Asthma Severity Index Research Articles

Release of sputum neutrophil granules is associated with pulmonary function and disease severity in childhood asthma

BackgroundMyeloperoxidase (MPO) and human neutrophil lipocalin or neutrophil gelatinase-associated lipocalin (HNL/NGAL) are stored in neutrophil granulocytes and secreted upon activation of the cells. They have been proposed to reflect the degree of inflammation in the airways. However, their role as potential markers of disease severity in childhood asthma remains unknown. This study investigated the relationship between the expression of MPO and HNL/NGAL and childhood asthma.MethodsA total of 83 pediatric patients with asthma and 59 controls were enrolled. Using enzyme-linked immunosorbent assays, the human MPO and HNL/NGAL levels were measured in sputum supernatants. Assessments including spirometry, methacholine challenge test, and atopy test were conducted.ResultsNo difference in sputum neutrophil counts was observed between pediatric patients with asthma and controls. However, sputum MPO and HNL/NGAL levels were significantly higher in patients with asthma than in controls (p = 0.021 and p < 0.001, respectively), especially in patients with moderate-to-severe persistent asthma. In patients with asthma, sputum MPO and HNL/NGAL levels showed a positive correlation with sputum neutrophil counts (MPO, r = 0.433, p < 0.001; HNL/NGAL, r = 0.584, p < 0.001) and with each other (r = 0.628, p < 0.001). Moreover, sputum HNL/NGAL level demonstrated better ability to accurately reflect current pulmonary function, airway inflammation, and limitations than MPO level in this study.ConclusionsSputum MPO and HNL/NGAL levels, which reflect neutrophil activation in airways, were increased in pediatric patients with asthma. Moreover, sputum MPO and HNL/NGAL may serve as appropriate assessment indicators of asthma severity in pediatric patients.

Treating severe paediatric asthma with mepolizumab or omalizumab: a protocol for the TREAT randomised non-inferiority trial

IntroductionA minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death....

Home and school pollutant exposure, respiratory outcomes, and influence of historical redlining

BackgroundThe discriminatory and racist policy of historical redlining in the United States (U.S.) during the 1930s played a role in perpetuating contemporary environmental health disparities. ObjectiveOur objectives were to determine associations between home and school pollutant exposure (fine particulate matter (PM2.5), nitrogen dioxide (NO2)) and respiratory outcomes (Composite Asthma Severity Index (CASI), lung function) among school-aged children with asthma and examine whether associations differed between children who resided and/or attended school in historically redlined compared to non-redlined neighborhoods. MethodsChildren ages 6 to 17 with moderate-to-severe asthma (N=240) from 9 U.S. cities were included. Combined home and school exposure to PM2.5 and NO2 was calculated based on geospatially assessed monthly averaged outdoor pollutant concentrations. Repeated measures of CASI and lung function were collected. ResultsOverall, 37.5% of children resided and/or attended schools in historically redlined neighborhoods. Children in historically redlined neighborhoods had greater exposure to NO2 (median: 15.4 vs 12.1 ppb) and closer distance to a highway (median: 0.86 vs 1.23 km), compared to those in non-redlined neighborhoods (p<0.01). Overall, PM2.5 was not associated with asthma severity or lung function. However, among children in redlined neighborhoods, higher PM2.5 was associated with worse asthma severity (p<0.005). No association was observed between pollutants and lung function or asthma severity among children in non-redlined neighborhoods (p>0.005). ConclusionsOur findings highlight the significance of historical redlining and current environmental health disparities among school-aged children with asthma, specifically, the environmental injustice of PM2.5 exposure and its associations with respiratory health.

The Child Opportunity Index 2.0 and exacerbation-prone asthma in a cohort of urban children.

