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Introduction: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/μL., Methods: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92μg/umeclidinium (UMEC) 55μg/vilanterol (VI) 22μg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia., Results: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026., Conclusions: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Rationale: COPD and bronchiectasis are commonly reported together. Studies report varying impacts of co-diagnosis on outcomes, which may be related to different definitions of disease used across studies. Objectives: To investigate the prevalence of chronic obstructive pulmonary disease (COPD) associated with bronchiectasis and its relationship with clinical outcomes. We further investigated the impact of implementing the standardized ROSE criteria (radiological bronchiectasis [R], obstruction [FEV 1 /FVC ratio <0.7; O], symptoms [S], and exposure [⩾10 pack-years of smoking; E]), an objective definition of the association of bronchiectasis with COPD. Methods: Analysis of the EMBARC (European Bronchiectasis Registry), a prospective observational study of patients with computed tomography-confirmed bronchiectasis from 28 countries. The ROSE criteria were used to objectively define the association of bronchiectasis with COPD. Key outcomes during a maximum of 5 years of follow-up were exacerbations, hospitalization, and mortality. Measurements and Main Results: A total of 16,730 patients with bronchiectasis were included; 4,336 had a clinician-assigned codiagnosis of COPD, and these patients had more exacerbations, worse quality of life, and higher severity scores. We observed marked overdiagnosis of COPD: 22.2% of patients with a diagnosis of COPD did not have airflow obstruction and 31.9% did not have a history of ⩾10 pack-years of smoking. Therefore, 2,157 patients (55.4%) met the ROSE criteria for COPD. Compared with patients without COPD, patients who met the ROSE criteria had increased risks of exacerbations and exacerbations resulting in hospitalization during follow-up (incidence rate ratio, 1.25; 95% confidence interval, 1.15-1.35; vs. incidence rate ratio, 1.69; 95% confidence interval, 1.51-1.90, respectively). Conclusions: The label of COPD is often applied to patients with bronchiectasis who do not have objective evidence of airflow obstruction or a smoking history. Patients with a clinical label of COPD have worse clinical outcomes.

Introduction: N-acetylcysteine (NAC) is a mucolytic agent with antioxidant properties. Oxidative stress is a key pathogenic mechanism in chronic respiratory conditions such as COPD and chronic bronchitis (CB). In these meta-analyses we investigated the efficacy of NAC in subjects with COPD or CB, the latter being a potential pre-COPD condition (CB/pre-COPD)., Methods: The meta-analyses were conducted according to PRISMA guidelines. Exacerbations were assessed using total number of exacerbations. Improvement in patients' respiratory symptoms and/or patients quality of life (QoL) were measured by validated tools or assessed at the end of the study., Results: Twenty studies were included, of which seven evaluated NAC in patients with symptoms of CB/pre-COPD as entry criterion. NAC treated patients showed a significant reduction of the incidence of exacerbations as compared to placebo both in COPD (IRR=0.76; 95% confidence interval (CI) 0.59-0.99) and CB/pre-COPD (IRR=0.81; 95% CI 0.69-0.95). Sensitivity analyses in studies with duration higher than 5 months, confirmed the overall results. CB/pre-COPD patients treated with NAC were significantly more likely to experience an improvement in symptoms and/or QoL compared to placebo (odds ratio (OR)=3.47; 95% CI 1.92-6.26). A similar trend was observed in the few COPD studies evaluable. Sensitivity analyses showed a significant association of NAC with improvement in symptoms and/or QoL both in CB/pre-COPD and COPD patients., Conclusions: These findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD. PROSPERO registry no. CRD42023468154., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

The treatable traits approach represents a strategy for patient management. It is based on the identification of characteristics susceptible to treatments or predictive of treatment response in each individual patient. With the objective of accelerating progress in research and clinical practice relating to such a treatable traits approach, the Portraits event was convened in Barcelona, Spain, in November 2022. Here, while reporting the key concepts that emerged from the discussions during the meeting, we review the current state of the art related to treatable traits and chronic respiratory diseases management, and we describe the possible actions that clinicians can take in clinical practice to implement the treatable traits framework. Furthermore, we explore the new concept of GETomics and the new models of research in the field of COPD., Competing Interests: Conflicts of interest: A Papi reports honoraria from AstraZeneca, Chiesi Farmaceutici, Boehringer Ingelheim, GlaxoSmithKline, Gentili, Pfizer, Novartis, Mundipharma, Novartis, TEVA and Zambon; research grants from AstraZeneca, Chiesi Farmaceutici, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Fondazione Maugeri and Fondazione Chiesi; participation in a company sponsored bureau with AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Edmondpharma, GlaxoSmithKline, Mundipharma, Novartis, Sanofi/Regeneron, TEVA and Zambon. R. Faner reports honoraria from AstraZeneca and Chiesi, and research grants from GSK, AstraZeneca and Menarini. I. Pavord reports honoraria from AstraZeneca, Boehringer Ingelheim, Aerocrine, Chiesi, Novartis, Sanofi, Regeneron and GSK; research grants from Boehringer Ingelheim, GSK, AstraZeneca, Chiesi and Napp; participation in a company sponsored bureau with Almirall, AstraZeneca, Boehringer Ingelheim, GSK, MSD, Schering-Plough, Novartis, Dey, Napp, Sanofi and Regeneron. F. Baraldi reports no conflicts. V.M. McDonald reports honoraria from GSK and AstraZeneca; research grants from NHMRC and the Medical Reseach Futures Fund; other support or other potential conflict of interest: committee member for the COPD X guideline committee. M. Thomas reports honoraria from GSK, Boehringer Ingelheim and Chiesi. M. Miravitlles reports honoraria from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Inhibrx, Laboratorios Esteve, Ferrer, Menarini, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols; research grants from Grifols; participation in a company sponsored bureau with AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Kamada, Takeda, Sandoz, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis. N. Roche reports honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Zambon, Novartis, Pfizer, Sanofi, Teva, MSD and Austral; research grants from GSK, Novartis, Pfizer and Boehringer Ingelheim; other support or other potential conflict of interest: GOLD science committee, Respiratory Effectiveness Group, European Respiratory Society. A. Agustí reports honoraria from AstraZeneca, Chiesi, GSK, Menarini, MSD, Sanofi and Zambon; and research grants from AstraZeneca, GSK and Menarini., (Copyright ©The authors 2024.)

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, respiratory symptoms, inflammation of the airways, and systemic manifestations of the disease. Genetic susceptibility and environmental factors are important in the development of the disease, particularly exposure to cigarette smoke which is the most notable risk factor. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are the cause of cystic fibrosis (CF), which shares several pathophysiological pulmonary features with COPD, including airway obstruction, chronic airway inflammation and bacterial colonization; in addition, both diseases also present systemic defects leading to comorbidities such as pancreatic, gastrointestinal, and bone-related diseases. In patients with COPD, systemic CFTR dysfunction can be acquired by cigarette smoking, inflammation, and infection. This dysfunction is, on average, about half of that found in CF. Herein we review the literature focusing on acquired CFTR dysfunction and the potential role in the pathogenesis of comorbidities associated with COPD and chronic bronchitis., Competing Interests: Declaration of competing interest In the past 36 months, M. Miravitlles has received consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi and Grifols, speaker fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Cipla, Janssen, Kamada, Menarini, Takeda, Speciality Therapeutics, Zambon, CSL Behring, Grifols and Novartis, support for attending meetings/travel from Novartis, Boehringer Ingelheim and Menarini, research grants from Grifols, and has participated on a data safety monitoring board for Mereo. G.J. Criner has no declarations. M.A. Mall declares editorial support from Novartis Pharma AG since the initial planning of the work, and declares grants from German Ministry for Education and Research and the German Research Foundation, consulting fees from Abbvie, Antabio, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotech, Pieris Pharmaceuticals, Santhera, Sterna Biologicals and Vertex Paharmaceuticals, lecture fees from Arrowhead Pharmaceuticals, Boehringer Ingelheim and Vertex Pharmaceuticals, travel reimbursement from Boehringer Ingelheim and Vertex Pharmaceuticals, and personal fees for participation on advisory boards from Boehringer Ingelheim, Arrowhead Pharmaceuticals, Vertex Pharmaceuticals, Santhera, Enterprise Therapeutics, Antabio, Kither Biotech, Pari and Abbvie; an elected unpaid member of the ECFS board. S.M. Rowe declares grant support for clinical trials conducted through university grants/contracts from Novartis, TranslateBio, Galapagos/Abbvie, Vertex Pharmaceuticals, research grant through University grants/contracts from Synedgen/Synspira, Eloxx, Ionis and AstraZeneca, consulting fees services on the design and conduct of clinical trials from Arcturus, Cystetic Medicines, Galapagos/Abbvie, Ionis, Novartis, Renovion, Synedgen/Synspira, Vertex Pharmaceuticals, support for travel to attend meetings from Vertex Pharmaceuticals; co-chair of the Next Generation Steering Committee with Vertex Pharmaceuticals, research product for investigator initiated research provided from Synedgen/Synspira and Renovion, consulting services on the design and conduct of clinical trials including stock options for Synedgen/Synspira and Renovion within the past 36 months; MTAs for investigator-initiated and externally funded research efforts from Ionis, Galapagos/Abbvie and Synedgen/Synspira, all in the past 36 months; and declares six patents. C.F. Vogelmeier declares institution grants from German Ministry of Education and Science (BMBF), AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols and Novartis, consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed, Menarini, Novartis and Nuvaira, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed, Menarini and Novartis, in the past 36 months. B. Hederer was an employee of Novartis Pharma AG at the timing of writing this manuscript. M. Schoenberger is a full-time employee of Novartis Pharma AG and retains Novartis stock. P. Altman was an employee of Novartis Pharmaceutical Corporation at time of writing this manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Physical activity (PA) has shown great benefits in patients with chronic obstructive pulmonary disease (COPD); however, their PA is below average. Motivational factors associated with PA in COPD have not been widely studied and could be a target for improving adherence to PA. The objective of our study was to identify and understand the different motivational and confidence factors related to low levels of PA in a COPD cohort., Method: Observational, prospective, multicenter study of COPD patients. Sociodemographic data, respiratory symptoms, comorbidities, spirometry, and exercise capacity were collected. PA was measured using the Dynaport accelerometer and patient motivation and confidence in PA were assessed by a questionnaire previously used in a COPD population in the USA., Results: Eighty six COPD patients were included, 68.6% being male, with a mean (SD) age of 66.6 (8.5) years and a mean forced expiratory volume in the first second (%) of 50.9% (17.3%). The mean walking time was 82.8 (37.8) minutes/day. Questions related to health benefits and enjoying exercise were ranked highest in the motivation questionnaire and statistically significant differences were found in PA measures between patients with low and high motivation. A lack of confidence regarding hot weather and health-related issues significantly influenced PA levels. Advice from third parties, including healthcare providers, was not associated with higher PA levels., Conclusions: Improving the health of COPD patients is their main motivation to perform PA. Lack of confidence when it is hot or when they fear for their health is related to low levels of PA. Advice from third parties, including healthcare professionals, is not associated with higher PA. These results are relevant for developing strategies to increase the adherence of COPD patients to PA programs., (© 2024 S. Karger AG, Basel.)

