Racial/Ethnic-Specific Differences in the Effects of Inhaled Corticosteroid Use on Bronchodilator Response in Patients With Asthma.
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ABSTRACT:
SUBMITTER: Samedy-Bates LA
PROVIDER: S-EPMC6778006 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Racial/Ethnic-Specific Differences in the Effects of Inhaled Corticosteroid Use on Bronchodilator Response in Patients With Asthma.
Samedy-Bates Lesly-Anne LA Oh Sam S SS Nuckton Thomas J TJ Elhawary Jennifer R JR White Marquitta M Elliot Tyronda T Zeiger Andy M AM Eng Celeste C Salazar Sandra S LeNoir Michael A MA Meade Kelley K Farber Harold J HJ Serebrisky Denise D Brigino-Buenaventura Emerita E Rodriguez-Cintron William W Bibbins-Domingo Kirsten K Kumar Rajesh R Thyne Shannon S Borrell Luisa N LN Rodriguez-Santana José R JR Pino-Yanes Maria M Burchard Esteban G EG
Clinical pharmacology and therapeutics 20190723 5
American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association wa ...[more]
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Project description:ImportanceAsthma is a multifactorial disease composed of endotypes with varying risk profiles and outcomes. African Americans experience a high burden of asthma and of psychosocial stress, including racial discrimination. It is unknown which endotypes of asthma are vulnerable to racial/ethnic discrimination.ObjectiveWe examined the association between self-reported racial/ethnic discrimination and bronchodilator response (BDR) among African American youth with asthma ages 8 to 21 years (n = 576) and whether this association varies with tumor necrosis factor alpha (TNF-α) level.Materials and methodsSelf-reported racial/ethnic discrimination was assessed by a modified Experiences of Discrimination questionnaire as none or any. Using spirometry, BDR was specified as the mean percentage change in forced expiratory volume in one second before and after albuterol administration. TNF-α was specified as high/low levels based on our study population mean. Linear regression was used to examine the association between self-reported racial/ethnic discrimination and BDR adjusted for selected characteristics. An interaction term between TNF-α levels and self-reported racial/ethnic discrimination was tested in the final model.ResultsAlmost half of participants (48.8%) reported racial/ethnic discrimination. The mean percent BDR was higher among participants reporting racial/ethnic discrimination than among those who did not (10.8 versus 8.9, p = 0.006). After adjustment, participants reporting racial/ethnic discrimination had a 1.7 (95% CI: 0.36-3.03) higher BDR mean than those not reporting racial/ethnic discrimination. However, we found heterogeneity of this association according to TNF-α levels (p-interaction = 0.040): Among individuals with TNF-α high level only, we observed a 2.78 higher BDR mean among those reporting racial/ethnic discrimination compared with those not reporting racial/ethnic discrimination (95%CI: 0.79-4.77).ConclusionsWe found BDR to be increased in participants reporting racial/ethnic discrimination and this association was limited to African American youth with TNF-α high asthma, an endotype thought to be resistant to traditional asthma medications. These results support screening for racial/ethnic discrimination in those with asthma as it may reclassify disease pathogenesis.
| S-EPMC5469454 | biostudies-literature
Project description:BackgroundSingle nucleotide polymorphisms (SNPs) influence a patient's response to inhaled corticosteroids and β2-agonists, and the effect of treatment with inhaled corticosteroids is synergistic with the effect of β2-agonists. We hypothesized that use of inhaled corticosteroids could influence the effect of SNPs associated with a bronchodilator response.ObjectiveTo assess whether, among subjects with asthma, the association of SNPs with bronchodilator response is different between those treated with inhaled corticosteroids versus those on placebo.MethodsA genome-wide association analysis was conducted by using 581 white subjects from the Childhood Asthma Management Program. By using data for 449,540 SNPs, we conducted a gene by environment analysis in PLINK with inhaled corticosteroid treatment as the environmental exposure and bronchodilator response as the outcome measure. We attempted to replicate the top 12 SNPs in the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial.ResultsThe combined P value for the Childhood Asthma Management Program and Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial populations was 4.8 × 10(-8) for rs3752120, which is located in the zinc finger protein gene ZNF432 and has an unknown function.ConclusionsInhaled corticosteroids appear to modulate the association of bronchodilator response with variant(s) in the ZNF432 gene among adults and children with asthma.
