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Luis Pérez de Llano,1 Marc Miravitlles,2 Rafael Golpe,1 Francisco Javier Alvarez-Gutiérrez,3 Carolina Cisneros,4 Carlos Almonacid,5 Eva Martinez-Moragon,6 Francisco-Javier Gonzalez-Barcala,7 David Ramos-Barbón,8 Vicente Plaza,8 Jose Luis Lopez-Campos,3 Juan Pablo de-Torres,9 Ciro Casanova,10 Juan Luis Garcia Rivero,11 Juan Rodriguez Hermosa,12 Myriam Calle Rubio,12 Juan Jose Soler-Cataluña,13 Borja G Cosio14 1Pneumology Service, University Hospital Lucus Augusti, Lugo, EOXI Cervo, Lugo, Monforte, Spain; 2Pneumology Service, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBERES, Barcelona, Spain; 3Pneumology Service, Hospital Universitario Virgen del Rocio, Seville, Spain; 4Pneumology Service, La Princesa University Hospital, Madrid, Research Institute La Princesa IIP, Madrid, Spain; 5Pneumology Service, Ramón y Cajal Hospital (Ramon y Cajal Health Research Institute, IRYCIS), Madrid, Spain; 6Pneumology Service, Hospital Universitario Dr Peset, Valencia, Spain; 7Faculty of Medicine at the University of Santiago de Compostela, Pneumology Service of the University Clinical Hospital of Santiago de Compostela, CIBERES, Santiago de Compostela, Spain; 8Pneumology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 9Division of Respirology and Sleep Medicine, Queen’s University, Canada, ON, Canada; 10Pneumology Service, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain; 11Pneumology Service, Hospital de Laredo, Laredo, Spain; 12Pneumology Service and Faculty of Medicine, Hospital Clínico San Carlos, Complutense University of Madrid, Madrid, Spain; 13Pneumology Service, Hospital Arnau de Vilanova, Valencia, Spain; 14Pneumology Service, Son Espases University Hospital, IdISBa, CIBERES, Clínica Quirón-Rotger, Palma, SpainCorrespondence: Borja G CosioPneumology Service, Hospital Universitario Son Espases, IdISBa, CIBERES, Clínica Quirón-Rotger, Ctra. de Valldemossa 79, Palma de Mallorca 07010, SpainTel +34 871 206714 Ext 76714Fax +34 871 909724Email borja.cosio@ssib.esAbstract: Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) – understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis.Keywords: airflow obstruction, biomarker, personalised medicine, COPD asthma overlap

Several studies have described the proteomic profile of different immune cell types, but only a few have also analysed the content of their delivered small extracellular vesicles (sEVs). The aim of the present study was to compare the protein signature of sEVs delivered from granulocytes (i.e., neutrophils and eosinophils) and CD4 + T cells (i.e., TH1, TH2, and TH17) to identify potential biomarkers of the inflammatory profile in chronic inflammatory diseases. Qualitative (DDA) and quantitative (DIA-SWATH) analyses of in vitro-produced sEVs revealed proteome variations depending on the cell source. The main differences were found between granulocyte- and TH cell-derived sEVs, with a higher abundance of antimicrobial proteins (e.g., LCN2, LTF, MPO) in granulocyte-derived sEVs and an enrichment of ribosomal proteins (RPL and RPS proteins) in TH-derived sEVs. Additionally, we found differentially abundant proteins between neutrophil and eosinophil sEVs (e.g., ILF2, LTF, LCN2) and between sEVs from different TH subsets (e.g., ISG15, ITGA4, ITGB2, or NAMPT). A "proof-of-concept" assay was also performed, with TH2 biomarkers ITGA4 and ITGB2 displaying a differential abundance in sEVs from T2 high and T2 low asthma patients. Thus, our findings highlight the potential use of these sEVs as a source of biomarkers for diseases where the different immune cell subsets studied participate, particularly chronic inflammatory pathologies such as asthma or chronic obstructive pulmonary disease (COPD).

Background: Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels. Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26 -/lo , CD26 int and CD26 hi subsets within different lymphocyte populations., Methods: The proportion of CD26 -/lo , CD26 int and CD26 hi subsets within CD4 + effector T cells (T eff ), total CD4 - lymphocytes, γδ-T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K-means clustering analysis and further characterised the CD4 + CD26 -/lo T eff cell subset by LC-MS/MS and immunofluorescence., Results: Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4 - CD26 hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26 -/lo subsets. Specifically, CD4 + CD26 -/lo T eff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a T EM /T EMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4 + T cells, and an enrichment in 'flower-like' nuclei and MMP9/RNASE2 levels in CD4 + CD26 -/lo T eff compared to CD4 + T lymphocytes., Conclusion: There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4 + CD26 -/lo T EMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long-term inflammation in adult allergic asthma., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Refractory chronic cough (RCC) and unexplained chronic cough (UCC) adversely affect patients' quality of life (QoL). This multicenter, non-interventional study evaluates the relationship between cough severity and QoL and other patient-reported outcomes (PROs) in Spanish outpatients., Methods: RCC/UCC patients self-administered a printed survey comprising the cough-severity visual analog scale (VAS), adapted Cough Severity Diary (CSD), and Leicester Cough Questionnaire (LCQ), plus purpose-designed items regarding the physical and everyday-life impact of cough. Patients were stratified into VAS score tertiles. The impact of cough on QoL and other PROs in each tertile, and relationships between LCQ scores and the tertiles, were assessed., Results: The VAS was completed by 189 patients, and VAS score tertiles were identified as 0-50, 60-70, and 80-100 