Introduction: The aim of this study was to analyze the impact of occupational exposure on chronic obstructive pulmonary disease (COPD) and respiratory symptoms in the general Spanish population., Methods: This was a study nested in the Spanish EPISCAN II cross-sectional epidemiological study that included participants who had completed a structured questionnaire on their occupational history, a questionnaire on respiratory symptoms, and forced spirometry. The data were analyzed using Chi-square and Student's t tests and adjusted models of multiple linear regression and logistic regression., Results: We studied 7502 subjects, 51.1% women, with a mean age of 60±11 years. Overall, 53.2% reported some respiratory symptoms, 7.9% had respiratory symptoms during their work activity, 54.2% were or had been smokers, and 11.3% (851 subjects) met COPD criteria on spirometry. A total of 3056 subjects (40.7%) reported exposure to vapors, gases, dust or fumes (VGDF); occupational exposure to VGDF was independently associated with the presence of COPD (OR 1.22, 95% CI: 1.03-1.44), respiratory symptoms (OR 1.45, 95%: CI 1.30-1.61), and respiratory symptoms at work (OR 4.69, 95% CI: 3.82-5.77), with a population attributable fraction for COPD of 8.2%., Conclusions: Occupational exposure is associated with a higher risk of COPD and respiratory symptoms in the Spanish population. These results highlight the need to follow strict prevention measures to protect the respiratory health of workers., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Augmentation therapy with intravenous alpha-1 antitrypsin is the only specific treatment for alpha-1 antitrypsin deficiency (AATD)-associated emphysema. This treatment has been available and remained basically unchanged for more than 35 years, but many questions persist regarding its indications, regimen of administration and efficacy. Because AATD is a rare disease, it has not been possible to conduct randomised, placebo-controlled trials that are adequately powered for the usual outcomes analysed in non-AATD-related COPD, such as lung function decline, exacerbations, symptoms or quality of life. New outcomes such as lung densitometry measured by computed tomography are more sensitive for identifying emphysema progression but are not widely accepted by regulatory agencies. In addition, clinical manifestations, severity and the natural history of lung disease associated with AATD are very heterogeneous, which means that individual prediction of prognosis is challenging. Therefore, the indication for augmentation is sometimes a dilemma between initiating treatment in individuals who may not develop significant lung disease or in whom disease will not progress and delaying it in patients who will otherwise rapidly and irreversibly progress.Other areas of debate are the possible indication for augmentation in patients with severe AATD and respiratory diseases other than emphysema, such as bronchiectasis or asthma, and the use of therapy after lung transplant in AATD patients. All these uncertainties imply that the indication for treatment must be personalised in expert reference centres after in-depth discussion of the pros and cons of augmentation with the patient., Competing Interests: Conflict of interest: M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi, Zambon and Grifols; and research grants from Grifols. A. Anzueto has received consultant fees from AstraZeneca, Boehringer Ingelheim, Grifols, GlaxoSmithKline, Verona Pharma, TEVA and Mylan/Theravance. M. Barrecheguren has received speaker fees from Grifols, Menarini, CSL Behring, GSK and Boehringer Ingelheim; and consulting fees from GSK, Novartis, CSL Behring and Boehringer Ingelheim., (Copyright ©The authors 2023.)

Background: Poor sleep and attention deficits are common in COPD., Objectives: To assess the relationship between self-reported poor sleep and attention deficits in COPD. We also studied the association between self-reported sleep and the attention tests with the objective characteristics of sleep., Methods: Fifty-nine COPD patients were prospectively studied. Self-reported sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Objective characteristics of sleep were assessed by actigraphy and polysomnography. Attention was evaluated with the Oxford sleep resistance test (OSLER) and the Psychomotor vigilance test (PVT)., Results: 28 (47 %) patients referred poor sleep (PSQI >5). In the OSLER test they showed earlier sleep onset than patients with good sleep, median (Interquartil range): 31.2 min (25.4-40) vs 40 min (28.5-40), p: 0.048. They also spent more time making errors: 4.5 % (0.6-7.6) of total test time vs 0.7 % (0.2-5.3), p: 0.048. In PVT, patients with poor sleep presented a greater dispersion of the reaction time values with a higher value in the slowest 10 % of the reactions, 828 (609-1667) msec. vs 708 (601-993) msec, p: 0.028. No association was found between self-reported poor sleep and objective sleep variables. We found no correlation between OSLER and PVT results and polysomnographic variables except between sleep efficiency and PVT response speed (β: 0.309, p: 0.018)., Conclusion: Self-reported poor sleep in COPD is associated with attention deficits. Sleep quality should be included in future studies of this facet of cognition in COPD, as well as to assess its potential usefulness as a therapeutic target., Competing Interests: Declaration of competing interest Júlia Sampol declares to have no conflict of interest. Jaume Ferrer has received fees from AstraZeneca, Novartis, Boehringer Ingelheim, Chiesi and GlaxoSmihtKline, and a research grant from Air Liquide Foundation. Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi, Zambon and Grifols and research grants from Grifols. María Sáez declares to have no conflict of interest. Odile Romero declares to have no conflict of interest. Gabriel Sampol declares to have no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this analysis was to describe the patterns of inhaled maintenance therapy according to risk level and to explore the determinants associated with the decision to prescribe inhaled corticosteroids (ICS) in addition to bronchodilator therapy according to risk level as strategy in the follow-up of COPD in daily clinical practice., Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021 and January 31, 2022., Results: 4225 patients from 45 hospitals in Spain were audited. Risk levels were analyzed in 2678 patients. 74.5% of patients were classified as high risk and 25.5% as low risk according to GesEPOC criteria. Factors associated with the prescription of ICS in low-risk COPD were symptoms suggestive of asthma [OR: 6.70 (3.14-14.29), p<0.001], peripheral blood eosinophilia>300mm 3 [OR: 2.16 (1.10-4.24), p=0.025], and having a predicted FEV1%<80% [OR: 2.17 (1.15-4.08), p=0.016]. In high-risk COPD, factors associated with triple therapy versus dual bronchodilator therapy were a mMRC dyspnea score of ≥2 [OR: 1.97 (1.41-2.75), p<0.001], symptoms suggestive of asthma [OR: 6.70 (3.14-14.29), p<0.001], and a predicted FEV1%<50% [OR: 3.09 (1.29-7.41), p<0.011]., Conclusions: Inhaled therapy in the follow-up of COPD does not always conform to the current guidelines. Few changes in inhaled therapy are made at follow-up visits. The use of ICS is common in COPD patients who meet low-risk criteria in their follow-up and triple therapy in high-risk COPD patients is used as an escalation strategy in patients with high clinical impact. However, a history of exacerbations and eosinophil count in peripheral blood were not factors predicting triple therapy., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: There is still uncertainty about which aspects of cigarette smoking influence the risk of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to estimate the COPD risk as related to duration of use, intensity of use, lifetime tobacco consumption, age of smoking initiation and years of abstinence., Methods: We conducted an analytical cross-sectional study based on data from the EPISCAN-II study (n=9092). All participants underwent a face-to-face interview and post-bronchodilator spirometry was performed. COPD was defined as post-bronchodilator FEV1/FVC<70%. Parametric and nonparametric logistic regression models with generalized additive models were used., Results: 8819 persons were included; 858 with COPD and 7961 without COPD. The COPD risk increased with smoking duration up to ≥50 years [OR 3.5 (95% CI: 2.3-5.4)], with smoking intensity up to ≥39cig/day [OR 10.1 (95% CI: 5.3-18.4)] and with lifetime tobacco consumption up to >29 pack-years [OR 3.8 (95% CI: 3.1-4.8)]. The COPD risk for those who started smoking at 22 or later was 0.9 (95% CI: 0.6-1.4). The risk of COPD decreased with increasing years of cessation. In comparison with both never smokers and current smokers, the lowest risk of COPD was found after 15-25 years of abstinence., Conclusion: COPD risk increases with duration, intensity, and lifetime tobacco consumption and decreases importantly with years of abstinence. Age at smoking initiation shows no effect. After 15-25 years of cessation, COPD risk could be equal to that of a never smoker. This work suggests that the time it takes to develop COPD in a smoker is about 30 years., (Copyright © 2023 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Poor sleep quality is frequent among COPD patients and it has been related to worse outcomes. The objective of this study was to compare the COPD and Asthma Sleep Impact Scale (CASIS) and the generic Pittsburgh Sleep Quality Index (PSQI) questionnaires as reliable tools for evaluating sleep quality and its relationship with COPD characteristics and survival. Stable COPD patients were prospectively evaluated. Anthropometric, sociodemographic, comorbidity, lung function and treatment data were collected. All patients completed CASIS and PSQI, mMRC dyspnea severity scale, COPD Assessment Test (CAT), sleep apnoea STOP-Bang and Hospital Anxiety and Depression Scale (HADS) questionnaires. Body mass index, airflow Obstruction, Dyspnea and Exacerbations (BODEx) index was calculated. Life status was determined after a mean follow-up of 3.7 (SD 1) years. We included 200 patients, 69.5% male, mean age 65.8 (9) years. Poor sleep was detected in 100 (50%) and 84 patients (42%) according to PSQI and CASIS questionnaires, respectively, with an agreement of 63%. Poor sleep was related to female gender, more severe dyspnea and worse BODEx, HADS and CAT scores according to both questionnaires. PSQI was associated to chronic pain or inferior urinary tract symptoms and CASIS to exacerbations, shorter walked distance in the 6-min walking test and treatment with oral corticosteroids or chronic oxygen. Thirty nine (19.5%) patients died during follow-up. Mortality was not associated to PSQI nor CASIS results. Unlike PSQI, CASIS is more related to COPD severity and its results are not influenced by comorbidities with known impact on sleep quality. In our sample, poor sleep quality was not associated with increased mortality., (© 2023. The Author(s).)

Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient's discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation., (© 2023. The Author(s).)

