Observational study of inhaled corticosteroid treatment for improved expiratory variability index in steroid-naive asthmatic children.
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ABSTRACT:
SUBMITTER: Burman J
PROVIDER: S-EPMC8819251 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Observational study of inhaled corticosteroid treatment for improved expiratory variability index in steroid-naïve asthmatic children.
Burman Janne J Malmberg Pekka P Seppä Ville-Pekka VP Jartti Tuomas T Remes Sami S Mickelsson Ove O Pelkonen Anna S AS Mäkelä Mika J MJ
ERJ open research 20210207 1
<b>Inhaled corticosteroid treatment improves expiratory variability index in steroid-naïve asthmatic children aged 4-7 years</b> https://bit.ly/3n4vBT3. ...[more]
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Project description:BackgroundAdrenal suppression is a side effect of long-term use of inhaled corticosteroids (ICS). Hair cortisol concentration (HCC) measurement is a noninvasive tool for measuring adrenal function that may be useful for asthmatic patients who are on long-term ICS treatment. The aim of this study was to compare HCC between children with and without asthma and to explore the association between HCC and ICS dose in asthmatic children.MethodsA cross-sectional observational study in subjects with or without asthma (n = 72 and 226, respectively, age 6-21 years). Hair samples were obtained from the posterior vertex for each subject and data on medication use were collected using questionnaires. HCC was analyzed by liquid chromatography-mass spectrometry in the most proximal 3 cm of hair.ResultsMedian HCC was significantly lower in subjects with asthma than in subjects without asthma: 1.83 pg/mg and 2.39 pg/mg, respectively (P value after adjustment for age, sex, and body mass index: .036). Median HCC was 1.98 pg/mg in asthmatics using no ICS, 1.84 pg/mg in those using a low dose, 1.75 pg/mg in those on a medium dose, and 1.46 in those using a high ICS dose (P = .54).ConclusionWe observed a significantly lower HCC in asthmatics than in healthy controls and a nonsignificant trend of lower HCC with increasing ICS dose. Whether HCC measurement may be used to detect individuals at risk for hypocortisolism and may be useful to monitor adrenal function in asthmatic children using ICS needs to be further investigated.
| S-EPMC7003950 | biostudies-literature
Project description:Background: The impact of inhaled corticosteroid (ICS) in the interaction between asthma, COVID-19 and COVID-19 associated outcomes remain largely unknown. The objective of this study is to investigate the risk of COVID-19 and its related outcomes in patients with asthma using and not using inhaled corticosteroid (ICS). Methods: We used the TriNetX Network, a global federated network that comprises 55 healthcare organizations (HCO) in the United States, to conduct a retrospective cohort study. Patients with a diagnosis of asthma with and without ICS between January 2020 and December 2022 were included. Propensity score matching was used to match the case cohorts. Risks of COVID-19 incidence and medical utilizations were evaluated. Results: Out of 64,587 asthmatic patients with ICS and without ICS, asthmatic patients with ICS had a higher incidence of COVID-19 (Hazard ratio, HR: 1.383, 95% confidence interval, CI: 1.330-1.437). On the contrary, asthmatic patients with ICS revealed a significantly lower risk of hospitalization (HR: 0.664, 95% CI: 0.647-0.681), emergency department visits (HR: 0.774, 95% CI: 0.755-0.793), and mortality (HR:0.834, 95% CI:0.740-0.939). In addition, subgroup or sensitivity analyses were also conducted to examine the result of different vaccination status, disease severity, or COVID-19 virus variants. Conclusion: For asthmatic patients using ICS, risk of COVID-19 was significantly higher than non-users. The observed association could provide potential guidance for primary care physicians regarding the risk of COVID-19 in asthmatic patients.
| S-EPMC10646298 | biostudies-literature
Project description:Background and purposeInhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking ICS, we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma.Experimental approachBronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-PCR for the corticosteroid-inducible genes (official gene symbols with aliases in parentheses): TSC22D3 [glucocorticoid-induced leucine zipper (GILZ)], dual-specificity phosphatase-1 (MAPK phosphatase-1), both anti-inflammatory effectors, and FKBP5 [FK506-binding protein 51 (FKBP51)], a regulator of GR function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis.Key resultsCompared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects.Conclusions and implicationsExpression of the corticosteroid-induced genes, GILZ and FKBP51, is up-regulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease GR-dependent transcription may correspondingly affect corticosteroid efficacy.
