Exploring Factors Underlying Poorly-Controlled Asthma in Adults by Integrating Phenotypes and Genotypes Associated with Obesity and Asthma: A Case-Control Study

Abstract

Background Uncontrolled asthma in adults leads to poor clinical outcome, while the clinical heterogeneity of phenotypes interferes the applicable genetic determinants. This study aimed to identify phenotypes and genetic impact on poorly-controlled asthma to optimize individualized treatment strategies. Methods This propensity score-matched case-control study included 340 and 1020 asthmatics with poorly-controlled asthma and well-controlled asthma, respectively. Data were obtained from the 2008–2015 Taiwan Biobank Database and linked to the National Health Insurance Research Database. All asthmatics were aged ≥30 years, without cancer history, and each completed a questionnaire, physical examination, and genome-wide single nucleotide polymorphisms (SNPs). Multivariate adjusted odds ratios (ORs) for genetic risk scores were calculated using conditional logistic regression, stratified by age and sex. A model integrating obesity- and asthma-associated phenotypes and genotypes was applied for poorly-controlled asthma risk prediction. Results General obesity with body mass index (BMI) ≥27 kg/m 2 (OR:1.49, 95% confidence interval (CI) 1.09–2.03), central obesity with waist-to-height ratio (WHtR) ≥0.5 (OR:1.62, 95% CI 1.22–2.15), and parental history of asthma (OR:1.65, and 1.68; for BMI model and WHtR model, respectively) were significantly associated with poorly-controlled asthma in adults, and the combination effect of both obesity phenotypes was 1.66 (95% CI 1.17–2.35). A total of 16 obesity-associated SNPs and 9 asthma-associated SNPs were converted into genetic scores, and the aforementioned phenotypes were incorporated into the risk prediction model for poorly-controlled asthma, with an area under curve 0.72 in the receiver operating characteristic curve. The potential biological functions of genes are involved in immunity pathways. Conclusion The prediction model integrating obesity-asthma phenotypes and genotypes for poorly-controlled asthma can facilitate the prediction of high-risk asthma and provide potential targets for novel treatment.

Exploring the association between asthma and chronic comorbidities: impact on clinical outcomes

“…The bidirectional relationship is evident not only in adults but also in childhood and adolescence, indicating that the development of asthma is influenced by childhood obesity (172,173), creating a complex interplay between these health conditions. Individuals who simultaneously suffer from asthma and obesity are more prone to experiencing poorly controlled asthma symptoms (86,(174)(175)(176) and lower quality of life (176). Furthermore, individuals in this context demonstrate reduced responsiveness to asthma medications, as evidenced by a higher likelihood of utilizing asthma medications such as short-acting β2-agonists, frequently dispensed and OCS use (177), increased doses of ICS (178,179), a heightened risk of exacerbations (14,180), increased emergency room visits and a higher likelihood of hospitalization, including extended hospital length of stay and a higher risk of mechanical ventilation (68, 87, 177, 181).…”