| S-EPMC3943570 | biostudies-literature
Project description:Inhaled corticosteroids (ICS) suppress eosinophilic airway inflammation in asthma, but patients may not adhere to prescribed use. Mean adherence-averaging total doses taken over prescribed-fails to capture many aspects of adherence. Patients with difficult-to-treat asthma underwent electronic monitoring of ICS, with data collected over 50 days. These were used to calculate entropy (H) a measure of irregular inhaler use over this period, defined in terms of transitional probabilities between different levels of adherence, further partitioned into increasing (Hinc) or decreasing (Hdec) adherence. Mean adherence, time between actuations (Gapmax), and cumulative time- and dose-based variability (area-under-the-curve) were measured. Associations between adherence metrics and 6-month asthma status and attacks were assessed. Only H and Hdec were associated with poor baseline status and 6-month outcomes: H and Hdec correlated negatively with baseline quality of life (H:Spearman rS = - 0·330, p = 0·019, Hdec:rS = - 0·385, p = 0·006) and symptom control (H:rS = - 0·288, p = 0·041, Hdec: rS = - 0·351, p = 0·012). H was associated with subsequent asthma attacks requiring hospitalisation (Wilcoxon Z-statistic = - 2.34, p = 0·019), and Hdec with subsequent asthma attacks of other severities. Significant associations were maintained in multivariable analyses, except when adjusted for blood eosinophils. Entropy analysis may provide insight into adherence behavior, and guide assessment and improvement of adherence in uncontrolled asthma.
| S-EPMC8289909 | biostudies-literature
Project description:Inhaled corticosteroids (ICS) are the most commonly used controller medications prescribed for asthma. Two single-nucleotide polymorphisms (SNPs), rs1876828 in corticotrophin releasing hormone receptor 1 and rs37973 in GLCCI1, have previously been associated with corticosteroid efficacy. We studied data from four existing clinical trials of asthmatics, who received ICS and had lung function measured by forced expiratory volume in 1?s (FEV1) before and after the period of such treatment. We combined the two SNPs rs37973 and rs1876828 into a predictive test of FEV1 change using a Bayesian model, which identified patients with good or poor steroid response (highest or lowest quartile, respectively) with predictive performance of 65.7% (P=0.039 vs random) area under the receiver-operator characteristic curve in the training population and 65.9% (P=0.025 vs random) in the test population. These findings show that two genetic variants can be combined into a predictive test that achieves similar accuracy and superior replicability compared with single SNP predictors.
| S-EPMC3434304 | biostudies-literature
Project description:Metabolomic indicators of asthma treatment responses have yet to be identified. In this study, we aimed to uncover plasma metabolomic profiles associated with asthma exacerbations while on inhaled corticosteroid (ICS) treatment. We determined whether these profiles change with age from adolescence to adulthood. We utilized data from 170 individuals with asthma on ICS from the Mass General Brigham Biobank to identify plasma metabolites associated with asthma exacerbations while on ICS and examined potential effect modification of metabolite-exacerbation associations by age. We used liquid chromatography-high-resolution mass spectrometry-based metabolomic profiling. Sex-stratified analyses were also performed for the significant associations. The age range of the participating individuals was 13-43 years with a mean age of 33.5 years. Of the 783 endogenous metabolites tested, eight demonstrated significant associations with exacerbation after correction for multiple comparisons and adjusting for potential confounders (Bonferroni p value < 6.2 × 10-4). Potential effect modification by sex was detected for fatty acid metabolites, with males showing a greater reduction in their metabolite levels with ICS exacerbation. Thirty-eight metabolites showed suggestive interactions with age on exacerbation (nominal p-value < 0.05). Our findings demonstrate that plasma metabolomic profiles differ for individuals who experience asthma exacerbations while on ICS. The differentiating metabolites may serve as biomarkers of ICS response and may highlight metabolic pathways underlying ICS response variability.
| S-EPMC8622526 | biostudies-literature
Project description:RationaleSubstantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies.MethodsA genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed.Results10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10-6). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found.ConclusionsThe intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.
