Efficacy of an exercise intervention among children with comorbid asthma and obesity.

OBJECTIVES: Children with comorbid asthma and obesity present with more severe and harder-to-control disease than asthmatic children at healthy weight. Weight loss has been shown to improve asthma symptoms, yet physical activity may be difficult due to exercise-induced bronchospasm. Children with asthma have lower exercise rates than non-asthmatics. The objective of this study was to retrospectively evaluate attrition rates and program outcome measures (Body Mass Index [BMI] and maximum oxygen consumption [VO2max]) among asthmatic and non-asthmatic participants. STUDY DESIGN: Clinical data were collected from the Healthy Hearts Program, a 12-week nutrition and activity intervention program for children who are overweight, obese, or at risk for heart disease and other conditions, and used for the study. METHODS: Intervention data and demographics were obtained from medical records at the Children's Heart Center Nevada. Descriptive statistics, paired t-tests, Cox regression analysis, and analysis of covariance were conducted. RESULTS: The mean age of this population (N = 232) was 11 years; 54% were male, 64% were Hispanic, and 37% had asthma. Median time in the program was 9 weeks, and 58% of the population completed the program. