Publications by authors named "Gordon R Bloomberg"

47 Publications

Oral challenge outcomes in children with adverse aminopenicillin reactivity.

Ann Allergy Asthma Immunol 2019 04 11;122(4):422-424. Epub 2019 Jan 11.

Washington University School of Medicine, St Louis, Missouri.

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April 2019

A computerized decision support tool to implement asthma guidelines for children and adolescents.

J Allergy Clin Immunol 2019 05 5;143(5):1760-1768. Epub 2018 Dec 5.

Department of Medicine, Division of Allergy and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Background: Multicenter randomized controlled trials (RCTs) for asthma management that incorporate usual-care regimens could benefit from standardized application of evidence-based guidelines.

Objective: We sought to evaluate performance of a computerized decision support tool, the Asthma Control Evaluation and Treatment (ACET) Program, to standardize usual-care regimens for asthma management in RCTs.

Methods: Children and adolescents with persistent uncontrolled asthma living in urban census tracts were recruited into 3 multicenter RCTs (each with a usual-care arm) between 2004 and 2014. A computerized decision support tool scored asthma control and assigned an appropriate treatment step based on published guidelines. Control-level determinants (symptoms, rescue medication use, pulmonary function measure, and adherence estimates) were collected at visits and entered into the ACET Program. Changes in control levels and treatment steps were examined during the trials.

Results: At screening, more than half of the participants were rated as having symptoms that were not controlled or poorly controlled. The proportion of participants who gained good control between screening and randomization increased significantly in all 3 trials. Between 51% and 70% had symptoms that were well controlled by randomization. The proportion of well-controlled participants remained constant or improved slightly from randomization until the last posttreatment visit. Nighttime symptoms were the most common control-level determinant; there were few (<1%) instances of complete overlap of factors. FEV was the driver of control-level assignment in 30% of determinations.

Conclusion: The ACET Program decision support tool facilitated standardized asthma assessment and treatment in multicenter RCTs and was associated with attaining and maintaining good asthma control in most participants.
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May 2019

Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma.

J Allergy Clin Immunol 2018 12 5;142(6):1856-1866. Epub 2018 Mar 5.

University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Background: Childhood asthma in inner-city populations is a major public health burden, and understanding early-life immune mechanisms that promote asthma onset is key to disease prevention. Children with asthma demonstrate a high prevalence of aeroallergen sensitization and T2-type inflammation; however, the early-life immune events that lead to T2 skewing and disease development are unknown.

Objective: We sought to use RNA sequencing of PBMCs collected at age 2 years to determine networks of immune responses that occur in children with allergy and asthma.

Methods: In an inner-city birth cohort with high asthma risk, we compared gene expression using RNA sequencing in PBMCs collected at age 2 years between children with 2 or more aeroallergen sensitizations, including dust mite, cockroach, or both, by age 3 years and asthma by age 7 years (cases) and matched control subjects who did not have any aeroallergen sensitization or asthma by age 7 years.

Results: PBMCs from the cases showed higher levels of expression of natural killer (NK) cell-related genes. After cockroach or dust mite allergen but not tetanus antigen stimulation, PBMCs from the cases compared with the control subjects showed differential expression of 244 genes. This gene set included upregulation of a densely interconnected NK cell-like gene network reflecting a pattern of cell activation and induction of inflammatory signaling molecules, including the key T2-type cytokines IL9, IL13, and CCL17, as well as a dendritic cell-like gene network, including upregulation of CD1 lipid antigen presentation molecules. The NK cell-like response was reproducible in an independent group of children with later-onset allergic sensitization and asthma and was found to be specific to only those children with both aeroallergen sensitization and asthma.

Conclusion: These findings provide important mechanistic insight into an early-life immune pathway involved in T2 polarization, leading to the development of allergic asthma.
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December 2018

Spirometry and Impulse Oscillometry in Preschool Children: Acceptability and Relationship to Maternal Smoking in Pregnancy.

J Allergy Clin Immunol Pract 2018 Sep - Oct;6(5):1596-1603.e6. Epub 2018 Feb 13.

Pharmacy Practice Division, University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Background: Comparisons of the technical acceptability of spirometry and impulse oscillometry (IOS) and clinical correlations of the measurements have not been well studied in young children. There are no large studies focused on African American and Hispanic children.

Objectives: We sought to (1) compare the acceptability of spirometry and IOS in 3- to 5-year-old children and (2) examine the relationship of maternal smoking during pregnancy to later lung function.

Methods: Spirometry and IOS were attempted at 4 sites from the Urban Environmental and Childhood Asthma Study birth cohort at ages 3, 4, and 5 years (472, 471, and 479 children, respectively). We measured forced expiratory flow in 0.5 s (forced expiratory volume in 0.5 seconds [FEV]) with spirometry and area of reactance (A), resistance and reactance at 5 Hz (R and X, respectively) using IOS.