Purpose: Role of triple therapy in chronic obstructive pulmonary disease (COPD) management is supported by growing evidence, but consensus is lacking on various aspects. We conducted a Delphi survey in respiratory experts on the effects of triple therapy on exacerbation reduction, early optimization, pneumonia risk, and mortality benefits in COPD management., Methods: The study comprised 2-round online surveys and a participant meeting with 21 respiratory experts from 10 countries. The 31-statement questionnaire was prepared using Decipher software after literature review. Responses were recorded using Likert scale ranging from 1 (disagreement) to 9 (agreement) with a consensus threshold of 75%., Results: All experts participated in both surveys and 14/21 attended participant meeting. Consensus was reached on 13/31 questions in first survey and 4/14 in second survey on: mortality benefits of triple therapy; comparable pneumonia risk between single inhaler triple therapy (SITT) and multiple inhaler triple therapy (81%); preference of SITT for patients with high eosinophil count (95%); exacerbation risk reduction and healthcare cost benefits with early initiation of SITT post exacerbation-related hospitalization (<30 days) (86%). No consensus was reached on first line SITT use after first exacerbation resulting in COPD diagnosis (62%)., Conclusion: This study demonstrated that there is consensus among experts regarding many of the key concepts about appropriate clinical use and benefits of triple therapy in COPD. More evidence is required for evaluating the benefits of early optimisation of triple therapy., Competing Interests: Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GSK, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GSK, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi, Zambon and Grifols and research grants from Grifols. Sudeep Acharya is an employee of GSK and holds shares in GSK. Bhumika Aggarwal is an employee of GSK and holds shares in GSK. Frederico LA Fernandes has received consulting fees from GSK, Chiesi, AstraZeneca, Zambon, Abbott and Boehringer Ingelheim and speaker fees from Abbott, GSK, ACHE, AstraZeneca, Novartis, Zambon and Boehringer Ingelheim. Jorge Dreyse Dañobeitía has received grants from Boehringer Ingelheim and AstraZeneca and consulting and speaker fees from GSK. José R. Jardim has received grants from GSK and speaker fees from Zambon, Grifols and GSK. Siwasak Juthong declares no conflicts of interest in this work. Gur Levy is an employee of GSK and holds shares in GSK. Martin Sivori has received speaker fees from AstraZeneca, TEVA, ELEA and GSK. The authors report no other conflicts of interest in this work., (© 2023 Miravitlles et al.)

Background: In 2008, a dedicated American Thoracic Society/European Respiratory Society task force published a paper on the possible use and limitations of clinical outcomes and biomarkers to evaluate the impact of pharmacological therapy in patients with chronic obstructive pulmonary disease. Since then, our scientific understanding of chronic obstructive pulmonary disease has increased considerably; there has been a progressive shift from a one-size-fits-all diagnostic and therapeutic approach to a personalized approach; and many new treatments currently in development will require new endpoints to evaluate their efficacy adequately. Objectives: The emergence of several new relevant outcome measures motivated the authors to review advances in the field and highlight the need to update the content of the original report. Methods: The authors separately created search strategies for the literature, primarily based on their opinions and assessments supported by carefully chosen references. No centralized examination of the literature or uniform criteria for including or excluding evidence were used. Measurements and Main Results: Endpoints, outcomes, and biomarkers have been revisited. The limitations of some of those reported in the American Thoracic Society/European Respiratory Society task force document have been highlighted. In addition, new tools that may be useful, especially in evaluating personalized therapy, have been described. Conclusions: Because the "label-free" treatable traits approach is becoming an important step toward precision medicine, future clinical trials should focus on highly prevalent treatable traits, and this will influence the choice of outcomes and markers to be considered. The use of the new tools, particularly combination endpoints, could help better identify the right patients to be treated with the new drugs.

Purpose: Administration of exogenous alpha-1 antitrypsin (AAT) is the only specific therapy for the management of pulmonary morbidity in patients with AAT deficiency. It requires weekly or biweekly intravenous infusions, which may impact patient independence and quality of life. Self-administration of AAT therapy is an alternative to reduce the burden for patients who require AAT therapy. We presented herein experts' recommendations for the implementation of a program for the self-administration of AAT., Methods: This project was conducted using a modified nominal group technique and was undertaken in two online meetings involving the participation of 25 experts: specialists in pulmonology (n=17), nurses (n=5) and hospital pharmacists (n=3)., Results: The following issues were discussed, and several recommendations were agreed upon on the following topics: a) patient profile and clinical evaluation, establishing selection criteria that should include clinical as well as social criteria; b) role of health care professionals, suggested roles for specialists in pulmonology, nurses, and hospital pharmacists; c) training by the nurse, including recommendations before initiating the training and the content of the training sessions; and d) logistic issues and follow-up, adherence, and patient support., Conclusion: We expect this proposal to increase awareness of this therapeutic alternative and facilitate the implementation of self-administration programs, thus contributing to optimizing the patient experience with AAT therapy. Further research on the outcomes of these programs, especially from the patient perspective, will also help to improve their design and implementation., Competing Interests: MT-D: has received consulting fees from CSL Behring and Grifols; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from CSL Behring and Grifols; and support for attending meetings and/or travel from CSL Behring, Grifols and Chiesi. JLL-C: has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies or writing for publications from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, CSL Behring, Ferrer, Gebro, GlaxoSmithKline, Grifols, Menarini, Megalabs, Novartis and Rovi. MCR: has received speaker fees from AstraZeneca, Bial, Chiesi, CSL Behring, GlaxoSmithKline, Menarini, and Grifols; and consulting fees from GlaxoSmithKline, CSL Behring and Bial. CM-M: has received speaker fees and/or consulting fees and/or support to attend congresses from Astra-Zeneca, Boehringer-Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols and Menarini. APC: has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from CSL Behring. MB: has received speaker fees from Grifols, Menarini, CSL Behring, GSK, Boehringer Ingelheim and consulting fees from GSK, Novartis, CSL Behring and Boehringer Ingelheim. FJC-G: has received speaker honorarium from GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Mundipharma, Menarini, Pfizer, Novartis, Esteve, Teva Pharmaceutical, Ferrer, Rovi, Roche, Astra Zeneca, Bial, Actelion, Alter, CSL Behring, Faes Farma, Alter, Grifols, Sanofi Genzyme and Gebro Pharma; consulting honorarium from Chiesi, Boehringer Ingelheim, Teva Pharmaceutical, Astra Zeneca, Bial, CSL Behring and Sanofi Genzyme; and travel grants from GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Teva Pharmaceutical, Astra Zeneca and CSL Behring. FC-M: has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi, Vertex, CSL Behring and Grifols; and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, CSL Behring, and Grifols. JMH-P: Speaker honorarium from Grifols, CSL Behring, Astra-Zeneca, GSK, Bial laboratory, Teva laboratory and FAES Farma. Advisory honorarium from CSL Behring. Travel grants from Grifols and CSL Behring. LL-A: has received speaker honorarium from CSL Behring and Grifols SA; research grants from Grifols SA; consulting honorarium from CSL Behring; and travel grants from CSL Behring and Grifols SA. CMR: has received speaker honorarium from Astra Zeneca, CSL Behring CSL, Chiesi, Gebro, GSK, Mundipharma, TEVA and Sanofi; research grants from AstraZeneca, GSK and TEVA; and consulting and advisory honorarium from Astra Zeneca, CSL Behring, Chiesi, Mundipharma and TEVA. FJM: has received speaker fees and/or consulting fees and/or support to attend congresses from Astra-Zeneca, Boehringer-Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols, Menarini, Novartis, Sanofi Aventis and Teva. J-BM-R: has received speaker fees and/or consulting fees and/or support to attend congresses from CSL Behring and Grifols. RS: has received speaker fees and/or consulting fees and/or support to attend congresses from CSL Behring, Astra Zeneca, Chiesi, GlaxoSmithKline, Grifols, Teva, Novartis and Menarini. MO-P: has received speaker honorarium from Biogen, Novartis, Roche, Genzyme Sanofi and Takeda. JPQG: Advisory board member for CSL Behring. MM: has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Kamada, Takeda, Sandoz, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Inhibrx, Laboratorios Esteve, Ferrer, Menarini, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols; and research grants from Grifols. RAR, MABG, LD-C, PGM, CM-G, IP, MRR-S-E and BT-G: have no conflict of interest., (© 2023 Torres-Durán et al.)

