Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

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.

Prevalence of Seasonal Influenza Vaccination in Chronic Obstructive Pulmonary Disease (COPD) Patients in the Balearic Islands (Spain) and Its Effect on COPD Exacerbations: A Population-Based Retrospective Cohort Study.

To determine the prevalence of influenza vaccination in chronic obstructive pulmonary disease (COPD) patients and its effect on COPD exacerbations, we conducted a retrospective population-based cohort study analyzing real-life data. We included all registered COPD patients ≥40 years old using respiratory medication during the study period (2012-2013). Influenza vaccination during the 2012/2013 campaign was the parameter studied. Moderate and severe exacerbations during 2013 were the dependent outcome variables. Logistic regression adjusting for age, gender, concomitant asthma diagnosis, COPD severity, smoking status, number of moderate and severe exacerbations the previous year, and comorbidities was performed, and 59.6% of the patients received seasonal influenza vaccination. The percentage of patients with exacerbations was higher among those vaccinated. Influenza vaccination had a statistically significantly negative (non-protective) crude effect favoring the risk of severe exacerbations: OR: 1.20 (95% CI; 1.05-1.37). This association diminished and lost statistical significance after adjustment: aOR: 0.93 (95% CI; 0.74-1.18). The protective effect in the analysis restricted to the epidemic period was not significant: aOR: 0.82 (95% CI; 0.58-1.16). We concluded that prevalence of influenza vaccination was suboptimal. In contrast with most of the available evidence, our results did not support a protective effect of influenza vaccination on the risk of admission for COPD exacerbation.

[Association between the use of short-acting bronchodilators and the risk of hospitalization for asthma in a real-life clinical practice population cohort]. / Asociación entre la utilización de broncodilatadores de corta duración y el riesgo de hospitalización por asma en condiciones de práctica clínica habitual en una cohorte poblacional.

OBJECTIVE: To determine the number of short-acting beta-agonists (SABA) canisters dispensed in a pharmacy during one year that is associated with higher asthma hospitalization risk in the same period in patients with active asthma. Multi-centre cross-sectional descriptive design. LOCATION: Primary care, MAJORICA cohort including sociodemographic, clinical and electronic prescription system data coded during clinical practice from 68,578 patients with COPD and asthma in the Balearic Islands. PARTICIPANTS: A total of 7,648 patients older than 18 years with active asthma, who got any SABA canister from the pharmacy during the 2014-2015 period were included. COPD patients were excluded. MAIN MEASUREMENTS: Asthma hospitalization, respiratory medication, tobacco, co-morbidities, age and gender. RESULTS: Mean age 47 years, 38% women, 23.2% active smokers. Seventy-seven patients (1%) were admitted for asthma exacerbation in the study period. Patients who received more than 8 SABA containers per year increased the risk of hospitalization (OR 2.81; 95% CI 1.27-6.24). Severity by therapeutic step and amount of inhaled corticosteroids, as well as heart failure and sleep apnea were also significantly associated with hospitalization. CONCLUSIONS: There is a significant association between the risk of hospitalization and the higher number of SABA canisters dispensed from the pharmacy. The number of canisters/year that best defines a higher risk of hospitalization is≥8 and could be used to identify asthma at risk.

Prevalence and Characteristics of Asthma-Chronic Obstructive Pulmonary Disease Overlap in Routine Primary Care Practices.

