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BACKGROUND: Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies on PAL in asthma have included relatively small populations, mostly restricted to severe asthma, or have no included longitudinal data. The aim of this post-hoc analysis was to investigate the determinants, clinical implications, and outcome of PAL in patients with asthma who were included in the ATLANTIS study.METHODS: In this post-hoc analysis of the ATLANTIS study, we assessed the prevalence, clinical characteristics, and implications of PAL across the full range of asthma severity. The study population included patients aged 18-65 years who had been diagnosed with asthma at least 6 months before inclusion. We defined PAL as a post-bronchodilator FEV1/forced vital capacity (FVC) of less than the lower limit of normal at recruitment. Asthma severity was defined according to the Global Initiative for Asthma. We used Mann-Whitney U test, t test, or χ2 test to analyse differences in baseline characteristics between patients with and without PAL. Logistic regression was used for multivariable analysis of the associations between PAL and baseline data. Cox regression was used to analyse risk of exacerbation in relation to PAL, and a linear mixed-effects model was used to analyse change in FEV1 over time in patients with versus patients without PAL. Results were validated in the U-BIOPRED cohort.FINDINGS: Between June 30, 2014 and March 3, 2017, 773 patients were enrolled in the ATLANTIS study of whom 760 (98%) had post-bronchodilator FEV1/FVC data available. Of the included patients with available data, mean age was 44 years (SD 13), 441 (58%) of 760 were women, 578 (76%) were never-smokers, and 248 (33%) had PAL. PAL was not only present in patients with severe asthma, but also in 21 (16%) of 133 patients with GINA step 1 and 24 (29%) of 83 patients with GINA step 2. PAL was independently associated with older age at baseline (46 years in PAL group vs 43 years in non-PAL group), longer duration of asthma (24 years vs 12 years), male sex (51% vs 38%), higher blood eosinophil counts (median 0·27 × 109 cells per L vs 0·20 × 109 cells per L), more small airway dysfunction, and more exacerbations during 1 year of follow-up. Associations between PAL, age, and eosinophilic inflammation were validated in the U-BIOPRED cohort, whereas associations with sex, duration of asthma, and risk of exacerbations were not validated.INTERPRETATION: PAL is not only present in severe disease, but also in a considerable proportion of patients with milder disease. In patients with mild asthma, PAL is associated with eosinophilic inflammation and a higher risk of exacerbations. Our findings are important because they suggest that increasing treatment intensity should be considered in patients with milder asthma and PAL.FUNDING: Chiesi Farmaceutici and Dutch Ministry of Economic Affairs and Climate Policy (by means of the public-private partnership programme).

Chronic obstructive pulmonary disease (COPD) has been traditionally considered a self-inflicted disease caused by tobacco smoking. Current available evidence, however, indicates that the pathogenesis of COPD needs to consider the dynamic and cumulative nature of a series of environment (including smoking plus other exposures)-host interactions that eventually determine lung development, maintenance, repair, and aging. By doing so, these factors modulate the trajectory of lung function of the individual through life and the odds of developing COPD through different routes, which likely represent different forms of the disease that require different preventive and therapeutic strategies.

Rationale: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS) is controversial, because it can reduce the risk of future exacerbations of the disease at the expense of increasing the risk of pneumonia.Objectives: To assess the relationship between the presence of chronic bronchial infection (CBI), reduced number of circulating eosinophils, ICS treatment, and the risk of pneumonia in patients with COPD.Methods: This was a post hoc long-term observational study of an historical cohort of 201 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV) who were carefully characterized (including airway microbiology) and followed for a median of 84 months. Results were analyzed by multivariate Cox regression and network analysis.Measurements and Main Results: Mean age was 70.3 years, 90.5% of patients were male, mean FEV1 was 49%, 71.6% of patients were treated with ICS, 57.2% of them had bronchiectasis, and 20.9% had