Introduction: The prevalence of α1-antitrypsin PI*ZZ genotypes in patients with COPD is only partially known. We aimed to estimate this prevalence worldwide., Method: A systematic review of the literature was conducted for studies investigating the prevalence of COPD and the prevalence of severe alpha-1-antitrypsin deficiency (AATD) PI*ZZ genotype. Results are shown in tables and on a whole world interpolation map., Results: Studies from 48 countries with available data (21 from Europe, 9 from the Americas, 5 from Africa, 11 from Asia and 2 from Australasia) were selected. About 235,000 individuals with PI*ZZ genotypes were accounted: 50% in Europe, 37% in America, 9% in Asia, 3% in Australasia and 1% in Africa. The estimated crude prevalence of COPD in adults older than 40 years was 12.45% in Europe, 13.51% in America, 13.22% in Africa, 11.70% in Asia and 11.86% in Australasia. The highest PI*ZZ weighted average prevalence among COPD subjects (expressed as 1/x [95% confidence intervals]) were found in Northern Europe (395 [252-576]) followed by Western (797 [538-1165]), Southern (944 [600-1475]) and Central Europe (1096 [687-1738]). Outside Europe, high values were found in Australia-New Zealand (1007 [684-1509]), Saudi Arabia (1276 [563-2961]), United States (1298 [1094-1540]), Canada (1482 [1057-2083]) and Thailand (1807 [717-4692]). In the rest of the world, prevalence was significantly lower, especially in vast regions of Asia and Africa where the PI*Z gene is practically non-existent., Conclusions: Severe AATD is associated with a significant number of cases of COPD, especially in Europe, USA, Canada, New Zealand and Australia., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: The aim of our work has been to describe the results of the clinical audit carried out in 2021 and to compare the results with 2015 EPOCONSUL audit., Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021, and January 31, 2022., Results: A total of 45 hospitals participated in the 2021 audit and 4.225 clinical records of patients were evaluated. Clinical phenotype according to the Spanish National Guidelines for COPD care (GesEPOC) was reported in 63.1% of the audited patients, and the COPD type assessment for the Global initiative for chronic Obstructive Lung Disease (GOLD) was present in 38.3%. There was an improved compliance with clinical practice guideline (CPG) recommendations in the 2021 audit with respect to the 2015 audit. There was an increase in the proportion of cases with alfa-1-antitrypsin serum level testing available (audit 1: 18.9%; audit 2: 38.7%, p<0.001) and 6-min walk test carried out (audit 1: 24%; audit 2: 45.2%, p<0.001). However, these significant variations adherence to CPG recommendations were not reached for the clinical evaluation and therapeutic intervention category when adjusting for patient and resource variables., Conclusions: The 2021 EPOCONSUL audit showed increased adherence to recommendations although they seem to be related to the availability of resources for care. These results should be taken into account in order to establish improvements in resources to achieve a better quality of care., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel for transport of chloride and bicarbonate anions. Functional roles of CFTR have been identified in a broad range of cell types including epithelial, endothelial, immune and structural cells. While CFTR has been investigated largely in the context of inborn dysfunction in cystic fibrosis, recent evidence shows that CFTR is also affected by acquired dysfunction in COPD. In patients with COPD and smokers, CFTR impairment has been demonstrated in the upper and lower airways, sweat glands and intestines, suggesting both pulmonary and systemic defects. Cigarette smoke, a key factor in COPD development, is the major cause of acquired CFTR dysfunction. Inflammation, bacterial byproducts and reactive oxygen species can further impair CFTR expression and function. CFTR dysfunction could contribute directly to disease manifestation and progression of COPD including disturbed airway surface liquid homeostasis, airway mucus obstruction, pathogen colonisation and inflammation. Mucus plugging and neutrophilic inflammation contribute to tissue destruction, development of dysfunction at the level of the small airways and COPD progression. Acquired CFTR dysfunction in extrapulmonary organs could add to common comorbidities and the disease burden. This review explores how CFTR dysfunction may be acquired and its potential effects on patients with COPD, particularly those with chronic bronchitis. The development of CFTR potentiators and the probable benefits of CFTR potentiation to improve tissue homeostasis, reduce inflammation, improve host defence and potentially reduce remodelling in the lungs will be discussed., Competing Interests: Conflict of interest: M.A. Mall declares editorial support from Novartis Pharma AG since the initial planning of the work, and declares grants from German Ministry for Education and Research and the German Research Foundation, consulting fees from Abbvie, Antabio, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotech, Pieris Pharmaceuticals, Santhera, Sterna Biologicals and Vertex Paharmaceuticals, lecture fees from Arrowhead Pharmaceuticals, Boehringer Ingelheim and Vertex Pharmaceuticals, travel reimbursement from Boehringer Ingelheim and Vertex Pharmaceuticals, and personal fees for participation on advisory boards from Boehringer Ingelheim, Arrowhead Pharmaceuticals, Vertex Pharmaceuticals, Santhera, Enterprise Therapeutics, Antabio, Kither Biotech and Abbvie; until 2020, M.A. Mall was also an elected unpaid member of the ECFS board. G.J. Criner has no declarations. In the past 36 months, M. Miravitlles has received consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Inhibrx, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols, speaker fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, support for attending meetings/travel from Novartis, Boehringer Ingelheim and Menarini, research grants from Grifols, and has participated on a data safety monitoring board for Mereo. S.M. Rowe declares grant support for clinical trials conducted through university grants/contracts, consulting services on the design and conduct of clinical trials and support for travel to attend meetings from Novartis; support for clinical trials conduct through university grants/contracts, consulting services on the design and conduct of clinical trials, support for travel to attend meetings, co-chair of the Next Generation Steering Committee and providing research product for investigator initiated research from Vertex; grant support for clinical trials conducted through university grants/contracts, consulting services on the design and conduct of clinical trials, material transfer agreements (MTAs) for investigator-initiated and externally funded research efforts from Galapagos/Abbvie since the initial planning of the work; grant support for clinical trials conducted through university grants/contracts from Bayer, TranslateBio and Proteostasis; research grants through university grants/contracts from Synedgen/Synspira; research contract through university grants/contracts from Celtaxsys, Arrowhead, Ionis and AstraZeneca; research contract through university grants/contracts from Eloxx; declares consulting services on the design and conduct of clinical trials from Bayer, Renovion, Arrowhead, Ionis, Cystetic Medicines, Arcturus and Synedgen/Synspira, including stock options for Synedgen/Synspira within the past 36 months; receipt of research products for investigator initiated research from Renovion; MTA agreements for research efforts from Proteostasis; MTAs for investigator-initiated and externally funded research efforts from Ionis, Galapagos/Abbvie and Synedgen/Synspira; all in the past 36 months; and declares six patents. C.F. Vogelmeier declares institution grants from German Ministry of Education and Science (BMBF), AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols and Novartis, consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed, Menarini, Novartis and Nuvaira, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed, Menarini and Novartis, in the past 36 months. D.J. Rowlands is an employee of Novartis Pharma AG and retains Novartis stock. M. Schoenberger is a full-time employee of Novartis Pharma AG and retains Novartis stock. P. Altman is a full-time employee of Novartis Pharmaceutical Corporation., (Copyright ©The authors 2023.)

Competing Interests: GlaxoSmithKline (GSK) supports the ANTES programme, which is run by an independent Scientific Committee; ANTES panellists (appendix p 1) were invited to participate in the debate leading to the proposal presented here according to their experience in the area of COPD exacerbations. GSK did not participate in the discussion or contribute to the scientific content of this Comment or the decision to submit for publication. JJS-C reports grants from GSK; speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GSK, Menarini, and Novartis; and consulting fees from Bial, Chiesi, GSK, and Novartis. MM reports speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Kamada, Takeda, Sandoz, Zambon, CSL Behring, Specialty Therapeutics, Grifols, and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GSK, Bial, Gebro Pharma, CSL Behring, Inhibrx, Laboratorios Esteve, Ferrer, Menarini, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma, Takeda, Novartis, Sanofi, and Grifols; and research grants from Grifols. AF-V reports honoraria for lectures, scientific advice, participation in clinical studies, or writing of publications for AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GSK, Grifols, Menarini, and Novartis. JLI reports personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Grifols, Menarini, Novartis, Orion, Pfizer, Sandoz, and Teva. JLG-R reports speaker fees from Gebro Pharma, Novartis, GSK, Boehringer Ingelheim, AstraZeneca, Chiesi, ALK, Teva, Menarini, Viso, and Sanofi; consulting fees from Novartis, GSK, AstraZeneca, Teva, Boehringer Ingelheim, ALK, Viso, Gebro Pharma, and Sanofi; and research grants from AstraZeneca. BGC reports grants from Boehringer Ingelheim, Menarini, and Teva; speaker fees from AstraZeneca, Sanofi, Chiesi, GSK, Menarini, and Novartis; and consulting fees from AstraZeneca, Chiesi, Teva, Sanofi, GSK, and Novartis. JLL-C reports honoraria during the past 3 years for lectures, scientific advice, participation in clinical studies, or writing of publications for AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, CSL Behring, Ferrer, Gebro, GSK, Grifols, Menarini, Megalabs, Novartis, and Rovi. AA reports grants from AstraZeneca, GSK, and Menarini; speaker fees from AstraZeneca, Chiesi, GSK, Menarini, and Zambon; and consulting fees from AstraZeneca, Chiesi, GSK, and Menarini.

Introduction: We aim to describe the changes in prevalence and risk factors associated to chronic obstructive pulmonary disease (COPD) in Spain, comparing three population-based studies conducted in three timepoints., Methods: We compared participants from IBERPOC conducted in 1997, EPISCAN conducted in 2007 and EPISCAN II in 2017. COPD was defined as a postbronchodilator FEV 1 /FVC (forced expiratory volume in 1s/forced vital capacity) ratio <0.70, according to GOLD criteria; subsequently, also as the FEV 1 /FVC below the lower limit of normal (LLN)., Results: COPD prevalence in the population between 40 and 69 years decreased from 21.6% (95% CI 20.7%-23.2%) in 1997 to 8.8% (95% CI 8.2%-9.5%) in 2017, a 59.2% decline (p<0.001). In 2007, the prevalence was 7.7% (95% CI 6.8%-8.7%) with an upward trend of 1.1 percentage points in 2017 (p=0.073). Overall COPD prevalence decreased in men and women, although a significant increase was observed in the last decade in females (p<0.05). Current smokers significantly increased in the last decades (25.4% in 1997, 29.1% in 2007 and 23.4% in 2017; p<0.001). Regrettably, COPD underdiagnosis was constantly high, 77.6% in 1997, 78.4% in 2007, and to 78.2% in 2017 (p=0.95), higher in younger ages (40-49 yrs and 50-59 yrs) and also higher in women than in men in all three studies (p<0.05)., Conclusions: We report a significant reduction of 59.2% in the prevalence of COPD in Spain from 1997 to 2017 in subjects aged 40-69 years. Our study highlights the significant underdiagnosis of COPD, particularly sustained in women and younger populations., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Badkground: Physical capacity (PC) and daily physical activity (PA) are two crucial factors in the clinical course of COPD, although they do not always maintain a close relationship. The objectives were to evaluate the frequency of PC-PA dissociation in patients with COPD and subjects without airflow limitation (AL) and to identify its risk factors., Methods: A sample of 319 COPD patients and 399 subjects without AL was consecutively obtained from a population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, lung function testing, blood analysis and low-dose computed tomography (CT) scan with evaluation of lung density and airway wall thickness. A distance walked in 6 min > 70% predicted was considered an indicator of normal PC, while a Yale Physical Activity Survey summary index score <51 was used to identify with sedentary lifestyle., Results: 166 COPD patients (52.0%) reported a sedentary lifestyle with evidence of preserved PC, while this phenomenon was present in 188 (47.1%) subjects without AL. In the COPD group, symptoms of chronic bronchitis, depression and elevated hematocrit and blood eosinophil count were identified as independent risk factors for PC-PA dissociation. In turn, in the subjects without AL, the risk factors for PC-PA dissociation were low fat-free mass, obesity and anxiety, as well as reduced levels of HDL-cholesterol and the absence of osteoporosis., Conclusions: Almost half of COPD patients and subjects without airflow limitation with preserved PC maintain a sedentary lifestyle, with different risk factors for sedentarism between both groups., Competing Interests: Declaration of competing interest Francisco García-Río has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Pfizer and Rovi, and research grants from Chiesi, Esteve, Gebro Pharma, GlaxoSmithKline, Menarini and TEVA. Marc Miravitlles has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Gebro Pharma, Kamada, GlaxoSmithKline, Grifols, Menarini, Mereo Biopharma, Novartis, pH Pharma, Palobiofarma SL, Rovi, TEVA, Spin Therapeutics, Verona Pharma and Zambon, and research grants from Grifols. Joan B. Soriano has no conflict of interest. Borja G Cosio has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Sanofi, TEVA, and research grants from Menarini, AstraZeneca and Boehringer-Ingelheim. Juan José Soler-Cataluña has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GlaxoSmithKline, Menarini, Novartis and Teva, and consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, GlaxoSmithKline, Ferrer and Novartis. Ciro Casanova has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, and research grants from GlaxoSmithKline, Menarini and AstraZeneca. Pilar de Lucas has no conflict of interest. Inmaculada Alfageme has no conflict of interest. José Miguel Rodríguez González-Moro has no conflict of interest. María Guadalupe Sánchez Herrero is a GSK employee within the Medical Department. Julio Ancochea has received speaker or consulting fees from Actelion, Air Liquide, Almirall, AstraZeneca, Boehringer Ingelheim, Carburos Médica, Chiesi, Faes Farma, Ferrer, GlaxoSmithKline, InterMune, Linde Healthcare, Menarini, MSD, Mundipharma, Novartis, Pfizer, Roche, Rovi, Sandoz, Takeda y Teva, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation., Methods: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative., Results: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals., Conclusion: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation., (© 2023. The Author(s).)

