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Borja G Cosio,1,2 Hanaa Shafiek,1,3 Nuria Toledo-Pons,1,2 Amanda Iglesias,1,2 Margalida Barcelo,1 Cristina Represas-Represas,4 Lorena Comeche,5 Pablo Catalan,6 Alberto Fernandez-Villar,4 Jose Luis Lopez- Campos,7 Jose Echave-Sustaeta,5 Juan Jose Soler-Cataluna8 1Respiratory Medicine, Hospital Universitario Son Espases-IdISBa, Palma de Mallorca, Spain; 2CIBERES-IDISBa, Palma de Mallorca, Spain; 3Chest Diseases Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 4Respiratory Medicine, Hospital Alvaro Cunqueiro, Vigo, Spain; 5Respiratory Medicine, Hospital Universitario Quironsalud Madrid, Madrid, Spain; 6Respiratory Medicine, Hospital General de Castellón, Castellón, Spain; 7Respiratory Medicine, Hospital Virgen del Rocio-CIBERES, Sevilla, Spain; 8Respiratory medicine, Hospital Arnau de Vilanova-CIBERES, Valencia, SpainCorrespondence: Borja G CosioHospital Universitario Son Espases, Ctra de Valldemossa 79, Palma de Mallorca, 07010, SpainTel +34 871 20 6714Email borja.cosio@ssib.esPurpose: Exacerbations of COPD (ECOPD) are a frequent cause of hospitalization that seemed to ameliorate during the COVID outbreak. We aimed to evaluate the clinical characteristics of COPD-related hospital admissions and mortality in relation to the presence of COVID-19.Patients and Methods: We conducted a case–control study of patients admitted in four teaching hospitals throughout Spain between March 15 and April 30, 2020. Hospital admissions of respiratory cause with and without PCR-proven SARS-CoV-2 infection in patients with COPD were evaluated. Baseline and episode-related clinical characteristics were analyzed. Logistic regression analysis was performed to evaluate the risk for mortality.Results: During the study period, 2101 patients were admitted for respiratory worsening, 1200 (57.1%) with COVID-19. A total of 228 (10.8%) were admitted due to COPD worsening, of whom 52 (22.8%) tested positive for COVID-19. COPD patients with COVID-19, when compared to those without COVID-19, were more frequently males with better lung function (FEV1 postbronchodilator 71% vs 46% respectively, p< 0.001) and had higher mortality (44.9% vs 13.6% respectively, p< 0.001) despite similar age, comorbidities, total days of hospitalization and admission to intensive care unit. COVID-19 and eosinopenia were the strongest risk factors for mortality in the multivariate analysis in the overall COPD population. Inhaled corticosteroid use was not associated to mortality.Conclusion: Hospitalizations for ECOPD without COVID-19 were more frequent than COPD with COVID-19 during the first outbreak, but the latter were associated with higher mortality and low eosinophil counts that warrant further analysis.Keywords: COPD exacerbation, mortality, inhaled corticosteroids, hospitalization

Background: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. Methods: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. Results: Overall, 2004 patients with mild asthma were included; 22.8% experienced >= 1 exacerbation in the previous 12 months, of whom 72.3% experienced >= 1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation +/- 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score = 2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring >= 1 emergency department visit and 1.1% requiring >= 1 hospital admission. Conclusions: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.

Sin financiación 4.872 JCR (2020) Q2, 18/64 Respiratory System 0.262 SJR (2021) Q3, 102/144 Pulmonary and Respiratory Medicine No data IDR 2020 UEM

Introduction: Obesity is associated with increased asthma severity, poor asthma control, and poor response to inhaled corticosteroids. Dupilumab (DPL), a fully human monoclonal antibody blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In the phase 3 QUEST trial (NCT02414854), add-on DPL 200/300 mg every 2 wks (q2w) vs placebo (PBO) reduced severe exacerbations and improved pre-bronchodilator (BD) FEV1 in patients (pts) with uncontrolled, moderate-to-severe asthma. Aim: To assess the effect of baseline (BL) body mass index (BMI) on DPL efficacy in uncontrolled, moderate-to-severe asthma pts. Methods: Annualized rate of severe exacerbations during the 52-wk treatment period and LS mean (LSM) change from BL at Wk 12 in pre-BD FEV1 were assessed by BL BMI subgroups ( Results: Across all BL BMI subgroups, both DPL 200 and 300 mg q2w vs PBO consistently reduced severe exacerbations (–35.1 to –51.4%; all P Conclusion: Dupilumab reduced severe exacerbations and improved FEV1 in pts with uncontrolled, moderate-to-severe asthma, regardless of BL BMI or DPL dose received.

