Inner-city Asthmatic Children Research Articles

Effect of radon exposure on asthma morbidity in the School Inner-City Asthma study.

Radon may have a role in obstructive lung disease outside its known carcinogenicity. Little is known about radon's effects on asthma morbidity. To determine the effect of radon on fractional exhaled nitric oxide (FE NO), asthma symptom-days, and lung function in inner-city asthmatic school children. Two hundred ninety-nine school-aged asthmatic children enrolled in the School Inner-City Asthma Study (SICAS-1) were followed. One and two-month averaged radon was assessed using a spatiotemporal model predicting zip code-specific monthly exposures. FE NO and spirometry were measured twice during the academic year. Asthma symptoms were assessed four times during the academic year. The interaction between indoor radon exposure (Bq/m3 ) and seasonality predicting log-transformed FE NO, forced expiratory volume in 1 s (FEV1 ) % predicted, forced vital capacity (FVC) % predicted, FEV1 /FVC, and asthma symptom-days was evaluated. Participants with high radon exposure had greater change in FE NO from warm to cold periods compared to low radon exposure (interaction p = 0.0013). Participants with >50th percentile radon exposure experience significant FE NO increase from warm to cold weather ( = 0.29 [95% confidence interval [CI]: 0.04-0.54], p = 0.0240). We report a positive association between radon 1-month moving average (incidence rate ratio [IRR] = 1.01, p = 0.0273) and 2-month moving average (IRR = 1.01, p = 0.0286) with maximum asthma symptom-days (n = 299, obs = 1167). In asthmatic children, radon may be associated with increased asthma morbidity, suggesting radon may be a modifiable environmental risk factor for airway inflammation.

Epigenetic marks identify asthma susceptibility in African Americans

Despite advances in therapeutics and a better understanding of environmental contributions, ethnic disparities are profound in asthma; asthma prevalence is >2 times higher in African compared to European Americans, and African American children are >3 times more likely to be hospitalized and die from asthma than whites. Epigenetic marks, including DNA methylation, are a key mechanistic component of gene‐environment interactions that affect gene expression, respiratory epithelial dysfunction, and immune cell skewing in asthma. Our group performed pioneering work to identify asthma associated‐DNA methylation changes that affect gene expression in African American inner city children. Our work identified 81 differentially methylated regions (DMRs) in peripheral blood mononuclear cells (PBMCs) associated with allergic asthma. DNA methylation changes in PBMCs are small (median 1.3%; range 0.02%‐3.1%) but consistent with the majority of DMRs hypomethylated in asthma, including important immune genes such as IL‐13, RUNX3, and TIGIT. In the nasal epithelia, we identified much larger (median 9.5%, range: 2.6‐29.5%) methylation changes, both in the form of single CpG methylation (differentially methylated positions[DMPs]) and regions (DMRs). 60% of genes that are differentially expressed in the asthmatic nasal epithelium have significant associations of DNA methylation and gene expression; these include asthma genes (ALOX15, CAPN14, POSTN), genes involved in inflammation and immunity, cell adhesion, extracellular matrix, obesity and autophagy, and epigenetic regulators, among others. Importantly, these results have been replicated in multiple cohorts, including a cohort of Puerto Rican children, another population that shares an unproportional disease burden. We are currently involved in projects that aim to integrate genetic ancestry, DNA methylation, and gene expression data to better understand genetic underpinnings of these DNA methylation changes. Our earlier work also showed that nasal epithelia capture disease activity seen in the lung airway epithelia but that there are many more significant associated DNA methylation changes in the nasal epithelia, suggesting an important role for the environment in influencing these epigenetic changes and the need to understand environmental exposures that are driving these changes. In summary, our findings that epigenetic marks in respiratory epithelia are associated with allergic asthma in inner‐city children provide new targets for understanding the biology of the disease, developing biomarkers of exposure or disease, and potentially identifying novel therapeutic approaches for this disease.