Results: Children were more likely to achieve acceptable maneuvers with spirometry than with IOS at age 3 (60% vs 46%, P < .001) and 5 years (89% vs 84%, P = .02). Performance was consistent among the 4 study sites. In children without recurrent wheeze, there were strong trends for higher FEV and lower R and A over time. Maternal smoking during pregnancy was associated with higher A at ages 4 and 5 years (P < .01 for both years). There was no significant difference in FEV between children with and without in utero exposure to smoking.

Conclusion: There is a higher rate of acceptable maneuvers with spirometry compared with IOS, but IOS may be a better indicator of peripheral airway function in preschool children.
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November 2019

Early-life home environment and risk of asthma among inner-city children.

J Allergy Clin Immunol 2018 04 19;141(4):1468-1475. Epub 2017 Sep 19.

Department of Pediatrics, University of Wisconsin-Madison, Madison, Wis.

Background: Environmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain.

Objective: We sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children.

Methods: We examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children.

Results: Higher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P < .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate < 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores.

Conclusion: Among high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk.
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April 2018

Screen Time Engagement Is Increased in Urban Children With Asthma.

Clin Pediatr (Phila) 2017 Oct 20;56(11):1048-1053. Epub 2017 Mar 20.

2 Washington University School of Medicine, St Louis, MO, USA.

Physical activity in children has been shown to play a role in its relationship to asthma, both in terms of prevalence and incidence. One measure of physical activity in children is sedentary behavior, which might be measured by the degree of engagement with media electronic screens. We found that children with asthma, as compared with children without asthma, engage in significantly more hours of screen time (median 35 vs 26 h/wk, P = .004). In this birth cohort, those who developed a diagnosis of asthma at 8 years of age were significantly more engaged in electronic screen time than their peers. No other clinical or lifestyle behaviors were significantly associated with a diagnosis of asthma. Further study will be needed to determine directionality of this finding.
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October 2017

Patterns of immune development in urban preschoolers with recurrent wheeze and/or atopy.

J Allergy Clin Immunol 2017 Sep 13;140(3):836-844.e7. Epub 2017 Jan 13.

Washington University School of Medicine and St Louis Children's Hospital, St Louis, Mo.

Background: Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2-biased immunity.

Objective: We sought to determine whether environmental exposures in early life influence cytokine responses that affect the development of recurrent wheezing illnesses and allergic sensitization.

Methods: A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children were followed until 3 years of age. Cytokine responses were measured in blood cell samples obtained at birth (cord blood) and ages 1 and 3 years. Cytokine responses were examined in relation to personal characteristics and environmental exposures to allergens and endotoxin and to the development of allergic sensitization and recurrent wheeze assessed at age 3 years.

Results: Cytokine responses generally increased with age, but responses at birth were poorly predictive for those at ages 1 and 3 years. Exposure to certain allergens (cockroach, mouse, dust mite) was significantly associated with enhanced cytokine responses at age 3 years, including IFN-α and IL-10 responses to certain stimulants and responses to phytohemagglutinin. Regarding the clinical outcomes, reduced LPS-induced IL-10 responses at birth were associated with recurrent wheeze. In contrast, reduced respiratory syncytial virus-induced IL-8 responses and increased 5'-cytosine-phosphate-guanine-3' (CpG)-induced IL-12p40 and allergen-induced IL-4 responses were associated with atopy.

Conclusions: These findings suggest that diverse biologic exposures, including allergens and endotoxin, in urban homes stimulate the development of cytokine responses in early life, and that cytokine responses to specific microbial and viral stimuli are associated with the development of allergic sensitization and recurrent wheeze.
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September 2017

Relationships among Maternal Stress and Depression, Type 2 Responses, and Recurrent Wheezing at Age 3 Years in Low-Income Urban Families.

Am J Respir Crit Care Med 2017 03;195(5):674-681

7 Kravis Children's Hospital and Mindich Child Health & Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Rationale: Maternal depression and prenatal and early life stress may influence childhood wheezing illnesses, potentially through effects on immune development.

Objectives: To test the hypothesis that maternal stress and/or depression during pregnancy and early life are associated with recurrent wheezing and aeroallergen sensitivity and altered cytokine responses (enhanced type 2 or reduced virus-induced cytokine responses) from stimulated peripheral blood mononuclear cells at age 3 years.

Methods: URECA (Urban Environment and Childhood Asthma) is a birth cohort at high risk for asthma (n = 560) in four inner cities. Maternal stress, depression, and childhood wheezing episodes were assessed by quarterly questionnaires beginning at birth. Logistic and linear regression techniques were used to examine the relation of maternal stress/depression to recurrent wheezing and peripheral blood mononuclear cell cytokine responses at age 3 years.