Kai-Michael Beeh,1 Eric Derom,2 José Echave-Sustaeta,3 Lars Grönke,4 Alan Hamilton,5 Dongmei Zhai,6 Leif Bjermer71Insaf GmbH Institut für Atemwegsforschung, Wiesbaden, Germany; 2Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium; 3Servicio de Neumología, Hospital Universitario Quirón, Madrid, Spain; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 5Boehringer Ingelheim, Burlington, ON, Canada; 6InVentiv Health Clinical, Wilmington, DE, USA; 7Department of Respiratory Medicine and Allergology, Lund University, Lund, SwedenBackground: Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.Objective: The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.Methods: This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5µg and 2.5/5µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500µg and 50/250µg) via Accuhaler® for 6weeks. The primary end point was change in forced expiratory volume in 1second (FEV1) area under the curve from 0hour to 12hours (AUC0–12) relative to the baseline after 6weeks.Results: Tiotropium + olodaterol 5/5µg and 2.5/5µg demonstrated statistically significant improvements in FEV1 AUC0–12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317mL and 295mL with tiotropium + olodaterol 5/5µg and 2.5/5µg, and 188mL and 192mL with salmeterol + fluticasone propionate 50/500µg and 50/250µg, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0hour to 24hours (AUC0–24).Conclusion: Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. Keywords: COPD, maintenance treatment, lung function, tiotropium, FEV1, inhaled corticosteroid

Resumen Introduccion Los pacientes con EPOC que sobreviven a una exacerbacion grave que necesita ventilacion mecanica no invasiva son un grupo de mal pronostico. Objetivo Conocer las tasas de reingreso y mortalidad durante el ano siguiente a su alta y analizar los factores asociados a ambos desenlaces. Metodos Una cohorte de 93 pacientes con EPOC, que sobrevivieron a una exacerbacion de la EPOC que preciso ventilacion mecanica no invasiva, fue seguida tras el alta. Se midieron la necesidad de hospitalizacion por motivos respiratorios y la supervivencia, y se analizaron frente a posibles factores asociados a esos eventos mediante una regresion multivariante de riesgos proporcionales de Cox. Resultados Durante el ano siguiente al alta, 61 pacientes (66%) precisaron una nueva hospitalizacion. En el analisis multivariante, un valor bajo de FEV1 y una elevada estancia media durante la hospitalizacion se asociaron de forma independiente con un elevado riesgo de reingreso hospitalario. La probabilidad de supervivencia al ano fue de 0,695 (IC95%: 0,589–0,778). En el analisis multivariante la edad, la PaCO2 antes de iniciar la ventilacion mecanica no invasiva y los dias de hospitalizacion en el ano previo se asociaron de forma independiente con un elevado riesgo de mortalidad. Conclusiones Este grupo de pacientes con EPOC presenta una alta mortalidad y necesidad de rehospitalizacion en el ano siguiente al alta. Las variables estudiadas relacionadas con la gravedad de la enfermedad de base y de la propia agudizacion demostraron estar asociadas a esos eventos y podrian utilizarse para la aplicacion en este subgrupo de pacientes de programas especificos de seguimiento.