Immune Profiles in Inner-city Asthmatic Children Receiving Frequent Systemic Steroids

Immune Profiles in Inner-city Asthmatic Children Receiving Frequent Systemic Steroids

A Randomized Trial of Subcutaneous Allergy Immunotherapy in Inner-city Children With Asthma Less Than 4 Years of Age

To evaluate the effect of subcutaneous immunotherapy (SCIT) on asthma in inner-city children <4 years of age.Children between the ages of 18 to 47 months were recruited when seen in the asthma or allergy clinic at Jacobi Medical Center in Bronx, New York, which cares for a mostly low-income, inner-city population. Participants were required to have physician-diagnosed asthma or at least 2 lifetime episodes of wheezing and be at high risk of persistent asthma on the basis of an Asthma Predictive Index. Patients with any other chronic medical condition, history of severe prematurity, or a sustained oxygen requirement at birth were excluded. Although all patients had at least 1 common environmental allergen positive on skin-prick testing, most had multiple and mainly indoor allergen sensitizations. The majority of patients were male and used an asthma controller medication, with an average asthma symptom score indicating mild persistent asthma.Participants were randomly assigned to the SCIT (n = 27) or control group (n = 23). SCIT was administered per published guidelines, with biweekly maintenance injections. Asthma, nasal-ocular, and skin symptom scores and medication use were monitored by a phone call every 2 weeks. In interim power analysis, it was indicated there was an insufficient sample size to reach the planned power of 80%, so the study was terminated early before some participants had completed SCIT for 3 years.On the basis of intention-to-treat analysis, there was no statically significant difference in asthma, nasal-ocular, or skin symptom scores in the SCIT and control groups. Quality of life, as assessed by the parent, showed significant improvement in the SCIT group (β coefficient: 0.32; SE: 0.09; P ≤ .01), particularly related to interference of child’s asthma on family or work plans and nighttime symptoms. Allergen specific serum immunoglobulin G4 levels increased in the SCIT group only (P ≤ .04). New allergen sensitization or loss of sensitization rates at the end of the study were not significantly different between the SCIT and control groups. Systemic reactions occurred in in 22% of children and 1.8% of injections, all of which were mild and resolved with antihistamine administration. Children in the SCIT group missed 28% of injection visits.Apart from improved quality of life, allergen immunotherapy in inner-city children with asthma <4 years of age did not show significant improvement in asthma, allergy, or eczema clinical outcomes.Although perhaps limited by small sample size and a high rate of missed appointments, with the results, the authors support the common practice of waiting until near 5 years of age to start SCIT. Factors unique to an inner-city, younger pediatric population may warrant larger studies to determine the efficacy of early immunotherapy in improving asthma.

T Cell Profile After Systemic Steroid Burst in Inner-City Asthmatic Children with Recurrent Infections.

Background: Systemic corticosteroids are the standard of care for acute asthma exacerbation. Respiratory infections are known as common triggers of asthma exacerbation, but the risk of immune suppression from frequent periodic use of systemic steroids in poorly controlled asthmatic children is not well studied. Materials and Methods: We conducted a retrospective chart review of 26 children, 3-15 years old with poorly controlled, moderate-to-severe persistent asthma who received ≥2 systemic corticosteroid/year. The data collected include absolute T cell, B cell, and natural killer (NK) cell counts; lymphocyte proliferation studies to phytohemagglutinin (PHA), concanavalin A (CON A), and pokeweed mitogen; immunoglobulin G and M; and antibody titers to tetanus, diphtheria, and pneumococcus. Frequency tables and crosstabs were used to analyze the data. Results: Low CD4+ T cell counts were found in 47.8% of the patients, and 45.8% had low CD3+ T cell counts. The lymphocyte proliferation studies data exhibited variability, but 21.4%-75% of the subjects who demonstrated normal T cell counts had decreased lymphocyte proliferation studies to PHA and CON A. All the patients had normal immunoglobulins, B cell, and NK cell counts. All but 1 patient had adequate antibody responses to Streptococcus pneumoniae. Conclusions: Frequent systemic corticosteroid use may suppress T cell number and function in asthmatic children. This can potentially lead to increase susceptibility for future infections and asthma exacerbations. Depressed lymphocyte proliferations are observed even in patients who demonstrated normal T cell counts. This emphasizes the importance of adherence to asthma controller medications, and control of asthma triggers, to limit the frequency of steroid use.

Inner-City Asthma in Children.