mm. The only between-tertile difference in demographic or cough characteristics was cough duration. VAS score tertiles were linearly associated with mean LCQ domain and total scores, as well as the proportion of patients with the highest scores on all adapted CSD items, and almost all physical and everyday-life impact items. In multiple linear-regression models, an increase of one tertile in the VAS score was associated with a decrease of 2.23 points in the LCQ total score, indicating poorer cough-related QoL., Conclusion: As self-assessed in patients with RCC/UCC, cough-severity VAS scores were strongly associated with the impact of cough on QoL and everyday life. Patients with VAS scores of 60-100 mm reported the greatest impact and thus may benefit the most from targeted cough therapies., Competing Interests: Declaration of competing interest Christian Domingo has received consultant and speaker's honoraria from MSD, Novartis, Boehringer, Sanofi, TEVA, AstraZeneca, ALK, Allergy Therapeutics. Santiago Quirce has received speaking, lecture and consulting fees from Allergy Therapeutics, AstraZeneca, GSK, Mundipharma, Novartis, Sanofi, and Teva. Ignacio Dávila has received consulting fees from Allergy Therapeutics, AstraZeneca, GSK, MSD, Novartis, and Sanofi. Lectures for Allergy Therapeutics, AstraZeneca, Chiesi, Diater, GSK, LETI, Novartis, and Sanofi. Grants to his institution from ISCIII (public entity), Junta de Castilla de León (public entity), and ThermoFisher. Astrid Crespo-Lessman has received consultant's honoraria from AstraZeneca, Sanofi, GlaxoSmithKline, and her institution has received grants from AstraZeneca and GlaxoSmithKline. Luis Puente-Maestu declares no conflict of interest. Ebymar Arismendi declares no conflict of interest. Alfredo De Diego declares no conflict of interest. Francisco Javier González-Barcala has received consulting fees and speaker's honoraria from ALK, AstraZeneca, Bial, Chiesi, GebroPharma, GlaxoSmithKline, Menarini, Novartis, Rovi, Roxall, Sanofi, Stallergenes-Greer and Teva. Luis Pérez De Llano has received consulting fees and speaker's honoraria from AstraZeneca, Chiesi, GlaxoSmithKline, FAES, MSD, Sanofi, Techdow Pharma and Teva, and his institution has received grants from AstraZeneca, FAES and Sanofi. Luis Cea-Calvo, Marta Sánchez-Jareño, and Pilar López-Cotarelo are full-time employees of MSD Spain. Assessed using an 11-point Likert scale, where higher numbers indicate greater severity/impact. Results pertain to the day before the study visit. Not all patients responded to all items. The total number of respondents is specified for each item. Percentages in each cough-severity VAS tertile are calculated based on the number of respondents in that tertile., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Background: Stress urinary incontinence (SUI) is common in women with chronic cough but may be overlooked. Objective: To determine the frequency of underdiagnosis of cough-related SUI and its impact on women's general health status and quality of life (QoL). Methods: Data were analyzed for 147 women with refractory/unexplained chronic cough. Relevant details were collected from clinical charts and a patient-completed survey. General health status was assessed using the EuroQoL visual analogue scale (EQ-VAS) and QoL with the cough-specific Leicester Cough Questionnaire (LCQ). Results: Women were classified into diagnosed ( n = 32; 21.8%) or undiagnosed ( n = 33; 22.4%) cough-related SUI, and no SUI ( n = 82; 55.6%) groups. Women with versus without cough-related SUI perceived poorer health status and greater impact of cough on everyday lives. Mean LCQ scores were significantly lower in cough-related SUI groups versus no SUI group. In multivariate analysis, the presence of cough-related SUI was significantly associated with lower EQ-VAS and LCQ scores. Conclusion: In our cohort, 44% of women had cough-related SUI, and half were undiagnosed. Irrespective of diagnosis, impairment to everyday lives and QoL was similar. Diagnosing cough-related SUI may identify additional patients who can benefit from therapies to suppress cough and improve QoL., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ebymar Arismendi has received honoraria for consultancy and conferences from AstraZeneca, Gebro-Pharma, GSK, Menarini, MSD, Novartis, and Sanofi-Genzyme. Luis Puente-Maestu has received consulting fees from MSD; payments for lectures from Chiesi, Grifols, and Pulmonx; grants from AstraZeneca, Chiesi, GSK, and Pulmonx. Christian Domingo has received consultant and speaker’s honoraria from Allergy Therapeutics, ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, MSD, Novartis, and Sanofi. Ignacio Dávila has received consulting fees from Allergy Therapeutics, AstraZeneca, GSK, MSD, Novartis, and Sanofi; payments for lectures from Allergy Therapeutics, AstraZeneca, Chiesi, Diater, GSK, LETI, Novartis, and Sanofi; grants to his institution from ISCIII, Junta de Castilla de León, and ThermoFisher. Santiago Quirce has received speaking, lecture and consulting fees from Allergy Therapeutics, AstraZeneca, GSK, Mundipharma, Novartis, Sanofi, and Teva. Francisco Javier González-Barcala has received consulting fees and speaker’s honoraria from ALK, AstraZeneca, Bial, Chiesi, GebroPharma, GlaxoSmithKline, Menarini, Novartis, Rovi, Roxall, Sanofi, Stallergenes-Greer and Teva. Astrid Crespo-Lessmann has received speaker’s honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, MSD, Novartis, Orion Pharma, Sanofi, and Zambón; conference travel and attendance expenses from Gebro, GSK and Novartis; funds/grants for research projects from several state agencies, non-profit foundations, AstraZeneca, and GSK. Marta Sánchez-Jareño, Cristina Rivas-Pardinas, and Luis Cea-Calvo are full-time employees of MSD Spain.

