Type 2 inflammation in asthma and other airway diseases.

Chronic inflammatory airway diseases, including asthma, chronic rhinosinusitis, eosinophilic COPD and allergic rhinitis are a global health concern. Despite the coexistence of these diseases and their common pathophysiology, they are often managed independently, resulting in poor asthma control, continued symptoms and poor quality of life. Understanding disease pathophysiology is important for best treatment practice, reduced disease burden and improved patient outcomes. The pathophysiology of type 2 inflammation is driven by both the innate immune system triggered by pollutants, viral or fungal infections involving type 2 innate lymphoid cells (ILC2) and the adaptive immune system, triggered by contact with an allergen involving type 2 T-helper (Th2) cells. Both ILC2 and Th2 cells produce the type-2 cytokines (interleukin (IL)-4, IL-5 and IL-13), each with several roles in the inflammation cascade. IL-4 and IL-13 cause B-cell class switching and IgE production, release of pro-inflammatory mediators, barrier disruption and tissue remodelling. In addition, IL-13 causes goblet-cell hyperplasia and mucus production. All three interleukins are involved in trafficking eosinophils to tissues, producing clinical symptoms characteristic of chronic inflammatory airway diseases. Asthma is a heterogenous disease; therefore, identification of biomarkers and early targeted treatment is critical for patients inadequately managed by inhaled corticosteroids and long-acting ß-agonists alone. The Global Initiative for Asthma guidelines recommend add-on biological (anti IgE, IL-5/5R, IL-4R) treatments for those not responding to standard of care. Targeted therapies, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab, were developed on current understanding of the pathophysiology of type 2 inflammation. These therapies offer hope for improved management of type 2 inflammatory airway diseases.

Prevalence of COPD in 6 Urban Clusters in Argentina: The EPOC.AR Study. / Prevalencia de enfermedad pulmonar obstructiva crónica en 6 aglomerados urbanos de Argentina: el estudio EPOC.AR.

INTRODUCTION: The prevalence of chronic obstructive pulmonary disease (COPD) has not been studied in Argentina. OBJECTIVES: To determine the prevalence and relevant clinical characteristics of COPD in a representative sample. MATERIAL AND METHODS: We performed a cross-sectional study in a population of adults aged ≥ 40 years randomly selected by cluster sampling in 6 urban locations. Subjects answered a structured survey and performed pre- and post-bronchodilator spirometry (PBD). COPD was defined as FEV1/FVC ratio < 0.7 predicted value. The total prevalence was estimated for each cluster with its 95% confidence interval (CI). RESULTS: Of 4,599 surveys and 3,999 spirometries, 3,469 were considered of adequate quality (86.8%) for our study. The prevalence of COPD was 14.5% (CI: 13.4-15.7). The distribution of COPD cases according to FEV1 (GOLD 2017) was stage 1: 38% (CI: 34-43); stage 2: 52% (CI: 47-56); stage 3: 10% (CI: 7-13); and stage 4: 1% (CI: 0-2), and according to the refined ABCD (GOLD 2017) assessment: A: 52% (CI: 47-56); B: 43% (CI: 39-48); C: 1% (CI: 0-2); D: 4% (CI: 2-6). The rate of underdiagnosis was 77.4% (CI 73.7-81.1%) and diagnostic error 60.7% (CI 55.1-66.3%). A significant association was found between COPD and age (OR 3.77 in individuals 50-59 years of age and 19.23 in those > 80 years), male gender (OR 1.62; CI 1.31-2), smoking (OR 1.95; CI 1.49-2.54), low socioeconomic status (OR 1.33; CI 1.02-1.73), and previous tuberculosis (OR 3.3; CI 1.43-7.62). CONCLUSIONS: We estimate that more than 2.3 million Argentineans have COPD, with high rates of underdiagnosis and diagnostic error.

Prevalencia de enfermedad pulmonar obstructiva crónica en 6 aglomerados urbanos de Argentina: el estudio EPOC. AR / Prevalence of COPD in 6 Urban Clusters in Argentina: The EPOC. AR Study

Introducción: La prevalencia de la enfermedad pulmonar obstructiva crónica (EPOC) en Argentina no había sido estudiada. Objetivos: Determinar la prevalencia de EPOC y rasgos clínicos relevantes en una muestra representativa. Material y métodos: Estudio de corte transversal en población ≥40 años en 6 aglomerados urbanos seleccionada aleatoriamente mediante muestreo por conglomerados. Se aplicó una encuesta estructurada y espirometrías pre y postbroncodilatador (PBD). Se definió EPOC en quienes presentaban un cociente FEV1/FVC PBD<0,7. Se estimó la prevalencia total y para cada aglomerado con intervalo de confianza del 95% (IC). Resultados: Se realizaron 4.599 encuestas y 3.999 espirometrías, de las cuales 3.469 fueron útiles (86,8%). La prevalencia de EPOC fue de 14,5% (IC: 13,4-15,7). La distribución de los casos compatibles con EPOC según FEV1 (GOLD-2017) fue: 1: 38% (IC: 34-43); 2: 52% (IC: 47-56); 3: 10% (IC: 7-13); y 4: 1% (IC: 0,-2) y de acuerdo al modelo combinado ABCD (GOLD 2017): A: 52% (IC: 47-56); B: 43% (IC: 39-48); C: 1% (IC: 0-2) y D: 4% (IC: 2-6). El subdiagnóstico fue del 77,4% (IC 73,7-81,1%) y el error diagnóstico de 60,7% (IC 55,1-66,3%). Encontramos asociación significativa de presencia de EPOC con edad (OR 3,77 en 50-59 años a 19,23 en >80 años), sexo masculino (OR: 1,62; IC: 1,31-2), tabaquismo (OR: 1,95; IC: 1,49-2,54), nivel socieconómico bajo (OR: 1,33; IC: 1,02-1,73) y antecedentes de tuberculosis (OR: 3,3; IC: 1,43-7,62). Conclusiones: Se estima que más de 2,3 millones de argentinos padecen EPOC con elevada tasa de subdiagnóstico y error diagnóstico

