Genetic epidemiology of alpha-1 antitrypsin deficiency in Macaronesia.

INTRODUCTION: The prevalence of alpha-1 antitrypsin deficiency (AATD) in Macaronesia (i.e., Azores, Madeira, Canary Islands and Cape Verde archipelagos) is poorly known. Our goal is to update it by selecting the most reliable available articles. METHOD: Literature search using Medline, EMBASE (via Ovid) and Google Scholar, until December 2023, for studies on prevalence of AATD in the general population and in screenings, published in peer-reviewed journals. RESULTS: Three studies carried out in the general population of Madeira, La Palma and Cape Verde, and three screenings carried out in La Palma (2) and Gran Canaria (1) were selected. The frequencies of PI*S in the general population showed an ascending gradient, from South to North, with values (per thousand) of 35 in Cape Verde, 82 in La Palma and 180 in Madeira. The PI*Z frequencies showed this same gradient, with values of 2 x1,000 in Cape Verde, 21 in La Palma and 25 in Madeira. Screenings detected high percentages of defective alleles, including several rare and null alleles, some unique to these islands. CONCLUSION: The frequencies of PI*S and PI*Z in Madeira are comparable to the highest in the world. Those of the Canary Islands are similar to those of the peninsular population of Spain, and contrast with the low rates of Cape Verde. Screenings detected high numbers of deficient alleles. These results support the systematic investigation of AATD in clinically suspected patients and in relatives of index cases, to reduce underdiagnosis and apply early preventive and therapeutic measures in those affected.

N-acetylcysteine Treatment in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis/Pre-COPD: Distinct Meta-analyses.

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.

Detection of Alpha-1 Antitrypsin Levels in Chronic Obstructive Pulmonary Disease in Respiratory Clinics in Spain: Results of the EPOCONSUL 2021 Audit.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed condition despite being one of the most common inherited disorders in adults that is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD). The aim was to evaluate the frequency of performing AAT levels and associated factors in COPD patients in an audit conducted in 2021-2022, as well as to compare with a previous audit conducted in 2014-2015. METHODS: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to COPD patients in respiratory clinics in Spain based on available data from medical registries. RESULTS: 4225 patients with a diagnosis of COPD from 45 centers were audited in 2021. A total of 1670 (39.5%) patients underwent AAT determination. Being treated at a specialized COPD outpatient clinic (OR 1.88, p = 0.007), age ≤ 55 years old (OR 1.84, p = 0.007) and a FEV1 < 50% (OR 1.86, p < 0.001) were associated with a higher likelihood of being tested for AAT, while Charlson index ≥ 3 (OR 0.63, p < 0.001) and genotyping of AATD availability (OR 0.42, p < 0.001) showed a statistically significant negative association. The analysis of cases included in respiratory units that participated in both audits showed an increase in the proportion of cases with AAT serum level testing available (adjusted OR 2.81, p < 0.001). The percentage of individuals with serum AAT levels < 60 mg/dL (a severe AATD) was 4%. CONCLUSIONS: Our analysis identifies significant improvements in adherence to the recommendation to test AAT levels in COPD patients, performed in 4 out of 10 patients, being more likely at younger ages and with higher COPD severity, and with a detection of severe AATD of 4% among those tested, suggesting that clinicians still perform AAT testing in COPD patients selectively. Therefore, efforts are still needed to optimize AATD screening and establish new early detection strategies to reduce morbidity and mortality in these patients.

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

The Association Between Bronchiectasis and Chronic Obstructive Pulmonary Disease: Data from the European Bronchiectasis Registry (EMBARC).

