Mary Beth Hogan

Regulation of Eosinophilopoiesis in a Murine Model of Asthma

Eosinophilic inflammation plays a key role in tissue damage that characterizes asthma. Eosinophils are produced in bone marrow and recent observations in both mice and humans suggest that allergen exposure results in increased output of eosinophils from hemopoietic tissue in individuals with asthma. However, specific mechanisms that alter eosinophilopoiesis in this disease are poorly understood. The current study used a well-characterized murine animal model of asthma to evaluate alterations of eosinophil and eosinophil progenitor cells (CFU-eo) in mice during initial sensitization to allergen and to determine whether observed changes in either cell population were regulated by T lymphocytes. Following the first intranasal installation of OVA, we observed sequential temporal elevation of eosinophils in bone marrow, blood, and lung. In immunocompetent BALB/c mice, elevation of bone marrow eosinophils was accompanied by transient depletion of CFU-eo in that tissue. CFU-eo rebounded to elevated numbers before returning to normal baseline values following intranasal OVA exposure. In T cell-deficient BALB/c nude (BALB/cnu/nu) mice, CFU-eo were markedly elevated following allergen sensitization, in the absence of bone marrow or peripheral blood eosinophilia. These data suggest that eosinophilia of asthma results from alterations in two distinct hemopoietic regulatory mechanisms. Elevation of eosinophil progenitor cells in the bone marrow is T cell independent and likely results from altered bone marrow stromal cell function. Differentiation of eosinophil progenitor cells and phenotypic eosinophilia is T cell dependent and does not occur in athymic nude mice exposed to intranasal allergen.

Cockroach and other inhalant allergies in infantile asthma

BACKGROUND Infantile asthma is commonly thought to be caused by viral respiratory infections and exposure to second-hand cigarette smoke. Allergy has not been felt to be a major cause of infantile asthma and infants and small children are not commonly skin tested. OBJECTIVE To determine the frequency of skin test reactivity in asthmatic children less than 3 years of age. METHODS We evaluated 196 (50 female/146 male) children with infantile asthma for allergy. Infantile asthma was defined as three or more episodes of wheezing in a child less than 3 years of age. A careful environmental history was obtained on all children. All were skin tested to alternaria, cat, dog, cockroach, and house dust mites (HDM) extracts using the prick technique with the Greer Dermapik. RESULTS Forty-five percent of the infants and children tested had at least one positive skin test. 51/196 (26%) of the children were skin test positive to cockroach, 17.3% to HDM, 13.8% to cat, 6.6% to alternaria, and 6.1% positive to dog. For the 49 children who were less than 1 year of age, 28.5% were positive to cockroach, 10.2% to HDM, 10.2% to cats, 4% to alternaria, and 0% to dog. CONCLUSIONS Allergy to cockroach and other indoor allergens may be a significant contributor to infantile asthma in a rural setting. Skin testing children with infantile asthma may provide useful information for institution of environmental controls measures in the childs home.

Efficacy of a Parent–Youth Teamwork Intervention to Promote Adherence in Pediatric Asthma

OBJECTIVE To determine whether a parent-youth teamwork intervention improved medication adherence and related outcomes among youth with asthma. METHODS We used a randomized clinical trial with 48 youth (aged 9-15 years) assigned to 1 of 3 groups: Teamwork Intervention (TI), Asthma Education (AE), or Standard Care (SC). Treatment occurred across 2 months, with a 3-month follow-up assessment. Adherence to inhaled corticosteroids was assessed via the MDILog-II. Parent-adolescent conflict, asthma functional severity, and spirometry assessments were obtained pre-treatment, post-treatment, and on follow-up. Mixed linear model analysis was used to evaluate group and time effects for outcome measures. RESULTS TI group had significantly higher adherence and lower functional severity scores than AE or SC conditions, and lower parent-reported conflict and a trend for higher spirometry values compared with the SC group. CONCLUSIONS Results suggest support for the efficacy of TI for improving medication adherence as youth acquire more responsibility for their asthma management.