Background: Population distribution of reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in smokers and main consequences are not properly recognised. The objectives of this study were to describe the prevalence of reduced DLCO in a population-based sample of current and former smoker subjects without airflow limitation and to describe its morphological, functional and clinical implications., Methods: A sample of 405 subjects aged 40 years or older with postbronchodilator forced expiratory volume in 1 s/forced vital capacity (FVC) >0.70 was obtained from a random population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, exhaled carbon monoxide (CO) measurement, spirometry, DLCO determination, 6 min walk test, routine blood analysis and low-dose CT scan with evaluation of lung density and airway wall thickness., Results: In never, former and current smokers, prevalence of reduced DLCO was 6.7%, 14.4% and 26.7%, respectively. Current and former smokers with reduced DLCO without airflow limitation were younger than the subjects with normal DLCO, and they had greater levels of dyspnoea and exhaled CO, greater pulmonary artery diameter and lower spirometric parameters, 6 min walk distance, daily physical activity and plasma albumin levels (all p<0.05), with no significant differences in other chronic respiratory symptoms or CT findings. FVC and exhaled CO were identified as independent risk factors for low DLCO., Conclusion: Reduced DLCO is a frequent disorder among smokers without airflow limitation, associated with decreased exercise capacity and with CT findings suggesting that it may be a marker of smoking-induced early vascular damage., Trial Registration Number: NCT03028207., Competing Interests: Competing interests: FG-R has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Pfizer and Rovi, and research grants from Chiesi, Esteve, Gebro Pharma, GlaxoSmithKline, Menarini and TEVA. MM has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Gebro Pharma, Kamada, GlaxoSmithKline, Grifols, Menarini, Mereo Biopharma, Novartis, pH Pharma, Palobiofarma SL, Rovi, TEVA, Spin Therapeutics, Verona Pharma and Zambon, and research grants from Grifols. JBS has no conflict of interest. BGC has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Sanofi, TEVA and research grants from Menarini, AstraZeneca and Boehringer-Ingelheim. JJS-C has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GlaxoSmithKline, Menarini, Novartis and Teva, and and consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, GlaxoSmithKline, Ferrer and Novartis. CC has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, and research grants from GlaxoSmithKline, Menarini and AstraZeneca. PdL has no conflict of interest. IA has no conflict of interest. JMRG-M has no conflict of interest. MGSH is a GSK employee within the Medical Department. JA has received speaker or consulting fees from Actelion, Air Liquide, Almirall, AstraZeneca, Boehringer Ingelheim, Carburos Médica, Chiesi, Faes Farma, Ferrer, GlaxoSmithKline, InterMune, Linde Healthcare, Menarini, MSD, Mundipharma, Novartis, Pfizer, Roche, Rovi, Sandoz, Takeda y Teva., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Inhaled bronchodilator therapy with long-acting muscarinic antagonists (LAMAs) and long-acting β 2 -agonists (LABAs) in combination is currently the mainstay of treatment for chronic obstructive pulmonary disease (COPD). Treatment guidelines recommend the addition of inhaled corticosteroids (ICS) to LABA/LAMA only in patients with a history of frequent/severe exacerbations and high blood eosinophil counts, or in those with concomitant asthma. Despite this, real-world data suggest that clinicians are not adhering to this guidance and that ICS are frequently overused. This is possibly due to the incorrect assumption that when LABA/LAMA therapy is not sufficient, adding an ICS to the treatment regimen is the logical next step. In this narrative review, we describe global and country-specific guideline recommendations from Germany, Spain, and Japan and compare these with real-world data on LABA/LAMA and ICS use in clinical practice. We also provide a clinical guide to the use of add-on therapies with LABA/LAMA for different patient phenotypes, including (1) patients still symptomatic (but not exacerbating) despite LABA/LAMA treatment; (2) patients still exacerbating despite LABA/LAMA treatment who have high blood eosinophil counts; and (3) patients still exacerbating despite LABA/LAMA treatment who do not have high blood eosinophils or concomitant asthma.

Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history., Methods: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022., Results: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%)., Conclusions: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www., Clinicaltrials: gov (ID: NCT04180319)., (© 2022. The Author(s).)

Background: Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes., Methods: A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted., Results: Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0-1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities., Conclusions: LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes., (© 2022. The Author(s).)

Introduction: Quantifying physical activity in chronic obstructive pulmonary disease (COPD) with questionnaires and activity monitors in clinical practice is challenging. The aim of the present study was to analyse the discriminant validity of a single clinical question for the screening of inactive individuals living with COPD., Methods: A multicentre study was carried out in stable COPD individuals both in primary and tertiary care. Patients wore the Dynaport accelerometer for 8 days and then answered 5 physical activity questions developed for the study, referring to the week in which their physical activity was monitored. Receiver operating characteristic (ROC) curve analysis with physical activity level (PAL) as the gold standard reference was used to determine the best cut-off point for each of the 5 clinical physical activity questions tested., Results: A total of 86 COPD participants were analysed (males 68.6%; mean (SD) age 66.6 (8.5) years; FEV 1 50.9 (17.3)% predicted; mean of 7305 (3906) steps/day). Forty-two (48.8%) participants were considered physically inactive (PAL ≤1.69). Answers to 4 out of 5 questions significantly differed in active vs inactive patients. The Kappa index and ROC curves showed that the answer to the question "On average, how many minutes per day do you walk briskly?" had the best discriminative capacity for inactivity, with an area under the curve (AUC) (95% Confidence interval (CI)) of 0.73 (0.63-0.84) and 30 min/day was identified as the best cut-off value (sensitivity (95% CI): 0.75 (0.60-0.87); specificity: 0.76 (0.61-0.88))., Conclusion: The present results indicate that self-reported brisk walk time lower than 30 min/day may be a valid tool for the screening of inactivity in individuals living with COPD in routine care, if more detailed physical activity measures are not feasible., Competing Interests: Cristóbal Esteban has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi and GlaxoSmithKline. Ines Carrascosa has received speaker fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Sandon, Pfizer and, consulting fees from CSL BEHRING and Sanofi. Patricia Sobradillo has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Rovi, TEVA and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Laboratorios Esteve. Juan José Soler-Cataluña has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Menarini, Novartis, and Teva, and consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis. Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Jansen, Kamada, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Palobiofarma SL, Takeda, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi and Grifols and research grants from Grifols. Francisco García-Río has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Menarini, Rovi, Sanofi and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Laboratorios Esteve, and research grants from GlaxoSmithKline, Menarini, ROCHE Pharma and Chiesi. The remaining authors have no conflicts of interest to disclosure., (© 2022 Ramon et al.)

Background: Initiation of treatment of COPD with a combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS) is frequent irrespective of the risk of exacerbations., Method: We performed a retrospective, population-based, observational study aimed at comparing the effectiveness of a LABA/long-acting antimuscarinic agent (LAMA) and LABA/ICS in patients with COPD over a one-year follow-up. Data were obtained from an administrative healthcare claims database. The primary outcome was the risk of first exacerbation. A sensitivity analysis was conducted in a propensity-score matched population., Results: The population consisted of 14,046 COPD patients; 11,329 (80.6%) initiated LABA/ICS and 2717 (19.4%) LABA/LAMA. The matched population included 1650 patients in each arm. During follow-up, 69.6% patients in the LABA/ICS group and 64.4% in the LABA/LAMA group presented an exacerbation. The mean time to the first exacerbation was 6.03 months (95% confidence interval (CI): 5.94-6.12) for LABA/ICS and 6.4 months (95%CI: 6.21-6.59) for LABA/LAMA; p<0.001. The time to scalation to triple therapy was also significantly prolonged in LABA/LAMA. Similar results were obtained in the matched population. LABA/LAMA was associated with a significantly lower risk of exacerbations and escalation to triple therapy compared to LABA/ICS, except in patients with frequent exacerbations and high blood eosinophils in which no differences were observed in the time to first exacerbation., Conclusion: Initiation of treatment with LABA/LAMA was associated with a lower risk of exacerbation and escalation to triple therapy compared to LABA/ICS in the majority of patients with COPD in primary care., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Some patients with chronic obstructive pulmonary disease (COPD) experience frequent exacerbations despite maximal inhaled therapy ("triple therapy"), possibly leading to high health care resource utilization (HCRU)., Aim: Describe characteristics, future HCRU, and mortality of patients with COPD who experience frequent exacerbations despite triple therapy; characterize individuals who may be candidates for biologic therapies., Methods: This descriptive observational study used primary care data of patients aged ≥40 years in the United Kingdom receiving maintenance therapy for COPD who had ≥1 year of data prior to index date and ≥1 year of follow-up data. We described these patients' clinical and demographic characteristics, including blood eosinophil counts (BEC), pattern of exacerbations, hospitalizations, and corticosteroid exposure, as well as future exacerbations, hospitalizations, and death., Results: Of 43,753 patients with maintenance-treated COPD, 6480 experienced exacerbations despite ≥3 months of triple therapy. Of these, 5669 had available BEC: 1287 (22.7%) had BEC ≥250 cells/µL and ≥3 exacerbations in the year prior to the index date; 471 (36.6%) received ≥4 acute courses of oral corticosteroids. Patients with a pattern of high disease burden continued to have high disease burden: 51.1% experienced ≥3 exacerbations and 2.6% experienced ≥3 hospitalizations. Patients who experienced exacerbations despite triple therapy had a significantly higher risk of COPD-related death than other maintenance-treated patients (5.8% vs 2.1%)., Conclusion: Nearly one-quarter of patients receiving triple therapy for COPD who experienced frequent exacerbations had elevated BEC and ≥3 exacerbations, suggesting a potential mechanism of persistent eosinophilic inflammation that could be a target for eosinophil-depleting biologic therapy., Competing Interests: SC and BE are employees of AstraZeneca. MA was an employee of AstraZeneca at the time of the study. Her current affiliation is CSL Behring, Milan, Italy. DBP has advisory board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Thermofisher, Zentiva (Sanofi Generics); consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, UK National Health Service, Zentiva (Sanofi Generics); payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Merck, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Zentiva (Sanofi Generics); payment for the development of educational materials from Mundipharma, Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; funding for patient enrolment or completion of research from Novartis; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; Consultancy agreements - Fees paid to Observational and Pragmatic Research Institute from Airway Vista Secretariat, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L, Talos Health Solutions, WebMD Global LLC; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp, which develops adherence monitoring technology; is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. In the last 5 years, IDP has received speaker’s honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi, Regeneron, Menarini, and GlaxoSmithKline and payments for organizing educational events from AstraZeneca, GlaxoSmithKline, Sanofi/Regeneron, and Teva. He has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Teva, Merck, Circassia, Chiesi, and Knopp and payments to support Food and Drug Administration approval meetings from GlaxoSmithKline. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Teva, and Chiesi. He has received a grant from Chiesi to support a Phase 2 clinical trial in Oxford. He is co-patent holder of the rights to the Leicester Cough Questionnaire and has received payments for its use in clinical trials from Merck, Bayer, and Insmed. In 2014-5, he was an expert witness for a patent dispute involving AstraZeneca and Teva. VC is affiliated with the Observational and Pragmatic Research Institute and an employee of Optimum Patient Care Global. CKR received consulting/lecture fees from MSD, AstraZeneca, GlaxoSmithKline, Novartis, Takeda, Mundipharma, Boehringer Ingelheim, Teva, Sanofi, and Bayer. RJ declares grants from AstraZeneca, GlaxoSmithKline, Novartis, and Teva and personal fees for consultancy, speaker’s fees, or travel support from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Nutricia, and the Observational and Pragmatic Research Institute. RJ was an employee of the University of Plymouth at the time of the study. His current affiliation is Plymouth Marjon University, Plymouth, UK. MM has received speaker’s fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Takeda, Zambon, CSL Behring, Grifols, and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Inhibrx, Mereo Biopharma, ONO Pharma, Palobiofarma SL, Takeda, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi, and Grifols and research grants from Grifols., (© 2022 Chen et al.)

