were males. 42 and 15% of patients were EGFR- and ALK-positive, respectively. The most frequent EGFR alterations were exon 19 deletions and exon 21 (L858R) single-point substitution mutations. ALK-positive patients were 10 years younger than ALK-negative patients. Residential radon levels were two-fold higher in patients with exon 19 deletions compared with patients with exon 21 (L858R) single-point substitution mutations (216 versus 118 Bq·m -3 ; p=0.057). There were no differences in residential radon levels by EGFR mutation status. ALK-positive patients (n=12) essentially had two-fold residential radon levels compared with ALK-negative patients (290 versus 164 Bq·m -3 , respectively).Residential radon may have a role in the molecular signature of lung cancer in never-smokers, although more studies with larger sample sizes are needed to support this hypothesis., (Copyright ©ERS 2016.)

Background and Objective: Pulmonary arterial hypertension (PAH) is a rare and progressive disease that can be inherited as autosomal dominant form. The BMPR2, ACVRL1 and ENG genes are main genes involved in the pathology. PAH associated to human immunodeficiency virus (HIV) is another rare disease with a low incidence, prevalence and survival. The main objective of this analysis was to study the clinical and molecular characteristics of PAH associated to HIV patients., Patients: We present 4 cases of HIV patients who developed PAH and have been treated with ambrisentan., Results: Pathogenic mutations have been identify in analyzed genes in 3 of the four analyzed patients. In addition, these patients present other changes classified as benign after a thorough in silico analysis. We identified some changes in genetic modifiers that predispose to these patients to more severe phenotype., Conclusions: The clinical analysis can help to define monitoring for these patients and the administration of appropriate treatment. These patients also have shown several pathogenic mutations., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Our aim was to describe the characteristics of a case-series of never-smoker small cell lung cancer (SCLC) cases.Cases of SCLC were selected from a prospective, multicenter, hospital-based case-control study performed in Spain. Participants were never-smokers older than 30 years with an anatomo-pathological confirmation of primary lung cancer. We collected clinical and epidemiological variables according to the study's protocol.We included 19 SCLC cases, 18 females (94.7%), median age 75 years (interquartile range (IQR) 70-80 years). Median residential radon concentration was 195 Bq·m(-3) (IQR 130-229 Bq·m(-3)). 10 patients had limited disease and nine had extended disease. Median survival was 242 days (IQR 94-496 days); 1- and 2-year survival were 36.8% and 17.6%, respectively. Survival was much higher for individuals with limited disease than for those with extended disease (median 336 versus 235 days; 1-year survival 50% versus 22.2% and 2-year survival 27% versus 0%, respectively). Performance status at diagnosis was closely related to survival.SCLC is an infrequent, highly aggressive disease in never-smokers. Survival is poor, even for limited disease. Age at diagnosis in SCLC is higher than that observed for never-smokers with adenocarcinoma. Residential radon exposure is higher than the action levels recommended by the World Health Organization., (Copyright ©ERS 2016.)

Background: Never-smokers comprise up to 25% of all lung cancer cases. They could have different molecular pathways for lung cancer induction compared with smokers. Alpha-1 antitrypsin (AAT) deficiency is a hereditary trait whose main characteristic is early onset of lung emphysema. Our aim is to know if AAT-deficient carriers have a higher risk of lung cancer in a study performed exclusively in never-smokers., Methods: We designed a multicentre hospital-based case-control study, which included incident never-smoking lung cancer cases. Controls were never-smokers attending nonmajor surgery at the participating hospitals. Controls were frequency matched on age and gender with cases. We determined AAT variants (alleles S and Z) through polymerase chain reaction., Results: Two hundred and twelve cases and 318 controls were included. PiSS individuals showed a lung cancer risk of 4.64 (95% confidence interval: 1.08-19.92) compared with those with normal genotype (PiMM). When the analysis was restricted to women, the risk for PiSS increased to 7.58 (95% confidence interval: 1.40-40.87). This risk for homozygous SS was even higher for individuals exposed to environmental tobacco smoke (greater than 20 years). The presence of other alleles did not show any effect on lung cancer risk., Conclusions: Never smoking SS homozygous individuals pose an increased risk of lung cancer. The risk is higher for individuals exposed to environmental tobacco smoke.