Background: Evaluation of biologic therapy response is vital to monitor its effectiveness. Authors have proposed various response criteria including good responder, super-responder, non-responder, and clinical remission., Objectives: To ascertain the prevalence of response and clinical remission after long-term treatment (>6 months) of anti-IgE and anti-IL-5/IL-5Rα biologics, compare these results with existing criteria, and identify predictors for non-responders and clinical remission., Methods: A multicenter, real-life study involving severe asthma patients in Spain. Various outcomes were assessed to gauge response and clinical remission against established criteria., Results: The study included 429 patients, 209 (48.7%) omalizumab, 112 (26.1%) mepolizumab, 19 (4.4%) reslizumab and 89 (20.7%) benralizumab, with a mean treatment duration of 55.3±38.8 months. In the final year of treatment, 218 (50.8%) were super-responders, 173 (40.3%) responders, 38 (8.9%) non-responders, and clinical remission in 116 (27%), without differences among biologics. The short-term non-responders (<6 months) were 25/545 (4.6%). Substantial variations in response and clinical remission were observed when applying different published criteria. Predictors of non-response included higher BMI (OR:1.14; 95% CI:1.06-1.23; p<0.001), admissions at ICU (2.69; 1.30-5.56; p=0.01), high count of SAE (1.21; 1.03-1.42; p=0.02) before biologic treatment. High FEV 1 % (0.96; 0.95-0.98; p<0.001), a high ACT score (0.93; 0.88-0.99; p=0.01) before biologic treatment or NSAID-ERD (0.52; 0.29-0.91; p=0.02) showed strong associations with achieving clinical remission., Conclusion: A substantial proportion of severe asthma patients treated long-term with omalizumab or anti-IL5/IL-5Rα achieved a good response. Differences in response criteria highlight the need for harmonization in defining response and clinical remission in biologic therapy to enable meaningful cross-study comparisons., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Exposure to certain agents in the workplace can trigger occupational asthma or work-exacerbated asthma, both of which come under the heading of work-related asthma (WRA). Understanding the burden that WRA represents can help in the management of these patients., Objective: To assess the influence of occupation on asthma in real life and analyze the characteristics of patients with WRA included in an asthma cohort., Methods: This was a prospective multicenter study of a cohort of consecutive patients with asthma. A standardized clinical history was completed. Patients were classified as having WRA or non-WRA. All patients underwent respiratory function tests, FeNO test, and methacholine challenge (methacholine concentration that causes a 20% drop in FEV 1 ) at the beginning of the study. They were classified into two groups, depending on their employment status: employed (group 1) or unemployed (group 2)., Results: Of the 480 patients included in the cohort, 82 (17%) received the diagnosis of WRA. Fifty-seven patients (70%) were still working. Mean age (SD) was 46 (10.69) years in group 1 and 57 (9.91) years in group 2 (P < .0001). Significant differences were observed in adherence to treatment (64.9% in group 1 vs 88% in group 2; P = .0354) and in severe asthma exacerbations (35.7% in group 1 vs 0% in group 2; P = .0172). No significant differences were observed in the rest of the variables analyzed., Conclusions: The burden of WRA in specialized asthma units is not negligible. The absence of differences in the severity of asthma, the treatment administered, alterations in lung function, and the number of exacerbations in those working versus not working may support the idea that advice regarding changing jobs should be customized for individual patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic cough (cough lasting for ≥8 weeks) can lead to significant impairment in quality of life (QoL). Using patient-reported outcomes, this cohort study assessed the perceived impact of chronic cough on QoL and everyday life in patients from outpatient hospital clinics with refractory chronic cough (RCC) or unexplained chronic cough (UCC)., Methods: This was a multicentre, non-interventional survey study. Cough severity was assessed on a 0-100 mm Visual Analogue Scale (VAS). Frequency, intensity and disruptiveness of cough were assessed using an adaptation of the Cough Severity Diary. The impact of cough on QoL was assessed using the Leicester Cough Questionnaire (LCQ). The physical impact of cough and associated impact on everyday life activities were explored using purpose-designed questions., Results: 191 patients responded to the survey; 121 (63.4%) had RCC and 149 were women (78.0%). Mean score on the cough severity VAS was 62.9 mm. Mean LCQ total score of 11.9 indicated reduced QoL. Cough impaired patients' everyday life, including the inability to speak fluently (58.0% of patients) and feeling tired/drained (46.6%). Women perceived poorer chronic cough-related QoL than men, as reflected by lower LCQ scores, and greater impairment of physical health, including cough-related stress urinary incontinence, and psychological health., Conclusions: Patients with RCC/UCC experience a significant burden in their everyday life, including impaired QoL, and perceive a negative impact on physical and psychological health and everyday activities, affecting work, relationships and leisure activities. The impact appears to be greater in women than men for several of the aspects studied., Competing Interests: Conflict of interest: S. Quirce has received advisory board and speaker's honoraria from ALK, Allergy Therapeutics, AstraZeneca, Chiesi, GlaxoSmithKline, Leti, Mundipharma, Novartis, Sanofi and Teva. Conflict of interest: I. Dávila has received consultant's honoraria from Allergy Therapeutics, AstraZeneca, MSD, GlaxoSmithKline, Novartis and Sanofi. Conflict of interest: E. Martínez-Moragón has received consultant and speaker's honoraria from AstraZeneca, Sanofi, GlaxoSmithKline, Bial and FAES. Conflict of interest: A. Crespo-Lessman has received consultant's honoraria from AstraZeneca, Sanofi and GlaxoSmithKline, and grants from AstraZeneca and GlaxoSmithKline. Conflict of interest: C. Domingo has received consultant and speaker's honoraria from MSD, Novartis, Boehringer, Sanofi, TEVA, AstraZeneca, ALK and Allergy Therapeutics. Conflict of interest: F.J. González-Barcala has received consulting fees and speaker's honoraria from ALK, AstraZeneca, Bial, Chiesi, GebroPharma, GlaxoSmithKline, Menarini, Novartis, Rovi, Roxall, Sanofi, Stallergenes-Greer and Teva, and is an associate editor of this journal. Conflict of interest: L. Cea-Calvo, M. Sánchez-Jareño and C. Rivas-Pardiñas are full-time employees of MSD Spain. Conflict of interest: The authors have no other financial or nonfinancial competing interests., (Copyright ©The authors 2023.)