Introduction Patients with chronic obstructive pulmonary disease (COPD) who survived an acute exacerbation with acute respiratory failure that required non-invasive mechanical ventilation (NIMV) are a group with a poor medium-term prognosis. Objective To identify re-admission and mortality rates within one year from discharge and to analyse factors associated with both events in a consecutive series of COPD patients treated with NIMV. Methods A cohort of 93 COPD patients who survived an acute exacerbation and who required NIMV was followed up after discharge. Re-admissions due to respiratory causes and survival were measured and the outcomes were analysed against possible factors associated to such events using multivariate Cox proportional risk regression analysis. Results Over the year following discharge, 61 patients (66 %) had to be re-admitted into hospital due to respiratory complications. Upon multivariate analysis, a low FEV 1 value in stable phase and a high average length of stay were associated independently with a high risk of hospital readmission. The probability of survival at 1 year was 0.695. Age, PaCO 2 prior to initiation of NIMV and the number of hospitalisation days in the previous year were associated independently with a high mortality risk. Conclusions This group of COPD patients has a high mortality rate and need for re-hospitalisation in the ensuing year following discharge. The variables relating to the severity of the baseline disease and the actual exacerbation have been shown to be associated with these events, and could be applied to this subgroup of patients in specific follow-up programs.

Introduction: Combination of the well established muscarinic antagonist tiotropium (T) + olodaterol (O), a long-acting β 2 -agonist (LABA), has shown consistent improvements in lung function over T or O in Phase III studies in COPD. Addition of inhaled corticosteroid (ICS) to a LABA has also shown lung function improvements over LABA alone in some studies. The ENERGITO study (1237.11; NCT01969721) evaluated bronchodilator efficacy and safety of once-daily (QD) T+O compared to twice-daily (BID) fluticasone propionate (F) + salmeterol (S). Methods: A Phase IIIb, randomised, double-blind, double-dummy, 4-period crossover trial evaluated lung function after 6 weeks treatment with T+O 2.5/5 or 5/5 µg QD versus F+S 250/50 or 500/50 µg BID. End points were FEV 1 AUC 0–12 response (primary end point), FEV 1 AUC 0–24 , FEV 1 AUC 12–24 and trough FEV 1 responses. Key inclusion criteria were age ≥40 years, smoking history >10 pack-years, post-bronchodilator 30%≤FEV 1 Results: 229 patients were enrolled and treated: 64.6% male and 72.1% GOLD 2. T+O significantly improved FEV 1 AUC 0–12 response and all other FEV 1 end points compared to F+S (Table). No safety signals were identified. Conclusions: This study suggests that using LABA/ICS, F+S in this study, in moderate/severe COPD may provide sub-optimal lung-function improvements compared to T+O. Funding: Boehringer Ingelheim.

Antecedentes. La neumonia adquirida en la comunidad (NAC) por Streptococcus pneumoniae es una causa frecuente de mortalidad y morbilidad. Se describen 2 casos de NAC tratadas con levofloxacino que se complicaron. En ambos casos se aislo en liquido pleural S. pneumoniae resistente al antibiotico empleado. El primer caso correspondia a un varon de 51 anos, no tratado previamente con quinolonas. Ingreso en el hospital por NAC tratada inicialmente con levofloxacino (500 mg/24 h i.v.). A los 4 dias aparece un derrame pleural en el que se aisla S. pneumoniae resistente a levofloxacino (concentracion inhibitoria minima [CIM] > 32 µg/ml). El paciente evoluciono favorablemente mediante drenaje del derrame y tratamiento con antibiotico betalactamico. El segundo caso era un varon de 73 anos con antecedentes de enfermedad pulmonar obstructiva cronica. Ingresa por NAC tratada inicialmente con levofloxacino (500 mg/24 h i.v.). Fue remitido a nuestro hospital por presencia de derrame pleural en el que crecio S. pneumoniae resistente a levofloxacino (CIM = 12 µg/ml) tras 10 dias de tratamiento antibiotico. El paciente evoluciono de manera favorable mediante drenaje del derrame y tratamiento con antibiotico betalactamico. Conclusiones. Los pacientes con NAC en los que se inicia tratamiento antibiotico empirico deben vigilarse estrechamente desde el punto de vista clinico y radiologico, para la deteccion precoz de complicaciones por resistencia bacteriana al antibiotico empleado. En los pacientes con NAC que hayan recibido quinolonas en las semanas previas al desarrollo de la neumonia no es recomendable iniciar tratamiento empirico con estos antibioticos dado el riesgo de desarrollo de resistencias.

Background and objective: Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients. This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients. Patients and methods: In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists. The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected. The Charlson comorbidity score was calculated. Results: Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%. Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage. Conclusion: COPD patients attended to in internal medicine departments show high scores of comorbidity. However, GOLD stage was not an independent predictor of comorbidity., The authors have no conflicts of interest to disclose in this work. This work was partially funded by Boehringer Ingelheim.