Asthma in inner-city children is often severe and difficult to control. Residence in poor and urban areas confers increased asthma morbidity even after adjusting for ethnicity, age, and gender. Higher exposure to household pests, such as cockroaches and mice, pollutants and tobacco smoke exposure, poverty, material hardship, poor-quality housing, differences in health care quality, medication compliance, and heath care access also contribute to increased asthma morbidity in this population. Since 1991, the National Institutes of Allergy and Infectious Diseases established research networks: the National Cooperative Inner-City Asthma Study (NCICAS), the Inner-City Asthma Study (ICAS), and the Inner-City Asthma Consortium (ICAC), to improve care for this at risk population. The most striking finding of the NCICAS is the link between asthma morbidity and the high incidence of allergen sensitization and exposure, particularly cockroach. The follow-up ICAS confirmed that reductions in household cockroach and dust mite were associated with reduction in the inner-city asthma morbidity. The ICAC studies have identified that omalizumab lowered fall inner-city asthma exacerbation rate; however, the relationship between inner-city asthma vs immune system dysfunction, respiratory tract infections, prenatal environment, and inner-city environment is still being investigated. Although challenging, certain interventions for inner-city asthma children have shown promising results. These interventions include family-based interventions such as partnering families with asthma-trained social workers, providing guidelines driven asthma care as well as assured access to controller medication, home-based interventions aim at elimination of indoor allergens and tobacco smoke exposure, school-based asthma programs, and computer/web-based asthma programs.

Asthma in inner city children: recent insights: United States.

Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016-2017) advances in the understanding of asthma in US inner city children. Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children.

Development of Asthma in Inner-City Children: Possible Roles of MAIT Cells and Variation in the Home Environment.

Humans have populations of innate-like T lymphocytes with an invariant TCR α-chain that recognize nonpeptide Ags, including invariant NKT (iNKT) cells and mucosal-associated invariant T (MAIT) cells. iNKT cell involvement in human asthma is controversial, whereas there has been little analysis of MAIT cells. Using peripheral blood cells from 110 participants from the Urban Environment and Childhood Asthma (URECA) birth cohort study, these cells were analyzed for number and function. We determined whether iNKT cell or MAIT cell frequency at 1 y is correlated with the cytokine polarization of mainstream CD4+ T cells and/or the development of asthma by age 7 y. Dust samples from 300 houses were tested for iNKT cell antigenic activity. Our results show that a higher MAIT cell frequency at 1 y of age was associated with a decreased risk of asthma by age 7 y. The frequency of MAIT cells was associated with increased production of IFN-γ by activated CD4+ T cells from the URECA cohort. iNKT cell antigenic activity in bedroom dust samples was associated with higher endotoxin concentration and also with reduced risk of asthma. In conclusion, MAIT cell frequency at 1 y may reflect the tendency of the immune system toward Th1 responses and is associated with protection from asthma. Additionally, iNKT cell antigenic activity may be a marker of houses with increased microbial exposures and therefore also with protection from asthma.

P238 The effect of animal exposures on asthma morbidity independent of allergen among inner-city asthmatic children

Animal allergen exposures are associated with asthma morbidity in children with existing allergic asthma, but the effects of other factors associated with animal exposures are unclear. Therefore, our objectives were to determine if allergen exposures fully mediated the risk from animal exposure on asthma morbidity and identify the impact of animal exposures independent of allergen.

Allergy and asthma in inner-city children: possible roles of MAIT cells and variation in the home environment

Abstract Humans have two populations of innate-like T lymphocytes with an invariant T cell antigen receptor (TCR) a chain: invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells. iNKT cell involvement in human asthma has been suggested, but is controversial, while there has been little analysis of MAIT cells. Using peripheral blood cells from the urban environment and childhood asthma (URECA) birth cohort study, we carried out a comprehensive investigation to determine if iNKT cell frequency or MAIT cell frequency early in life is correlated with the cytokine polarization of mainstream CD4+T cells and/or the development of asthma by age seven. We also determined if iNKT cell antigenic activity in house dust samples was associated with environmental endotoxin or clinical outcomes including aeroallergen sensitization and recurrent wheeze at 3 and asthma at age 7. We also analyzed the correlation between cytokines released by activated iNKT and MAIT cells and various clinical outcomes. Our results shows that the frequency of MAIT cells was associated with increased production of IFNg by activated CD4+ T cells from children that did not go on to develop asthma. Moreover, an increased MAIT cell frequency early in life was associated with a decreased risk of asthma by age seven. In contrast, iNKT cell frequency early in life was not correlated with the development of asthma or allergic sensitization. iNKT cell antigen content in house dust varied greatly, and increased antigen was associated not only with endotoxin levels in the surroundings but also with protection from asthma. Together, these data suggest that MAIT cell frequency and iNKT cell antigen content at one year correlates with protection from asthma development.