RATIONALE AND OBJECTIVE: Bronchiectasis and COPD are associated conditions but misdiagnosis is believed to be common. A recently published international consensus definition of bronchiectasis (BE) and COPD association: The ROSE criteria (radiological bronchiectasis(R), obstruction: FEV1/FVC ratio<0.7 (O), symptoms (S) and exposure:≥10 pack year smoking (E) allows objective diagnosis of the BE-COPD association. METHODS: Analysis of the EMBARC registry, a prospective observational study of patients with CT confirmed bronchiectasis from 28 countries. The ROSE criteria were used to objectively defined BE-COPD association. Key outcomes during up to 5-years follow-up were exacerbations, hospitalization and mortality. MEASUREMENT AND MAIN RESULTS: 16730 patients with bronchiectasis were included. 4336 had a co-diagnosis of COPD and these patients had more exacerbations, worse quality of life and higher severity scores. We observed marked overdiagnosis of COPD using the ROSE criteria: 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 smoking. Therefore the proportion meeting the ROSE criteria for COPD was 2157 (55.4%). Compared to patients without COPD, patients meeting ROSE criteria had increased risk of exacerbations and exacerbations resulting in hospitalisation during follow-up (IRR 1.25 95%CI 1.15-1.35 and 1.69 95%CI 1.51-1.90 respectively) but patients with a diagnosis of COPD who did not meet ROSE criteria also had increased risk of exacerbations. CONCLUSIONS: The label of COPD is often applied to bronchiectasis patients without objective evidence of airflow obstruction and smoking history. Patients with a clinical label of COPD have worse clinical outcomes.

Association between occupational exposure and chronic obstructive pulmonary disease and respiratory symptoms in the Spanish population

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.MethodsThis 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.ResultsWe 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%.ConclusionsOccupational 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. (AU)

From treatable traits to GETomics in airway disease: moving towards clinical practice.

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.

Association between occupational exposure and chronic obstructive pulmonary disease and respiratory symptoms in the Spanish population.

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.

Alpha-1 Antitrypsin Augmentation and the Liver Phenotype of Adults With Alpha-1 Antitrypsin Deficiency (Genotype Pi∗ZZ).

BACKGROUND & AIMS: α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown. METHODS: Liver-related parameters were assessed in a multinational cohort of 760 adults with severe AATD (Pi∗ZZ genotype) and available liver phenotyping, of whom 344 received augmentation therapy and 416 did not. Liver fibrosis was evaluated noninvasively via the serum test AST-to-platelet ratio index and via transient elastography-based liver stiffness measurement. Histologic parameters were compared in 15 Pi∗ZZ adults with and 35 without augmentation. RESULTS: Compared with nonaugmented subjects, augmented Pi∗ZZ individuals displayed lower serum liver enzyme levels (AST 71% vs 75% upper limit of normal, P < .001; bilirubin 49% vs 58% upper limit of normal, P = .019) and lower surrogate markers of fibrosis (AST-to-platelet ratio index 0.34 vs 0.38, P < .001; liver stiffness measurement 6.5 vs 7.2 kPa, P = .005). Among biopsied participants, augmented individuals had less pronounced liver fibrosis and less inflammatory foci but no differences in AAT accumulation were noted. CONCLUSIONS: The first evaluation of AAT augmentation on the Pi∗ZZ-related liver disease indicates liver safety of a widely used treatment for AATD-associated lung disease. Prospective studies are needed to confirm the beneficial effects and to demonstrate the potential efficacy of exogenous AAT in patients with Pi∗ZZ-associated liver disease.

Effects of a telerehabilitation program and detraining on cardiorespiratory fitness in patients with post-COVID-19 sequelae: A randomized controlled trial.

BACKGROUND: This study aimed to evaluate the effects of a 15-week telerehabilitation program and a detraining period on cardiorespiratory fitness and mechanical efficiency in patients with post-COVID-19 sequelae. METHODS: 131 patients with post-COVID-19 sequelae were randomly assigned to one of two groups: patients who carried out the supervised telerehabilitation program (TRG, n = 66) and a control group (CG, n = 65). An incremental cardiopulmonary exercise testing (CPET) was performed on cycle ergometer to compare cardioventilatory responses between experimental groups. RESULTS: A significant increase in the CPET duration, peak power output, and mechanical efficiency was observed in TRG compared to CG after the telerehabilitation program (p ≤ 0.001). A significant increase in the CPET duration, peak power output, and mechanical efficiency was verified at 3 months compared to the pretest and after detraining in TRG (p < 0.001). A significant increase in peak oxygen uptake (V̇O2peak ) was identified after the intervention and in the detraining period compared to the pretest in both experimental groups (p < 0.001). A higher ventilatory efficiency was observed after the telerehabilitation program (p = 0.021) than in pretest only in TRG. CONCLUSIONS: A 15-week supervised home telerehabilitation program improved exercise capacity, power output, and mechanical efficiency in TRG compared to a CG. The telerehabilitation program was not more effective in improving V̇O2peak than the activities of the CG. However, ventilatory efficiency was improved only after the telerehabilitation program. The reported results after the detraining period highlight the need to maintain the rehabilitation program over time.