Purpose: The aim of this study is to assess if there is a relationship between residential radon and lung cancer histological types and patients' age at diagnosis., Materials and Methods: We conducted a multicenter hospital-based case-control study with eight participating hospitals. We included 216 never-smoking cases with primary lung cancer and 329 never-smoking controls. Controls were frequency matched with cases on age and sex distribution. Of them, 198 cases (91.7%) and 275 controls (83.5%) had residential radon measurements., Results: Lung cancer risk reached statistical significance only for adenocarcinoma (Odds ratio [OR] 2.19; 95% Confidence interval [CI] 1.44-3.33), for other histologies the results were marginally significant. Residential radon level was higher for patients diagnosed before 50 and 60 years old than for older lung cancer cases., Conclusions: Residential radon in never smokers seems to be a risk factor for all lung cancer histologies. Individuals diagnosed at a younger age have a higher residential radon concentration, suggesting an accumulative effect on lung cancer appearance.

Introduction: Little is known about survival and prognostic factors in chronic obstructive pulmonary disease (COPD) due to biomass smoke exposure (BS-COPD)., Objectives: (1) To determine the value of two indices of COPD severity: BODEx (body mass index, obstruction, dyspnea, and previous severe exacerbations) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) categories system (ABCD) to predict all-cause mortality in BS-COPD, compared with COPD due to tobacco (T-COPD); (2) to verify the usefulness of 2 comorbidity indices, Charlson index and COTE (COPD comorbidity index); and (3) to put side by side the value of these indices., Methods: 612 consecutive COPD patients were retrospectively studied. Prognostic factors were evaluated taking into account the exposure to biomass or tobacco smoke. The relative predictive values of the prognostic indices were compared using receiver-operating characteristic analysis., Results: Mortality in the BS-COPD and T-COPD groups was not significantly different, when sex was taken into account. BODEx, Charlson and COTE indices-but not type of exposure-predicted mortality in multivariate analysis. The value of the C-statistic for the BODEx index was not different than that of GOLD ABCD for BS-COPD, but was higher for T-COPD. The discriminatory value of the Charlson index was higher than that of COTE for BS-COPD, but no significant differences were found for T-COPD., Conclusions: Multidimensional indices of COPD severity and comorbidity predict all-cause mortality in BS-COPD. The behavior of the different indices is different for BS-COPD and T-COPD.

Aim: To study whether mortality and cardiovascular morbidity differ in non-invasive ventilation (NIV)-treated patients with severe obesity-hypoventilation syndrome (OHS) as compared with CPAP-treated patients with obstructive sleep apnea syndrome (OSAS), and to identify independent predictors of mortality in OHS., Material and Methods: Two retrospective cohorts of OHS and OSAS were matched 1:2 according to sex, age (± 10 year) and length of time since initiation of CPAP/NIV therapy (± 6 months)., Results: Three hundred and thirty subjects (110 patients with OHS and 220 patients with OSAS) were studied. Mean follow-up time was 7 ± 4 years. The five year mortality rates were 15.5% in OHS cohort and 4.5% in OSAS cohort (p< 0.05). Patients with OHS had a 2-fold increase (OR 2; 95% CI: 1.11-3.60) in the risk of mortality and 1.86 fold (OR 1.86; 95% CI: 1.14-3.04) increased risk of having a cardiovascular event. Diabetes, baseline diurnal SaO2 < 83%, EPAP < 7 cmH2O after titration and adherence to NIV < 4 hours independently predicted mortality in OHS., Conclusion: Mortality of severe OHS is high and substantially worse than that of OSAS. Severe OHS should be considered a systemic disease that encompasses respiratory, metabolic and cardiovascular components that require a multimodal therapeutic approach.

