ABSTRACT
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.
ABSTRACT
Asthma affects a large number of people living in the Americas, a vast and diverse geographic region comprising 35 nations in the Caribbean and North, Central, and South America. The marked variability in the prevalence, morbidity, and mortality from asthma across and within nations in the Americas offers a unique opportunity to improve our understanding of the risk factors and management of asthma phenotypes and endotypes in children and adults. Moreover, a better assessment of the causes and treatment of asthma in less economically developed regions in the Americas would help diagnose and treat individuals migrating from those areas to Canada and the United States. In this focused review, we first assess the epidemiology of asthma, review known and potential risk factors, and examine commonalities and differences in asthma management across the Americas. We then discuss future directions in research and health policies to improve the prevention, diagnosis, and management of pediatric and adult asthma in the Americas, including standardized and periodic assessment of asthma burden across the region; large-scale longitudinal studies including omics and comprehensive environmental data on racially and ethnically diverse populations; and dissemination and implementation of guidelines for asthma management across the spectrum of disease severity. New initiatives should recognize differences in socioeconomic development and health care systems across the region while paying particular attention to novel or more impactful risk factors for asthma in the Americas, including indoor pollutants such as biomass fuel, tobacco use, infectious agents and the microbiome, and psychosocial stressor and chronic stress.
Subject(s)
Asthma , Americas , Asthma/epidemiology , Asthma/etiology , Asthma/therapy , Brazil , Canada/epidemiology , Child , Humans , Latin America , United StatesABSTRACT
El síndrome de Kartagener es una enfermedad autosómica recesiva poco frecuente (uno de cada 32.000 nacimientos), caracterizada por la tríada de bronquiectasias, sinusitis crónica y situs tnversus. El artículo presenta el caso de un hombre de veinticuatro años de edad con dicha enfermedad, a partir del cual se revisa su fisiopatología, las estrategias diagnósticas y terapéuticas y su pronóstico.
Kartagener syndrome us a rare autosomal recessive disease (one ¿n every 32,000 births), oharactenzed by a triad of bronchiectasis, chroníc sinusitis and situs mversus. We present the case of a 24'veai'old male with this disease and we review the pathophysiology, prognosis as well as the main diagnostic and therapeutic strategies.