Social determinants of health underlie disparities in asthma. However, the effects of individual determinants likely interact, so a summary metric may better capture their impact. The Child Opportunity Index 2.0 (COI) is one such tool, yet its association with exacerbation-prone (EP) asthma is unknown. To investigate the association between the COI and EP asthma and clinical measures of asthma severity in children. We analyzed data from two prospective observational pediatric asthma cohorts (n = 193). Children were classified as EP (≥1 exacerbation in the past 12 months) or exacerbation-null (no exacerbations in the past 5 years). Spirometry, exhaled nitric oxide, IgE, and Composite Asthma Severity Index (CASI) were obtained. The association between COI and EP status was assessed with logistic regression. We fit linear and logistic regression models to test the association between COI and each clinical measure. A 20-point COI decrease conferred 40% higher odds of EP asthma (OR 1.4; 95%CI 1.1-1.76). The effect was similar when adjusted for age and sex (OR 1.38, 95%CI 1.1-1.75) but was attenuated with additional adjustment for race and ethnicity (OR 1.19, 95%CI 0.92-1.54). A similar effect was seen for the Social/Economic and Education COI domains but not the Health/Environment Domain. A 20-point COI decrease was associated with an increase in CASI of 0.34. COI was not associated with other clinical measures. Lower COI was associated with greater odds of EP asthma. This highlights the potential use of the COI to understand neighborhood-level risk and identify community targets to reduce asthma disparities.

Evaluation of the implementation of evidence-based pediatric asthma exacerbation treatments in a regional consortium of emergency medical Services Agencies

Objective Asthma exacerbations are a frequent reason for pediatric emergency medical services (EMS) encounters. The objective of this study was to examine the implementation of evidence-based treatments for pediatric asthma in a regional consortium of EMS agencies. Methods This retrospective study applied the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) implementation framework to data from an EMS agency consortium in the Cincinnati, Ohio region. The study analyzed one year before an oral systemic corticosteroid (OCS) option was added to the agencies’ protocol, and five years after the protocol change. We constructed logistic regression models for the primary outcome of Reach, defined as the proportion of pediatric asthma patients who received a systemic corticosteroid. We modeled Maintenance (Reach measured monthly over time) using time series models. Results A total of 713 patients were included, 133 pre- and 580 post-protocol change. In terms of Reach, 3% (n = 4) of eligible patients received a systemic corticosteroid pre-OCS versus 20% (n = 116) post-OCS. Multivariable modeling of Reach revealed the study period, EMS transport time, months since implementation of OCS, and number of bronchodilators administered by EMS as significant covariates for the administration of a systemic corticosteroid. For Maintenance, it took approximately two years to reach maximal administration of systemic corticosteroids. Conclusions Indicators of asthma severity and time since the protocol change were significantly associated with EMS administration of systemic corticosteroids to pediatric asthma patients. The two-year time for maximal Reach suggests further work is required to understand how to best implement evidence-based pediatric asthma treatments in EMS.

Do nocturnal asthma attacks influence sleep parameters and inflammatory markers? A cross-sectional population-based study.

To evaluate the effects of nocturnal asthma on sleep parameters and inflammatory markers according to the severity of the condition in participants in the São Paulo Epidemiologic Sleep Study (EPISONO). Data from the 2007 and 2018 editions of the EPISONO studywere utilized. Subjects completed validated sleep and respiratory questionnaires, underwent nocturnal polysomnography and spirometry tests, and provided blood samples for the assessment of inflammatory parameters. Of 72 participants (67% women), 53% (n = 38) had intermittent nocturnal asthma symptoms and 47% (n = 34) had persistent asthma (mild, moderate, and severe). Individuals with persistent nocturnal symptoms had a higher body mass index (BMI), were more likely to have respiratory symptoms, and had worse lung function, a higher apnea-hypopnea index (AHI), and higher desaturation index than individuals with intermittent nocturnal symptoms. Positive associations were identified between nocturnal asthma and obstructive sleep apnea (OSA). A higher frequency of OSA was observed in participants with persistent asthma and participants with OSA were more likely to have persistent than intermittent asthma. However, there were no significant differences between the immunological parameters of those with intermittent or persistent asthma. This study highlights the relevance of nocturnal symptoms as a valuable indicator of asthma severity. The findings also add to the existing body of evidence linking nocturnal asthma and OSA.