| S-EPMC3372826 | biostudies-literature
Project description:BackgroundInterleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source.MethodsBronchial biopsies from 114 patients with mild-to-moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17.ResultsIn non-ICS users, nonatopic asthmatics had more IL-17+ cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17+ cells, independent of smoking. The number of IL-17+ cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17-0.35) and eosinophils (B: 0.18, 95% CI: 0.07-0.29). The majority of IL-17+ cells were neutrophils, as confirmed by double immunostaining.ConclusionsWe show for the first time that atopy and ICS use are associated with lower numbers of IL-17+ cells in asthmatic airways. Importantly, IL-17+ cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17.
| S-EPMC4994949 | biostudies-literature
Project description:BackgroundInhaled corticosteroids (ICSs) are considered first-line treatment for persistent asthma, yet there is significant variability in treatment response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids.ObjectiveWe sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment.MethodsStudy participants with asthma were drawn from the following multiethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study; the Study of African Americans, Asthma, Genes & Environments (SAGE); and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). We screened GALA study participants for genetic variants that modified the relationship between ICS use and bronchodilator response. We then replicated our findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants treated with ICSs for 6 weeks, we examined whether a DUSP1 polymorphism was associated with changes in FEV(1) and self-reported asthma control.ResultsThe DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA study participants. This interaction was also seen for rs881152 among SAPPHIRE but not SAGE participants. Among the group of SAPPHIRE participants prospectively treated with ICSs for 6 weeks, rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV(1).ConclusionDUSP1 polymorphisms were associated with clinical response to ICS therapy and therefore might be useful in the future to identify asthmatic patients more likely to respond to this controller treatment.
| S-EPMC2943151 | biostudies-literature
Project description:BackgroundInhaled corticosteroids (ICSs) are the preferred treatment for achieving asthma control. However, little is known regarding the factors contributing to treatment response and whether treatment response differs by population group.ObjectiveWe sought to assess behavioral, sociodemographic, and genetic factors related to ICS response among African American and European American subjects with asthma.MethodsStudy participants were part of the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). The analytic sample included asthmatic subjects aged 12 to 56 years with greater than 12% bronchodilator reversibility and percent predicted FEV1 of between 40% and 90%. Participants received 6 weeks of inhaled beclomethasone dipropionate. The primary measure of ICS response was a change in Asthma Control Test (ACT) score; the secondary measure was a change in prebronchodilator FEV1. Adherence was measured with electronic monitors. Genetic ancestry was estimated for African American participants by using genome-wide genotype data.ResultsThere were 339 study participants; 242 self-identified as African American and 97 as European American. Baseline ACT score, percent predicted FEV1, degree of bronchodilator response, and ICS adherence were significantly associated with ICS response. A baseline ACT score of 19 or less was useful in identifying those who would respond, as evidenced by the significant dose-response relationship with ICS adherence. Neither self-reported race-ethnicity among all participants nor proportion of African ancestry among African American participants was associated with ICS responsiveness.ConclusionsOur findings suggest that baseline lung function measures and self-reported asthma control predict ICS response, whereas self-reported race-ethnicity and genetic ancestry do not.
| S-EPMC5313277 | biostudies-literature
Project description:IntroductionSputum and blood eosinophil counts have attracted attention as potential biomarkers in chronic obstructive pulmonary disease (COPD). One question regarding the use of blood eosinophils as a biomarker in COPD is whether their levels are affected by the use of inhaled corticosteroids (ICS), which are commonly prescribed for COPD.MethodsWe performed a retrospective analysis of peripheral blood leucocytes from a previously completed clinical trial that examined effects of ICS in steroid-naïve patients with COPD.Results and conclusionThe data show that the ICS-containing treatment arms (containing fluticasone propionate) had a small effect on peripheral blood eosinophils in steroid-naïve patients with COPD.Trial registration numberNCT00358358; Post-results.