| S-EPMC8122045 | biostudies-literature
Project description:ImportanceDaily use of inhaled corticosteroids is a widely recommended treatment for mild persistent asthma in children. There is concern that, similar to systemic corticosteroids, inhaled corticosteroids may have adverse effects on bone health.ObjectiveTo determine whether there is an increased risk of bone fracture associated with inhaled corticosteroid use in children with asthma.Design, setting, and participantsIn this population-based nested case-control study, we used health administrative databases to identify a cohort of children aged 2 to 18 years with a physician diagnosis of asthma between April 1, 2003, and March 31, 2014, who were eligible for public drug coverage through the Ontario Drug Benefit Program (Ontario, Canada). We matched cases of first fracture after asthma diagnosis to fracture-free controls (ratio of 1 to 4) based on date of birth (within 1 year), sex, and age at asthma diagnosis (within 2 years). We used a 1-year lookback period to ascertain history of inhaled corticosteroid use. Multivariable conditional logistic regression was used to obtain an odds ratio (OR) with 95% confidence interval for fracture, comparing no inhaled corticosteroid use vs current, recent, and past use.ExposuresInhaled corticosteroid use during the child's 1-year lookback period, measured as current user if the prescription was filled less than 90 days prior to the index date, recent user (91-180 days), past user (181-365 days), or no use.Main outcomes and measuresFirst emergency department visit for fracture after asthma diagnosis, identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes.ResultsThis study included 19 420 children (61.0% male; largest proportion of children, 31.5%, were aged 6-9 years at their index date). The multivariable regression results did not show a significant association between first fracture after asthma diagnosis and current use (OR, 1.07; 95% CI, 0.97-1.17), recent use (OR, 0.96; 95% CI, 0.86-1.07), or past use (OR, 1.00; 95% CI, 0.91-1.11) of inhaled corticosteroids, compared with no use, while adjusting for sociodemographic factors and other medication use. However, use of systemic corticosteroids in the 1-year lookback period resulted in greater odds of fracture (OR, 1.17; 95% CI, 1.04-1.33).Conclusions and relevanceSystemic corticosteroids, but not inhaled corticosteroids, were significantly associated with increased odds of fracture in the pediatric asthma population.
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Project description:BackgroundInhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response.ObjectiveWe aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings.MethodsA meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10-6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations.ResultsA total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10-6 ). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10-3 ) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10-3 ). Additionally, the reported association of the L3MBTL4-ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified.Conclusions and clinical relevanceThis study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.
| S-EPMC7054824 | biostudies-literature
Project description:ObjectiveTo examine racial-ethnic differences in asthma controller medication use among insured U.S. children.Data sourcesLinked nationally representative data from the Medical Expenditure Panel Survey (2005-2008), the 2000 Decennial Census, and the National Health Interview Survey (2004-2007).Study designThe study quantifies the portion of racial-ethnic differences in children's controller use that are attributable to differences in need, enabling and predisposing characteristics.Principal findingsNon-Hispanic black and Hispanic children were less likely to use controllers than non-Hispanic white children. Blinder-Oaxaca decomposition results indicated that observable characteristics explain less than 40 percent of the overall differential in controller use between non-Hispanic whites and non-Hispanic blacks. In contrast, observable characteristics explain more than two-thirds (71.3 percent) of the overall non-Hispanic white-Hispanic differential in controller use. For non-Hispanic blacks, a majority of the explained differential in controller use were attributed to enabling characteristics. For Hispanics, a significant portion of the explained differential in controller use was attributed to predisposing characteristics. In addition, a larger portion of the differential in controller use was explained by observable characteristics for publicly insured non-Hispanic black and Hispanic children.ConclusionsThe large observed differences in controller use highlight the continuing challenges of ensuring that all U.S. children have access to quality asthma care.
| S-EPMC3876393 | biostudies-literature
Project description:PurposePrevious work has shown that asthma-related emergency department (ED) use is greatest among Black and Latine populations, but it is unknown whether health care use for exacerbations differs across settings (outpatient, ED, inpatient) and correlates with use of routine outpatient services. We aimed to measure disparities by race, ethnicity, and language in pediatric acute asthma care using data from US primary care community health centers.MethodsIn an observational study using electronic health records from community health centers in 18 states, we compared non-Hispanic Black, English-preferring Latine, Spanish-preferring Latine, and non-Hispanic White children aged 3 to 17 years on visits for clinic-coded asthma exacerbations (2012-2018). We further evaluated asthma-related ED use and inpatient admissions in a subsample of Oregon-Medicaid recipients. Covariate-adjusted odds ratios (ORs) and rate ratios (RRs) were derived using logistic or negative binomial regression analysis with generalized estimating equations.ResultsAmong 41,276 children with asthma, Spanish-preferring Latine children had higher odds of clinic visits for asthma exacerbation than non-Hispanic White peers (OR = 1.10; 95% CI, 1.02-1.18). Among the subsample of 6,555 children insured under Oregon-Medicaid, non-Hispanic Black children had higher odds and rates of asthma-related ED use than non-Hispanic White peers (OR = 1.40; 95% CI, 1.04-1.89 and RR = 1.49; 95% CI, 1.09-2.04, respectively). We observed no differences between groups in asthma-related inpatient admissions.ConclusionsThis study is the first to show that patterns of clinic and ED acute-care use differ for non-Hispanic Black and Spanish-preferring Latine children when compared with non-Hispanic White peers. Non-Hispanic Black children had lower use of clinics, whereas Spanish-preferring Latine children had higher use, including for acute exacerbations. These patterns of clinic use were accompanied by higher ED use among Black children. Ensuring adequate care in clinics may be important in mitigating disparities in asthma outcomes.VISUAL ABSTRACT.
| S-EPMC8959738 | biostudies-literature