Dexamethasone versus methylprednisolone for critical asthma: A single center, open‐label, parallel‐group clinical trial

Evidence for the use of dexamethasone for pediatric critical asthma is limited. We sought to compare the clinical efficacy and safety of dexamethasone versus methylprednisolone among children hospitalized in the pediatric intensive care unit (PICU) for critical asthma. A prospective, single center, open-label, two-arm, parallel-group, nonrandomized trial among children ages 5-17 years hospitalized within the PICU from April 2019 toDecember 2021 for critical asthma consented to receive methylprednisolone (standard care) or dexamethasone (intervention) at a 2:1 allocation ratio, respectively. The intervention arm received intravenous dexamethasone 0.25 mg/kg/dose (max: 15 mg/dose) every 6 h for 48 h and the standard care arm intravenous methylprednisolone 1 mg/kg/dose every 6 h (max dose: 60 mg/dose) for 5 days. Study endpoints were clinical efficacy (i.e., length of stay [LOS], continuous albuterol duration, and a composite of adjunctive asthma interventions) and safety (i.e., corticosteroid-related adverse events). Ninety-two participants were analyzed of whom 31 were allocated to the intervention arm and 61 the standard care arm. No differences in demographics, clinical characteristics, or acute/chronic asthma severity indices were observed. Regarding efficacy and safety endpoints, no differences in hospital LOS, continuous albuterol duration, adjunctive asthma intervention rates, or corticosteroid-related adverse events were noted. Compared to the intervention arm, participants in the standard care arm more frequently were prescribed corticosteroids at discharge (72% vs. 13%, p < 0.001). Among children hospitalized for critical asthma, dexamethasone appears safe and warrants further investigation to fully assess clinical efficacy and potential advantages over commonly applied agents such as methylprednisolone.

A Study on The Levels of Serum Vitamin D and Magnesium in Asthma Severity

Serum magnesium levels influence the concentration of circulating vitamin D in blood, which in turn influence immunity; thus, it plays an important role in the asthma pathogenesis. Adult asthma is less studied, hypomagnesemia along with the vitamin D deficiency and insufficiency, is common in asthmatic patients, causing frequent attacks of asthma, infections of respiratory tract, severe exacerbations, and poor bronchodilator response. AIMS AND OBJECTIVES: To measure vitamin D insufficiency and deficiency levels, as well as levels of serum magnesium in asthmatic patients, and correlate them with asthma severity. MATERIAL AND METHODS: This is a cross-sectional case-control study with 60 chronic stable asthma patients and 60 healthy controls. A pulmonary function test was performed following the clinical history and systemic examination. All subjects had their serum levels of magnesium, 25-hydroxycholecalciferol [25(OH)D] measured. RESULTS: A significant relationship was observed between vitamin D deficiency, hypomagnesemia, and asthma severity. CONCLUSION: Vitamin D and serum magnesium deficiency are frequent in asthma patients. Lower levels of one or both are associated with increased asthma severity, frequency of attacks, and exacerbation. Serum 25(OH)D and magnesium levels may be useful indicators of asthma severity.

Effect of School Integrated Pest Management or Classroom Air Filter Purifiers on Asthma Symptoms in Students With Active Asthma: A Randomized Clinical Study