The best therapeutic approach to patients with asthma-chronic obstructive pulmonary disease overlap (ACO) is unknown. Current treatment recommendations rely on expert opinions, roundtable discussions, and strategy documents, because patients with ACO have been excluded from most clinical studies in asthma and COPD. Because of the underlying asthma initial therapy, early use of inhaled corticosteroids along with a long-acting bronchodilator is recommended. If maintenance inhaler therapy is not effective, advanced therapies based on phenotyping and identification of treatable traits may be considered., Competing Interests: Disclosure Dr N. Hanania reports receiving consulting fees from GSK, Astra Zeneca, Sadslnofi, Regeneron, Teva, Amgen, Roche/Genentech, Boehringer Ingelheim, and Novartis; his institution has received research support from Boehringer Ingelheim, GlaxoSmithKline, and AstraZeneca, Sanofi, Teva, Genentech. M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols, and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Spin Therapeutics, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi, and Grifols; and research grants from Grifols., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Identifying the variables that guide decision-making in relation to the use of inhaled corticosteroids (ICS) can contribute to the appropriate use of these drugs. The objective of this study was to identify the clinical variables that physicians consider most relevant for prescribing or withdrawing ICS in COPD., Methods: A cross-sectional survey was conducted in Spain from November 2020 to May 2021. Therapeutic decisions on the use of ICS in 11 hypothetical COPD patient profiles were collected using an online survey answered by specialists with experience in the management of patients with COPD. Mixed-effects logistic regression was used to analyze the impact of patients' characteristics in the therapeutic decision for prescribing ICS or proceeding to its withdrawal., Results: A total of 74 pulmonologists agreed to collaborate in the survey and answered the questionnaire. The results showed great variability, with only 2 profiles achieving consensus for starting or withdrawing the treatment. The frequency and severity of exacerbations influenced the decision to prescribe ICS in a dose-response fashion (1 exacerbation odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.02 to 3.43, two exacerbations OR = 11.6, 95% CI: 4.47 to 30.2 and three OR = 123, 95% CI: 25 to 601). Similarly, increasing blood eosinophils and history of asthma were associated with ICS use. On the other hand, pneumonia reduced the probability of initiating treatment with ICS (OR = 0.54 [0.29 to 0.98]). Lung function and dyspnea degree did not influence the clinician's therapeutic decision. The results for withdrawal of ICS were similar but in the opposite direction., Conclusion: In accordance with guidelines, exacerbations, blood eosinophils and history of asthma or pneumonia are the factors considered by pulmonologist for the indication or withdrawal of ICS. However, the agreement in prescription or withdrawal of ICS when confronted with hypothetical cases is very low, suggesting a great variability in clinical practice., Competing Interests: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment related to the development of the manuscript. MM has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, Kamada, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols and research grants from Grifols. FG has received economic compensation for consulting, lectures at various congresses and scientific training sessions, manuscript writing and support for attending meetings from Boehringer Ingelheim, GSK, Novartis, Astrazeneca, Chiesi, Pfizer, Esteve and Rovi. CRR reports no disclosure related to this paper. XP has received speaker fees from Boehringer Ingelheim, GlaxoSmithKline, Rovi and Chiesi. EMM has received economic compensation for consulting, lectures, presentations, manuscript writing, educational events, support for attending meetings, participation in data safety monitoring or advisory board from Boehringer Ingelheim, Glaxo Smith Kline, Novartis, Aflofarm, Bial, Chiesi, Meranini and GSK. CG has received economic compensation for consulting, support for attending meetings from Chiesi, Boehringer Ingelheim, Glaxo Smith Kline, Novartis, Meranini, Ferrer and Teva. CA has received speaker fees and/or consulting fees from Boehringer Ingelheim, Pfizer, AstraZeneca, Novartis, Chiesi, Faes farma, Esteve and GlaxoSmithKline. CF has received economic compensation by GOC Health Consulting for statistical analysis. SA has received economic compensation for support for attending meetings, other sessions and consulting from Novartis, Astra Zeneca, Menarini, GSK, Boeringer Ingelheim, Chiesi, Mundipharma, FAES, Pfizer and Teva. BA reports personal fees from GSK, grants, personal fees and non-financial support from Novartis, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Chiesi, grants, personal fees and non-financial support from Laboratorios BIAL, Menarini, personal fees from Gebro, Astra- Zeneca, and Gilead, outside the submitted work. In addition, has a patent P201730724 pending. EN has received economic compensation for consulting, lectures, presentations, manuscript writing and educational events from Novartis, Boehringer Ingelheim, Chiesi and Glaxo Smith Kline. MB reports personal fees from Grifols, Menarini, CSL Behring, GSK, Boehringer Ingelheim, and Novartis, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Miravitlles et al.)

Introduction: Currently, strategies for improving alpha1 antitrypsin deficiency (AATD) diagnosis are needed. Here we report the performance of a multinational multiplex-based genotyping test on dried blood spots and buccal swabs sent by post or courier and with web registration for subjects with suspected AATD in Argentina, Brazil, Chile, Colombia, Spain, and Turkey., Methods: This was an observational, cross-sectional analysis of samples from patients with suspected AATD from March 2018 to January 2022. Samples were coded on a web platform and sent by post or courier to the central laboratory in Northern Spain. Allele-specific genotyping for the 14 most common mutations was carried out with the A1AT Genotyping Test (Progenika-Grifols, Spain). SERPINA1 gene sequencing was performed if none of the mutations were found or one variant was detected in heterozygous status and the AAT serum level was < 60 mg/dl, or if requested by the clinician in charge., Results: The study included 30,827 samples: 30,458 (94.7%) with final results after direct genotyping and 369 (1.1%) with additional gene sequencing. Only 0.3% of the samples were not processed due to their poor quality. The prevalence of the most frequent allele combinations was MS 14.7%, MZ 8.6%, SS 1.9%, SZ 1.9%, and ZZ 0.9%. Additionally, 70 cases with new mutations were identified. Family screening was conducted in 2.5% of the samples. Samples from patients with respiratory diseases other than COPD, including poorly controlled asthma or bronchiectasis, also presented AATD mutations., Conclusions: Our results confirm the viability of this diagnostic system for genotyping AATD conducted simultaneously in different countries. The system has proved satisfactory and can improve the timely diagnosis of AATD., (© 2022. The Author(s).)

Introduction: Diaphragmatic dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the prognostic significance of impaired diaphragmatic movement at rest and after exercise., Methods: This was a prospective study of patients with stable COPD. Diaphragmatic movements were examined at rest and after a 6-minute walking test (6MWT) with a convex transducer with a frequency of 3.5-5-7.5 MHz. Maximal movement of the diaphragm was measured in both right and left diaphragm, and the side with higher amplitude was selected for further analysis. Measurements obtained were evaluated for their prognostic value for a composite endpoint of moderate and severe COPD exacerbations and death in 1 year time period was assessed. In addition, postbronchodilator spirometry, symptoms, quality of life, and demographic and clinical information were collected., Results: A total of 96 patients were analyzed (62.5% male, mean age 65.1 years (standard deviation (SD): 8.1), mean FEV1 (% predicted): 55.8%, SD: 18.3%, mean CAT: 15.6 units, SD: 9.2). Sixty-four patients (67%) presented the composite endpoint. In the multivariate Cox analysis, FVC (HR = 0.944, p = 0.005), CAT score (HR = 1.133, p = 0.011), previous severe exacerbations (HR = 5.446, p = 0.004) and diaphragmatic movement at rest (HR = 0.932, p = 0.033) were found to be predictors of the composite endpoint. This model correctly classified 86.5% (83/96) of the patients., Conclusion: Non-invasive assessment of diaphragmatic movement by ultrasound measurement both at rest and after exercise could contribute to the assessment of disease severity and prognosis of COPD., Competing Interests: Evgeni Mekov has received grants and personal fees from Chiesi, and speaker or consulting fees from Astra Zeneca and Chiesi. Nikolay Yanev has received speaker or consulting fees from Astra Zeneca, Boehringer Ingelheim, Berlin Chemie and Chiesi. Nedelina Kurtelova has received speaker or consulting fees from Astra Zeneca, Boehringer Ingelheim, and Chiesi. Marc Miravitlles has received speaker or consulting fees from AstraZeneca, Atriva Therapeutics, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Ferrer, Gebro Pharma, GlaxoSmithKline, Grifols, Kamada, Menarini, Mereo Biopharma, Novartis, ONO Pharma, Palobiofarma SL, pH Pharma, Rovi, Sanofi, Sandoz, Spin Therapeutics, Takeda, TEVA, Verona Pharma and Zambon, and research grants from Grifols. Rosen Petkov has received speaker or consulting fees from Astra Zeneca and Boehringer Ingelheim. The authors report no other conflicts of interest in this work., (© 2022 Mekov et al.)