Introduction: COPD causes high morbidity and mortality and high health costs. Thus, identifying and analyzing the distinctive and treatable traits seems useful to optimize the management of AEPOC patients. While various biomarkers have been researched, no solid data for systematic use have been made available., Aim: Assessing the short-term prognostic usefulness of clinical and analytical parameters available in routine clinical practice in COPD exacerbations., Material and Methods: Multicenter prospective observational study conducted between 2016 and 2018. Patients admitted for COPD exacerbation who agreed to participate and signed an informed consent form were included. Prolonged stay, in-hospital mortality or early readmission was considered an unfavorable progression. 30-Day mortality was also analyzed., Results: 615 patients were included. Mean age was 73.9 years (SD 10.6); 86.2% were male. Progression of 357 patients (58%) was considered unfavorable. Mortality at 1 month from discharge was 6.7%. The multivariate analysis shows a relationship between the CRP/Albumin ratio and unfavorable progression (OR 1.008, 95% CI 1.00; 1.01), as well as increased risk of death at 1 month from discharge with elevated urea (OR 1.01, 95% CI 1.005; 1.02) and troponin T (OR 2.21, 95% CI 1.06; 4.62)., Conclusion: Elevated CRP/Albumin, urea and TnT are prognostic indicators of poor short-term outcome in patients admitted for COPD exacerbation. Cardiovascular comorbidity and systemic inflammation could explain these findings., (© 2023 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Introduction: Data on the clinical efficacy and remodeling of omalizumab therapy in patients on oral corticosteroids (OC) are limited., Objective: The purpose of the study is to show that in patients with corticosteroid-dependent asthma, omalizumab is a corticosteroid-sparing therapy able to inhibit airway remodeling and to reduce disease burden (lung function impairment, exacerbations)., Methods: This study is a randomised open-label study evaluating the addition of omalizumab to the standard of care in patients with severe asthma receiving oral corticosteroids. The primary endpoint was represented by the change in OC monthly dose by the end of treatment and secondary endpoints included spirometry changes, airway inflammation (FeNO), number of exacerbations and airways remodelling assessed by bronchial biopsies studied by transmission electron microscopy. As a safety variable, adverse effects were recorded., Results: Efficacy was assessed for 16 patients in the omalizumab group and 13 in the control group. The final cumulative mean monthly OC doses were 34.7 mg and 217 mg for the omalizumab and control group, respectively; the mean difference between groups adjusted for baseline was -148.1 [95% confidence interval (CI) -243.6, -52.5; p = 0.004]. OC withdrawal of 75% versus 7.7% (p = 0.001) was observed in the omalizumab and control group, respectively. Omalizumab provided a slowing of forced expiratory volume in one second (FEV 1 ) loss (70 mL versus 260 mL), a significant decrease in FeNO values and a reduction in the annual relative risk of clinically significant exacerbations of 54%. The treatment was well tolerated. The morphological study showed a significant decrease in basement membrane thickness in the omalizumab group (6.7 µm versus 4.6 µm) compared with controls (6.9 µm versus 7 µm) [mean difference between groups adjusted for baseline was -2.4 (95% CI -3.7, -1.2; p < 0.001], as well as a decrease in intercellular spaces (1.18 µm versus 0.62 µm and 1.21 µm versus 1.20 µm, p = 0.011, respectively). A qualitative improvement was also observed in the treated group., Conclusions: Omalizumab showed a marked OC-sparing capacity and was associated with an improvement in clinical management that correlated with bronchial epithelial repair. In OC-dependent asthma, reversibility of remodelling is possible; the concepts that basement membrane enlargement is detrimental and that chronic airway obstruction is systematically irreversible are outdated (EudraCT: 2009-010914-31)., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Evidence of the effect of statins on patients with coronavirus disease (2019) COVID-19 is inconsistent. The aim of this study was to evaluate the association between chronic use of statins-both overall and by active ingredient-and severe outcomes of COVID-19 (risk of hospitalization and mortality), progression to severe outcomes, and susceptibility to the virus. We conducted a population-based case-control study with data from electronic records to assess the risk of (1) hospitalization: cases were patients admitted due to COVID-19 and controls were subjects without COVID-19; (2) mortality: cases were hospitalized patients who died due to COVID-19 and controls were subjects without COVID-19; (3) progression: cases were hospitalized COVID-19 subjects and controls were nonhospitalized COVID-19 patients; and (4) susceptibility: cases were patients with COVID-19 (both hospitalized and nonhospitalized) and controls were subjects without COVID-19. We collected data on 2821 hospitalized cases, 26 996 nonhospitalized cases, and 52 318 controls. Chronic use of atorvastatin was associated with a decreased risk of hospitalization (adjusted odds ratios [aOR] = 0.83; 95% confidence interval [CI]: 0.74-0.92) and mortality (aOR = 0.70; 95% CI: 0.53-0.93), attributable in part to a lower risk of susceptibility to the virus (aOR = 0.91; 95% CI: 0.86-0.96). Simvastatin was associated with a reduced risk of mortality (aOR = 0.59; 95% CI: 0.40-0.87). The wide degree of heterogeneity observed in the estimated odds ratios (ORs) of the different statins suggests that there is no class effect. The results of this real-world study suggest that chronic use of atorvastatin (and to a lesser degree, of simvastatin) is associated with a decrease in risk of severe COVID-19 outcomes., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Introduction and Objectives: The use of monoclonal antibody (mAb)-based therapies is becoming the new standard of care for severe uncontrolled asthma (SUA). Even though patients may qualify for one or more of these targeted treatments, based on different clinical criteria, a global vision of mAb prescription management in a large sample of hospitals is not well characterised in Spain.The objective was to give a global vision of mAb prescription management in a large sample of hospitals in Spain., Materials and Methods: We used an aggregate data survey method to interview pulmonology specialists in a large sample of Spanish centres (90). The following treatment-related information was obtained on patients treated with mAbs: specific mAbs prescribed, treatment interruption, switch and restart and the reasons for these treatment changes., Results: mAb prescription was more frequent in females (13.3% females vs 7.4% males; p  < 0.001). There were no differences in prevalence by hospital complexity level. In contrast, there were differences by geographical area. Omalizumab was the most prescribed mAb (6.2%), followed by mepolizumab (2.9%). Discontinuation of Omalizumab (due to a lack of effectivity) and switches from this mAb to mepolizumab were more frequent. Very few restarts to the first treatment were observed after a switch from ≥2 