Asthma inflammatory phenotypes on four continents: most asthma is non-eosinophilic

Abstract

Background Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). Methods We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016–20. All centres studied children and adolescents (age range 8–20 years), except the UK centre which involved 26–27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. Results Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37–2.94) with lower odds in the LMICs: Brazil (0.73, 0.42–1.27), Ecuador (0.40, 0.24–0.66) and Uganda (0.62, 0.37–1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. Conclusions This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

“…Asthma is a heterogeneous pulmonary disease comprised of several different endotypes which depict various pathways of the inflammatory and immune response [38]. In general, most of the current research concentrates on eosinophilic airway inflammation, with poor knowledge of principal causes and mechanisms related to non-eosinophilic phenotypes, which are less receptive to inhaled corticosteroids (ICS), the current treatment of choice for asthma [39][40][41]. In the present study, we demonstrated that sphingolipid metabolism is abnormal in asthmatic patients, whereas sphingosine metabolites, altered largely in the untargeted lipidomics analysis, failed to distinguish between the different endotypes of asthma both in plasma and induced sputum in the targeted lipidomics analysis.…”

Time‐dependent gene–environment interactions are essential drivers of asthma initiation and persistence

“…However, it should be noted that asthma is not uniform across the globe and failure to validate the importance of a gene across ethnic groups may reflect the diversity of asthma, and not a false positive finding in a single population. 103 Current understanding of GWAS is that to detect subtle effects of common genetic variants that have previously gone undetected, it is necessary to use larger sample sizes. In recent years, there has been a significant increase in the establishment of international consortiums, with collaboration playing a central role in conducting research.…”

“…In the field of epidemiology, it is commonly accepted that when several investigative teams, in various populations, using diverse designs and methods, consistently observe relationships between covariates, it is considered as proof that the association is not a result of chance or error. However, it should be noted that asthma is not uniform across the globe and failure to validate the importance of a gene across ethnic groups may reflect the diversity of asthma, and not a false positive finding in a single population 103 . Current understanding of GWAS is that to detect subtle effects of common genetic variants that have previously gone undetected, it is necessary to use larger sample sizes.…”

Design and Development of an IoT-based Pulmonary Function and Oxygen Saturation Measurement Device

“…The number of people with bronchial asthma continued to increase by 0.5% in 2018. This disease causes narrowing of the airways due to hyperactivity, which leads to disrupted breathing patterns and decreased oxygen levels [2] [3]. Individuals with asthma experience increased resistance in the smaller airways to expiratory airflow, thus requiring more time to exhale their entire vital capacity (FVC) [4] [5].…”