Measurements And Main Results: Overall, 166 (36%) children had recurrent wheeze at age 3 years. Measures of maternal perceived stress at Years 2 and 3 were positively associated with recurrent wheeze (P < 0.05). Maternal depression (any year) was significantly associated with recurrent wheezing (P ≤ 0.01). These associations were also significant when considered in a longitudinal analysis of cumulative stress and depression (P ≤ 0.02). Neither stress nor depression was significantly related to aeroallergen sensitization or antiviral responses. Contrary to our original hypothesis, prenatal and Year 1 stress and depression had significant inverse associations with several type 2 cytokine responses.

Conclusions: In urban children at high risk for asthma, maternal perceived stress and depression were significantly associated with recurrent wheezing but not increased atopy or reduced antiviral responses.
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March 2017

Relation between stress and cytokine responses in inner-city mothers.

Ann Allergy Asthma Immunol 2015 Nov 26;115(5):439-445.e3. Epub 2015 Sep 26.

University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Background: Women in poor urban neighborhoods have high rates of stress and allergic diseases, but whether stress or stress correlates such as depression promote inflammatory and type 2 cytokine responses is unknown.

Objective: To examine associations among external stressors, perceived stress, depression, and peripheral blood mononuclear cell cytokine responses of mothers enrolled in the Urban Environment and Childhood Asthma Study and test the hypothesis that stress would be positively associated with type 2 and selected proinflammatory (tumor necrosis factor-α and interleukin-8) responses.

Methods: Questionnaire data from mothers living in 4 inner cities included information about external stress, stress perception, and depression. The external stress domains (interpersonal problems, housing, and neighborhood stress) were combined into a Composite Stressor score. Peripheral blood mononuclear cells were stimulated ex vivo and cytokine responses to innate, adaptive, and polyclonal immune stimuli were compared with stress and depression scores for 469 of the 606 study participants.

Results: There were no significant positive associations between Composite Stressor scores, perceived stress, or depression scores and proinflammatory or type 2 cytokine responses, and these findings were not modified by allergy or asthma status. There were some modest associations with individual stressors and cytokine responses, but no consistent relations were noted. Depression was associated with decreased responses to some stimuli, particularly dust mite.

Conclusion: Composite measurements of stressors, perceived stress, or depression were not positively related to proinflammatory or type 2 cytokine responses in these young urban women. These data do not support the hypothesis that these factors promote cytokine responses associated with allergy.

Trial Registration:, identifier NCT00114881.
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November 2015

Seasonal risk factors for asthma exacerbations among inner-city children.

J Allergy Clin Immunol 2015 Jun 18;135(6):1465-73.e5. Epub 2015 Mar 18.

University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Background: Asthma exacerbations remain common, even in children and adolescents, despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes.

Objective: We sought to define host risk factors for asthma exacerbations unique to their season of occurrence.

Methods: This is a retrospective analysis of patients aged 6 to 20 years who comprised the control groups of the Asthma Control Evaluation study and the Inner City Anti-IgE Therapy for Asthma study. Univariate and multivariate models were constructed to determine whether patients' demographic and historical factors, allergic sensitization, fraction of exhaled nitric oxide values, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations.

Results: The analysis included 400 patients (54.5% male; 59.0% African American; median age, 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis exacerbation in the previous season was the strongest predictor in fall and winter, whereas a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed).

Conclusions: Among a large cohort of inner-city children with asthma, patients' risk factors for exacerbation vary by season. Thus information on individual patients might be beneficial in strategies to prevent these seasonal events.
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June 2015

Influence of early-life exposures on food sensitization and food allergy in an inner-city birth cohort.

J Allergy Clin Immunol 2015 Jan 13;135(1):171-8. Epub 2014 Aug 13.

Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Md. Electronic address:

Objective: Previous data suggest that food allergy (FA) might be more common in inner-city children; however, these studies have not collected data on both sensitization and clinical reactivity or early-life exposures.

Methods: Children in the Urban Environment and Childhood Asthma birth cohort were followed through age 5 years. Household exposures, diet, clinical history, and physical examinations were assessed yearly; levels of specific IgE to milk, egg, and peanut were measured at 1, 2, 3, and 5 years of age. On the basis of sensitization (IgE ≥0.35 kU/L) and clinical history over the 5-year period, children were classified as having FA or being possibly allergic, sensitized but tolerant, or not allergic/not sensitized.

Results: Five hundred sixteen children were included. Overall, 55.4% were sensitized (milk, 46.7%; egg, 31.0%; and peanut, 20.9%), whereas 9.9% were categorized as having FA (peanut, 6.0%; egg, 4.3%; and milk, 2.7%; 2.5% to >1 food). The remaining children were categorized as possibly allergic (17.0%), sensitized but tolerant (28.5%), and not sensitized (44.6%). Eighteen (3.5%) reported reactions to foods for which IgE levels were not measured. Food-specific IgE levels were similar in children with FA versus sensitized but tolerant children, except for egg, levels of which were higher in patients with FA at ages 1 and 2 years. FA was associated with recurrent wheeze, eczema, aeroallergen sensitization, male sex, breast-feeding, and lower endotoxin exposure in year 1 but not with race/ethnicity, income, tobacco exposure, maternal stress, or early introduction of solid foods.