mAbs., Conclusions: Omalizumab appeared as the most prescribed mAb in SUA but was also the most withdrawn; a specific and objective characterisation of patients with SUA, along with asthma phenotyping, and together with further evaluation of safety and effectiveness profiles, will lead to future progress in the management of SUA with mAbs., (© 2023 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Aims: To assess changes in prevalence and the effects on hospital outcomes of dementia among patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD); and to evaluate sex-differences, as well as the impact of COVID-19 pandemic in this relationship., Methods: We used a nationwide discharge database to select patients admitted with AE-COPD in Spain from 2011 to 2020. We identified those with any type of dementia, vascular dementia (VaD) or Alzheimer's disease (AD)., Results: We identified 658,429 hospitalizations with AE-COPD (4.45% had any type of dementia, 0.79% VaD and 1.57% AD). The presence of any type of dementia remained stable from 2011 to 2015, and increased significantly between 2016 and 2020. For VaD, the time trend showed no change until 2020, when a significant increment was found. The probability of AD decreased significantly overtime. The in-hospital mortality (IHM) among patients with any type of dementia remained stable overtime until 2020, when it increased significantly. Older age, higher comorbidity, COVID-19, and use of mechanical ventilation were variables associated to IHM. Women had lower risk of dying in the hospital than men in all subgroups., Conclusions: After a previous period of stability, the prevalence of any type of dementia increased over the last 5 years of the study, although we identified different trends depending on the specific cause of dementia. The IHM remained stable overtime until 2020, when it increased, probably related to the COVID-19 pandemic. It is remarkable the protective effect of female sex for IHM., Competing Interests: Declaration of competing interest All authors declare that they have none Conflict of Interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction and Objectives: Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The Pi*S and Pi*Z variants of the SERPINA1 gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma. The link between AAT deficiency and asthma might be represented by the elastase/antielastase imbalance. However, their role in asthma exacerbations remains unknown. Our objective was to assess whether SERPINA1 genetic variants and reduced AAT protein levels are associated with asthma exacerbations., Materials and Methods: In the discovery analysis, SERPINA1 Pi*S and Pi*Z variants and serum AAT levels were analyzed in 369 subjects from La Palma (Canary Islands, Spain). As replication, genomic data from two studies focused on 525 Spaniards and publicly available data from UK Biobank, FinnGen, and GWAS Catalog (Open Targets Genetics) were analyzed. The associations between SERPINA1 Pi*S and Pi*Z variants and AAT deficiency with asthma exacerbations were analyzed with logistic regression models, including age, sex, and genotype principal components as covariates., Results: In the discovery, a significant association with asthma exacerbations was found for both Pi*S (odds ratio [OR]=2.38, 95% confidence interval [CI]= 1.40-4.04, p-value=0.001) and Pi*Z (OR=3.49, 95%CI=1.55-7.85, p-value=0.003)Likewise, AAT deficiency was associated with a higher risk for asthma exacerbations (OR=5.18, 95%CI=1.58-16.92, p-value=0.007) as well as AAT protein levels (OR= 0.72, 95%CI=0.57-0.91, p-value=0.005). The Pi*Z association with exacerbations was replicated in samples from Spaniards with two generations of Canary Islander origin (OR=3.79, p-value=0.028), and a significant association with asthma hospitalizations was found in the Finnish population (OR=1.12, p-value=0.007)., Conclusions: AAT deficiency could be a potential therapeutic target for asthma exacerbations in specific populations., Competing Interests: Conflicts of interest Authors declare they have no competing interests or other interests that might be perceived to influence the interpretation of the manuscript. No supporting institution may gain or lose financially through this publication. E.M.G. report funding from the Board of Economy, Industry, Trade, and Knowledge of the Canary Islands Government, with a European Social Fund co-financing rate managed by the Canary Islands Agency for Research, Innovation, Society and Information (ACIISI). E.H.L. was supported by a fellowship awarded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future” (PRE2018–083,837). V.P. has received grant support from MSD. V.d.P. was supported by CIBER de Enfermedades Respiratorias, ISCIII, Spain. E.H.L., and M.P.Y. report funding from the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033) and by the European Social Fund “ESF Investing in your future” by the European Union. J.P.G reports funding from the Spanish Ministry of Universities. M.P.Y. report grants from the European Regional Development Fund “ERDF A way of making Europe” by the European Union. M.P.Y. reports grant support from GlaxoSmithKline, Spain paid to Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC) for a project outside the submitted work and grants from Instituto de Salud Carlos III, Madrid, Spain. M.P.Y. and J.V. report grants from Instituto de Salud Carlos III, Madrid, Spain., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Asthma is a disease with high prevalence, which affects all age groups and generates high health and social care costs. Studies carried out in a number of populations show great variability in its prevalence, even in geographically close populations, with data suggesting a relevant influence of socio-economic factors. At present, we do not have reliable data on the prevalence of this disease in the adult population of Spain. The objectives of this study are to estimate the prevalence of asthma in the Spanish population for those aged 18-79, to describe the variability between autonomous communities, to estimate the prevalence of under and overdiagnosis, to analyse the prevalence of uncontrolled asthma and steroid-dependent asthma, to evaluate the health care cost, to identify the most frequent phenotypes and to establish a starting point to evaluate the temporal trend with subsequent studies., Methods: A cross-sectional, two-stage study will be carried out, including patients from 50 catchment areas. The study will be carried out in 3 phases: 1) screening and confirmation in the clinical history, in which patients with a previously correctly established diagnosis of asthma will be identified; 2) diagnosis of asthma to evaluate patients without a confirmed or excluded diagnosis; 3) characterization of asthma, where the characteristics of the asthmatic patients will be analysed, identifying the most frequent phenotypes., Discussion: It seems necessary and feasible to carry out an epidemiological study of asthma in Spain to identify the prevalence of asthma, to optimize healthcare planning, to characterize the most frequent phenotypes of the disease, and to evaluate inaccurate diagnoses., (© 2023 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Introduction: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes., Methods: We performed a multicentre prospective cohort study, including adult patients with asthma (N=512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm., Results: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities., Conclusion: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups., Methods: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab)., Results: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups., Conclusions: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