To determine if environmental control measures (1) school-wide integrated pest management (IPM) program and/or (2) use of high-efficiency particulate air (HEPA) filter purifiers in inner city elementary school classrooms would reduce asthma morbidity in students with active asthma.Forty-one inner city elementary schools in the Northeastern United States were recruited for this study. There were 236 students with active, physician-diagnosed asthma randomized to IPM (by school) and/or HEPA filter purifiers (by classroom). Physician-diagnosed asthma was defined as the child having had unscheduled doctor visits, hospitalization, corticosteroid bursts, symptoms, or controller medication use in the past year. Fifty seven percent of the children were Hispanic and 24% were Black. Mean age was 8.1 years, 48% female, mean FEV1 97% to 99.7% predicted at randomization. Forty-fifty percent of the children were using short acting β agonists alone and the rest were on inhaled corticosteroids and/or leukotriene modifiers. The study was conducted during the school years 2015 to 2020.All students with active physician-diagnosed asthma had a screening visit with questionnaires, skin testing, and spirometry as well as 2 follow-up visits with the same assessments during the year. Baseline environmental assessment for a panel of allergens (mouse, rat, dust mite, cockroach, cat, dog, Alternaria alternate, and Aspergillus fumigatus) were conducted at the schools by collecting a 1-week air sample, immediately followed by vacuum–settled dust samples from each students’ primary classroom and in the participants homes. The allergens were analyzed using a multiplex assay (MARIA, Indoor Biotechnologies). Follow-up environmental assessment after randomization took place once each winter and spring during the school year.The allocation to free standing classroom HEPA filter purifiers, active or sham, was blinded to the participants and those assessing the outcomes. The IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for the school staff. Infestation was assessed every 3 months and IPM reapplied as needed. Trained pest management specialists providing the school-wide IPM program were unblinded, but the student participants and trial investigators remained blinded throughout the trial.Four groups of 59 students each were randomized using a factorial design to either intervention alone, both interventions together, or neither for the entire school year. Classroom and home allergen and particle levels at randomization were balanced between the 4 groups.The asthma-related health outcomes of the students were assessed by parent survey at baseline and every 2 months until the end of the school year. The primary outcome was the number of symptom-days with asthma during a 2-week period assessed over the 10 months of randomization. Prespecified secondary outcomes were school absences, Composite Asthma Severity Index score, healthcare utilization, and spirometry measurements.Ninety eight percent of the classrooms had detectable levels of mouse allergen and 26% of the participants were sensitized to mouse allergen. More than 90% of baseline classroom allergen levels for cockroach, rat, Alternaria, Aspergillus and dust mite were undetectable.Use of the school-wide IPM program resulted in a mean of 1.5 symptom-days with asthma during a 2-week period versus 1.9 symptom-days for no IPM; use of HEPA filter purifiers resulted in a mean of 1.6 symptom-days with asthma versus 1.8 symptom-days for sham HEPA filter purifiers; neither comparison was statistically significant. Other prespecified secondary outcomes, including healthcare utilization or missed school days because of asthma also did not differ significantly between the intervention groups. The HEPA filter purifiers significantly reduced mouse and dog allergens in the classrooms. The IPM program did not significantly reduce concentrations of any of the allergens or particles measured. A post hoc exploratory analysis found a statistically significant association of reduction in asthma symptoms with the school wide IPM program but only for a limited time (mid-November to February).In an inner-city population of elementary school students with active asthma, use of a school-wide IPM program or HEPA filter purifiers in the classrooms did not significantly reduce symptom-days with asthma.It is possible that these children had asthma that was too mild to see a significant difference in these environmental interventions. Also unclear is whether resources to perform environmental control measures are best used at the school level or at home. As an accompanying editorial notes, “as allergen sensitization is related to the pathogenesis and pathophysiology of childhood asthma,” allergen avoidance should still be a basic tenet of treatment and worth continued investigation.URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1001/jama.2021.11559

TFR1 expression in induced sputum is associated with asthma severity.

BackgroundAsthma is characterized as a chronic inflammatory airway disease. Iron accumulation is related to asthma pathogenesis. Transferrin receptor 1(TFR1) expression is associated with intracellular iron overload in macrophages. In our study, we explored the association among TFR1 expression, the inflammatory macrophage phenotype, and asthma severity.MethodsInduced sputum was collected from 50 asthma patients. Real-time PCR was used to evaluate mRNA expression. The status of inflammatory macrophage phenotype was assessed using flow cytometry.ResultsTFR1 levels were inversely correlated with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1/vital capacity (VC). Among inflammatory cytokines, TFR1 expression was positively correlated with IL-1β, TNF-α, IL-6, IFN-γ, and IL-17A mRNA expression in induced sputum. Moreover, TFR1 expression was positively correlated with the number of proinflammatory M1 macrophages and iNOS expression in induced sputum. Neutrophil counts in induced sputum were significantly and positively related to TFR1 expression. Furthermore, TFR1 expression showed an increasing trend in asthma patients with no family history. Our findings indicated that TFR1 expression was consistent with the asthma severity index, especially the proinflammatory M1 macrophage phenotype. TFR1 expression may be a good marker to indicate asthma severity.

Dexamethasone for Pediatric Critical Asthma: A Multicenter Descriptive Study.