Conclusions: Even given that this was designed to be a high-risk cohort, the cumulative incidence of FA is extremely high, especially considering the strict definition of FA that was applied and that only 3 common allergens were included.
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January 2015

Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children.

J Allergy Clin Immunol 2014 Sep 4;134(3):593-601.e12. Epub 2014 Jun 4.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Background: Wheezing illnesses cause major morbidity in infants and are frequent precursors to asthma.

Objective: We sought to examine environmental factors associated with recurrent wheezing in inner-city environments.

Methods: The Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n = 560) in Baltimore, Boston, New York, and St Louis. Environmental assessments included allergen exposure and, in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age 3 years.

Results: Cumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively; P ≤ .01). Differences in house dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze.

Conclusions: In inner-city environments children with the highest exposure to specific allergens and bacteria during their first year were least likely to have recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial and suggest new preventive strategies for wheezing and allergic diseases.
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September 2014

A telephone coaching intervention to improve asthma self-management behaviors.

Pediatr Nurs 2013 May-Jun;39(3):125-30, 145

St. Louis Children's Hospital Answer Line, St. Louis Children's Hospital, St. Louis, MO, USA.

Long recognizing that asthma, one of the most common chronic childhood diseases, is difficult to manage, the National Asthma Education Prevention Program developed clinical practice guidelines to assist health care providers, particularly those in the primary care setting. Yet, maintenance asthma care still fails to meet national standards. Therefore, in an attempt to improve and support asthma self-management behaviors for parents of children 5 to 12 years of age with persistent asthma, a novel nurse telephone coaching intervention was tested in a randomized, controlled trial. A detailed description of the intervention is provided along with parent satisfaction results, an overview of the training used to prepare the nurses, and a discussion of the challenges experienced and lessons learned.
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August 2013

Lack of a relation between serum 25-hydroxyvitamin D concentrations and asthma in adolescents.

Am J Clin Nutr 2013 Jun 17;97(6):1228-34. Epub 2013 Apr 17.

National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.

Background: Decreased 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with an increased prevalence and severity of asthma and a lower response to inhaled corticosteroids.

Objective: The objective was to determine the association between serum 25(OH)D concentrations and asthma prevalence, severity, and response to asthma treatment.

Design: Secondary analyses were conducted in 2 samples of adolescents 12-20 y of age: 1) NHANES 2001-2006 (n = 6487), a cross-sectional nationally representative sample of the US population, and 2) a cohort of inner-city adolescents with asthma managed prospectively for 46 wk with guidelines-based therapy in the Asthma Control Evaluation (ACE; n = 226) trial.

Results: Mean (±SD) serum 25(OH)D concentrations in the NHANES and ACE samples were lower in African Americans than in non-African Americans (NHANES: 14.9 ± 6.5 compared with 23.0 ± 8.4 ng/mL, P < 0.0001; ACE: 11.2 ± 6.9 compared with 15.8 ± 7.1 ng/mL, P < 0.0001). In the NHANES sample, mean concentrations did not differ between participants without and with asthma (African Americans: 14.9 ± 6.4 compared with 15.0 ± 6.6 ng/mL, respectively, P = 0.87; non-African Americans: 23.0 ± 8.5 compared with 23.6 ± 8.2 ng/mL, respectively, P = 0.16). In the ACE models that used either a predefined cutoff (<20 ng/mL) or linear regression, 25(OH)D concentrations showed either no relation or minor contradictory correlations with indicators of asthma severity, treatment requirements, spirometry, or atopy/inflammation.

Conclusion: In 2 samples of adolescents, overall serum 25(OH)D concentrations were low and were not consistently associated with the presence of asthma, multiple asthma characteristics, asthma morbidity, or response to treatment. The ACE trial was registered at as NCT0011441.
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June 2013

Comparison of the etiology of viral respiratory illnesses in inner-city and suburban infants.

J Infect Dis 2012 Nov 25;206(9):1342-9. Epub 2012 Sep 25.

Department of Pediatrics, University of Wisconsin, Madison, WI, USA.

Background: The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct.

Methods: We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin. Nasal secretions were sampled during periods of respiratory illness and at 1 year of age and were analyzed for viral pathogens by multiplex polymerase chain reaction.

Results: Overall, inner-city infants had lower rates of viral detection. Considering specific viruses, sick urban infants had lower rates of detectable rhinovirus or respiratory syncytial virus infection and higher rates of adenovirus infection. Every urban site had a higher proportion of adenovirus-positive samples associated with illnesses (10%-21%), compared with Madison (6%).

Conclusions: These findings provide evidence that inner-city babies have different patterns of viral respiratory illnesses than babies who grow up in a more suburban location. These findings raise important questions about the etiology of virus-negative illnesses in urban infants and the possibility of long-term consequences of early life infections with adenovirus in this population.
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November 2012

Antiviral IFN-γ responses of monocytes at birth predict respiratory tract illness in the first year of life.

