Hospital admission associates with higher total IgE level in pediatric patients with asthma.
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ABSTRACT:
SUBMITTER: Sherenian MG
PROVIDER: S-EPMC4500743 | biostudies-literature | 2015 Jul-Aug
REPOSITORIES: biostudies-literature
Publications
Hospital admission associates with higher total IgE level in pediatric patients with asthma.
Sherenian Michael G MG Wang Yu Y Fulkerson Patricia C PC
The journal of allergy and clinical immunology. In practice 20150225 4
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Project description:What is already known about this subjectOmalizumab is a humanized anti-IgE monoclonal antibody that binds and captures circulating IgE, preventing interaction with receptors on mast cells and basophils, thereby interrupting the allergic cascade. It has a well-characterized efficacy and safety profile in patients with asthma. While omalizumab is known to reduce serum free IgE concentrations, effects on total IgE and IgE production are less well characterized.What this study adds(i) Confirmation of prior hypotheses that IgE production can decrease with time when patients are given anti-IgE therapy; (ii) guidance on a biomarker, total IgE, which can be used to ascertain whether individual patients experience a change in their IgE production; and (iii) a way to assess whether patients' IgE production has been sufficiently down-regulated such that they may consider stopping anti-IgE therapy.AimTo determine whether excessive IgE production by patients with atopic allergic asthma decreases with omalizumab therapy.MethodsOmalizumab, free and total IgE data were obtained from an epidemiological study and six randomized, double-blind, placebo-controlled trials in patients with allergic asthma. The binding between omalizumab and IgE together with the production and elimination of IgE were modelled as previously, except that, in order to explain why total IgE was decreasing over a period of 5 years, the expression of IgE was allowed to change.ResultsThe prior constant IgE production model failed to converge on the data once long-term observations were included, whereas models allowing IgE production to decrease fitted. A feedback model indicated that, on average, IgE production decreased by 54% per year. This model was further developed with covariate searches indicating clinically small but statistically significant effects of age, gender, body mass index and race on some parameters. Model predictions were checked internally and externally against 3-5 year data from paediatric and adult atopic asthmatic patients and externally against extensive total IgE data from a long-duration (>1 year) phase 1 study which was not used in the model building.ConclusionsA pharmacokinetic-pharmacodynamic model incorporating omalizumab-IgE binding and feedback for control of IgE production indicates that omalizumab reduces production of IgE. This raises the possibility that indefinite treatment may not be required, only for perhaps a few years. After the initial accumulation, total IgE should provide a means to monitor IgE production and guide individual treatment decisions.
| S-EPMC3162660 | biostudies-literature
Project description:BackgroundOmalizumab (OMA) is an effective anti-immunoglobulin E (IgE) treatment for moderate-to-severe asthma. However, predicting an individual's response is difficult. Monitoring change of total serum IgE may be useful for predicting the response to OMA. The purpose of this study was to determine if measuring the change in total IgE level could predict the response to OMA in patients with moderate-to-severe asthma.MethodsThis study included 25 patients (11 females and 14 males; mean age =46.1 years; mean pre-bronchodilator FEV1% =67.8%) with moderate-to-severe asthma. All patients were treated with OMA, and total IgE serum concentrations were measured at baseline before treatment (median baseline total serum IgE =210 IU/mL) and at 4 weeks after beginning treatment. Patients were divided into responders (i.e., excellent or good response) and non-responders (i.e., moderate or poor response) using the global treatment effectiveness (GETE) response method after 16 weeks of treatment. The characteristics of responders and non-responders were compared, and receiver operating characteristic (ROC) curve analysis was used to determine the ability of change in IgE level to predict treatment response.ResultsThere were 20 responders (80%) and 5 non-responders (20%), and responders demonstrated better improvements of asthma control test (ACT) and asthma control questionnaire (ACQ) scores, and reduction of oral corticosteroid use as compared with non-responders. Twenty-one patients had a total serum IgE 4-week-to-baseline ratio ≥2, and 20 of the patients responded to OMA. The area under the ROC curve (AUC) for baseline IgE level for predicting treatment response was 0.53 (95% CI: 0.18-0.88), and that of the week 4 IgE level was 0.69 (95% CI: 0.42-0.96). Using a cutoff value of 2, the 4-week: baseline IgE ratio achieved the highest AUC of 0.87 (95% CI: 0.64-1), with a sensitivity and specificity of 100% and 80%, respectively, for predicting treatment response.ConclusionsA total week 4 serum IgE level:baseline level ratio ≥2 can predict the response to OMA in patients with moderate-to-severe asthma after 16 weeks of treatment with high likelihood. Monitoring changes of total IgE level in asthma patients treated OMA may be useful for predicting clinical response.