Systemic corticosteroids are vital to critical asthma management. While intravenous methylprednisolone is routinely used in the pediatric intensive care unit (PICU) setting, recent data supports dexamethasone as an alternative. Using the Pediatric Health Information System (PHIS) registry, we assessed trends and variation in corticosteroid prescribing among children hospitalized for critical asthma. We performed a multicenter retrospective cohort study using PHIS data among children 3-17 years of age admitted for critical asthma from 2011 through 2019. Primary outcomes were corticosteroid prescribing rates by year and participating sites. Exploratory outcomes were corticosteroid-related adverse effects, rates of adjunctive pharmaceutical and respiratory interventions, mortality and length of stay. Of the 49 children's hospitals assessed, 26 907 encounters were included for study. Mean dexamethasone exposure rates were 18.1 ± 2.4% where 2.4 ± 1.2% represented dexamethasone-alone prescribing. Dexamethasone alone prescribing exhibited a linear trend (annual increase of 0.5 ± 0.1% annually R2 = 0.845) without correlation to cumulative site critical asthma admission rates. Compared to encounters prescribed solely methylprednisolone or a combination of dexamethasone and methylprednisolone, subjects provided dexamethasone alone had reduced asthma severity indices, length of stay, and exposure rates to adjunctive asthma interventions. Adverse events were rare and the dexamethasone-alone group less frequently experienced gastritis and hyperglycemia. In this multicenter retrospective study from 49 children's hospitals, dexamethasone prescribing rates appear increasing for pediatric critical asthma. Observed variability in corticosteroid prescribing implies a continued need for controlled prospective comparative analyses to define ideal corticosteroid regimens for pediatric critical asthma.

Use of the composite asthma severity index in a pediatric subspecialty clinic

BackgroundThe Composite Asthma Severity Index (CASI) is a comprehensive tool to assess asthma severity, which has been applied in the research setting. ObjectiveTo evaluate, in an outpatient setting, whether a CASI score accurately predicts asthma severity or control as determined by means of subspecialist assessment. Asthma Control Test (ACT) and childhood ACT (C-ACT) scores were generated to provide additional context for CASI scores in relationship to assessments using another clinical tool. MethodsChildren aged 5 to 18 years with a physician diagnosis of persistent asthma were recruited from a tertiary care center. A pediatric pulmonologist made determinations on each participant’s asthma severity and control during a clinic visit. A CASI and ACT/C-ACT score was generated for each patient. Logistic regression and Spearman correlations were used to determine how well CASI scores predicted physician assessments. Agreement between ACT/C-ACT scores and physician assessment of asthma control was determined in supplemental analyses. ResultsCASI scores strongly predicted physician assessment of severity (Spearman correlation = 0.61, P < .001); unadjusted odds ratio (OR) equal to 36.67 (95% confidence interval [CI]: 8.83-152.34); and adjusted OR equal to 32.76 (95% CI: 85.70-188.44). In supplemental analyses, ACT/C-ACT scores strongly predicted physician assessment of control (Spearman correlation = 0.72, P < .001) with an unadjusted OR equal to 42.12 (95% CI: 13.34-133.00) and adjusted OR equal to 55.34 (95% CI: 13.62-224.89). ConclusionUse of the CASI was feasible and accurately predicted physician assessments of asthma severity and control in this sample, which are not distinct entities. The CASI is a robust tool that may be used successfully in ambulatory pediatric asthma care.

Clinical features of asthma with comorbid bronchiectasis: A systematic review and meta-analysis.

Background:This meta-analysis aimed to systematically estimate the prevalence of comorbid bronchiectasis in patients with asthma and to summarize its clinical impact.Methods:Embase, PubMed, and Cochrane Library electronic databases were searched to identify relevant studies published from inception until March 2020.Study Selection:Studies were included if bronchiectasis was identified by high-resolution computed tomography. Outcomes included the prevalence of bronchiectasis and its association with demographic characteristics and indicators of asthma severity, including results of lung function tests and the number of exacerbations.Results:Five observational studies with 839 patients were included. Overall, the mean prevalence of bronchiectasis in patients with asthma was 36.6% (307/839). Patients with comorbid bronchiectasis had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (MD: −2.71; 95% CI: −3.72 to −1.69) and more frequent exacerbations (MD: 0.68; 95% CI: 0.03 to 1.33) than those with asthma alone, and there was no significant difference of sex, duration of asthma and serum levels of immunoglobulin(Ig)Es between asthmatic patients with or without bronchiectasis.Conclusion:The presence of bronchiectasis in patients with asthma was associated with greater asthma severity. There are important therapeutic implications of identifying bronchiectasis in asthmatic patients.

