Genetic Determinants of Poor Response to Treatment in Severe Asthma

Figueiredo, Ricardo G.; Costa, Rosane Dias; Figueiredo, Camila A.; Cruz, Ãlvaro A.

doi:10.3390/ijms22084251

Cited by 7 publications

(2 citation statements)

References 57 publications

(80 reference statements)

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“…In contrast to the reported SNPs associated with poorly-controlled asthma in previous studies, 38 we obtained 16 obesity-associated SNPs from a matched-case control study in an Asian population, which might be attributed to ethnic differences, and we did not access pharmacogenomic analysis for therapeutic responses to ICS or bronchodilators. The current predictive biological function of SNPs genes reflects the possible obesity-asthma shared genetic effects, involving the pro-inflammatory effects of adipose tissue fetal programming and epigenetics.…”

Section: Discussionmentioning

confidence: 99%

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

Huang¹,

Huang²,

Chu³

et al. 2023

JAA

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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.

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Section: Discussionmentioning

confidence: 99%

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

Huang¹,

Huang²,

Chu³

et al. 2023

JAA

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“…Additionally, accurate interpretation of lung function tests can be challenging because physiologic age-related respiratory changes mimic obstructive functional patterns and neurocognitive function could eventually impair the ability to perform spirometry in some patients [ 23 ]. Furthermore, epigenetic mechanisms mediate nonstructural changes in gene expression that are regulated by DNA methylation patterns, microRNA expression and histone modifications have been described with advancing age [ 24 ]. It is possible that some of the changes noted above might be associated with airway remodelling and poor treatment response.…”

Section: Introductionmentioning

confidence: 99%

Impact of frailty in elderly patients with moderate to severe asthma

et al. 2022

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Frailty assessment has been identified as critical approach in chronic respiratory diseases with substantial impact in the health status and functionality in later life. Aging modifies the immune response leading to a chronic pro-inflammatory state and increased susceptibility to airway infections. Since epigenetic changes, airway epithelium dysfunction and inflammatory cytokine activity seem to be more pronounced in the immunosenescence, elderly asthmatics are at higher risk of poor clinical outcomes. Therefore, we hypothesize that frailty would be associated with the degree of asthma control in elderly patients with moderate to severe asthma. The aims of this study are to investigate association between frailty and asthma control in patients over 60 years old to estimate the prevalence of frailty in this study population. We plan to conduct a cross-sectional study with at least 120 patients above 60 years old with diagnostic of moderate to severe asthma according to Global Initiative for Asthma (GINA) guidelines, treated at a referral outpatient clinic. We defined asthma control by the six-domain Asthma Control Questionnaire (ACQ-6) and frailty phenotype in accordance with Fried scale and visual scale of frailty (VS-Frailty). We hope to analyze the multidimensional relationships between frailty and asthma and contribute to innovative therapeutic plans in geriatric asthma.

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