Rationale: Adults may exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD), a situation recently described as asthma-COPD overlap (ACO). There is a paucity of information about ACO in primary care.Objectives: To estimate the prevalence and describe characteristics of individuals with ACO in primary care practices among patients currently diagnosed with asthma, COPD, or both; and to compare the prevalence and characteristics of ACO among the three source populations.Methods: The Respiratory Effectiveness Group conducted a cross-sectional study of individuals ≥40 years old and with ≥2 outpatient primary care visits over a 2-year period in the UK Optimum Patient Care Research Database. Patients were classified into one of three source populations based on diagnostic codes: 1) COPD only, 2) both asthma and COPD, or 3) asthma only. ACO was defined as the presence of all of the following 1) age ≥40 years, 2) current or former smoking, 3) post-bronchodilator airflow limitation (forced expiratory volume in 1 second/forced vital capacity <0.7), and 4) ≥12% and ≥200 ml reversibility in post-bronchodilator forced expiratory volume in 1 second.Results: Among 2,165 individuals (1,015 COPD only, 395 with both asthma and COPD, and 755 asthma only), the overall prevalence of ACO was 20% (95% confidence interval, 18-23%). Patients with ACO had a mean age of 70 years (standard deviation, 11 yr), 60% were men, 73% were former smokers (the rest were current smokers), and 66% were overweight or obese. Comorbid conditions were common in patients with ACO, including diabetes (53%), cardiovascular disease (36%), hypertension (30%), eczema (23%), and rhinitis (21%). The prevalence of ACO was higher in patients with a diagnosis of both asthma and COPD (32%) compared with a diagnosis of COPD only (20%; P < 0.001) or asthma only (14%; P < 0.001). Demographic and clinical characteristics of ACO varied across these three source populations.Conclusions: One in five individuals with a diagnosis of COPD, asthma, or both asthma and COPD in primary care settings have ACO based on the Respiratory Effectiveness Group ACO Working group criteria. The prevalence and characteristics of patients with ACO varies across the three source populations.

ACO: Time to move from the description of different phenotypes to the treatable traits.

BACKGROUND: Asthma-COPD overlap (ACO) is a term that encompasses patients with characteristics of two conditions, smoking asthmatics or COPD patients with asthma-like features such as high bronchodilator response or blood eosinophil count ≥300 cells/µL. The aim of this study was to compare the different phenotypes inside the ACO definition in a real-life population cohort. METHODS: We analyzed patients from the MAJORICA cohort who had a diagnosis of asthma and/or COPD based on current guidelines, laboratory data in 2014 and follow-up until 2015. Prevalence of ACO according to the different criteria, demographic, clinical and functional characteristics, prescriptions and use of health resources data were compared between three groups. RESULTS: We included 603 patients. Prevalence of smoking asthmatics was 14%, COPD patients with high bronchodilator response 1.5% and eosinophilic COPD patients 12%. Smoking asthmatics were younger and used more rescue inhalers, corticosteroids and health resources. Conversely, eosinophilic COPD patients were older than the other groups, often treated with corticosteroids and had lower use of health resources. Most of the COPD patients with high bronchodilator response were included in the eosinophilic COPD group. CONCLUSIONS: ACO includes two conditions (smoking asthmatics and eosinophilic COPD patients) with different medication requirement and prognosis that should not be pooled together. Use of ≥300 blood eosinophils/µL as a treatable trait should be recommended.

Determinants of the Appearance and Progression of Early-Onset Chronic Obstructive Pulmonary Disease in Young Adults. A Case-Control Study with Follow-up. / EARLY COPD: determinantes de la aparición y progresión de la enfermedad pulmonar obstructiva crónica en adultos jóvenes. Protocolo de un estudio caso-control con seguimiento.

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.

Consensus on the Asthma-COPD Overlap Syndrome (ACOS) Between the Spanish COPD Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma (GEMA). / Consenso sobre el solapamiento de asma y EPOC (ACO) entre la Guía española de la EPOC (GesEPOC) y la Guía Española para el Manejo del Asma (GEMA).