High-flow nasal cannula and bilevel positive airway pressure for pediatric status asthmaticus: a single center, retrospective descriptive and comparative cohort study

Introduction We aimed to describe patient characteristics and clinical outcomes for children hospitalized for status asthmaticus (SA) receiving high-flow nasal cannula (HFNC) or bilevel positive airway pressure (BiPAP). Methods We performed a single center, retrospective cohort study among 39 children admitted for SA aged 5–17 years from January 2016 to May 2019 to a quaternary pediatric intensive care unit (PICU). Cohorts were defined by BiPAP versus HFNC exposure and assessed to determine if differences existed in demographics, anthropometrics, comorbidities, asthma severity indices, historical factors, duration of noninvasive ventilation, and asthma-related clinical outcomes (i.e. length of stay, mechanical ventilation rates, exposure to concurrent sedatives/anxiolysis, and rate of adjunctive therapy exposure). Results Thirty-three percent (n = 13) received HFNC (33%) and 67% (n = 26) BiPAP. Children receiving BiPAP had greater age (10.9 ± 3.7 vs. 6.8 ± 2.2 years, P < 0.01), asthma severity (proportion with severe NHLBI classification: 38% vs. 0%, P < 0.01; median pediatric asthma severity score: 13[12,14] vs. 10[9,12], P < 0.01), previous PICU admissions (62% vs. 15%, P = 0.01), frequency of prescribed anxiolysis/sedation (42% vs. 8%, P = 0.02), and median duration of continuous albuterol (1.7[1,3.1] vs. 0.9[0.7,1.6] days, P = 0.03) compared to those on HFNC. Those on HFNC more commonly were treated comorbid bacterial pneumonia (69% vs. 19%, P < 0.01). No differences in NIV duration, mortality, mechanical ventilation rates, or LOS were observed. Conclusions Our data suggest a trial of BiPAP or HFNC appears well tolerated in children with SA. Prospective trials are needed to establish modality superiority and identify patient or clinical characteristics that prompt use of HFNC over BiPAP.

Serum magnesium level in asthmatic children as an indicator of asthma severity

Background Bronchial asthma is a chronic inflammatory disease of the respiratory tract, characterized by airway hyperresponsiveness. Magnesium (Mg++) has been shown to relax bronchial smooth muscle and influence the function of respiratory muscles. Hypomagnesemia has been associated with diminished respiratory muscle power. Objective This study aims to assess serum Mg level in children with asthma and its correlation with the severity of asthma. Patients and methods It was a case–control study carried out at Alzahraa University Hospital on two groups of children: group 1 consisted of 60 patients with bronchial asthma, comprising 41 males and 24 females, with age ranged from 6 to 15 years, with a mean 10.8±1.6 years, and the second group (control group) consisted of 30 apparently healthy children, with age and sex matched to the diseased patients. Pulmonary function test was done for the studied children, and serum levels of Mg were measured. Results The data hence collected were systematically tabulated and analyzed with SPSS software. The descriptive statistics for the case and control group showed there was a statistically significant decrease in mean serum Mg in asthmatic patients in comparison with controls (P&lt;0.05). Moreover, there was a highly significant lower level of Mg in patients with severe persistent asthma compared with those with mild intermittent asthma and mild, moderate, and persistent asthma (P&lt;0.001), and also, there were significant (P&lt;0.001) positive correlations between serum Mg level and each of forced expiratory volume in 1 s (FEV1)% (r=0.712) and FEV1/forced vital capacity% (0.680) (i.e. in most cases, serum Mg level tended to decrease with the decrease in FEV1% and FEV1/forced vital capacity% ratio). Conclusion Children with bronchial asthma have a great risk of Mg deficiency, and serum Mg level has a significant relation to the severity of asthma and pulmonary function test.