Lung cancer screening programs with computed tomography of the chest reduce mortality by more than 20%. Yet, they have not been implemented widely because of logistic and cost implications. Here, we sought to: (1) use real-life data to compare the outcomes and cost of lung cancer patients with treated medically or surgically in our region and (2) from this data, estimate the cost-benefit ratio of a lung cancer screening program (CRIBAR) soon to be deployed in our region (Catalunya, Spain). We accessed the Catalan Health Surveillance System (CHSS) and analysed data of all patients with a first diagnosis of lung cancer between 1 January 2014 and 31 December 2016. Analysis was carried forward until 30 months (t = 30) after lung cancer diagnosis. Main results showed that: (1) surgically treated lung cancer patients have better survival and return earlier to regular home activities, use less healthcare related resources and cost less tax-payer money and (2) depending on incidence of lung cancer identified and treated in the program (1-2%), the return on investment for CRIBAR is expected to break even at 3-6 years, respectively, after its launch. Surgical treatment of lung cancer is cheaper and offers better outcomes. CRIBAR is estimated to be cost-effective soon after launch.

Background: Genome-wide association studies (GWAS) have accelerated our understanding of the genetic underpinnings of chronic obstructive pulmonary disease (COPD); however, GWAS populations have typically consisted of European descent, with ∼1% of Latin American ancestry. Objective: To overcome this limitation, we conducted a GWAS in a rural Chilean population with increased COPD risk to investigate genetic variation of COPD risk in this understudied minority population. Method: We carried out a case-control study of 214 COPD patients (defined by the GOLD criteria) and 193 healthy controls in Talca, Chile. DNA was extracted from venous blood and genotyped on the Illumina Global Screening Array (n = 754,159 markers). After exclusion based on Hardy-Weinberg equilibrium (p ≤ 0.001), call rates (Results: PRDM15 rs1054761 C allele (p = 2.22 × 10–7) was associated with decreased COPD risk. Three PRDM15 SNPs located on chromosome 21 were significantly associated with COPD risk (p < 10–6). Two of these SNPs, rs1054761 and rs4075967, were located on a noncoding transcript variant region of the gene. Conclusion: PRDM15 overexpression may play a role in the B-cell dysregulation in COPD pathogenesis. To the best of our knowledge, the association between PRDM15 and COPD risk was not previously found in GWAS studies in largely European populations, highlighting the importance of investigating novel variants associated with COPD risk among ethnically diverse populations.

A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long-acting β2 adrenergic bronchodilators (LABA). The addition of long-acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single-inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS-LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.

International audience; Chronic Obstructive Pulmonary Disease (COPD) is a common disease associated with significant morbidity and mortality that is both preventable and treatable. However, a major challenge in recognizing, preventing, and treating COPD is understanding its complexity. While COPD has historically been characterized as a disease defined by airflow limitation, we now understand it as a multi-component disease with many clinical phenotypes, systemic manifestations, and associated co-morbidities. Evidence is rapidly emerging in our understanding of the many factors that contribute to the pathogenesis of COPD and the identification of "early" or "pre-COPD" which should provide exciting opportunities for early treatment and disease modification. In addition to breakthroughs in our understanding of the origins of COPD, we are optimizing treatment strategies and delivery of care that are showing impressive benefits in patient-centered outcomes and healthcare utilization. This special issue of Respiratory Medicine, "COPD: Providing the Right Treatment for the Right Patient at the Right Time" is a summary of the proceedings of a conference held in Stresa, Italy in April 2022 that brought together international experts to discuss emerging evidence in COPD and Pulmonary Rehabilitation in honor of a distinguished friend and colleague, Claudio Ferdinando Donor (1948-2021). Claudio was a true pioneer in the field of pulmonary rehabilitation and the comprehensive care of individuals with COPD. He held numerous leadership roles in in the field, provide editorial stewardship of several respiratory journals, authored numerous papers, statement and guidelines in COPD and Pulmonary Rehabilitation, and provided mentorship to many in our field. Claudio's most impressive talent was his ability to organize spectacular conferences and symposia that highlighted cutting edge science and clinical medicine. It is in this spirit that this conference was conceived and planned. These proceedings are divided into 4 sections which highlight crucial areas in the field of COPD: (1) New concepts in COPD pathogenesis; (2) Enhancing outcomes in COPD; (3) Non-pharmacologic management of COPD; and (4) Optimizing delivery of care for COPD. These presentations summarize the newest evidence in the field and capture lively discussion on the exciting future of treating this prevalent and impactful disease. We thank each of the authors for their participation and applaud their efforts toward pushing the envelope in our understanding of COPD and optimizing care for these patients. We believe that this edition is a most fitting tribute to a dear colleague and friend and will prove useful to students, clinicians, and researchers as they continually strive to provide the right treatment for the right patient at the right time. It has been our pleasure and a distinct honor to serve as editors and oversee such wonderful scholarly work.