(1) Background: To examine the clinical characteristics and hospital outcomes of hospitalization for lung transplantation in COPD patients in Spain from 2016 to 2020; and to assess if the COVID-19 pandemic has affected the number or the outcomes of lung transplantations in these patients. (2) Methods: We used the Spanish National Hospital Discharge Database to select subjects who had a code for COPD (ICD-10: J44) and had undergone a lung transplantation (ICD-10 codes OBYxxxx). (3) Results: During the study period, 704 lung transplants were performed among COPD patients (single 31.68%, bilateral 68.32%). The absolute number of transplants increased with raising rates of 8%, 14% and 19% annually from 2016 to 2019. However, a marked decrease of -18% was observed from 2019 to year 2020. Overall, 47.44% of the patients suffered at least one complication, being the most frequent lung transplant rejection (24.15%), followed by lung transplant infection (13.35%). The median length of hospital stay (LOHS) was 33 days and the in-hospital-mortality (IHM) was 9.94%. Variables associated with increased risk of mortality were a Comorbidity Charlson Index ≥ 1 (OR 1.82; 95%CI 1.08-3.05) and suffering any complication of the lung transplantation (OR 2.14; 95%CI 1.27-3.6). COPD patients in 2020 had a CCI ≥ 1 in a lower proportion than 2019 patients (29.37 vs. 38.51%; p = 0.015) and less frequently suffered any complications after the lung transplantation (41.26 vs. 54.6%; p = 0.013), no changes in the LOHS or the IHM were detected from 2019 to 2020. (4) Conclusions: Our study showed a constant increase in the number of lung transplantations from 2016 to 2019 in COPD patients, with a drop from 2019 to 2020, probably related to the COVID-19 pandemic. However, no changes in LOHS or IHM were detected over time.

Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV 1 /FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes ( FOXO3 , PTEN , and MAPK3 ) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment.

Asthma is the most common chronic respiratory disease and a major public health problem. Although the causal relationship between air pollution and asthma remains controversial, a large number of studies have provided increasingly consistent evidence of the involvement of air pollutants in asthma onset and exacerbations. We conducted a keyword search-based literature review using PubMed, Scopus and Web of Science databases for studies with titles or abstracts containing predefined terms. This narrative review discusses the current evidence on the pathological effects of pollution throughout life and the mechanisms involved in the onset, development, and exacerbation of asthma, and presents current measures and interventions for pollution damage control. Further global efforts are still needed to improve air quality., (© 2022 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Background: Asthma is a heterogeneous disease with several phenotypes, endotypes and severity degrees, in which different T-cell subpopulations are involved. These cells express specific miRNAs (i.e. inflamma-miRs) that can be released to serum in exosomes after activation and be used as biomarkers of underlying inflammation. Thus, we aim to evaluate specific T-cell miRNA signatures in serum exosomes from different subgroups of asthmatic patients., Methods: Samples from healthy donors (N = 30) and patients (N = 119) with different asthma endotypes (T2 high -Atopic/T2 high -Non-atopic/T2 low ) and severity degrees (mild/MA and moderate-severe/MSA) were used. Demographic, clinical, haematological and biochemical characteristics were collected. Twelve miRNAs previously associated with different Th subsets were preselected and their levels in serum exosome samples were measured using RTqPCR., Results: We detected five miRNAs with high confidence in serum exosomes: miR-16-5p, miR-21-5p, miR-126-3p, miR146a-5p and miR-215-5p. All of them, except miR-16-5p were upregulated in MSA patients compared to MA. A logistic regression model including each of these miRNAs was created to discriminate both conditions, rendering a ROC curve AUC of 0.896 (0.830-0.961). miR-21-5p and miR-126-3p, both involved in Th1/Th2 differentiation, were specifically augmented in T2 high -Atopic patients. Of note, all these changes were found in samples collected in autumn. On the contrary, IL-6 high patients with MSA, which were more obese, older, with higher neutrophil and basophil counts and TNF levels, displayed a decrease of miR-21-5p, miR-126-3p and miR-146a-5p., Conclusion: Immune-related miRNAs, including miR-21-5p, miR-126-3p, miR-146a-5p and miR-215-5p, can be used as clinically relevant non-invasive biomarkers of the phenotype/endotype and severity of asthma., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Few studies have compared the prevalence of asthma in urban and rural settings or explored the issue of whether these two manifestations of the disease may represent different phenotypes. The aim of this study was: (a) to establish whether the prevalence of asthma differs between rural and urban settings, and b) to identify differences in the clinical presentation of asthma in these two environments. Descriptive epidemiological study involving individuals aged 18 or over from a rural (n = 516) and an urban population (n = 522). In the first phase, individuals were contacted by letter in order to organize the administration of a first validated questionnaire (Q1) designed to establish the possible prevalence of bronchial asthma. In the second phase, patients who had presented association patterns in the set of variables related to asthma in Q1 completed a second validated questionnaire (Q2), designed to identify the characteristics of asthma. According to Q1, the prevalence of asthma was 15% (n = 78) and 11% (n = 59) in rural and urban populations respectively. Sixty-five individuals with asthma from the rural population and all 59 individuals from the urban population were contacted and administered the Q2. Thirty-seven per cent of the individuals surveyed had previously been diagnosed with bronchial asthma (35% in the rural population and 40% in the urban setting). In the urban asthmatic population there was a predominance of women, a greater personal history of allergic rhinitis and a family history of allergic rhinitis and/or eczema. Asthma was diagnosed in adulthood in 74.8% of the patients, with no significant differences between the two populations. Regarding symptoms, cough (morning, daytime and night) and expectoration were more frequent in the urban population. The prevalence of asthma does not differ between urban and rural settings. The differences in exposure that characterize each environment may lead to different manifestations of the disease and may also affect its severity., (© 2022. The Author(s).)