Benefits and challenges of combining data from the CHEAR consortia

Background/Aim: The constraints of sample size in environmental epidemiology studies can limit the detection of meaningful associations. Additionally, study-specific biases may arise from differences in data collection methods, exposure and outcome definitions, and confounder selection. Pooling individual level data across studies may reduce implicit study bias. Methods: Using the Children’s Health Exposure Analysis Resource (CHEAR), we assessed the benefits and potential challenges of pooling data by combining study participants (206 children ages 4-16 years) from the School Inner-City Asthma Intervention Study and the Denver Asthma Panel Study who submitted urine samples to CHEAR laboratories for phthalate metabolite measurement. Composite Asthma Severity Index (CASI) score was used to assess the relationship of phthalates, singularly and as a mixture, on asthma severity in each cohort and combined. All models controlled for age, sex, race, income, body mass index percentile, and creatinine with a random effect for study when appropriate to account for intra-study correlation. Results: For individual log2 transformed phthalate analyses conducted for each study alone, no significant associations with CASI score were observed after applying a false discovery rate (FDR) p-value. However, when the studies were combined, four phthalate metabolites had significant associations with CASI after FDR adjustment. One challenge of pooling data was the need to harmonize covariates - for example, income definition: yearly income compared to last month’s income. An additional challenge was the range in exposure distributions across cohorts. We utilized CHEAR quality control samples to evaluate potential systematic lab differences versus study-specific differences. Conclusion: Although pooling data poses several challenges, we were able to overcome some of them and identified associations in the pooled data that were null in the individual cohorts. The increased sample size may be more suitable for studying potential effect modifiers, such as sex, that could not be found in one cohort alone.

KLF2 regulates neutrophil migration by modulating CXCR1 and CXCR2 in asthma

Neutrophils are key inflammatory cells in the immunopathogenesis of asthma. Neutrophil migration can be initiated through activation of the CXCR1 and CXCR2 receptors by CXC chemokines, such as IL-8. Although transcription factor KLF2 has been found to maintain T cell migration patterns through repression of several chemokine receptors, whether KLF2 can regulate neutrophil migration via modulation of CXCR1 and CXCR2 is unknown. Here, we aimed to explore the functions of KLF2, CXCR1 and CXCR2 in neutrophil migration in asthma and to establish a regulatory role of KLF2 for CXCR1/2. We demonstrate that with asthma aggravation, the percentages and migration rates of peripheral blood neutrophils gradually increased in asthmatic patients and the guinea pig asthma model. Correspondingly, both the KLF2 mRNA and protein levels in neutrophils were gradually reduced. While CXCR1 and CXCR2 expression was negatively correlated with KLF2. In vitro knockdown of KLF2 dramatically increased the migration of HL-60-drived neutrophil-like cells, which was accompanied by an increase in the CXCR1 and CXCR2 mRNA and protein expression levels. Taken together, our results indicate that decreased KLF2 aggravates asthma progression by promoting neutrophil migration, which is associated with the transcriptional upregulation of CXCR1 and CXCR2. The KLF2 and/or CXCR1/2 expression levels may represent an indicator of asthma severity.

Urban-rural differences in health care utilization and prescription filling for childhood asthma

Despite lower asthma prevalence in rural compared with urban children, 1 Asher M.I. Montefort S. Bjorksten B. et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC phases one and three repeat multicountry cross-sectional surveys. Lancet. 2006; 368: 733-743 Abstract Full Text Full Text PDF PubMed Scopus (3051) Google Scholar ,2 Lawson J.A. Rennie D.C. Cockcroft D.W. et al. Childhood asthma, asthma severity indicators, and related conditions along an urban-rural gradient: a cross-sectional study. BMC Pulm Med. 2017; 17: 4 Crossref PubMed Scopus (20) Google Scholar studies suggest that rural children have higher asthma morbidity and uncontrolled asthma. 2 Lawson J.A. Rennie D.C. Cockcroft D.W. et al. Childhood asthma, asthma severity indicators, and related conditions along an urban-rural gradient: a cross-sectional study. BMC Pulm Med. 2017; 17: 4 Crossref PubMed Scopus (20) Google Scholar , 3 Pesek R.D. Vargas P.A. Halterman J.S. Jones S.M. McCracken A. Perry T.T. A comparison of asthma prevalence and morbidity between rural and urban schoolchildren in Arkansas. Ann Allergy Asthma Immunol. 2010; 104: 125-131 Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar , 4 Valet R.S. Gebretsadik T. Carroll K.N. et al. High asthma prevalence and increased morbidity among rural children in a Medicaid cohort. Ann Allergy Asthma Immunol. 2011; 106: 467-473 Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Investigation into potential differences in management and health care utilization after asthma diagnosis would help provide a better understanding of these results. Potential barriers to health care access in rural areas may contribute to poor management of asthma and help explain uncontrolled disease in these areas.