Los estudios de anatomía patológica (AP) del pulmón en pacientes que fallecen por COVID-19 nos han permitido entender el daño pulmonar producido por el virus SARS-CoV-21,2. En el contexto de la pandemia COVID-19, la realización de una autopsia tiene varias limitaciones. Ante estas limitaciones, la SEAP propuso la obtención de muestras postmortem de pacientes como una alternativa a la autopsia en los centros en que no se reuniese las condiciones de bioseguridad. Este estudio presenta datos de biopsias pulmonares percutáneas por neumonía COVID-19 publicado por primera vez en nuestro país, demostrándose que es una técnica segura y eficaz, como alternativa a la autopsia.

Chronic obstructive pulmonary disease (COPD) is a public health problem due to its high prevalence (11% in the adult population in Spain), increasing incidence, and great social and economic impact. Despite this, it is underdiagnosed (and, therefore, undertreated) at a rate of around 80%. In this paper, a group of respiratory physicians specializing in COPD discuss 7 fundamental problems ("cardinal sins") that contribute to this situation, with the explicit aim of proposing specific solutions that may help to improve this unfavorable state of affairs.

SLICE Trial Group., [Importance] Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD)., [Objective] To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation., [Design, Setting, and Participants] Randomized clinical trial conducted across 18 hospitals in Spain. A total of 746 patients were randomized from September 2014 to July 2020 (final follow-up was November 2020)., [Interventions] Usual care plus an active strategy for diagnosing PE (D-dimer testing and, if positive, computed tomography pulmonary angiogram) (n = 370) vs usual care (n = 367)., [Main Outcomes and Measures] The primary outcome was a composite of nonfatal symptomatic venous thromboembolism (VTE), readmission for COPD, or death within 90 days after randomization. There were 4 secondary outcomes, including nonfatal new or recurrent VTE, readmission for COPD, and death from any cause within 90 days. Adverse events were also collected., [Results] Among the 746 patients who were randomized, 737 (98.8%) completed the trial (mean age, 70 years; 195 [26%] women). The primary outcome occurred in 110 patients (29.7%) in the intervention group and 107 patients (29.2%) in the control group (absolute risk difference, 0.5% [95% CI, −6.2% to 7.3%]; relative risk, 1.02 [95% CI, 0.82-1.28]; P = .86). Nonfatal new or recurrent VTE was not significantly different in the 2 groups (0.5% vs 2.5%; risk difference, −2.0% [95% CI, −4.3% to 0.1%]). By day 90, a total of 94 patients (25.4%) in the intervention group and 84 (22.9%) in the control group had been readmitted for exacerbation of COPD (risk difference, 2.5% [95% CI, −3.9% to 8.9%]). Death from any cause occurred in 23 patients (6.2%) in the intervention group and 29 (7.9%) in the control group (risk difference, −1.7% [95% CI, −5.7% to 2.3%]). Major bleeding occurred in 3 patients (0.8%) in the intervention group and 3 patients (0.8%) in the control group (risk difference, 0% [95% CI, −1.9% to 1.8%]; P = .99)., [Conclusions and Relevance] Among patients hospitalized for an exacerbation of COPD, the addition of an active strategy for the diagnosis of PE to usual care, compared with usual care alone, did not significantly improve a composite health outcome. The study may not have had adequate power to assess individual components of the composite outcome., [Trial Registration] ClinicalTrials.gov Identifier: NCT02238639.