Introduction: The prevalence of chronic obstructive pulmonary disease (COPD) has not been studied in Argentina. Objectives: To determine the prevalence and relevant clinical characteristics of COPD in a representative sample. Material and methods: We performed a cross-sectional study in a population of adults aged ≥ 40 years randomly selected by cluster sampling in 6 urban locations. Subjects answered a structured survey and performed pre- and post-bronchodilator spirometry (PBD). COPD was defined as FEV1/FVC ratio < 0.7 predicted value. The total prevalence was estimated for each cluster with its 95% confidence interval (CI). Results: Of 4,599 surveys and 3,999 spirometries, 3,469 were considered of adequate quality (86.8%) for our study. The prevalence of COPD was 14.5% (CI: 13.4-15.7). The distribution of COPD cases according to FEV1 (GOLD 2017) was stage 1: 38% (CI: 34-43); stage 2: 52% (CI: 47-56); stage 3: 10% (CI: 7-13); and stage 4: 1% (CI: 0-2), and according to the refined ABCD (GOLD 2017) assessment: A: 52% (CI: 47-56); B: 43% (CI: 39-48); C: 1% (CI: 0-2); D: 4% (CI: 2-6). The rate of underdiagnosis was 77.4% (CI 73.7-81.1%) and diagnostic error 60.7% (CI 55.1-66.3%). A significant association was found between COPD and age (OR 3.77 in individuals 50-59 years of age and 19.23 in those > 80 years), male gender (OR 1.62; CI 1.31-2), smoking (OR 1.95; CI 1.49-2.54), low socioeconomic status (OR 1.33; CI 1.02-1.73), and previous tuberculosis (OR 3.3; CI 1.43-7.62). Conclusions: We estimate that more than 2.3 million Argentineans have COPD, with high rates of underdiagnosis and diagnostic error

Primary care physician perceptions on the diagnosis and management of chronic obstructive pulmonary disease in diverse regions of the world.

Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality. Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little information on the management of COPD patients in primary care. A web-based pilot survey was conducted to evaluate the primary care physician's, or general practitioner's (GP's), knowledge, understanding, and management of COPD in twelve territories across the Asia-Pacific region, Africa, eastern Europe, and Latin America, using a 10-minute questionnaire comprising 20 questions and translated into the native language of each participating territory. The questionnaire was administered to a total of 600 GPs (50 from each territory) involved in the management of COPD patients and all data were collated and analyzed by an independent health care research consultant. This survey demonstrated that the GPs' understanding of COPD was variable across the territories, with large numbers of GPs having very limited knowledge of COPD and its management. A consistent finding across all territories was the underutilization of spirometry (median 26%; range 10%-48%) and reliance on X-rays (median 14%; range 5%-22%) for COPD diagnosis, whereas overuse of blood tests (unspecified) was particularly high in Russia and South Africa. Similarly, there was considerable underrecognition of the importance of exacerbation history as an important factor of COPD and its initial management in most territories (median 4%; range 0%-22%). Management of COPD was well below guideline-recommended levels in most of the regions investigated. The findings of this survey suggest there is a need for more ongoing education and information, specifically directed towards GPs outside of Europe and North America, and that global COPD guidelines appear to have limited reach and application in most of the areas studied.

Formoterol for acute asthma in the emergency department: a systematic review with meta-analysis.

BACKGROUND: Although several published studies have suggested that formoterol fumarate could be equivalent to short-acting beta2-agonists (SABAs) for the treatment of asthma exacerbations, its role in acute asthma treatment remains undefined. OBJECTIVE: To evaluate the efficacy and safety of inhaled formoterol (compared with SABAs) for the emergency department treatment of patients with acute asthma. METHODS: Systematic searches were conducted in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manufactures' trial registers, without language restriction. The primary outcomes were spirometric measures. The secondary outcomes included final serum potassium level, heart rate, electrocardiographic QT interval corrected for heart rate, and total withdrawals. RESULTS: Nine randomized controlled trials (including 576 participants) were selected. No significant difference could be detected between formoterol and SABAs for any of the selected time points: at 30 to 40 minutes after the first administration of study drugs (standardized mean difference, -0.19; 95% confidence interval, -0.56 to 0.17; I2 = 75%), at the end of treatment (standardized mean difference, -0.25; 95% confidence interval, -0.72 to 0.13; I2 = 89%), and at 60 to 90 minutes after the last dose (standardized mean difference, -0.13; 95% confidence interval, -0.55 to 0.28; I2 = 80%). Similarly, there were no significant differences between formoterol and SABAs regarding final serum potassium level, heart rate, QT interval, hospitalization rate, and total withdrawals. CONCLUSIONS: This review suggests that high-dose formoterol administered via dry powder inhaler is well tolerated and provides rapid and effective bronchodilation, similar to high-dose salbutamol or terbutaline via metered-dose inhaler or nebulizer. Formoterol may be used in the treatment of acute asthma in the emergency department setting.