Following a proposal by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), sponsor of the Spanish COPD Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma (GEMA), authors of both papers have unified the criteria for the diagnosis of asthma-COPD overlap syndrome (ACOS). This consensus defines ACOS as the presence in a given patient of three elements: significant smoking exposure, chronic airflow limitation and asthma. Diagnosis is confirmed when a patient (35years of age or older), smoker or ex-smoker of more than 10 pack-years, presents airflow limitation (post-bronchodilator FEV1/FVC<0.7) that persists after treatment with bronchodilators and inhaled corticosteroids (even after systemic corticosteroids in selected cases), and an objective current diagnosis of asthma (according to GEMA criteria). In cases in which the diagnosis of asthma cannot be demonstrated, marked positive results on a bronchodilator test (FEV1≥15% and ≥400mL) or elevated blood eosinophil count (≥300eosinophils/µL) will also be diagnostic of ACOS. The opinion of another 33 experts who had not participated in the consensus was sought using a modified Delphi survey. Up to 80% of respondents gave a very positive opinion of the consensus, and declared that it was better than other previous proposals. The GesEPOC-GEMA consensus on ACOS provides a unique perspective of the diagnostic problem, using a simple proposal and a pragmatic diagnostic algorithm that can be applied at any healthcare level.

Factors associated with inhaled corticosteroids prescription in primary care patients with COPD: A cross-sectional study in the Balearic Islands (Spain).

BACKGROUND: There is a worldwide over-prescription of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), off-label prescribing, and unnecessary prescription of high doses. OBJECTIVES: Our aim was to assess the prescription rate of ICS and to identify sociodemographic and clinical factors associated with ICS prescription among patients with COPD, treated in Balearic primary healthcare. METHODS: This cross-sectional study included all patients with a clinical COPD diagnosis, who attended a primary care centre of the Balearic Islands (Spain) during 2012. Also, a sub-population with spirometry-confirmed COPD was defined. Data were obtained on patient demographics, smoking status, spirometry, ICS prescriptions, other respiratory medication, exacerbations and comorbidities. Associations with ICS and high-dose ICS prescription were assessed using multivariate regression analyses. RESULTS: In total, 15,440 patients were included (70% men, mean age 68.6 years), and 44.6% were prescribed ICS. The largest association with ICS prescription was asthma comorbidity (OR: 3.50; 95%CI: 3.12-3.92), followed by exacerbation history (OR: 2.23; 95%CI: 2.07-2.47). In addition, smoking status, spirometry, atopic dermatitis, allergic rhinitis and mean age were significantly (P < 0.001) associated with ICS treatment. In the spirometry-confirmed population, asthma (OR: 2.89; 95%CI: 2.29-3.64) and exacerbations were also the major factors (OR: 2.85; 95%CI: 2.45-3.32) followed by severe bronchial-obstruction (OR: 2.63; 95%CI: 2.24-3.08). High-dose ICS prescription was mainly associated with severe obstruction (OR: 2.27; 95%CI: 1.93-2.68). CONCLUSION: The percentage of COPD patients prescribed ICS in Balearic primary care is relatively low. Asthma comorbidity, exacerbation history, severe bronchial-obstruction, smoking status and a spirometry-confirmed COPD diagnosis were significantly associated with ICS prescription. [Box: see text].

Comorbidome, Pattern, and Impact of Asthma-COPD Overlap Syndrome in Real Life.