Prevalence of allergic sensitization to indoor fungi in West Virginia

Exposure to indoor fungi is of growing concern in residential and occupational environments in the United States. The purpose of this study was to determine the prevalence of sensitization to common indoor fungal species in an atopic population. We evaluated 102 patients (73 female and 29 male patients) for immunoglobulin E (IgE) reactivity to a panel of skin-prick test (SPT) reagents used for routine allergy testing. Patients also were tested for six additional fungi that are common indoor contaminants. All patients had symptoms consistent with allergic rhinitis or asthma. The presence of specific IgE against the fungal species was determined using immunoblotting. Of the 102 eligible patients, 68% had at least one positive skin test. The most prevalent positive SPTs were to dust mites, cats, vernal grass, and short ragweed. Overall, 21/102 (21%) patients with asthma or allergic rhinitis were skin test positive to at least one fungal extract. Of the patients with a positive SPT to fungi, 12/21 (58%) showed sensitivity to one or more of the newly tested species; most notably Trichoderma viride (8%), Chaetomium globosum (7%), Paecilomyces variotii (7%), and Acremonium strictum (6%). Immunoblotting revealed specific IgE against a number of protein bands belonging to these fungal species. The prevalence of fungal sensitization was common, particularly for indoor fungal contaminants that are not routinely included in SPT panels. Cross-reactivity with other fungi may partially explain our results; however, skin testing for these indoor fungi may provide useful diagnostic information.

Providing dust mite-proof covers improves adherence to dust mite control measures in children with mite allergy and asthma

INTRODUCTION The most critical dust mite avoidance technique for asthmatic children with mite allergy is the use of dust mite-proof bedding covers. Adherence to allergen control measures is poor due to cost. The purpose of this study was to determine whether giving families mite-proof bedding encasings at the time of the diagnosis with mite allergy would improve adherence at a home visit 2 months later. METHODS Parents of children (mean age 7.7 years) with asthma and positive skin tests for dust mite were assigned either to an intervention group, which received dust mite covers upon enrollment or a comparison group, which did not. Both groups were instructed in dust mite control measures by a medical provider and told to invest in the covers as part of standard care. Two months after enrollment, parent report and observational measures from each family were obtained during a home visit. RESULTS The group provided allergen encasings was found to be significantly more likely to have used the casings at the home visit, t(22) = 2.77, P < 0.05. There were no differences between groups in adherence to other mite control strategies. Parenting stress was significantly related to poorer mite control compliance. The most common reason reported for nonadherence to control measures was cost. CONCLUSIONS Providing mite bedding encasings at the time of diagnosis significantly increases compliance at a 2-month home visit. Medicaid and insurance companies should be encouraged to pay for casings as a cost effective measure to improve asthma care in children with mite allergy.

Idiopathic anaphylaxis in children.

BACKGROUND Idiopathic anaphylaxis is a disease where no identifiable antigen or disease initiates an anaphylactoid reaction. Unlike classic IgE antibody-mediated anaphylaxis, severe idiopathic anaphylaxis is treatable with corticosteroids. To date, only 22 pediatric cases from one referral center have been reported. OBJECTIVE To describe the characteristics of children with idiopathic anaphylaxis METHODS A retrospective review of medical records for children presenting to the pediatric allergy clinic with the diagnosis of idiopathic anaphylaxis was performed. RESULTS The review identified eight children with idiopathic anaphylaxis. All eight patients had a cutaneous finding of either urticaria, angioedema, or generalized flushing. Six of the eight patients were noted to have wheezing or angioedema of the airway causing respiratory difficulties. Diarrhea was noted among six patients. Many of the children clearly had life threatening events. Response to appropriate therapy was generally good. CONCLUSIONS Pediatric idiopathic anaphylaxis can present at any age. It may be that many pediatric cases are assumed to be anaphylaxis due to some unknown antigen, and the correct diagnosis is never appreciated. It is important to recognize this disease in children so that it may be appropriately treated, because its specific therapeutic regimen has been shown to prevent the potentially fatal consequences of this disease.

Child and caregiver psychosocial functioning in pediatric immunodeficiency disorders

BACKGROUND Children with chronic illness have been found to be at an increased risk of behavioral and emotional difficulties. To date, children with pediatric immunodeficiency disorders (PIDDs) and their families have not been the focus of extensive published psychosocial research. OBJECTIVE To determine if children with PIDDs and their caregivers have altered psychosocial function and whether the severity of the PIDD was associated with such difficulties. METHODS Twenty children with PIDDs and 20 children with asthma were recruited for this study. Children and their caregivers completed various psychosocial questionnaire forms. Responses were compared with normative data for the appropriate measure and with other variables. RESULTS Higher frequencies of children with PIDDs were found to have a number of elevated psychosocial concerns when contrasted with normative data, particularly from parent report. These concerns included depression, anxiety, somatization, social withdrawal, and social skills. The severity of the PIDDs was significantly associated with a number of behavioral adjustment issues, including receiving psychiatric diagnoses and special education services. Although children with PIDDs had significantly more psychiatric diagnoses than did asthmatic children, these groups did not differ significantly on questionnaire scores regarding child or caregiver psychosocial adjustment. CONCLUSIONS Children with PIDDs have significant behavioral problems. Children receiving intravenous immunoglobulin or immunomodulatory treatments were reported to have more problems than children not receiving them. This study highlights the need for further research in psychosocial functioning of children with PIDDs in an effort to develop interventions to promote their overall adjustment.