J Allergy Clin Immunol 2012 May 27;129(5):1267-1273.e1. Epub 2012 Mar 27.

Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.

Background: Viral respiratory tract infections are the leading cause of acute illness during infancy and are closely linked to chronic inflammatory airway diseases later in life. However, the determinants of susceptibility to acute respiratory tract infections still need to be defined.

Objective: We investigated whether the individual variation in antiviral response at birth determines the risk for acute respiratory tract illness in the first year of life.

Methods: We studied 82 children who were enrolled in a birth cohort study of inner-city children with at least 1 parent with allergy or asthma. We cultured cord blood monocytes and assessed IFNG and CCL5 mRNA production at 24 hours after inoculation with respiratory syncytial virus. We also monitored the frequency of acute respiratory tract illness at 3-month intervals and analyzed nasal lavage samples for respiratory tract viruses at the time of illness during the first year.

Results: Respiratory tract infection was reported for 88% of subjects, and respiratory tract viruses were recovered in 74% of symptomatic children. We observed a wide range of antiviral responses in cord blood monocytes across the population. Furthermore, a decrease in production of IFNG (but not CCL5) mRNA in response to respiratory syncytial virus infection of monocytes was associated with a significant increase in the frequency of upper respiratory tract infections (r = -0.42, P < .001) and the prevalence of ear and sinus infections, pneumonias, and respiratory-related hospitalizations.

Conclusion: Individual variations in the innate immune response to respiratory tract viruses are detectable even at birth, and these differences predict the susceptibility to acute respiratory tract illness during the first year of life.
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May 2012

Development and validation of the Composite Asthma Severity Index--an outcome measure for use in children and adolescents.

J Allergy Clin Immunol 2012 Mar 12;129(3):694-701. Epub 2012 Jan 12.

Rho Federal Systems Division, Inc, Chapel Hill, NC 27517, USA.

Background: Asthma severity is reflected in many aspects of the disease, including impairment and future risks, particularly for exacerbations. According to the Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, however, to assess more comprehensively the severity of asthma the level of current treatment needed to maintain a level of control should be included.

Objective: Development and validation of a new instrument, the Composite Asthma Severity Index (CASI), which can quantify disease severity by taking into account impairment, risk, and the amount of medication needed to maintain control. At present, there is no instrument available to measure and assess the multidimensional nature of asthma.

Methods: Twenty-six established asthma investigators, who are part of the National Institutes of Health-supported Inner City Asthma Consortium, participated in a modified Delphi consensus process to identify and weight the dimensions of asthma. Factor analysis was performed to identify independent domains of asthma by using the Asthma Control Evaluation trial. CASI was validated by using the Inner City Anti-IgE Therapy for Asthma trial.

Results: CASI scores include 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. At Asthma Control Evaluation trial enrollment, CASI ranged from 0 to 17, with a mean of 6.2. CASI was stable, with minimal change in variance after 1 year of treatment. In external validation, CASI detected a 32% larger improvement than did symptoms alone.

Conclusion: CASI retained its discriminatory ability even with low levels of symptoms reported after months of guidelines-directed care. Thus, CASI has the ability to determine the level of asthma severity and provide a composite clinical characterization of asthma.
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March 2012

The influence of environment, as represented by diet and air pollution, upon incidence and prevalence of wheezing illnesses in young children.

Curr Opin Allergy Clin Immunol 2011 Apr;11(2):144-9

Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri, USA.

Purpose Of Review: The purpose of this review is to consider the collective influence of factors affecting recurrent wheezing in young children.

Recent Findings: Specific allergen sensitization, upper respiratory infections, genetic polymorphisms and environmental factors have collectively been reported in the prevalence of and induction of recurrent wheezing in young children. Two examples of environmental factors are diet and exposure to air pollution, both of which are potentially modifiable. Recent investigations provide evidence that a 'Mediterranean diet' and a diet that emphasizes polyunsaturated fatty acids during pregnancy and early infancy, as well as breastfeeding, may be protective for wheezing, and that exposure to traffic-related pollution may be an independent factor in the incidence of wheezing in young children.

Summary: Recent studies of early childhood wheezing demonstrate a potentially protective effect of diet and exposure to air pollution as a significant risk factor. An evaluation of collective factors influencing the presence of disease may help to broaden the clinical assessment and give parents and physicians the opportunity to potentially modify circumstances that promote the incidence of recurrent wheezing in infants and preschool aged children.
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April 2011

Relationships among environmental exposures, cord blood cytokine responses, allergy, and wheeze at 1 year of age in an inner-city birth cohort (Urban Environment and Childhood Asthma study).

J Allergy Clin Immunol 2011 Apr 18;127(4):913-9.e1-6. Epub 2011 Feb 18.

Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Background: The Urban Environment and Childhood Asthma study was established to investigate the immunologic and environmental causes of asthma in inner-city children.