| S-EPMC7797858 | biostudies-literature
Project description:BackgroundEmerging data suggest that innate immunity may play a role in asthma, particularly the toll-like receptors (TLRs). Some studies pointed to an involvement of TLRs 2 and 4 in the pathogenesis of allergic asthma, and other studies related TLRs to IgE. However, there are not any studies that have comprehensively evaluated the expression of TLRs 2 and 4 in inflammatory cells, in peripheral blood and induced sputum specimens from asthmatic patients, according to their total serum IgE.MethodsWe studied 44 asthmatic patients (15 with high total serum IgE and 29 with normal total serum IgE). On a single visit, all patients underwent: induced sputum, pulmonary function tests, determination of exhaled nitric oxide fraction, venipuncture for blood analysis and skin prick allergy tests. The induced sputum cellularity was analyzed by flow cytometry, where expression of TLRs 2 and 4 was studied using fluorochrome-conjugated monoclonal antibodies.ResultsAsthmatic patients with high total serum IgE showed, a higher percentage of macrophages expressing TLR4 (42.99 % ± 22.49) versus asthmatic patients with normal total serum IgE (28.84 % ± 15.16) (P = 0.048). Furthermore, we observed a correlation (but weak) between the percentage of macrophages expressing TLR4 in induced sputum and the total serum IgE level (R = 0.314; P = 0.040).ConclusionAsthmatic subjects with high total serum IgE show increased macrophage expression of TLR4 in induced sputum. This outcome may result from a link between innate immunity and IgE-mediated, adaptive immune responses in asthma, and point to TLR4 as a potential therapeutic target.
| S-EPMC4833957 | biostudies-literature
Project description:BackgroundT2-high asthma is characterized by elevated blood eosinophils (b-eos), and/or fractional exhaled nitric oxide (FeNO), and/or being "allergy-driven", which is not well-defined.ObjectiveTo investigate the role of total and specific immunoglobulin E (tIgE/sIgE) for defining and predicting T2-high asthma in childhood as biomarkers of "allergy-driven".MethodsWe utilized data from the COPSAC2000 (n = 411) and COPSAC2010 (n = 700) mother-child cohorts with repeated measurements of tIgE, sIgE, b-eos and FeNO through childhood. We defined T2-high asthma by elevated b-eos (≥0.3 × 109/L) and/or FeNO (≥20 ppb) and analyzed association with elevated tIgE (age-specific cut-offs) and sIgE (≥0.35 kU/L) using logistic regression at ages 7/10/13/18 years. Further, we analyzed the association between elevated tIgE and sIgE at age 0-4 years and later risk of T2-high asthma using logistic regression and ROC models.ResultsElevated tIgE was associated with risk of T2-high asthma at all time points, whereas elevated sIgE showed similar results at ages 10/13/18 years. There was no overall model fit preference for a combination of tIgE and sIgE instead of tIgE or sIgE alone using Vuong's Likelihood-Ratio-Test, Akaike or Bayesian Information Criterion. Further, elevated tIgE at age 0-4 years was associated with later risk of T2-high asthma at all time points (AUC = 0.63-0.70, sensitivity = 0.62-0.81, specificity = 0.57-0.78), whereas elevated sIgE at 0-4 years was only associated with T2-high asthma at 18 years (AUC = 0.66, sensitivity = 0.45, specificity = 0.88). There were no significant differences in AUC values between tIgE and sIgE (DeLong's test).ConclusionElevated tIgE and sIgE are equally useful stand-alone biomarkers for defining and predicting risk of T2-high asthma in childhood.