P117 The extent of immunosuppression from systemic steroid bursts in inner-city asthmatic children - an update

Systemic corticosteroids are mainstay treatment for acute asthma exacerbations. The effect of chronic administration of systemic steroids in patients with autoimmune disorders has been reported. However, the quantified severity and extent of immunosuppression in asthmatic children receiving frequent systemic steroids bursts has not been reported.

Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents

Treatment levels required to control asthma vary greatly across a population with asthma. The factors that contribute to variability in treatment requirements of inner-city children have not been fully elucidated. We sought to identify the clinical characteristics that distinguish difficult-to-control asthma from easy-to-control asthma. Asthmatic children aged 6 to 17years underwent baseline assessment and bimonthly guideline-based management visits over 1year. Difficult-to-control and easy-to-control asthma were defined as daily therapy with 500μg of fluticasone or greater with or without a long-acting β-agonist versus 100μg or less assigned on at least 4 visits. Forty-four baseline variables were used to compare the 2 groups by using univariate analyses and to identify the most relevant features of difficult-to-control asthma by using a variable selection algorithm. Nonlinear seasonal variation in longitudinal measures (symptoms, pulmonary physiology, and exacerbations) was examined by using generalized additive mixed-effects models. Among 619 recruited participants, 40.9% had difficult-to-control asthma, 37.5% had easy-to-control asthma, and 21.6% fell into neither group. At baseline, FEV1 bronchodilator responsiveness was the most important characteristic distinguishing difficult-to-control asthma from easy-to-control asthma. Markers of rhinitis severity and atopy were among the other major discriminating features. Over time, difficult-to-control asthma was characterized by high exacerbation rates, particularly in spring and fall; greater daytime and nighttime symptoms, especially in fall and winter; and compromised pulmonary physiology despite ongoing high-dose controller therapy. Despite good adherence, difficult-to-control asthma showed little improvement in symptoms, exacerbations, or pulmonary physiology over the year. In addition to pulmonary physiology measures, rhinitis severity and atopy were associated with high-dose asthma controller therapy requirement.

A primary care-based asthma program improves recognition and treatment of persistent asthma in inner-city children compared to routine care

Objective: To examine whether a primary care-based asthma program that applies the Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-2007 criteria to classify asthma severity increases detection of persistent asthma in inner-city children and affects “step of care” compared to routine care. Methods: A retrospective chart review was conducted of 97 consecutive children referred to the asthma program from 2011–2013. Asthma severity documented during routine health care maintenance visits was compared to the asthma severity assessed during the asthma program visit using five standardized questions and spirometry. Medication plan “step of care” was compared pre- and post- the asthma program visit. Results: 79 children, ages 5–19 years old (mean = 9.6), had spirometry tracings meeting American Thoracic Society criteria and were included in this study. 53% were male. The majority of children were Latino (45.6%) or African American (35.4%). At the asthma program visit, more children were identified with moderate or severe persistent asthma based upon clinical questions (47.9%), spirometry (56.9%) or combined criteria (75.3%) than had been identified during routine care (15.2%); all p < .05. After the asthma program visit, more children were prescribed controller medications (82.3% vs 63.3%; p < .05) and 40.6% had their medication plan stepped up. Conclusions: In this population of inner-city children, asthma severity was under-recognized and undertreated during routine care. A primary care based asthma program, which formalized applying EPR-3 criteria, increased detection of persistent asthma and led to “step-ups” in treatment plans.

Asthma control and need for future asthma controller therapy among inner-city Hispanic asthmatic children engaged in a pediatric asthma disease management program (the Breathmobile program, Mobile Asthma Care for Kids Network)

Objective: To determine whether significant numbers of asthmatic children with initially rated intermittent asthma later suffer poor asthma control and require the addition of controller medications. Methods: Inner-city Hispanic children were followed prospectively in an asthma-specific disease management system (Breathmobile) for a period of 2 years. Clinical asthma symptoms, morbidity treatment, and demographic data were collected at each visit. Treatment was based upon National Heart, Lung, and Blood Institute (NHLBI) Expert Panel Report 3 asthma guidelines. Primary outcome was percentage of patients with intermittent asthma who had not well or poorly controlled asthma during subsequent visits and required controller agents. Secondary outcomes were factors associated with the maintenance of asthma control. Results: About 30.9% of the patients with initial rating of intermittent asthma had not well controlled and poorly controlled asthma during subsequent visits and required the addition of controller agents. Factors associated with good asthma control were compliance, no previous emergency room visits and previous visit during spring season. Conclusion: Asthmatic children with intermittent asthma often lose asthma control and require controller therapy. This justifies asthma guideline recommendations to assess asthma control at follow-up visits and adjust therapy accordingly.