Objective: We sought to evaluate potential atopic outcomes in the first 12 months and their relationships to environmental exposures and immune development.

Methods: A birth cohort of 560 children with at least 1 parent with allergy or asthma was established in Baltimore, Boston, New York, and St Louis. Wheezing is assessed every 3 months, allergen-specific IgE yearly, and mononuclear cell cytokine responses at birth and yearly; environmental assessments include dust allergen and endotoxin, maternal stress, and indoor nicotine and nitrogen dioxide levels.

Results: Key outcomes in the first year include wheeze in 49%, 2 or more episodes of wheeze in 23%, eczema in 30%, and detectable IgE to milk, egg, and/or peanut in 32% and to cockroach in 4%. Household dust revealed levels of greater than 2 μg/g to cockroach in 40%, mite in 19%, cat in 25%, and mouse in 29%, and 66% of homes housed at least 1 smoker. Positive associations were detected between multiple wheeze and cotinine levels, maternal stress, and maternal depression, whereas cytokine responses to a variety of innate, adaptive, and mitogenic stimuli were inversely related to eczema.

Conclusions: This high-risk cohort of inner-city infants is exhibiting high rates of wheeze, eczema, and allergic sensitization. Low cytokine responses at birth might be a risk factor for eczema, whereas a variety of adverse environmental exposures contribute to the risk of wheezing in infancy. These findings provide evidence of specificity in the interactions between immune development, environmental exposures, and the development of early features that might predict future asthma.
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April 2011

Telephone coaching for parents of children with asthma: impact and lessons learned.

Arch Pediatr Adolesc Med 2010 Jul;164(7):625-30

Department of Medicine, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA.

Objective: To determine whether an asthma coaching program can improve parent and child asthma-related quality of life (QOL) and reduce urgent care events.

Design: Randomized controlled trial of usual care vs usual care with coaching. Comparisons were made between groups using mixed models.

Setting: A Midwest city.

Participants: A community-based sample of 362 families with a child aged 5 to 12 years with persistent asthma.

Intervention: A 12-month structured telephone coaching program in which trained coaches provided education and support to parents for 4 key asthma management behaviors.

Main Outcome Measures: Parental and child QOL measured with a validated, interview-administered, 7-point instrument and urgent care events in a year (unscheduled office visits, after-hours calls, emergency department visits, or hospitalizations) determined by record audit.

Results: Parental asthma-related QOL scores improved by an average of 0.67 units (95% confidence interval [CI], 0.49 to 0.84) in the intervention group and 0.28 units (95% CI, 0.10 to 0.46) in the control group. The difference between study groups was statistically significant (difference, 0.38; 95% CI, 0.14 to 0.63). No between-group difference was found in the change in the child's QOL (difference, -0.17; 95% CI, -0.47 to 0.12) or in the mean number of urgent care events per year (difference, 1.15; 95% CI, 0.82 to 1.61). The proportion of children with very poorly controlled asthma in the intervention group decreased compared with the control group (difference, 0.34; 95% CI, 0.21 to 0.48).

Conclusions: A telephone coaching program can improve parental QOL and can be implemented without additional physician training or practice redesign.
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July 2010

Asthma control, adiposity, and adipokines among inner-city adolescents.

J Allergy Clin Immunol 2010 Mar;125(3):584-92

Department of Pediatric Pulmonology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Background: There is an association between adiposity and asthma prevalence, but the relationship to asthma control is unclear.

Objectives: We sought to understand the relationships among adiposity, sex, and asthma control in inner-city adolescents with asthma.

Methods: We prospectively followed 368 adolescents with moderate-to-severe asthma (ages 12-20 years) living in 10 urban areas for 1 year. Asthma symptoms and exacerbations were recorded, and pulmonary function and exhaled nitric oxide levels were measured every 6 weeks. Adiposity measures (body mass index [BMI] and dual-energy X-ray absorptiometric scans) were made, and blood was collected for measurement of allergy markers, adiponectin, leptin, TNF-alpha, IL-6, and C-reactive protein levels.

Results: More than 60% of female subjects and 50% of male subjects were above the 85th percentile of BMI for age. Higher BMI was associated with more symptom days (R = 0.18, P = .02) and exacerbations (R = 0.18, P = .06) among female subjects only. Adiponectin was inversely related to asthma symptoms (R = -0.18, P < .05) and exacerbations (R = -0.20, P < .05) and positively with FEV(1)/forced vital capacity ratio (R = 0.15, P < .05) in male subjects only independent of body size. There was no relationship between adiposity or adipokines and total IgE levels, blood eosinophil counts, and exhaled nitric oxide levels. Dual-energy X-ray absorptiometry provided little additional value in relating adiposity to asthma outcome in this population of adolescents.

Conclusion: Adiposity is associated with poorer asthma control in female subjects. Adiponectin is associated with improved asthma control in male subjects.
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March 2010

Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort.