Background Anaemia is one of the extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). Its real prevalence, physiopathology and clinical repercussion are unknown. The objectives of our study were: to determine the prevalence of anaemia in patients with stable COPD not attributable to other causes and to establish the relationship of anaemia with clinical, prognostic and inflammatory markers with an important role in COPD. Methods The study included stable COPD patients with no other known causes of anaemia. The following tests were carried out: respiratory function tests; serum determination of erythropoietin and inflammatory markers: high sensitivity C -reactive protein (hs-CRP), fibrinogen, interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor α (TNF-α). Body mass index (BMI), Charlson and BODE indices, the number of exacerbations in the previous year, dyspnoea and quality of life were also calculated. Results One hundred and thirty patients were included. Anaemia prevalence was 6.2%. Mean haemoglobin value in anaemic patients was 11.9 ± 0.95 g/dL. Patients with anaemia had a lower BMI (P=.03), higher Charlson index (P=.002), more elevated erythropoietin levels (P=.016), a tendency to present a lower FEV1% value (P=.08) and significantly lower IL-6 values when compared to non-anaemic patients (P=.003). Conclusions In our series, the anaemia associated with COPD was less prevalent than that published in the literature to date, and was related to certain clinical and inflammatory markers.

Resumen Introduccion La anemia es una de las manifestaciones extrapulmonares de la enfermedad pulmonar obstructiva cronica (EPOC). Su prevalencia, su fisiopatologia y su repercusion clinica son desconocidas. Los objetivos de nuestro estudio son determinar la prevalencia de la anemia en pacientes con EPOC en fase estable no atribuible a otras causas y establecer la relacion de la anemia con variables clinicas, pronosticas y marcadores inflamatorios con un papel relevante en la EPOC. Metodos Se incluyeron pacientes con EPOC en fase estable sin otras causas conocidas de anemia. Se realizaron pruebas de funcion respiratoria, determinacion de eritropoyetina y marcadores inflamatorios sericos: PCR ultrasensible (PCR), fibrinogeno, interleucina 6 (IL-6), interleucina 8 (IL-8) y factor de necrosis tumoral alfa (TNF-α). Se registro el indice de masa corporal (IMC), el indice de Charlson y el BODE, el numero de exacerbaciones en el ano previo, la escala de disnea y la calidad de vida. Resultados Se incluyeron 130 pacientes. La prevalencia de anemia fue del 6,2%. El valor de hemoglobina en los pacientes con anemia fue de 11,9 ± 0,95 g/dl. Los pacientes con anemia tenian un IMC mas bajo (p = 0,03), un indice de Charlson mayor (p = 0,002), niveles de eritropoyetina mas elevados (p = 0,016), una tendencia a presentar niveles mas bajos de FEV 1 % (p = 0,08) y valores significativamente mas bajos de IL-6 (p = 0,003) cuando se comparan con los pacientes no anemicos. Conclusiones En nuestra serie, la anemia asociada a la EPOC es menos prevalente de lo publicado hasta la actualidad y guarda relacion con determinados factores clinicos y marcadores inflamatorios.

A 32 yr-old nonsmoking male, diagnosed as having X‐linked agammaglobulinemia, presented with fever, cough with purulent sputum, a very intense back pain and a mass of 10 centimetres in lower left lobe. Diagnostic evaluation revealed a squamous cell carcinoma with very aggressive metastases at L3. Malignancies are the second leading cause of death in children and adults with congenital immunodeficiency disorders, mostly non-Hodgkin lymphomas and gastric and colon adenocarcinomas, but this is the first report of lung cancer in a patient with X‐linked agammaglobulinemia. Lung cancer incidence has been reported to be higher in patients with other diseases of the lung, however, there is no clear evidence of the role of bronchiectasis in developing lung cancer. It is possible that a longer survival for patients with X‐LA recently diagnosed, and an association of chronic bronchial infection, could favour the development of pulmonary neoplasm.