Potential systemic effects of acquired CFTR dysfunction in COPD.

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.

Nine controversial questions about augmentation therapy for alpha-1 antitrypsin deficiency: a viewpoint.

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.

Effect of different types of supervised exercise programs on cardiorespiratory and muscular fitness, pain, fatigue, mental health and inflammatory and oxidative stress biomarkers in older patients with post-COVID-19 sequelae "EJerSA-COVID-19": a randomized controlled trial.

BACKGROUND: Many patients with COVID-19 present the so-called post-acute sequelae of COVID-19 such as fatigue, post-stress discomfort, dyspnea, headache, pain mental impairment, incapacity to perform daily physical tasks ant exercise intolerance. This study aims to investigate the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. METHODS: The sample will be made up of 120 eligible participants, over the age of 60 years who have had COVID-19 disease and are survivors and present persistent COVID-19 symptomatology diagnosed by the corresponding physician. The participants will be randomly assigned to the experimental groups: supervised endurance group (SEG, n = 30), supervised strength group (SSG, n = 30), supervised concurrent group (SCG, n = 30), which will perform the corresponding exercise program 3 days a week compared to the control group (CG, n = 30), which will not carry out a supervised exercise program. The design of this project will include measurements of four relevant dimensions; 1) Cardiorespiratory fitness; 2) Muscle fitness; 3) Pain and mental health; and 4) Biomarkers of inflammation and oxidative stress. CONCLUSIONS: The results of this study will provide insights into the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. These findings may be the basis for the formulation of health plans and rehabilitation programs that allow healthy aging and a reduction in the associated morbidity in patients with post-COVID-19 sequelae. TRIAL REGISTRATION: NCT05848518. Registered on May 8, 2023.

Poor sleep quality, COPD severity and survival according to CASIS and Pittsburgh questionnaires.

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.

Stepwise management of COPD: What is next after bronchodilation?

Inhaled bronchodilator therapy with long-acting muscarinic antagonists (LAMAs) and long-acting ß2-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.

What are the options for patients with COPD when LABA/LAMA is not enough?Treatment guidelines for chronic obstructive pulmonary disease (COPD) recommend dual bronchodilator therapy for the majority of patients, consisting of an inhaled combination of long-acting ß₂-agonist (LABA) and long-acting muscarinic antagonist (LAMA). Patients whose COPD is not well controlled on LABA/LAMA require further clinical intervention, which may or may not involve treatment with additional drugs.Data from observational studies reflecting routine clinical practice suggest that inhaled corticosteroids (ICS) are often added to LABA/LAMA, even though treatment guidelines recommend only adding ICS in a specific group of patients with a history of exacerbations and high levels of eosinophils (a type of inflammatory cell) in the blood, or in those with current asthma. As long-term ICS use may be associated with an increased risk of side effects such as pneumonia, it is important to avoid overuse of ICS. When a patient's COPD is not well controlled on LABA/LAMA, other treatable conditions should first be ruled out, and factors such as medication adherence, inhaler technique, and co-existing health conditions should also be considered.This review gives advice on what follow-up options physicians should consider when LABA/LAMA is not providing adequate control of a patient's COPD. Specifically, recommendations are given for three different patient profiles:1. Patients who still have symptoms of COPD (but no acute/sudden worsenings of symptoms, known as exacerbations).2. Patients who have exacerbations, as well as high levels of eosinophils in the blood.3. Patients who have exacerbations, but without high levels of eosinophils in the blood or current asthma.

Inhaled Maintenance Therapy in the Follow-Up of COPD in Outpatient Respiratory Clinics. Factors Related to Inhaled Corticosteroid Use. EPOCONSUL 2021 Audit

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>300mm3 [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. (AU)