Characteristics That Distinguish Difficult-to-Control Asthma in Inner-City Children

Characteristics That Distinguish Difficult-to-Control Asthma in Inner-City Children

Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations

Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure. We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school. A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined. Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; 95% CI, 0.25-0.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33-1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02-0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002-0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01-0.88). Adverse events were rare and similar among arms. Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.

Accurate Assessment of Personal Air Pollutant Exposures in Inner-City Asthmatic Children

Accurate Assessment of Personal Air Pollutant Exposures in Inner-City Asthmatic Children

Asthma in inner-city children at 5-11 years of age and prenatal exposure to phthalates: the Columbia Center for Children's Environmental Health Cohort.

Background: Studies suggest that phthalate exposures may adversely affect child respiratory health.Objectives: We evaluated associations between asthma diagnosed in children between 5 and 11 years of age and prenatal exposures to butylbenzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), and diethyl phthalate (DEP).Methods: Phthalate metabolites were measured in spot urine collected from 300 pregnant inner-city women. Children were examined by an allergist or pulmonologist based on the first parental report of wheeze, other respiratory symptoms, and/or use of asthma rescue/controller medication in the preceding 12 months on repeat follow-up questionnaires. Standardized diagnostic criteria were used to classify these children as either having or not having current asthma at the time of the physician examination. Children without any report of wheeze or the other asthma-like symptoms were classified as nonasthmatics at the time of the last negative questionnaire. Modified Poisson regression analyses were used to estimate relative risks (RR) controlling for specific gravity and potential confounders.Results: Of 300 children, 154 (51%) were examined by a physician because of reports of wheeze, other asthma-like symptoms, and/or medication use; 94 were diagnosed with current asthma and 60 without current asthma. The remaining 146 children were classified as nonasthmatic. Compared with levels in nonasthmatics, prenatal metabolites of BBzP and DnBP were associated with a history of asthma-like symptoms (p < 0.05) and with the diagnosis of current asthma: RR = 1.17 (95% CI: 1.01, 1.35) and RR = 1.25 (95% CI: 1.04, 1.51) per natural log-unit increase, respectively. Risk of current asthma was > 70% higher among children with maternal prenatal BBzP and DnBP metabolite concentrations in the third versus the first tertile.Conclusion: Prenatal exposure to BBzP and DnBP may increase the risk of asthma among inner-city children. However, because this is the first such finding, results require replication.Citation: Whyatt RM, Perzanowski MS, Just AC, Rundle AG, Donohue KM, Calafat AM, Hoepner LA, Perera FP, Miller RL. 2014. Asthma in inner-city children at 5–11 years of age and prenatal exposure to phthalates: the Columbia Center for Children’s Environmental Health Cohort. Environ Health Perspect 122:1141–1146; http://dx.doi.org/10.1289/ehp.1307670

Winter birth in inner-city asthmatic children is associated with increased food allergen sensitization risk

Winter birth in inner-city asthmatic children is associated with increased food allergen sensitization risk

Mouse allergen skin sensitization in asthmatic children of suburban, rural, and inner-city populations

Mouse allergen (MA) exposure is a well-known risk factor for allergic sensitization and is implicated in the pathogenesis of pediatric asthma. Although previous studies report high prevalence of MA sensitization in inner-city asthmatic children, no data exist on its comparison with either suburban or rural children with asthma. We did a retrospective cohort study by chart review of all children (≤18 years of age) who underwent allergy testing during a 6-month period in a tertiary care referral center. Patients were divided geographically into suburban, rural, and inner-city groups based on their zip codes. MA was tested using the standard allergy test panel by skin prick/puncture. Positive skin test reactivity was defined as wheal diameter ≥3 mm and erythema ≥5 mm. A total of 989 patients underwent allergy testing and 349 children were tested for MA with the overall positivity rate of 18.6% (65/349). In children with asthma (mean age, 12.8 years; SD ± 3.19) who had MA testing (n = 166), the rate of positive skin test reactivity was 18% (n = 30). Inner-city asthmatic children had significantly greater MA sensitization compared with either suburban or rural children. MA sensitization is highly prevalent among children with asthma, especially in inner-city populations but also among suburban and rural children. Although most allergists do not routinely test for MA sensitization during the initial evaluation, it may be useful to include it in the allergy testing for children with asthma.