The aim of the study was to assess the effect of residential radon exposure on the risk of lung cancer in never-smokers and to ascertain if environmental tobacco smoke modifies the effect of residential radon. We designed a multicentre hospital-based case-control study in a radon-prone area (Galicia, Spain). All participants were never-smokers. Cases had an anatomopathologically confirmed primary lung cancer and controls were recruited from individuals undergoing minor, non-oncological surgery. Residential radon was measured using alpha track detectors. We included 521 individuals, 192 cases and 329 controls, 21% were males. We observed an odds ratio of 2.42 (95% CI 1.45-4.06) for individuals exposed to ≥200 Bq·m(-3) compared with those exposed to <100 Bq·m(-3). Environmental tobacco smoke exposure at home increased lung cancer risk in individuals with radon exposure>200 Bq·m(-3). Individuals exposed to environmental tobacco smoke and to radon concentrations>200 Bq·m(-3) had higher lung cancer risk than those exposed to lower radon concentrations and exposed to environmental tobacco smoke. Residential radon increases lung cancer risk in never-smokers. An association between residential radon exposure and environmental tobacco smoke on the risk of lung cancer might exist., (©ERS 2014.)

Introduction: Exposure to biomass smoke is a risk factor for chronic obstructive pulmonary disease (COPD). It is unknown whether COPD caused by biomass smoke has different characteristics to COPD caused by tobacco smoke., Objective: To determine clinical differences between these two types of the disease., Methods: Retrospective observational study of 499 patients with a diagnosis of COPD due to biomass or tobacco smoke. The clinical variables of both groups were compared., Results: There were 122 subjects (24.4%) in the biomass smoke group and 377 (75.5%) in the tobacco smoke group. In the tobacco group, the percentage of males was higher (91.2% vs 41.8%, P<.0001) and the age was lower (70.6 vs 76.2 years, P<.0001). Body mass index and FEV1% values were higher in the biomass group (29.4±5.7 vs 28.0±5.1, P=.01, and 55.6±15.6 vs 47.1±17.1, P<.0001, respectively). The mixed COPD-asthma phenotype was more common in the biomass group (21.3% vs 5%, P<.0001), although this difference disappeared when corrected for gender. The emphysema phenotype was more common in the tobacco group (45.9% vs 31.9%, P=.009). The prevalence of the chronic bronchitis and exacerbator phenotypes, the comorbidity burden and the rate of hospital admissions were the same in both groups., Conclusion: Differences were observed between COPD caused by biomass and COPD caused by tobacco smoke, although these may be attributed in part to uneven gender distribution between the groups., (Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.)

We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78-2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93-5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To assess the value of the six-minute walk test (6MWT) to predict outcome in non-group 1 pulmonary hypertension (PH)., Background: Distance walked during 6MWT has been widely used as a prognostic test in pulmonary arterial hypertension (group 1 pulmonary hypertension); however, little is known regarding its prognostic value in other groups of PH., Methods: This was a retrospective study of 60 patients diagnosed of PH, Dana Point classification groups 2-5. 6MWT and echocardiography were performed in all cases., Results: Forty patients (66.6%) were females. Mean age was 70.8 ± 10.7 years (range: 32-85). Seven patients died after a mean follow-up of 23.2 ± 16.7 months. Distance <400 m during 6MWT was associated with a higher risk for death (RR: 4.39; 95% CI: 1.13-17.05; p = 0.03) and for clinical deterioration (death or need for hospitalization) (RR: 2.76; 95% CI: 1.18-6.42; p = 0.02)., Conclusions: 6MWT is useful to predict outcome in non-group 1 PH., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Objective: Although it has been reported that pulmonary hypertension is more frequent in patients with obesity-hypoventilation syndrome than in patients with 'pure' obstructive sleep apnoea syndrome, little is known about the haemodynamic repercussions of this entity. The aim was to describe the haemodynamic status, as assessed by echocardiography and 6-min walk test (6MWT), of patients with a newly diagnosed, most severe form of obesity-hypoventilation syndrome, and to evaluate the impact of non-invasive ventilation in these patients., Methods: A prospective, descriptive, and single-centre follow-up study was conducted. At baseline, patients underwent echocardiography, spirometry, static lung volume measurement, 6MWT, overnight pulse-oximetry and polygraphic recording. Changes in echocardiography and 6MWT were assessed after 6 months of non-invasive ventilation. Right ventricular overload was defined on the basis of right ventricular dilatation, hypokinesis, paradoxical septal motion and/or pulmonary hypertension., Results: Thirty patients (20 women; mean age 69 ± 11) were tested. The percentage of patients with right ventricular overload did not change significantly after non-invasive ventilation (43.3-41.6%; P = 0.24). In patients with right ventricular overload at diagnosis, pulmonary artery systolic pressure decreased significantly at six months (58 ± 11 to 44 ± 12 mm Hg; P = 0.014), and mean distance on 6MWT increased from 350 ± 110 to 426 ± 78 m (P = 0.006), without significant changes in body mass index., Conclusions: Right ventricular overload is a frequent finding in patients with the most severe form of obesity-hypoventilation syndrome. Treatment with non-invasive ventilation is associated with a decrease in pulmonary artery systolic pressure at six months and an increase in the distance covered during the 6MWT., (© 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.)

