RESUMO
BACKGROUND: Asthma prevalence is 339 million globally. 'Severe asthma' (SA) comprises subjects with uncontrolled asthma despite proper management. OBJECTIVES: To compare asthma from diverse ethnicities and environments. METHODS: A cross-sectional analysis of two adult cohorts, a Brazilian (ProAR) and a European (U-BIOPRED). U-BIOPRED comprised of 311 non-smoking with Severe Asthma (SAn), 110 smokers or ex-smokers with SA (SAs) and 88 mild to moderate asthmatics (MMA) while ProAR included 544 SA and 452 MMA. Although these projects were independent, there were similarities in objectives and methodology, with ProAR adopting operating procedures of U-BIOPRED. RESULTS: Among SA subjects, age, weight, proportion of former smokers and FEV1 pre-bronchodilator were similar. The proportion of SA with a positive skin prick tests (SPT) to aeroallergens, the scores of sino-nasal symptoms and quality of life were comparable. In addition, blood eosinophil counts (EOS) and the % of subjects with EOSâ¯>â¯300â¯cells/µl were not different. The Europeans with SA however, were more severe with a greater proportion of continuous oral corticosteroids (OCS), worse symptoms and more frequent exacerbations. FEV1/FVC pre- and post-bronchodilator were lower among the Europeans. The MMA cohorts were less comparable in control and treatment, but similar in the proportion of allergic rhinitis, gastroesophageal reflux disease and EOS >3%. CONCLUSIONS: ProAR and U-BIOPRED cohorts, with varying severity, ethnicity and environment have similarities, which provide the basis for global external validation of asthma phenotypes. This should stimulate collaboration between asthma consortia with the aim of understanding SA, which will lead to better management.
Assuntos
Asma , Classe Social , Adulto , Asma/diagnóstico , Asma/etnologia , Asma/fisiopatologia , Brasil , Estudos de Coortes , Estudos Transversais , Europa (Continente) , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.
Assuntos
Matriz Extracelular/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Adulto , Idoso , Biglicano/metabolismo , Estudos de Casos e Controles , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Colágeno/metabolismo , Decorina/metabolismo , Feminino , Fibronectinas/metabolismo , Humanos , Imuno-Histoquímica/métodos , Sulfato de Queratano/metabolismo , Lumicana , Pulmão/metabolismo , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Fumar/efeitos adversos , Tenascina/metabolismoRESUMO
Asthma is characterized by variable degrees of chronic inflammation and structural alterations in the airways. The most prominent abnormalities include epithelial denudation, goblet cell metaplasia, subepithelial thickening, increased airway smooth muscle mass, bronchial gland enlargement, angiogenesis, and alterations in extracellular matrix components, involving large and small airways. Chronic inflammation is thought to initiate and perpetuate cycles of tissue injury and repair in asthma, although remodeling may also occur in parallel with inflammation. In the absence of definite evidence on how different remodeling features affect lung function in asthma, the working hypothesis should be that structural alterations can lead to the development of persistent airway hyperresponsiveness and fixed airway obstruction. It is still unanswered whether and when to begin treating patients with asthma to prevent or reverse deleterious remodeling, which components of remodeling to target, and how to monitor remodeling. Consequently, efforts are being made to understand better the effects of conventional anti-inflammatory therapies, such as glucocorticosteroids, on airway structural changes. Animal models, in vitro studies, and some clinical studies have advanced present knowledge on the cellular and molecular pathways involved in airway remodeling. This has encouraged the development of biologicals aimed to target various components of airway remodeling. Progress in this area requires the explicit linking of modern structure-function analysis with innovative biopharmaceutical approaches.