| S-EPMC11621935 | biostudies-literature
Project description:OBJECTIVES:One quarter of pediatric hospitalizations begin as direct admissions, defined as hospitalization without receiving care in the hospital's emergency department (ED). Direct admission rates are highly variable across hospitals, yet previous studies have not examined reasons for this variation. We aimed to determine the relationships between hospital and community factors and pediatric direct admission rates, and to evaluate the degree to which these characteristics explain variation in risk-adjusted direct admission rates. METHODS:We conducted a cross-sectional study of the Healthcare Cost and Utilization Project's Kids Inpatient Database, American Hospital Association Database, and Area Health Resource File, including children <18 years of age who were admitted for a medical hospitalization in states contributing data to all data sets. Using hierarchical generalized linear modeling, we generated risk-adjusted direct admission rates and used generalized linear models to assess the association of hospital and community characteristics with these risk-adjusted rates. RESULTS:We included 211,458 children discharged from 933 hospitals and 26 states; 20.2% were admitted directly. One-fifth of the variance in risk-adjusted direct admission rates was attributed to observed hospital and community factors. The greatest proportion of this explained variance was related to ED volume (37%), volume of pediatric hospitalizations (27%), and size of the pediatrician workforce (12%). CONCLUSIONS:Direct admission rates were associated with several hospital and community characteristics, but the majority of variation in hospitals' direct admission rates was not explained by these factors. These findings suggest opportunities for diverse hospital types to develop the infrastructure and communication systems necessary to support pediatric direct admissions.
| S-EPMC5924569 | biostudies-literature
Project description:It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urban versus a rural environment. We enrolled 1441 children aged 13-15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants. Geometric means for total serum IgE were higher in Lima versus Tumbes (262 versus 192 kU·L(-1); p<0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3-2.0) versus 1.4 (95% CI 0.9-2.1) per log unit increase in total serum IgE in Lima versus Tumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5-2.7) and 1.0 (95% CI 0.7-1.4) per log unit increase in total serum IgE, respectively. Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship.
| S-EPMC5345487 | biostudies-literature
Project description:BackgroundSerum inhibition of allergen-specific IgE has been associated with competing IgG4 and non-specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth-associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low-income countries.MethodsAmong community residents of Ugandan rural Schistosoma mansoni (Sm)-endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non-asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)-specific, Schistosoma egg antigen (SEA)-specific and allergen (house dust mite [HDM] and German cockroach)-specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural-urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma.ResultsTotal IgE, total IgG4 and SWA-, SEA- and allergen-specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen-specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma-specific IgG4, allergen-specific IgG4/IgE ratios and total IgE/allergen-specific IgE ratios. Asthmatic schoolchildren, compared with non-asthmatic controls, had significantly higher levels of total and allergen-specific IgE, but lower ratios of allergen-specific IgG4/IgE and total IgE/allergen-specific IgE.Conclusions and clinical relevanceOur immuno-epidemiological data support the hypothesis that the IgG4-IgE balance and the total IgE-allergen-specific IgE balance are more important than absolute total, helminth- or allergen-specific antibody levels in inhibition of allergies in the tropics.
| S-EPMC7610822 | biostudies-literature
Project description:Variation in the use of ICUs for low-risk conditions contributes to health system inefficiency. We sought to examine the relationship between ICU use for patients with pulmonary embolism (PE) and cost, mortality, readmission, and procedure use.We performed a retrospective cohort study including 61,249 adults with PE discharged from 263 hospitals in three states between 2007 and 2010. We generated hospital-specific ICU admission rate quartiles and used a series of multilevel models to evaluate relationships between admission rates and risk-adjusted in-hospital mortality, readmission, and costs and between ICU admission rates and several critical care procedures.Hospital quartiles varied in unadjusted ICU admission rates for PE (range, ≤ 15% to > 31%). Among all patients, there was a small trend toward increased use of arterial catheterization (0.6%-1.1%, P < .01) in hospital quartiles with higher levels of ICU admission. However, use of invasive mechanical ventilation (14.4%-7.9%, P < .01), noninvasive ventilation (6.6%-3.0%, P < .01), central venous catheterization (14.6%-11.3%, P < .02), and thrombolytics (11.0%-4.7%, P < .01) in patients in the ICU declined across hospital quartiles. There was no relationship between ICU admission rate and risk-adjusted hospital mortality, costs, or readmission.Hospitals vary widely in ICU admission rates for acute PE without a detectable impact on mortality, cost, or readmission. Patients admitted to ICUs in higher-using hospitals received many critical care procedures less often, suggesting that these patients may have had weaker indications for ICU admission. Hospitals with greater ICU admission may be appropriate targets for improving efficiency in ICU admissions.