Treatment Benefit with Omalizumab in Children by Indicators of Asthma Severity

Greater severity in childhood asthma negatively impacts functioning and quality of life. Omalizumab is effective in children aged 6 years or older with moderate to severe persistent asthma, but predicting responsiveness in severe disease requires further study. To assess response to omalizumab treatment among children using indicators of asthma severity. Post hoc analyses of randomized placebo-controlled studies of omalizumab (Inner-City Anti-IgE Therapy for Asthma [ICATA], IA05, and Preventative Omalizumab or Step-up Therapy for Fall Exacerbations [PROSE]) stratified by body mass index, eosinophil count, fractional exhaled nitric oxide levels, and baseline severity indicators (baseline percent predicted FEV1, previous hospitalizations, asthma exacerbations). Poisson regression analysis examined exacerbation rate reductions for body mass index, biomarkers, and severity indicators. Children aged 6 to 11 years in IA05 (N= 576; 56% white, 17% black, 26% other/missing), ICATA (N= 237; 55% black, 43% Hispanic), and PROSE (N= 342; 59% black, 35% Hispanic) were included. Trends indicative of greater exacerbation rate change ([omalizumab - placebo]/placebo) were observed for low baseline lung function (IA05 percent predicted FEV1: <90%, 36% reduction, 95% CI,-53.3 to-13.5; ≥90%, 22% reduction, 95% CI,-52.1 to 27.5), previous hospitalizations (ICATA: 46% reduction with, 95% CI,-69.7 to-3.9; 24% reduction without, 95% CI,-48.1 to 10.3), frequent baseline exacerbations (IA05: ≥3, 42% reduction, 95% CI,-60.4 to-14.1; <3, 20% reduction, 95% CI,-45.2 to-15.9), and high baseline eosinophil count (IA05: ≥300 cells/μL, 39% reduction, 95% CI,-56.4 to-14.7; <300 cells/μL, 5% reduction, 95% CI,-40.6 to 52.1). Omalizumab reduces exacerbations in children with moderate to severe persistent allergic asthma, and may provide greater benefit in children with more severe asthma subtypes.

Telehealth delivery of adherence and medication management system improves outcomes in inner-city children with asthma.

Healthcare disparities exist in pediatric asthma in the United States. Children from minority, low‐income families in inner‐city areas encounter barriers to healthcare, leading to greater rates of poorly controlled asthma and healthcare utilization. Finding an effective way to deliver high‐quality healthcare to this underserved population to improve outcomes, reduce morbidity and mortality, and reduce healthcare utilization is of the utmost importance. The purpose of this study was to assess the feasibility and efficacy of a novel school‐based care delivery model that incorporates video‐based telehealth (VBT) medical and self‐management visits with electronic inhaler monitoring to improve asthma outcomes. Over a 6‐month period, children from inner‐city, low‐income schools with uncontrolled asthma completed seven scheduled medical visits with an asthma specialist and five self‐management visits with an adherence psychologist at school using VBT. Composite Asthma Severity Index (CASI) scores and electronic inhaler monitor data were recorded and analyzed. A total of 21 patients were enrolled in the study. Study subjects with higher baseline severity (CASI ≥ 4 at visit 1) demonstrated a greater reduction in their score than those with lower baseline severity (CASI < 4 at visit 1). The CASI domains showed improvement in daytime symptoms, nighttime symptoms, and exacerbations. Adherence results demonstrated a significant improvement in adherence from baseline to postintervention. Study retention was 100%. This study demonstrates that a multicomponent medical and behavioral interventional program delivered by VBT to a school‐based setting is feasible and can significantly improve asthma outcomes and care in a challenging population.