The 3TR (Taxonomy, Treatments, Targets and Remission) consortium is the largest IMI (Innovative Medicine Initiative) project ever started in the field of immune diseases (https://3tr-imi.eu/). 3TR is unique in bringing several medical specialties, encompassing respiratory medicine, rheumatology, neurology and gastroenterology, together, to study disease mechanisms across seven disease entities: asthma, COPD, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, ulcerative colitis and Crohn's disease. [...]

Asthma with fixed airflow obstruction (AFO) is an important understudied sub-phenotype encompassing features of both asthma and COPD. We aimed to determine the prevalence and comorbidities of AFO patients in a large multi-cohort sample. Patients at least 50 years of age with lung function data were from nine European cohorts (69,866 participants), including population-based studies, COPD-based studies and asthma-based studies. AFO was defined as a documented doctor diagnosis of asthma and FEV1/FVC ratio The prevalence of AFO (n=2,378) differed between population-based cohorts (2.0%, n=1,299/63,504), COPD-based cohorts (15.9%, n= 857/5,402) and asthma-based cohorts (23.1%, n= 222/960). The LLN-based definition showed lower AFO prevalence in the general and asthmatic populations (1.4% and 15.7%) but higher prevalence (20.6%) in a smoking COPD population. While hypertension was the most prevalent comorbidity in all 3 conditions, AFO patients were significantly more likely to be diagnosed with depression, osteoporosis, coronary artery disease and gastroesophageal reflux compared to asthma-alone or COPD-alone. AFO has a prevalence ranging from 2.0% in the general population to 23.1% in an asthma population. The LLN-based definition seems to detect more patients suffering from AFO in populations with substantial smoking history. AFO patients have frequent comorbidities which may underlie their worse health outcomes.

Rationale & Aim: There is increasing interest in lung function trajectories but the focus to date has been on obstructive patterns without taking restrictive patterns into account. We investigated these patterns concurrently over the lifespan Methods: Using group-based trajectory modelling of spirometry collected from 7 to 53 years in the Tasmanian Longitudinal Health Study (n=2,438), 6 FEV1/FVC and 5 FVC trajectories were identified. Three FEV1/FVC trajectories were collectively recognised as ‘low’ and one FVC trajectory as ‘low’. Based on whether trajectories of FEV1/FVC and FVC were ‘low’, 4 patterns of lifetime spirometry trajectories were identified. Risk factors and consequences of these patterns were investigated Results: The prevalence of the lifetime patterns were: low FEV1/FVC-only 25.8%; low FVC-only 10.4%; both low FEV1/FVC and low FVC, labelled as ‘mixed’ 3.5%, and neither low (60.2%). Those with the mixed pattern had the highest prevalence of COPD at age 53 years (36.9%) followed by the low FEV1/FVC-only pattern (21.6%). Those with the mixed pattern had the highest prevalence of parental asthma, childhood respiratory illnesses, adult asthma and mental health disorders. Those with the low FVC-only pattern had low total lung capacity and residual volume and had the highest prevalence of childhood underweight, adult obesity, diabetes and cardiovascular conditions Conclusion: We identified physiological patterns of lifetime spirometric airway obstruction, restriction and both/mixed. Mixed and obstructive patterns identify those who may benefit from early interventions. The restrictive pattern identifies those at higher risk of multi-morbidity by middle-age