Study objectives The aims of this study were to describe the different appearances of pleural fluid during thoracentesis and their frequency in relation to diagnosis, and to evaluate the causes and clinical implications of bloody pleural effusions. Setting Tertiary care, university-affiliated hospital. Subjects and methods Seven hundred fifteen patients with pleural effusion were prospectively assessed from December 1991 to December 1997. Interventions The appearance of the fluid was assessed in a glass assay tube containing 10 mL of pleural fluid. Results The most common presentations were serous and blood tinged, with 80% of the fluids fitting into one of these categories. The most frequent cause of watery fluid was transudate, although most transudates were classified as serous effusions. There were 59 bloody and 656 nonbloody pleural fluids. The most common cause of bloody pleural effusion (BPE) was malignancy (47%). Fluid with a bloody appearance slightly increased the probability of malignancy in our series (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.01 to 2.94; p = 0.04). Nevertheless, only 11% of the neoplastic effusions were BPE. Other common causes of BPE were posttraumatic (12%) or parapneumonic (10%) pleural effusions. Tuberculosis and transudates were uncommon causes of BPE. Fluid that was bloody in appearance decreased the probability for both diseases (OR, 0.15; 95% CI, 0.04 to 0.57; p = 0.003 and OR, 0.25; 95% CI, 0.06 to 0.95; p = 0.04, respectively). Conclusions Serous and blood tinged were the most common presentations of pleural fluid at thoracentesis. Almost half of BPEs were secondary to neoplasms, but only 11% of the neoplastic effusions were BPEs. Other common causes of BPE were parapneumonic and posttraumatic.

To describe clinical, endoscopic, radiographic, and follow-up characteristics of a series of patients in whom endobronchial hamartoma (EH) had been diagnosed.Retrospective study of all cases of hamartoma diagnosed by bronchial biopsy between 1974 and 1997 in a tertiary referral hospital in Madrid, Spain.EH was diagnosed 47 patients during the study period. Four patients were excluded from the study because no clinical history was available. We analyzed the cases of 43 patients (37 men and 6 women), with a mean (+/- SD) age of 62 +/- 12 years. Seven patients had a concurrent lung neoplasm, and the EH was an incidental endoscopic finding. Among the other 36 patients, 31 had a new onset of respiratory symptoms, most commonly, recurrent respiratory infections in 16 patients (44%) and hemoptysis in a further 12 patients (33.4%). Chest radiograph findings were abnormal in 38 of 43 patients. At bronchoscopy, the lesions were equally distributed throughout the right and left lungs with no clear lobar predilection. Endobronchial obstruction was evident in 26 patients (72.2%) without concurrent neoplasm, 17 of whom underwent resection with a rigid bronchoscope and laser, with total resolution in 13 patients. Partial resolution was achieved in four patients, two of whom needed a second endoscopic procedure. Five patients were treated with open lung surgery. Clinical and endoscopic follow-up was performed in 23 patients at 1 to 73 months (mean, 17 months), and recurrence was found in 4 patients.EH frequently produces respiratory complaints and radiographic abnormalities. Patients with endobronchial obstructions had satisfactory responses to endoscopic therapy.

The level of interferon-gamma (IFN-gamma) in pleural fluid has been reported to be increased in pleural tuberculosis. Nevertheless, its diagnostic value has not yet been well-established, and immunocompromised patients have not previously been evaluated. The aim of this study was to determine the value of the IFN-gamma level in pleural fluid for diagnosing tuberculous pleurisy in immunocompetent and immunocompromised patients. Three hundred and eighty eight consecutive patients were studied prospectively (73 with tuberculous pleural effusions, including nine with concurrent human immunodeficiency virus (HIV) infection and one after liver transplantation, and 315 with nontuberculous effusions). IFN-gamma was measured by radioimmunoassay. The sensitivity of the test, using a 3.7 U.mL-1 cut-off point, was 0.99 (95% confidence interval (95% CI) 0.93-1.00) and the specificity was 0.98 (95% CI 0.96-1.00). The sensitivity of the test did not differ in HIV-positive and HIV-negative patients. Patients with lymphoma, vasculitis or vascular connective tissue disease did not have abnormal IFN-gamma values. In conclusion, the level of interferon-gamma in pleural fluid is a very good diagnostic marker of tuberculous pleural effusion, even in immunocompromised patients.