Mouse allergy among asthmatic children from rural Appalachia.

BACKGROUND Mice are a common finding in the indoor environment of many homes. In a recent study, 18% of children with asthma from an inner-city environment were reported to be allergic to mouse allergen. OBJECTIVE To determine the frequency of skin test reactivity among asthmatic children in a rural environment. METHODS We consecutively evaluated 209 (82 female, 127 male) children between the ages of 5 months and 19 years with asthma for mouse allergy. A careful environmental history was obtained on all children. Children older than 3 years of age were skin tested to mouse allergen and other indoor/outdoor inhalant allergens. Children younger than 3 years were skin tested to mouse and indoor allergens. RESULTS Thirty-three percent of parents reported seeing mice in their homes. Overall, 25 of 209 (12%) children with asthma were skin test-positive for mouse. For children 3 years or younger, 6 of 52 were skin test-positive for mouse (12%). There was no correlation among socioeconomic status, skin test reactivity, and the presence of mice in the home. Children with multiple skin test reactions were more likely to be reactive to mouse (P < 0.01). Mice seen in the home did not correlate with positive mouse skin tests. CONCLUSIONS The frequency of skin test reactivity to mouse allergen in asthmatic children from rural areas appears slightly less than that in children from inner-city environments. However, a frequency of 12% suggests that skin testing for this allergen provides useful information for environmental control measures in the home.

Renal transplantation in a patient with common variable immunodeficiency

A 15-year-old girl developed end-stage renal disease requiring renal transplantation. Posttransplantation immunosuppression therapy consisted of antithymocyte globulin, glucocorticosteroids, cyclosporine A, and azathioprine. The patients clinical course after transplantation was complicated by several episodes of graft rejection, chronic anemia, oral candidiasis, and numerous infections of the sinopulmonary tract that were recalcitrant to antibiotics and surgical intervention. An immunologic evaluation showed marked immune abnormalities beyond that expected by the transplant immunosuppression. Examination of serum samples taken before the transplant confirmed a diagnosis of common variable immunodeficiency. The difficulties of managing posttransplantation immunosuppression in a patient with a primary immunodeficiency are discussed. Patients with end-stage renal disease and a history of recurrent sinopulmonary infections may require immunologic screening before renal transplantation.

Comparison of two disposable plastic skin test devices with the bifurcated needle for epicutaneous allergy testing

BACKGROUND The Greer DermaPIK and the Lincoln Diagnostics Duotip-Test are frequently used plastic, disposable, allergy skin testing devices. OBJECTIVES To compare the prick method of using the bifurcated needle and DermaPIK with the Duotip-Test using both the scratch (rotation) and prick methods for sensitivity, precision, and level of discomfort. METHODS Skin-testing was done with histamine and saline on the back in triplicate on 24 volunteers (mean age 32.8, seven males). Wheal and erythema were measured and a photograph was taken. Discomfort was rated on an analog scale. RESULTS The bifurcated needle and the Duotip-Test prick technique had significantly smaller histamine wheal and erythema responses than either the DermaPIK prick or Duotip-Test scratch techniques (P < .05). The Duotip-Test scratch produced significantly larger wheals (mean 1.1 mm, P < .001) to saline than the other three methods. Erythema to saline by Duotip-Test scratch (mean 3.16 mm) was significantly larger than the bifurcated needle (mean 1.2 mm, P < .001) and Duotip-Test prick method (mean 1.6 mm, P < .01). There was no statistical difference in the histamine coefficient of variation among the four methods. The Duotip-Test scratch method was rated significantly higher in patient discomfort (mean 21.6, P < .05) than the bifurcated needle (mean 7.8). No differences in discomfort were noted between the other methods. CONCLUSIONS The Duotip-Test scratch method had the largest mean wheal/erythema to histamine and the lowest CV. It had the most dermatographism and was more uncomfortable than the other methods. The other devices and methods were very similar in response to histamine and saline, and to precision and discomfort.