Background and objective Different lung function trajectories through life can lead to COPD in adulthood. This study investigated whether circulating levels of biomarkers can differentiate those with accelerated (AD) from normal decline (ND) trajectories. Methods The Tasmanian Longitudinal Health Study (TAHS) is a general population study that measured spirometry and followed up participants from ages 7 to 53 years. Based on their forced expiratory volume in 1 s (FEV1) trajectories from age 7 to 53 years, this analysis included those with COPD at age 53 years (60 with AD and 94 with ND) and controls (n=720) defined as never-smokers with an average FEV1 trajectory. Circulating levels of selected biomarkers determined at 53 and 45 years of age were compared between trajectories. Results Results showed that CC16 levels (an anti-inflammatory protein) were lower and C-reactive protein (CRP) (a pro-inflammatory marker) higher in the AD than in the ND trajectory. Higher CC16 levels were associated with a decreased risk of belonging to the AD trajectory (OR=0.79 (0.63–0.98) per unit increase) relative to ND trajectory. Higher CRP levels were associated with an increased risk of belonging to the AD trajectory (OR=1.07, 95% CI: 1.00–1.13, per unit increase). Levels of CC16 (area under the curve (AUC)=0.69, 95% CI: 0.56–0.81, p=0.002), CRP (AUC=0.63, 95% CI: 0.53–0.72, p=0.01) and the combination of both (AUC=0.72, 95% CI: 0.60–0.83, p, In the general population, two circulating biomarkers (CRP and CC16) are associated with different lung function trajectories leading to COPD in adulthood https://bit.ly/3wqWfb3

BackgroundStudies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort.MethodsPatients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis.ResultsOf 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses.ConclusionThis analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.

Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.

Severe pulmonary hypertension (PH) is prognostically highly relevant in patients with COPD. The criteria for severe PH have been defined based on hemodynamic thresholds in right heart catheterization.Can noninvasive clinical tools predict severe PH in patients with COPD? How does the mortality risk change with increasing severity of airflow limitation and pulmonary vascular disease?We retrospectively analyzed all consecutive patients with COPD with suspected PH undergoing in-depth clinical evaluation, including right heart catheterization, in our PH clinic between 2005 and 2018. Clinical variables potentially indicative of severe PH or death were analyzed using univariate and stepwise multivariate logistic regression and Cox regression analysis adjusted for age and sex.We included 142 patients with median FEVIn patients with COPD, the combination of echocardiography, NT-proBNP level, and PA to Ao diameter ratio predicts severe PH with high sensitivity and specificity. The contribution of severe PH and severe airflow limitation to impaired survival is comparable.

Rationale: Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes. Objectives: To explore the relationship between computed tomography measures of emphysema and distal pulmonary arterial morphology with RV volume, and their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study. Methods: Epicardial (myocardium and chamber) RV volume (RV(EV)), distal pulmonary arterial blood vessel volume (arterial BV5: vessels

Resumen En la mayoria de los ambitos de la neumologia se sigue utilizando un principio osleriano (basado en los sintomas y signos) en los que la enfermedad es el centro de toda actividad, pero este paradigma esta cambiando. Actualmente, gracias al reconocimiento de la heterogeneidad y complejidad de las enfermedades pulmonares, la tendencia es a realizar una medicina mas personalizada, de precision, o centrada en el paciente. En la presente revision se intentara establecer la situacion actual sobre el conocimiento de las bronquiectasias, o mejor, del sindrome bronquiectasico, como una enfermedad multidimensional, sistemica, heterogenea y compleja, los pasos que ya se han dado en este sentido, y sobre todo, en los muchos que quedan por dar. Asimismo, se propondran algunas herramientas que podrian facilitar la traslacion de estos conceptos a la practica clinica, y con ellos seguir avanzando hacia una imagen mas holistica de esta enfermedad.