Am J Respir Crit Care Med 2010 Jul 1;182(1):25-33. Epub 2010 Mar 1.

The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Rationale: Stress-elicited disruption of immunity begins in utero.

Objectives: Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families).

Methods: Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age).

Measurements And Main Results: Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-alpha to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced IFN-gamma.

Conclusions: Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.
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July 2010

The exacerbation component of impairment and risk in pediatric asthma.

Curr Opin Allergy Clin Immunol 2010 Apr;10(2):155-60

Department of Pediatrics, Division of Allergy, Immunology & Pulmonary Medicine, Washington University School of Medicine, St. Louis Children's Hospital, One Children's Place, St. Louis, Missouri, USA.

Purpose Of Review: The new guidelines for assessment of asthma control emphasize two domains: impairment and risk. Exacerbations of asthma are an important component of risk but have not received as much attention as the day-to-day symptoms that make up impairment. The purpose of this review is to report what has recently been learned about exacerbations.

Recent Findings: Exacerbations occur in the context of both controlled and uncontrolled asthma. Exacerbations are a strong independent risk factor of further exacerbations. This suggests that unrecognized factors may be involved in susceptibility to exacerbations in addition to more commonly recognized triggers such as viruses, allergens, and poorly controlled asthma. Such factors may be the result of genetic variation. Recent evidence now shows a residual effect on lung function from an exacerbation event. There are no current specific intervention measures to prevent exacerbations but attention to management practices continues to look at the role of the emergency department in improving care.

Summary: The presence of exacerbations is considered a risk factor of the likelihood of further exacerbations and requires assessment of the triggers identified with history of exacerbations, host factors, atopic disposition, exposure to allergens, adherence to prescribed medications, and preventive measures to reduce future risk of such an event.
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April 2010

Parental characteristics, somatic fetal growth, and season of birth influence innate and adaptive cord blood cytokine responses.

J Allergy Clin Immunol 2009 Nov;124(5):1078-87

Channing Laboratory, Brigham and Women's Hospital, Boston, Mass, USA.

Background: Immunologic responses at birth likely relate to subsequent risks for allergic diseases and wheezing in infancy; however, the influences of parental characteristics and prenatal factors on neonatal immune responses are incompletely understood.

Objective: This study investigates potential correlations between urban parental, prenatal, and perinatal factors on innate and adaptive stimuli-induced cytokine responses.

Methods: Five hundred sixty and 49 children of parents with and without allergic disease or asthma, respectively, were enrolled into a prospective birth cohort study (Urban Environment and Childhood Asthma). Cord blood mononuclear cells were incubated with innate and adaptive immune stimuli, and cytokine responses (ELISA) were compared with season of birth, parental characteristics, in utero stressors, and fetal growth.

Results: Many cytokine responses varied by season of birth, including 2-fold to 3-fold fluctuations with specific IFN-alpha and IFN-gamma responses. Birth weight was inversely associated with IFN-gamma responses to respiratory syncytial virus (R = -0.16), but positively associated with IL-8 responses to a variety of innate stimuli (R = 0.08-0.12). Respiratory syncytial virus-induced cytokine responses were 21% to 54% lower in children of mothers with asthma. Cytokine responses were generally lower in babies born to parents with allergy/asthma.

Conclusions: Innate cytokine responses are associated with parental allergic or airway disease, somatic fetal growth, ethnicity, and season of birth. Collectively, these findings suggest that urban prenatal exposures and familial factors affect the development of the fetal immune system.
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November 2009

Recurrent wheezing illness in preschool-aged children: assessment and management in primary care practice.

Postgrad Med 2009 Sep;121(5):48-55

Department of Pediatrics, St. Louis Children's Hospital, St. Louis, MO 63110, USA.

Recurrent wheezing is common in preschool-aged children, with 1 in 3 children experiencing at least 1 acute wheezing illness before the age of 3 years. These children represent a diverse group, with some going on to present with asthma at school age and others experiencing complete resolution of symptoms. The primary care physician is faced with a dilemma of when to recommend daily therapy. He or she must also answer parents' concerns, often expressed as, "Does my child have asthma?" and "Will my child have to take medication the rest of his or her life?" This article presents recent studies and recommendations that can guide the physician in approaching the child and the parent with rational management. The emphasis is on viewing recurrent wheezing as a continuum requiring a plan of monitoring that starts with the very first episode. Using background information from the parents and a history of the child's allergic disposition, one can discuss with parents the risks of developing asthma and, together with planned monitoring, prescribe appropriate management. The primary care physician can plan management by using the Asthma Predictive Index and employing specific questions for features present during the intervals between acute episodes. Together with close monitoring, the physician will have a compass that effectively directs rational management.
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September 2009

Relationship between infant weight gain and later asthma.

Pediatr Allergy Immunol 2010 Feb 27;21(1 Pt 1):82-9. Epub 2009 Aug 27.

Department of Pediatrics and Public Health, Science Penn State College of Medicine, Hershey, PA 17033-0850, USA.