| S-EPMC5020662 | biostudies-literature
Project description:BackgroundAsthma is a common chronic lung disease in children. We aimed to determine the associations between stress-induced phosphoprotein 1 (STIP1) and glucocorticoid-induced transcript 1 (GLCCI1) polymorphisms and susceptibility of childhood asthma and inhaled corticosteroid (ICS) response in children.MethodsA total of 263 Chinese Han asthmatic children were recruited from the Xiangya Hospital, Central South University. Pulmonary function tests were performed before the treatment and 3 months after the treatment. One hundred fifty non-asthmatic children were recruited. Each participant's DNA was extracted from the peripheral blood and Method of MassARRAY was used to genotype the single-nucleotide polymorphisms (SNPs).ResultsSTIP1 rs2236647 wild-type homozygote (CC) was associated with increased asthma risk of children (OR = 1.858, 95% CI:1.205-2.864), but not associated with the ICS response. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms were not associated with the risk of childhood asthma. However, rs37969 mutant genotypes (TT/GT) were significantly associated with less improvement in PD20 (p = 0.028). We also found significant associations between rs37969, rs37972 and rs37973 mutant genotypes and less improvement in maximal midexpiratory flow (MMEF) after ICS treatment for 3 months (p = 0.036, p = 0.010 and p = 0.003, respectively).ConclusionsSTIP1 rs2236647 was associated with asthma risk of children and GLCCI1 rs37969 mutant genotypes were associated with less improvement in airway hyper-responsiveness. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms might be associated with pulmonary function in childhood asthma patients after ICS treatment.
| S-EPMC7677774 | biostudies-literature
Project description:BackgroundInhaled corticosteroids are the most commonly used controller therapies for asthma, producing treatment responses in 6 clinical phenotypes: lung function, bronchodilator response, airway responsiveness, symptoms, need for oral steroids and frequency of emergency department visits and hospitalizations. We hypothesize that treatment response in all of these phenotypes is modulated by a single quantitative corticosteroid responsiveness endophenotype.ObjectiveWe sought to develop a composite phenotype that combines multiple clinical phenotypes to measure corticosteroid responsiveness with high accuracy, stability across populations, and robustness to missing data.MethodsWe used principal component analysis to determine a composite corticosteroid responsiveness phenotype that we tested in 4 replication populations. We evaluated the relative accuracy with which the composite and clinical phenotypes measure the endophenotype using treatment effect area under the receiver operating characteristic curve (AUC).ResultsIn the study population the composite phenotype measured the endophenotype with an AUC of 0.74, significantly exceeding the AUCs of the 6 individual clinical phenotypes, which ranged from 0.56 (P < .001) to 0.67 (P = .015). In 4 replication populations with a total of 22 clinical phenotypes available, the composite phenotype AUC ranged from 0.69 to 0.73, significantly exceeded the AUCs of 14 phenotypes, and was not significantly exceeded by any single phenotype.ConclusionThe composite phenotype measured the endophenotype with higher accuracy, higher stability across populations, and higher robustness to missing data than any clinical phenotype. This should provide the capability to model corticosteroid pharmacologic response and resistance with increased accuracy and reproducibility.
| S-EPMC4530065 | biostudies-literature
Project description:BackgroundCorticosteroids exert their anti-inflammatory action by binding and activating the intracellular glucocorticoid receptor heterocomplex.ObjectiveWe sought to evaluate the genes HSPCB, HSPCA, STIP1, HSPA8, DNAJB1, PTGES3, FKBP5, and FKBP4 on corticosteroid response.MethodsWhite asthmatic subjects (n = 382) randomized to once-daily flunisolide or conventional inhaled corticosteroid therapy were genotyped. Outcome measures were baseline FEV1, percent predicted FEV1, and percent change in FEV1 after corticosteroid treatment. Multivariable analyses adjusted for age, sex, and height were performed, fitting the most appropriate genetic model based on the quantitative mean derived from ANOVA models to determine whether there was an independent effect of polymorphisms on change in FEV1 independent of baseline level.ResultsPositive recessive model correlations for STIP1 single nucleotide polymorphisms were observed for baseline FEV1 (rs4980524, P = .009; rs6591838, P = .0045; rs2236647, P = .002; and rs2236648; P = .013), baseline percent predicted FEV1 (rs4980524, P = .002; rs6591838, P = .017; rs2236647, P = .003; and rs2236648, P = .008), and percent change in FEV1 at 4 weeks (rs4980524, P = .044; rs6591838, P = .016; and rs2236647, P = .01) and 8 weeks (rs4980524, P = .044; rs6591838, P = .016; and rs2236647; P = .01) or therapy. Haplotypic associations were observed for baseline FEV1 and percent change in FEV1 at 4 weeks of therapy (P = .05 and P = .01, respectively). Significant trends toward association were observed for baseline percent predicted FEV1 and percent change in FEV1 at 8 weeks of therapy. Positive correlations between haplotypes and percent change in FEV1 were also observed.ConclusionsSTIP1 genetic variations might play a role in regulating corticosteroid response in asthmatic subjects with reduced lung function. Replication in a second asthmatic population is required to confirm these observations.
| S-EPMC4317788 | biostudies-literature