Hiliar (pN1) and mediastinal lymph (pN2) nodal upstaging after surgery for early stage (IIB) non-small cell lung cancer (NSCLC) is a quality marker of surgical lymphadenectomy. It has been suggested that Video-Assisted Thoracoscopic Surgery (VATS) may result in suboptimal lymphadenctomy because nodal upstaging was lower than after open thoracothomy (THO). We sought to: (1) compare the prevalence of nodal upstaging after VATS and THO in NSCLC IIB; (2) investigate potential risk factors of nodal upstaging; and, (3) assess the impact of nodal upstaging on survival.Retrospective analysis of all anatomical resections for NSCLC IIB in our center (n = 323) from 2011 to 2017. The surgical procedure [THO (60.4%) or VATS (39.4%)] was chosen by the surgeon on the basis of experience and tumor characteristics (centrality and size).Baseline characteristics were similar between the two groups except for larger and more central tumors in THO (p 0.05). The prevalence of pN1 upstaging was higher after THO (20.5%) than after VATS (8.6%, p 0.05), but that of pN2 was similar in both groups (6% (THO) and 6.5% (VATS). Tumor centrality was an independent risk factor for pN1. Survival after THO or VATS was similar, irrespectively of nodal upstaging.In conclusion, VATS is as useful as THO to detect upstaging. Lower upstaging after VATS is attributable to bias selection. Central tumors are more often approached by thoracotomy and centrality is a risk factor for hiliar upstaging.

Introduction and objectives: Determinants of chronic obstructive pulmonary disease (COPD) in the early stages of its natural history are not well known. Improving our knowledge of these factors will help to design interventions that can modify prognosis. Study objectives are: a) to characterize a COPD population of young adults aged 35-50 years from a multidimensional point of view; b) to compare these patients with smokers with normal lung function: and c) to create a cohort of young adults aged 35-50 years (smokers or former smokers), with and without COPD, who will be followed in the future to improve understanding of the natural history of the disease. Participants and method: This is a case-control multicenter study aimed at establishing a well characterized cohort of young adults, smokers or former-smokers, with and without COPD, for subsequent follow-up. A total of 311 participants (101 cases and 210 controls) were selected from approximately 30 primary care settings and 12 hospitals in 8 Spanish regions. Subjects were smokers or former smokers (> 10 pack-years) aged 35-50 years. Diagnosis of COPD was based on a post-bronchodilator result of FEV1/FVC < 70%. The main study variables were: questionnaires on health, symptoms, exacerbations and daily physical activity, lung function tests, blood and sputum samples, and low-dose computed tomography. In the statistical analysis, COPD patient characteristics will be described and compared with control subjects using a logistic regression analysis. (C) 2018 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.

Resumen Introduccion y objetivos Los determinantes en fases iniciales de la historia natural de la enfermedad pulmonar obstructiva cronica (EPOC) son poco conocidos. Entenderlos mejor es de capital importancia para poder disenar intervenciones dirigidas a modificar su pronostico. Los principales objetivos del estudio son: a) caracterizar a una poblacion de adultos jovenes con EPOC de forma multidimensional; b) comparar estos pacientes con sujetos fumadores con funcion pulmonar normal; y c) establecer una cohorte de adultos jovenes con y sin EPOC, que pueda ser seguida a largo plazo para conocer mejor la historia natural de la enfermedad. Participantes y metodo EARLY COPD es un estudio multicentrico de casos y controles que permitira establecer una cohorte de sujetos para su seguimiento posterior. Se seleccionaron 311 (101 casos y 210 controles) participantes reclutados en una treintena de centros de atencion primaria y 12 hospitales de 8 comunidades autonomas espanolas. Los participantes eran fumadores o exfumadores (> 10 paquetes ano) de entre 35-50 anos de edad. Los casos presentaban una espirometria obstructiva con un FEV1/FVC