The current health care models described in GesEPOC indicate the best way to make a correct diagnosis, the categorization of patients, the appropriate selection of the therapeutic strategy and the management and prevention of exacerbations. In addition, COPD involves several aspects that are crucial in an integrated approach to the health care of these patients. The evaluation of comorbidities in COPD patients represents a healthcare challenge. As part of a comprehensive assessment, the presence of comorbidities related to the clinical presentation, to some diagnostic technique or to some COPD-related treatments should be studied. Likewise, interventions on healthy lifestyle habits, adherence to complex treatments, developing skills to recognize the signs and symptoms of exacerbation, knowing what to do to prevent them and treat them within the framework of a self-management plan are also necessary. Finally, palliative care is one of the pillars in the comprehensive treatment of the COPD patient, seeking to prevent or treat the symptoms of a disease, the side effects of treatment, and the physical, psychological and social problems of patients and their caregivers. Therefore, the main objective of this palliative care is not to prolong life expectancy, but to improve its quality. This chapter of GesEPOC 2021 presents an update on the most important comorbidities, self-management strategies, and palliative care in COPD, and includes a recommendation on the use of opioids for the treatment of refractory dyspnea in COPD., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

In addition to recommendations for pharmacological treatment stratified for risk and phenotype, the new 2021 edition of the Spanish COPD Guidelines (GesEPOC 2021) proposes a personalized approach to treatable traits, defined as a characteristic (clinical, physiological, or biological) that can be identified by diagnostic tests or biomarkers, for which a specific treatment is available. Some treatable traits, such as malnutrition, sedentarism, emphysema or respiratory failure, can be treated with non-pharmacological therapies, and this was not covered in detail in the guidelines. This section of GesEPOC 2021 includes a narrative update with recommendations on dietary treatment, physical activity, respiratory rehabilitation, oxygen therapy, non-invasive ventilation, volume reduction, and lung transplantation. A PICO question with recommendations on the use of supplemental oxygen during exercise in COPD patients without severe hypoxemia is also included., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Up to 50% of patients with chronic obstructive pulmonary disease (COPD) in stable state may carry potentially pathogenic microorganisms (PPMs) in their airways. The presence of PPMs has been associated with increased symptoms, increased risk and severity of exacerbations, a faster decline in lung function and impairment in quality of life. Although some clinical trials have demonstrated a reduction in exacerbations in patients chronically treated with systemic antibiotics, particularly macrolides, the selection of patients was based on the previous frequency of exacerbations and not on the presence of PPMs in their airways. Therefore, unlike in bronchiectasis, there is a lack of evidence-based recommendations for assessment and treatment of the presence of PPMs in either single or repeated isolations in COPD. In this article, we propose that chronic bronchial infection (CBI) in COPD be defined as the isolation of the same PPM in at least three sputum samples separated by more than one month; we review the impact of CBI on the natural course of COPD and suggest a course of action in patients with a single isolation of a PPM or suspected CBI. Antibiotic treatment in stable COPD should be recommended based on four main criteria: a) the presence of comorbid bronchiectasis, b) the demonstration of a single or multiple isolation of the same PPM, c) the clinical impact of CBI on the patients, and d) the type of PPM, either Pseudomonas aeruginosa or non-pseudomonal PPM. These recommendations are derived from evidence generated in patients with bronchiectasis and, until new evidence specifically obtained in COPD is available, they may help in the management of these challenging patients with COPD. Existing evidence suggests that inhaled therapy is insufficient to manage patients with moderate-to-severe COPD, frequent exacerbations, and CBI. New studies must be conducted in this particularly demanding population., Competing Interests: Miguel Angel Martinez-Garcia has received fees from Chiesi, GlaxoSmithKline, Menarini, Rovi, Bial, Zambon, Vitalaire, TEVA, Grifols and Novartis, consulting fees from Grifols, Zambon and TEVA, and research grants from TEVA, Zambon and Vitalaire. Marc Miravitlles has received speaker fees from AstraZeneca, Atrina Therapeutics, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Johnson & Johnson, Mereo Biopharma, Palobiofarma SL, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi, ONO Pharma, Takeda, and Grifols and research grants from Grifols. The authors report no other conflicts of interest in this work., (© 2022 Martinez-Garcia and Miravitlles.)

Background: Recent studies report a lower mortality rate during treatment with long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA)/inhaled corticosteroid (ICS) versus LAMA/LABA in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations., Objective: We compared time to all-cause mortality with LAMA/LABA versus LAMA/LABA/ICS in patients with mild-to-very-severe COPD and a predominantly low exacerbation risk., Methods: Data were pooled from six randomized controlled trials (TONADO 1/2, DYNAGITO, WISDOM, UPLIFT and TIOSPIR; LAMA/LABA: n = 3156, LAMA/LABA/ICS: n = 11,891). Analysis was on-treatment and data were censored at 52 weeks. Patients on LAMA/LABA/ICS received ICS prior to study entry, which was not withdrawn at randomization. Patients on LAMA/LABA/ICS were propensity score (PS)-matched to patients on LAMA/LABA who had not previously received ICS; covariates included age, sex, geographical region, smoking status, post-bronchodilator forced expiratory volume in 1 second percent predicted, exacerbation history in previous year, body mass index and time since diagnosis. Time to all-cause mortality was assessed using Cox proportional hazard regression models., Results: After PS matching, 3133 patients on LAMA/LABA and 3133 patients on LAMA/LABA/ICS were analyzed. Fewer than 20% of patients reported ≥2 exacerbations in the prior year (LAMA/LABA: 19.1%; LAMA/LABA/ICS: 19.0%). There were 41 (1.3%) deaths on LAMA/LABA and 45 (1.4%) deaths on LAMA/LABA/ICS. No statistically significant difference in time to death was observed between treatment arms (hazard ratio for LAMA/LABA 1.06; 95% confidence intervals 0.68, 1.64; P = 0.806). Sensitivity analyses conducted using different covariates or in an intent-to-treat population showed similar results., Conclusion: This pooled analysis of over 6000 patients with mild-to-very-severe COPD and predominantly low exacerbation risk showed no differences in mortality with LAMA/LABA versus LAMA/LABA/ICS, suggesting that the survival benefit of triple therapy seen in some recent studies may be specific to a high-risk population. This supports current Global Initiative for Chronic Obstructive Lung Disease recommendations that triple therapy should be reserved for the subpopulations of patients who need it the most (eg, those with an eosinophilic phenotype and a high risk of exacerbations) to avoid ICS overuse., Competing Interests: Marc Miravitlles has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, GlaxoSmithKline, Grifols, Menarini, Novartis, Rovi, Sandoz and Zambon; consulting fees from AstraZeneca, Atriva Therapeutics, Bial, Boehringer Ingelheim, Chiesi, CSL Behring, Gebro Pharma, Ferrer, GlaxoSmithKline, Grifols, Kamada, Laboratorios Esteve, Mereo Biopharma, Novartis, ONO Pharma, pH Pharma, Sanofi, Palobiofarma SL, Spin Therapeutics, Takeda, TEVA and Verona Pharma; and research grants from Grifols. Peter M.A. Calverley has received grants from GlaxoSmithKline; advisory board fees from Boehringer Ingelheim; and speaker and advisory board fees from Phillips Respironics, Recipharm and Zambon. Katia Verhamme has received consultancy fees from Boehringer Ingelheim; payment for a lecture to the Department of Medical Informatics from AstraZeneca; and received unconditional research grants from Yamanouchi, Pfizer/Boehringer Ingelheim, Novartis, GlaxoSmithKline, Amgen, UCB and Chiesi. Michael Dreher has received speaker or advisory fees from Actelion, AstraZeneca, Bayer, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Hamilton, Heinen und Löwenstein, Insmed, InterMune, Linde, Novartis, Pfizer, Philips Respironics, ResMed, Roche and Weinmann. Valentina Bayer, Asparuh Gardev and Alberto de la Hoz are employees of Boehringer Ingelheim. Jadwiga Wedzicha has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, GlaxoSmithKline, Johnson and Johnson, and Novartis, and meeting expenses from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Novartis. David Price has board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme and Thermo Fisher; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, Theravance and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Theravance and the UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis and Thermo Fisher; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. The authors report no other conflicts of interest in this work., (© 2022 Miravitlles et al.)

The aim of this observational, retrospective study was to describe characteristics, treatment patterns, and adherence among patients with asthma who initiated multiple-inhaler triple therapy (MITT) in Catalonia, Spain. This study used data of patients initiating MITT in 2016 from the SIDIAP (Information System for Research in Primary Care) database, which covers ~80% of the Catalonian population (5.8 million). Of 1,204 patients initiating MITT, 361 (30.0%) stepped down (discontinued ≥ 1 and continued ≥1 MITT component) and 89 (7.4%) stopped all three components of MITT for a period of 60 days during the following 12 months. In the follow-up period, 196 (16.3%) patients were considered adherent to MITT (>0.8 proportion of days covered [PDC]), with a mean (standard deviation) PDC of 0.52 (0.51) days. Given the low adherence and substantial rates of step down/discontinuation among patients initiating MITT, there is an urgent need to implement strategies to improve treatment adherence/persistence., (© 2022. The Author(s).)

Background: Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD., Methods: EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV 1 /FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed., Results: A total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/μL (SD: 125) vs. 160 cells/μL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC., Conclusions: This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC., (© 2022. The Author(s).)

Background: Chronic bronchial infection is frequent in chronic obstructive pulmonary disease (COPD), but the impact of the isolation of pathogenic bacteria, and in particular Pseudomonas aeruginosa (PA) in respiratory samples on the prognosis of COPD is unclear., Methods: We conducted a systematic review of prognostic studies including patients with isolation of PA in sputum in stable state or during exacerbations of COPD. The main outcomes were all-cause mortality, respiratory mortality, and number and severity of future exacerbations. Data were expressed as hazard ratio (HR) (95% confidence interval [CI]) whenever possible., Results: Of 2773 studies, eight were finally included (23,228 individuals). The mean age ranged from 65.5 to 73 years. Six studies reported data for all-cause mortality. The adjusted risk of death was almost double in patients with PA isolation (HR 1.95, 95% CI, 1.34 to 2.84; quality of evidence moderate). Patients with PA isolation showed a three times higher adjusted risk of readmission at 30 days after discharge (OR 3.60, 95% CI, 3.60 to 12.03, 1 study; quality of evidence very low), and more than double adjusted risk of death and hospitalization at two years (HR 2.80, 95% CI, 2.20 to 3.56, 1 study; quality of evidence very low)., Conclusion: There is moderate certainty that the isolation of PA in sputum is associated with an adjusted increased risk of death in patients with COPD., Competing Interests: Miguel Angel Martinez-Garcia has received fees from Chiesi, GlaxoSmithKline, Menarini, Rovi, Bial, Zambon, Vitalire, TEVA, Grifols and Novartis, consulting fees from Grifols, Zambon and TEVA, and research grants from TEVA, Zambon and Vitalaire. David Rigau reports grants from Boehringer Ingelheim. Miriam Barrecheguren has received speaker fees from Grifols, Menarini, CSL Behring, GSK, Boehringer Ingelheim and consulting fees from GSK, Novartis and Boehringer Ingelheim. Marc Miravitlles has received speaker fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Johnson & Johnson, Mereo Biopharma, Palobiofarma SL, Takeda, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, ONO Pharma, Novartis, Sanofi and Grifols and research grants from Grifols. The remaining authors have no conflicts of interest to disclosure., (© 2022 Martinez-García et al.)