BACKGROUND: Asthma-COPD overlap syndrome (ACOS) has been described and acknowledged as a distinct clinical entity; however, its characteristics in daily clinical practice are largely unknown. The aim of this study was to identify the prevalence of ACOS in the real-life population, its pattern of comorbidities, and its impact on hospitalization risk. METHODS: Data for this retrospective cohort study were extracted from the Majorca Real-Life Investigation in COPD and Asthma cohort, including primary care, hospitalization, and pharmacy data from the Balearic Islands, Spain. Patients who had received a physician-confirmed diagnosis of both asthma and COPD were identified as having ACOS and compared with a COPD-only population. In subanalyses, more stringent diagnostic criteria (Global Initiative for Asthma-Global Initiative for Chronic Obstructive Lung Disease) were applied. The pattern and impact of comorbidities on all-cause hospitalization were compared by multivariate logistic regression. RESULTS: In total, 5,093 patients with ACOS (prevalence, 5.55 per 1,000 inhabitants) were compared with 22,778 patients with COPD (30.40 per 1,000 inhabitants). Patients with ACOS were more frequently female (53.4%) than were patients with COPD (30.8%), younger (ACOS, 64.0 years; COPD, 65.8 years), and differed by nonsmoking status (ACOS, 41.4%; COPD, 22.1%) (all, P < .001). In adjusted analyses, allergic rhinitis (OR, 1.81; 95% CI, 1.63-2.00), anxiety (OR, 1.18; 95% CI, 1.10-1.27), gastroesophageal reflux disease (OR, 1.18; 95% CI, 1.04-1.33), and osteoporosis (OR, 1.14; 95% CI, 1.04-1.26) were more frequent in ACOS than COPD. In contrast, chronic kidney disease (OR, 0.79; 95% CI, 0.66-0.95) and ischemic heart disease (OR, 0.88; 95% CI, 0.79-0.98) were less frequent. In patients with ACOS, cardiovascular diseases showed the strongest association with hospitalization. CONCLUSIONS: ACOS is prevalent in the general population, and it affects to a large extent females with less smoking exposure compared with patients with COPD only. Cardiovascular comorbidities in particular contribute most to overall hospitalization risk of patients with ACOS.

Is a previous diagnosis of asthma a reliable criterion for asthma-COPD overlap syndrome in a patient with COPD?

BACKGROUND: Some patients share characteristics of both COPD and asthma. As yet, there is no gold standard to identify patients with the so-called asthma-COPD overlap syndrome (ACOS). OBJECTIVE: To describe the differences between ACOS patients and the remaining COPD patients, and to compare the clinical characteristics of patients diagnosed with ACOS by two different criteria: previous diagnosis of asthma before the age of 40 years; and the diagnostic criteria of the Spanish guidelines of COPD. METHODS: Multicenter, observational, cross-sectional study performed in 3,125 COPD patients recruited in primary care and specialized outpatient clinics. Patients with COPD and a history of asthma before the age of 40 years were diagnosed with ACOS and compared to the remaining COPD patients. Subsequently, ACOS patients were subdivided based on whether they fulfilled the Spanish guidelines of the COPD diagnostic criteria or not, and they were compared. RESULTS: ACOS was diagnosed in 15.9% of the patients. These patients had different basal characteristics compared to the remaining COPD patients, including a higher frequency of women and more exacerbations despite lower tobacco exposure and better lung function. They were more likely to have features of asthma, such as a positive bronchodilator test, higher peripheral eosinophilia, and higher total immunoglobulin E. Within the ACOS group, only one-third fulfilled the diagnostic criteria of the Spanish guidelines of COPD; these individuals were not significantly different from the remaining ACOS patients, except for having more exacerbations and poorer lung function. CONCLUSION: ACOS patients diagnosed on the basis of a previous diagnosis of asthma differed from the remaining COPD patients, but they were similar to ACOS patients diagnosed according to more restrictive criteria, suggesting that a history of asthma before the age of 40 years could be a useful criterion to suspect ACOS in a patient with COPD.

New horizons in early stage COPD--improving knowledge, detection and treatment.

Early stage COPD carries a significant healthcare burden that is currently underrecognised, underdiagnosed and undertreated. Furthermore, patients at this stage can rapidly decline to advanced disease, especially if they continue to smoke. The natural history of the disease in early stages remains largely unknown, and emerging evidence indicates that we are able to reduce lung function decline and exacerbations, and improve quality of life, in early stage COPD, mainly through smoking cessation. But new evidence from randomised clinical trials also suggests an impact of pharmacotherapy on clinical outcomes in early disease. Guidelines need to be updated to reflect this greater understanding of early stage disease, and trials need to be conducted to definitively show the benefits of intensive treatment so that we can meet the large, unmet clinical needs of this important patient group.