Like obesity, the prevalence of asthma has increased over the past several decades. Accelerated patterns of infant growth have been associated with obesity and its co-morbidities. We aimed to determine if infant weight gain pattern is associated with asthma development later in childhood. Birth weight, growth, pulmonary function, and symptom data were collected in a trial of 2- to 3-yr-old children at-risk for asthma randomized to a 2-yr treatment with inhaled corticosteroids or placebo followed by a 1-yr observation period of study medication. Patterns of infant weight gain between birth and study enrollment were categorized as accelerated, average, or decelerated. Regression analyses were used to test the effects of infant weight gain pattern prior to study enrollment on outcomes during the observation year and at study conclusion while adjusting for demographics, baseline symptom severity, study treatment, and atopic indicators. Among the 197 study participants, early life weight gain pattern was not associated with daily asthma symptoms or lung function at the study's conclusion. However, both prednisone courses (p = 0.01) and urgent physician visits (p < 0.001) were significantly associated with weight gain pattern with fewer exacerbations occurring amongst those with a decelerated weight gain pattern. We conclude that early life patterns of weight change were associated with subsequent asthma exacerbations, but were not associated with asthma symptoms or pulmonary function during the pre-school years for these children at-risk for asthma.
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February 2010

Asthma morbidity among inner-city adolescents receiving guidelines-based therapy: role of predictors in the setting of high adherence.

J Allergy Clin Immunol 2009 Aug 16;124(2):213-21, 221.e1. Epub 2009 Jul 16.

University of Texas Southwestern Medical Center, Dallas, Tex 75390-8859, USA.

Background: With the expanding effort to provide guidelines-based therapy to adolescents with asthma, attention must be directed to evaluating which factors predict future asthma control when guidelines-based management is applied.

Objective: We evaluated the role of fraction of exhaled nitric oxide in parts per billion, markers of allergic sensitization, airway inflammation, and measures of asthma severity in determining future risk of asthma symptoms and exacerbations in adolescents and young adults participating in the Asthma Control Evaluation study.

Methods: Five hundred forty-six inner-city residents, ages 12 through 20 years, with persistent asthma were extensively evaluated at study entry for predictors of future symptoms and exacerbations over the subsequent 46 weeks, during which guidelines-based, optimal asthma management was offered. Baseline measurements included fraction of exhaled nitric oxide in parts per billion, total IgE, allergen-specific IgE, allergen skin test reactivity, asthma symptoms, lung function, peripheral blood eosinophils, and, for a subset, airway hyperresponsiveness and sputum eosinophils.

Results: The baseline characteristics we examined accounted for only a small portion of the variance for future maximum symptom days and exacerbations--11.4% and 12.6%, respectively. Future exacerbations were somewhat predicted by asthma symptoms, albuterol use, previous exacerbations, and lung function, whereas maximum symptom days were predicted, also to a modest extent, by symptoms, albuterol use, and previous exacerbations, but not lung function.

Conclusion: Our findings demonstrate that the usual predictors of future disease activity have little predictive power when applied to a highly adherent population with persistent asthma that is receiving guidelines-based care. Thus, new predictors need to be identified that will be able to measure the continued fluctuation of disease that persists in highly adherent, well-treated populations such as the one studied.
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August 2009

The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population.

BMC Pulm Med 2009 May 8;9:17. Epub 2009 May 8.

University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Background: The incidence and morbidity of wheezing illnesses and childhood asthma is especially high in poor urban areas. This paper describes the study design, methods, and population of the Urban Environment and Childhood Asthma (URECA) study, which was established to investigate the immunologic causes of asthma among inner-city children.

Methods And Results: URECA is an observational prospective study that enrolled pregnant women in central urban areas of Baltimore, Boston, New York City, and St. Louis and is following their offspring from birth through age 7 years. The birth cohort consists of 560 inner-city children who have at least one parent with an allergic disease or asthma, and all families live in areas in which at least 20% of the population has incomes below the poverty line. In addition, 49 inner-city children with no parental history of allergies or asthma were enrolled. The primary hypothesis is that specific urban exposures in early life promote a unique pattern of immune development (impaired antiviral and increased Th2 responses) that increases the risk of recurrent wheezing and allergic sensitization in early childhood, and of asthma by age 7 years. To track immune development, cytokine responses of blood mononuclear cells stimulated ex vivo are measured at birth and then annually. Environmental assessments include allergen and endotoxin levels in house dust, pre- and postnatal maternal stress, and indoor air nicotine and nitrogen dioxide. Nasal mucous samples are collected from the children during respiratory illnesses and analyzed for respiratory viruses. The complex interactions between environmental exposures and immune development will be assessed with respect to recurrent wheeze at age 3 years and asthma at age 7 years.

Conclusion: The overall goal of the URECA study is to develop a better understanding of how specific urban exposures affect immune development to promote wheezing illnesses and asthma.
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May 2009