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) progression is variable and affects several disease domains, including decline in lung function, exercise capacity, muscle strength, and health status as well as changes in body composition. We aimed to assess the longitudinal association of physical activity (PA) with these a priori selected components of disease progression. METHODS: We studied 114 COPD patients from the PAC-COPD cohort (94% male, mean [SD], 70 yr [8 yr] of age, 54 [16] forced expiratory volume in 1 s % predicted) at baseline and 2.6 yr (0.6 yr) later. Baseline PA was assessed by accelerometry. Multivariable general linear models were built to assess the association between PA and changes in lung function, functional exercise capacity, muscle strength, health status, and body composition. All models were adjusted for confounders and the respective baseline value of each measure. RESULTS: Per each 1000 steps higher baseline PA, forced expiratory volume in 1 s declined 7 mL less (P < 0.01), forced vital capacity 9 mL less (P = 0.03) and carbon monoxide diffusing capacity 0.10 mL·min·mm Hg less (P = 0.04), while the St George's Respiratory Questionnaire symptom domain deteriorated 0.4 points less (P = 0.03), per year follow-up. Physical activity was not associated with changes in functional exercise capacity, muscle strength, other domains of health status or body composition. CONCLUSIONS: Higher PA is associated with attenuated decline in lung function and reduced health status (symptoms domain) deterioration in moderate-to-very severe COPD patients. ispartof: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE vol:51 issue:5 pages:833-840 ispartof: location:United States status: published

The normal lung function trajectory from birth to death has three phases: a growth phase (from birth to early adulthood), a plateau phase (that lasts for a few years), and a decline phase resulting from physiological lung ageing. Numerous genetic and environmental factors can alter one or more of these phases. Evidence shows that several lung function trajectories exist throughout the life course and, importantly, that some of them are associated with substantial implications for health and disease. Here, we review the evidence, formulate a series of questions, and identify various challenges that need to be addressed to identify potential opportunities to promote respiratory health.

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

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BackgroundThe relationship between asthma and coronavirus disease 2019 (COVID-19) risk is not clear and may be influenced by level of airway obstruction, asthma medication and known COVID-19 risk factors. We aimed to investigate COVID-19 risk in people with asthma.MethodsWe used UK Biobank data from all participants tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n=107 412; 17 979 test positive). Questions at baseline defined ever asthma and asthma medications. Baseline forced expiratory volume in 1 s (FEV1) was categorised into quartiles. Logistic regression modelled relationships between asthma, and asthma categories (age at onset, medications, FEV1 quartiles), and risk of SARS-CoV-2 positive test. We investigated modification by sex, ethnic group, smoking and body mass index.ResultsThere was a reduced risk of a positive test associated with early-onset asthma (ConclusionAmongst male, nonsmoking, overweight/obese and non-Black participants, having early-onset asthma was associated with lower risk of a SARS-CoV-2 positive test. We found no evidence of a protective effect from asthma medication. Individuals with early-onset asthma of normal weight and with better lung function may have lifestyle differences placing them at higher risk. Further research is needed to elucidate the contribution of asthma pathophysiology and different health-related behaviour, across population groups, to the observed risks.

Case Reports

Background and objective Cardiovascular (CV) diseases are frequent in patients with chronic obstructive pulmonary disease (COPD). Likewise, chronic bronchial infection (CBI) is also frequent in COPD and it is associated with systemic inflammation, a well-known CV risk factor. The objective of this study was to investigate the relationship between CBI, systemic inflammation and incident CV events. Methods A post hoc analysis of prospectively collected cohort of 201 COPD patients [Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV] followed up every 3-6 months for 84 months was conducted. CBI was defined as ≥3 positive pathogenic microorganisms sputum cultures over 1 year, separated by ≥3 months. Systemic inflammation was assessed by circulating levels of C-reactive protein and fibrinogen. Fatal and non-fatal CV events, including coronary and cerebrovascular events as well as arrhythmia episodes, were prospectively recorded. For analysis, they were analysed separately and combined in a composite variable. Results As hypothesized, CBI was associated with persistent systemic inflammation and a significantly higher incidence of CV events (HR: 3.88; 95% CI: 1.83-8.22), mainly of coronary origin independent of age, number and severity of exacerbations, comorbidities, other CV risk factors, lung function, BMI, smoking status and treatments. These associations were particularly significant in patients with CBI by Pseudomonas aeruginosa (PA). Conclusion CBI, particularly by PA, is associated with sustained and enhanced systemic inflammation and a higher incidence of CV events (especially coronary events). The possibility that treating CBI may decrease systemic inflammation and CV events in COPD deserves prospective, interventional studies.