This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm 3 . Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The best duration of antibiotic treatment for chronic obstructive pulmonary disease (COPD) exacerbations is uncertain., Objective: To evaluate whether a short course of antibiotic therapy is as effective as the standard longer treatment for exacerbations of patients with COPD., Methods: We searched Pubmed/MEDLINE and trials in relevant systematic reviews from the inception up to March 2021, with no language restrictions. Randomised controlled trials comparing short-course antibiotic therapy (≤5 days) with standard antibiotic therapy (≥6 days) for exacerbations of patients aged ≥40 with spirometrically-confirmed COPD were included. Three outcomes were considered: end-of-therapy clinical cure, bacterial eradication and adverse events. Statistical analyses included random effects meta-analyses using odds ratios and assessment of heterogeneity., Results: Of 1274 citations found, eight were eligible for inclusion, seven of which recruited outpatients. Overall, short-course antibiotic treatments were not significantly different from those of long-course treatments for clinical cure (odds ratio [OR] 1.14, 95% CI 0.91; 1.44) and for bacterial eradication (OR 1.16, 95% CI 0.91; 1.48). Adverse events were observed in 379 (21.1%) patients receiving short-term antibiotic regimens, while 412 (22.8%) patients receiving the standard regimens reported adverse events (OR 0.83, 95% CI 0.62; 1.11). The heterogeneity of the studies was low., Conclusion: In relation to clinical and bacteriological efficacy, a short course of antibiotic treatment is equivalent to longer conventional treatment in mainly outpatients with exacerbations of COPD. Moreover, shorter exposure to antibiotics may decrease the risk developing antimicrobial resistance and, hence, might become first-line therapy for the management of ambulatory COPD patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Inhaled corticosteroids (ICS) are frequently used to treat chronic obstructive pulmonary disease (COPD) outside the current recommendations. Our aim was to describe ICS use in COPD patients and to identify factors associated with ICS use among COPD patients treated within primary care in Spain., Patients and Methods: This was a cross-sectional, non-interventional and multicenter study of patients with COPD treated in primary care. Patient characteristics and exacerbations were described in terms of ICS use among the overall cohort, and among those with spirometry confirmed COPD (post-bronchodilator forced expiratory volume in 1 second [FEV 1 ]/forced vital capacity [FVC] ratio <70%). Multivariable logistic regression was used to identify factors associated with ICS use., Results: A total of 901 patients were included, of which 47.9% (n = 432) were treated with ICS. A total of 240 patients (26.6%) experienced moderate/severe exacerbations in the prior year, while 309 (34.3%) during the previous two years. History of asthma totaled 11.6% (n = 105). The most frequent phenotype was non-exacerbator (51.6%), and the proportion of patient with moderate or severe exacerbations was significantly higher among ICS treated patients compared to non-treated: 37.5% versus 16.6% during the previous year (p < 0.001), and 46.8% versus 22.8% during the previous 2-years (p < 0.001), respectively. Patient characteristics were similar among spirometry confirmed patients and the overall population. Factors significantly associated with ICS use were a history of asthma (OR = 4.39, 95% CI: 2.67-7.26), the presence of moderate or severe exacerbations in the last year (OR = 2.52, 95% CI: 1.81-3.49), followed by higher mMRC and higher CAT score., Conclusion: Nearly half of patients in primary care in Spain are treated with ICS, despite most of them being non-exacerbators. History of asthma, exacerbations, and worse dyspnea and CAT scores are associated with ICS use., Competing Interests: Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols and research grants from Grifols. Miguel Roman-Rodriguez has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Bial, consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and research grants from AstraZeneca in the last 3 years. Xavier Ribera is an employee of Boehringer Ingelheim Spain. John Ritz is an employee of Syneos Health – Boehringer Ingelheim Pharmaceuticals Inc. José Luis Izquierdo has received honoraria for consultancy, projects, and talks from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Glaxo, Grifols, Smith Kline, Menarini, Novartis, Orion, Pfizer, Sandoz, Teva, and Zambon. The authors report no other conflicts of interest in this work., (© 2022 Miravitlles et al.)

Background: Augmentation therapy (AT) is the only specific treatment licensed for patients with alpha-1 antitrypsin deficiency (AATD) associated lung disease. Since patients with severe AATD may have a very different prognosis and AT requires intravenous infusions for life, the decision to initiate AT may be challenging., Methods: This survey was conducted on 63 experts in AATD from 13 European countries about their opinions and attitudes regarding AT. Participants were asked to rank the importance of 11 identified factors related with the prescription of AT. In addition, each participant was asked to respond to the indication of AT for 30 out of 500 hypothetical cases developed with the combinations of the 11 factors. Each case was evaluated by 3 experts to check the concordance., Results: The variables that scored higher on preferences for initiating AT were AAT genotype (score 8.6 from a Likert scale 0-10 (SD: 1.7)), AATD serum level (8.2 (SD:2.4)) and FEV1 (%) decline (7.9 (SD:2.4)). Among the 500 different cases, there was an agreement in indication of AT among the 3 experts in 291 (58.2%). Regarding the variables associated with AT, it was indicated to 81.9% of Pi*ZZ, 52.4% of Pi*SZ and 9.8% of Pi*MZ (p < 0.0001). For Pi*ZZ patients, multivariate analysis identified younger age, reduced FEV1 (%), higher FEV1 decline and worse emphysema as significantly associated with prescription (AUC = 0.8114); for Pi*SZ variables were younger age, worse FEV1 (%) and worse emphysema (AUC = 0.7414); and for Pi*MZ younger age, worse DLCO (%), higher DLCO decline and dyspnea (AUC = 0.8387)., Conclusion: There is a high variability in the criteria for prescription of AT among European experts. Most cases were recommended AT according to guidelines, but a significant number of patients with genotype Pi*SZ and almost 10% Pi*MZ were recommended to initiate AT despite the lack of evidence of efficacy in these genotypes., Competing Interests: Timm Greulich reports grants from CSL-Behring, grants from Grifols, grants from Kamada, during the conduct of the study; personal fees from Astra Zeneca, personal fees from Berlin-Chemie, personal fees from Boehringer-Ingelheim, personal fees from Chiesi, personal fees from CSL-Behring, grants and personal fees from Grifols, personal fees from GSK, personal fees from Novartis, grants from German Centre for Lung Research (DZL), Marburg, Germany (Deutsches Zentrum für Lungenforschung), outside the submitted work. Christian Clarenbach received advisory fees from Roche, Novartis, Boehringer, GSK, Astra Zeneca, Sanofi, Vifor, OM Pharma, Grifols and Mundipharma. María L Torres-Duran has received speaker and consulting fees from CSL Behring and Grifols. Alice M Turner has received either grants or speaker fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, CSL Behring, Takeda, Vertex and Grifols Biotherapeutics. Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols and research grants from Grifols. The authors report no other conflicts of interest in this work., (© 2022 Greulich et al.)

Objective: The aim of this study was to analyze current data on the population's level of knowledge about COPD and to evaluate certain diagnostic interventions, such as the use of spirometry., Material and Methods: An epidemiological, observational, cross-sectional study by telephone interview, with random dialing of landline telephone numbers, was conducted in November 2019, in a nationally representative sample of adults over 40 years of age., Results: From a total of 51,079 telephone calls, a total of 1920 individuals responded. Mean age was 61.9 years and 31.6% were men. Overall, 19.4% were current smokers and 13.4% reported respiratory disease (5% reported COPD). In total, 27.9% had spontaneous knowledge of COPD, which is a relative increase from the 17% observed in 2011. The most frequent information channel was the media (35.5%), with a significant presence of social networks and the Internet (25.7%). Almost one fifth (18.1%) had chronic respiratory symptoms. Of these, 59.3% had requested medical care, and 66.2% had undergone spirometry. Spirometry was performed less frequently in subjects treated in primary care compared to respiratory medicine departments (51.9% versus 79.1%; P < .001)., Conclusions: Knowledge of COPD is still scarce, and strategies are needed to increase awareness and the importance of assessing respiratory symptoms and increased use of spirometry., (Copyright © 2020 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: The objective of this study was to assess the non-adherence level of Spanish clinical practice to guideline recommendations for the treatment of chronic obstructive pulmonary disease (COPD) and to estimate the potential impact on pharmaceutical expenditure resulting from transitioning current treatment patterns according to guidelines., Methods: A model was developed to compare current prescribing patterns with two alternative scenarios: the first aligned with the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2020) recommendations, and the second with the Spanish Guidelines for COPD (GesEPOC 2017). Current treatment practice was obtained from publications that describe treatment patterns by pulmonology departments in Spain. The economic impact between patterns was calculated from the perspective of the Spanish National Health System (NHS), considering the annual pharmacological costs of COPD inhaled maintenance therapy. Two additional analyses were performed: one that included current prescribing patterns of patients managed by pulmonology and primary care centers in Spain (published aggregated data); and another that only considered the appropriate use of inhaled corticosteroids (ICS) treatment according to guidelines., Results: It was estimated that 54% and 38% of patients were not treated in line with GOLD and GesEPOC recommendations, respectively, mainly due to a broader use of ICS-based therapies. Adapting treatment to recommendations could provide a potential annual cost-saving of €17,792,022 (according to GOLD) and €5,881,785 (according to GesEPOC). In scenario analysis 1, a 26% of non-adherence to GesEPOC guideline was observed with a potential annual pharmacological cost-saving of €2,707,554. In scenario analysis 2, considering only inappropriate use of ICS treatment, an annual cost-saving of €17,863,750 (according to GOLD) and €9,904,409 (according to GesEPOC) was calculated., Conclusion: More than a third of treatments for COPD patients in Spain are not prescribed in accordance with guideline recommendations. The adaptation of clinical practice to guideline recommendations could provide important cost-savings for the Spanish NHS., Competing Interests: Dr Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Spin Therapeutics, Palobiofarma SL, pH Pharma, Novartis, Sanofi and Grifols, and research grants from Grifols. Alexandra Solé, Helena Aguilar and Ana Ampudia are employees of Boehringer Ingelheim, S.A. Jaume Costa-Samarra, Maria Mallén-Alberdi and Diana Nieves work for an independent research entity, Oblikue Consulting, and have received remuneration for their contribution to the development of the draft. The authors affirm that the results of the research described in this manuscript, as well as the analysis and interpretation thereof, were the result of the free expression of opinions and the agreement of the publication’s co-authors, and that there were no conflicts, either to obtain or disclose said results., (© 2021 Miravitlles et al.)