Aims: Persistent, echocardiography-assessed right ventricle dysfunction (RVD) and/or pulmonary hypertension (PHT) are relatively frequent findings after an acute pulmonary embolism (PE). It has been suggested that echocardiography might predict long-term adverse events. Our objectives were to evaluate the prognostic value of RVD or isolated PHT 6 months after an acute PE with regard to all-cause mortality or venous thromboembolism (VTE) recurrence., Methods and Results: In a previous study, echocardiography was used to assess RVD or PHT on admission and 6 months after an acute PE in 101 consecutive, haemodynamically stable pulmonary patients. We assessed the subsequent vital status and incidence of recurrent VTE in these patients. Six patients were lost for follow-up. The other 95 patients were categorized as those (i) with RVD or PHT 6 months after PE (17 cases, 17.8%) and (ii) patients with neither RVD nor PHT (78 cases, 82.1%). After a mean±SD of 2.8±1.06 years, there were 9 (9.4%) deaths and 12 (12.6%) VTE recurrences. At multivariate analysis, only age predicted all-cause mortality [hazard ratio (HR): 1.081, 95% confidence interval (CI): 1.003-1.166, P=0.004]. RVD or PHT persistence did not appear to increase the risk of mortality or recurrent VTE., Conclusion: Persistent echocardiographic signs of right ventricular pressure overload 6 months after an acute PE did not predict long-term adverse outcome events in this study.

Background: Risk stratification of patients with pulmonary embolism (PE) is essential to guide therapy. The presence of right ventricle dysfunction (RVD) and the anatomic extent of PE have been suggested to predict clinical course. The aim of this study was to assess the ability of an electrocardiogram (ECG) scoring system to predict RVD or the clot load score in normotensive patients with PE., Methods: Consecutive patients presenting to the emergency room with PE and hemodynamic stability were prospectively included. ECG, echocardiography and computed tomography pulmonary angiography (CTPA) were performed on all patients., Results: A total of 103 patients were studied. ECG score correlated significantly with the clot load score (r = 0.41, 95% confidence interval [CI]: 0.22-0.57, P < 0.001), systolic pulmonary artery pressure (r= 0.31, 95% CI: 0.09-0.49, P = 0.006), pulmonary artery diameter (r = 0.28, 95% CI: 0.07-0.47, P = 0.011) and right ventricle to left ventricle ratio, both measured with echocardiography (r = 0.42, 95% CI: 0.22-0.57, P < 0.001) and with CTPA (r= 0.36, 95% CI: 0.13-0.56, P = 0.004). Area under the receiver operating characteristic curve for detecting RVD was 0.82 (95% CI: 0.72-0.89). Interobserver agreement regarding ECG score was substantial (κ = 0.80)., Conclusions: ECG score correlates with the severity of PE in hemodynamically stable patients. It is potentially useful for risk-stratification strategies in this setting., (Copyright © 2010 Society of Hospital Medicine.)