| S-EPMC4251611 | biostudies-other
Project description:BackgroundTotal serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE.ObjectiveWe aimed to increase understanding of genetic variants affecting tIgE production across the ancestry and allergic disease spectrum by leveraging data from the National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine program; the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA); and the Atopic Dermatitis Research Network (N = 21,901).MethodsWe performed genome-wide association within strata of study, disease, and ancestry groups, and we combined results via a meta-regression approach that models heterogeneity attributable to ancestry. We also tested for association between HLA alleles called from whole genome sequence data and tIgE, assessing replication of associations in HLA alleles called from genotype array data.ResultsWe identified 6 loci at genome-wide significance (P < 5 × 10-9), including 4 loci previously reported as genome-wide significant for tIgE, as well as new regions in chr11q13.5 and chr15q22.2, which were also identified in prior genome-wide association studies of atopic dermatitis and asthma. In the HLA allele association study, HLA-A∗02:01 was associated with decreased tIgE level (Pdiscovery = 2 × 10-4; Preplication = 5 × 10-4; Pdiscovery+replication = 4 × 10-7), and HLA-DQB1∗03:02 was strongly associated with decreased tIgE level in Hispanic/Latino ancestry populations (PHispanic/Latino discovery+replication = 8 × 10-8).ConclusionWe performed the largest genome-wide association study and HLA association study of tIgE focused on ancestrally diverse populations and found several known tIgE and allergic disease loci that are relevant in non-European ancestry populations.
| S-EPMC8665111 | biostudies-literature
Project description:Objective Patients admitted as emergencies to hospitals at the weekend have higher death rates than patients admitted on weekdays. This may be because the restricted service availability at weekends leads to selection of patients with greater average severity of illness. We examined volumes and rates of hospital admissions and deaths across the week for patients presenting to emergency services through two routes: (a) hospital Accident and Emergency departments, which are open throughout the week; and (b) services in the community, for which availability is more restricted at weekends. Method Retrospective observational study of all 140 non-specialist acute hospital Trusts in England analyzing 12,670,788 Accident and Emergency attendances and 4,656,586 emergency admissions (940,859 direct admissions from primary care and 3,715,727 admissions through Accident and Emergency) between April 2013 and February 2014.Emergency attendances and admissions to hospital and deaths in any hospital within 30 days of attendance or admission were compared for weekdays and weekends. Results Similar numbers of patients attended Accident and Emergency on weekends and weekdays. There were similar numbers of deaths amongst patients attending Accident and Emergency on weekend days compared with weekdays (378.0 vs. 388.3). Attending Accident and Emergency at the weekend was not associated with a significantly higher probability of death (risk-adjusted OR: 1.010). Proportionately fewer patients who attended Accident and Emergency at weekend were admitted to hospital (27.5% vs. 30.0%) and it is only amongst the subset of patients attending Accident and Emergency who were selected for admission to hospital that the probability of dying was significantly higher at the weekend (risk-adjusted OR: 1.054). The average volume of direct admissions from services in the community was 61% lower on weekend days compared to weekdays (1317 vs. 3404). There were fewer deaths following direct admission on weekend days than weekdays (35.9 vs. 80.8). The mortality rate was significantly higher at weekends amongst direct admissions (risk-adjusted OR: 1.212) due to the proportionately greater reduction in admissions relative to deaths. Conclusions There are fewer deaths following hospital admission at weekends. Higher mortality rates at weekends are found only amongst the subset of patients who are admitted. The reduced availability of primary care services and the higher Accident and Emergency admission threshold at weekends mean fewer and sicker patients are admitted at weekends than during the week. Extending services in hospitals and in the community at weekends may increase the number of emergency admissions and therefore lower mortality, but may not reduce the absolute number of deaths.
| S-EPMC5482385 | biostudies-literature