Background: Monoclonal antibodies (mABs) have become available to treat more efficiently patients with severe uncontrolled asthma (SUA). However, the use of mABs is lower than expected given the prevalence of SUA, with significant disparities in the use of these treatments., Objective: To evaluate the proportion of patients with SUA treated with mABs in Spain, and to analyze some of the factors that could determine these prescription patterns., Methods: An analysis was performed on the data provided from the Hospitals National Health System (NHS) 2018 catalogue where Chest Diseases Department and a Hospital Pharmacy were available. Random sampling was performed to determine the sample size, stratifying proportionally by geographic area and hospital level. Characteristics of the participating sites, as well as the prescribing of mABs were collected, which included geographic area, hospital levels, prescribing medical specialities, types of clinics, and mABs prescribed., Results: Data from 90 hospitals were analyzed (Response rate 64.3%). Level 4 hospitals, the Canary Islands geographical area, and the presence of a high complexity Asthma Healthcare Unit (ACU) were associated with a higher probability that the SUA was treated with mABs., Conclusion: The map of the prescribing of mABs for SUA in Spain shows a significant variation by geographic area, hospital level, type of clinic, and the accreditation level of the ACUs. At the current time, there appears to be significant under-prescribing of these treatments.

The use of devices for measuring the exhaled fraction of nitric oxide has proven to be very useful, especially in the diagnosis of asthma, prediction of response to corticosteroids, risk of exacerbations or compliance with treatment, among others, and their use is recommended by important clinical practice guidelines. In recent years we have witnessed a proliferation of options on the market with different characteristics. To help in choosing a device that suits the needs of the professionals involved in the management of asthma, this review presents some of the important characteristics of the most common devices. In addition, the existing comparative and pharmacoeconomic studies are analyzed so that professionals can make the choice of device guided by the most current evidence., (© 2022 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Background and Aims: Asthma is a heterogeneous respiratory disease that encompasses different inflammatory and functional endophenotypes. Many non-invasive biomarkers has been investigated to its pathobiology. Heany et al proposed a clinical algorithm that classifies severe asthmatic patients into likely-eosinophilic phenotypes, based on accessible biomarkers: PBE, current treatment, FeNO, presence of nasal polyps (NP) and age of onset., Materials and Methods: We assessed the concordance between the algorithm proposed by Heany et al. with sputum examination, the gold standard, in 145 asthmatic patients of the MEGA cohort with varying grades of severity., Results: No correlation was found between both classifications 0.025 (CI = 0.013-0.037). Moreover, no relationship was found between sputum eosinophilia and peripheral blood eosinophilia count in the total studied population., Discussion and Conclusion: In conclusion, our results suggest that grouping the biomarkers proposed by Heany et al. are insufficient to diagnose eosinophilic phenotypes in asthmatic patients. Sputum analysis remains the gold standard to assess airway inflammation., Competing Interests: Dr. Betancor is supported by a Rio Hortega Research Contract from Instituto Carlos III, Spanish Ministry of Science. Dr. Valverde has received lecturing fees from GSK and sits on the advisory board for Organon. Dr. Rial reports receiving personal fees from GSK, Allergy Therapeutics, and AstraZeneca outside the submitted work. Dr. González Barcala reports personal fees from ALK, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Gebro Pharma, GlaxoSmithKline, Laboratorios Esteve, Menarini, Mundipharma, Novartis, Rovi, Roxall, Stallergenes‐Greer, Teva, as well as grants from Mundipharma outside the submitted work. Dr. Quirce reports personal fees from AstraZeneca, Novartis, Sanofi, Boehringer Ingelheim, Teva, ALK, Mundipharma, GSK, Chiesi, and Leti outside the submitted work. Dr. Soto reports non‐financial support from CIBER de Enfermedades Respiratorias (CIBERES) during the conduct of the study; outside of the present work, she reports personal fees from Stallergennes‐Greer, Menarini, and Novartis, personal fees from GSK, Hal Allergy, Allergy Therapeutics, AstraZeneca, and grants from Sociedad Española de Alergología e Inmunología Clínica SEAIC and Sociedad Española de Neumología y Cirugía Torácica SEPAR. Dr. Martinez Rivera reports having received grants and personal fees from AstraZeneca, Teva, GSK, Novartis, and Mundipharma outside the submitted work. Dr. Munoz reports personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Teva, Mundifarma, Chiesi, and Faes outside the submitted work. Dr. Sastre reports grants and personal fees from Sanofi, GSK, Novartis, AstraZeneca, Mundipharma, and Faes Farma outside the submitted work. Dr. Olaguibel reports grants from Sanofi and/or personal fees from AstraZeneca and Mundipharma outside the submitted work. Dr. Plaza reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Merck, Chiesi, Novartis, Menarini, and Sanofi outside the submitted work. Dr. Mullol reports personal and other fees from Sanofi‐Genzyme & Regeneron, Novartis, Viatris (Mylan pharma), Uriach group, Mitsubishi‐Tanabe, Menarini, UCB, AstraZeneca, GSK, and MSD outside the submitted work. Dr. del Pozo reports personal and other fees from Sanofi, AstraZeneca, and GSK outside the submitted work. All other authors have no conflicts of interest., (© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Severe asthma is a heterogeneous syndrome with several clinical variants and often represents a complex disease requiring a specialized and multidisciplinary approach, as well as the use of multiple drugs. The prevalence of severe asthma varies from one country to another, and it is estimated that 50% of these patients present a poor control of their disease. For the best management of the patient, it is necessary a correct diagnosis, an adequate follow-up and undoubtedly to offer the best available treatment, including biologic treatments with monoclonal antibodies. With this objective, this consensus process was born, which began in its first version in 2018, whose goal is to offer the patient the best possible management of their disease in order to minimize their symptomatology. For this 2020 consensus update, a literature review was conducted by the authors. Subsequently, through a two-round interactive Delphi process, a broad panel of asthma experts from SEPAR and the regional pulmonology societies proposed the recommendations and conclusions contained in this document., (© 2022 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Introduction: Determining the risk of recurrence of primary spontaneous pneumothorax is challenging. The objective of this study was to develop a risk assessment model to predict the probability of recurrence in patients with spontaneous pneumothorax., Methods: A retrospective study was performed of all episodes of pneumothorax diagnosed in the last 12 years in a hospital, in patients not initially submitted to surgery. Logistic regression was used to estimate the probability of recurrence. Based on a set of variables, a predictive model was built with its corresponding ROC curve to determine its discrimination power and diagnostic precision., Results: Of the 253 patients included, 128 (50.6%) experienced recurrence (37% within the first year). Recurrence was detected within 110 days in 25% of patients. The median of time to recurrence for the whole population was 1120 days. The presence of blebs/bullae was found to be a risk factor of recurrence (OR: 5.34; 95% CI: 2.81-10.23; p=0.000), whereas chest drainage exerted protective effect (OR: 0.19; 95% CI: 0.08-0.40; p=0.000). The variables included in the regression model constructed were hemoglobin and leukocyte count in blood, treatment received, and presence of blebs/bullae, with a fair discriminative power to predict recurrence [AUC=0.778 (95% CI: 0.721-0.835)]., Conclusion: The overall recurrence rate was high and was associated with the presence of blebs/bullae, failure to perform an active intervention (chest drainage) and low levels of hemoglobin and leukocytes in blood. Recurrence rarely occurs later than three years after the first episode. Once validated, this precision model could be useful to guide therapeutic decisions., (Copyright © 2020 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression., Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10 -5 ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico., Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR T allele ) = 0.82, p = 9.05 × 10 -6 and replication: OR T allele  = 0.89, p = 5.35 × 10 -3 ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR C allele  = 0.85, p = 3.10 × 10 -5 and replication: OR C allele  = 0.89, p = 1.30 × 10 -2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood., Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Frequent and highly prevalent as comorbidities in Chronic Obstructive Pulmonary Disease (COPD) patients, both depression and anxiety seem to have an impact on COPD prognosis. However, they are underdiagnosed and rarely treated properly., Aim: To establish the prevalence of depression and anxiety in patients admitted for Acute Exacerbation of COPD (AECOPD) and determine their influence on COPD prognosis., Methods: Prospective observational study conducted from October 1, 2016 to October 1, 2018 at the following centers in Galicia, Spain: Salnés County Hospital, Arquitecto Marcide, and Clinic Hospital Complex of Santiago de Compostela. Patients admitted for AECOPD who agreed to participate and completed the anxiety and depression scale (HADS) were included in the study., Results: 288 patients (46.8%) were included, mean age was 73.7 years (SD 10.9), 84.7% were male. 67.7% patients were diagnosed with probable depression, and depression was established in 41.7%; anxiety was probable in 68.2% and established in 35.4%. 60.4% of all patients showed symptoms of both anxiety and depression. Multivariate analysis relates established depression with a higher risk of late readmission (OR 2.06, 95% CI 1.28; 3.31) and a lower risk of mortality at 18 months (OR 0.57, 95% CI 0.37; 0.90)., Conclusion: The prevalence of anxiety and depression in COPD patients is high. Depression seems to be an independent factor for AECOPD, so early detection and a multidisciplinary approach could improve the prognosis of both entities. The study was approved by the Ethical Committee of Galicia (code 2016/460)., (© 2022. The Author(s).)

Background: Gastroesophageal reflux disease (GORD) is highly prevalent and often coexists with asthma exacerbation. Divergent findings about the association between the two diseases were reported. We conducted a systematic review and meta-analysis to determine whether there exists an association between GORD and asthma., Methods: We searched MEDLINE, EMBASE, and other databases and then performed a manual search, to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using fixed- and random-effect models. We evaluated the quality of included studies, explored heterogeneity between studies, undertook subgroup analyses, assessed publication bias, and performed sensitivity analyses., Results: We identified 32 eligible studies, conducted in 14 countries and including a total of 1,612,361 patients of all ages. Overall, GORD shows a weak association with asthma exacerbation (OR = 1.27; 95% CI 1.18-1.35). This association was observed in cohort, case-control, and cross-sectional designs and in European as well as non-European populations. Subgroup analyses show that GORD is associated with frequent asthma exacerbations (≥3 exacerbations, OR = 1.59; 95% CI 1.13-2.24) and with exacerbations needing oral corticosteroid therapy (OR = 1.24; 95% CI 1.09-1.41). GORD pediatric patients are at higher odds of asthma exacerbation than adults. We did not detect any evidence of publication bias and the association between GORD and asthma exacerbation held in all undertaken sensitivity analyses., Conclusions: Gastroesophageal reflux disease and asthma exacerbation are weakly associated., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)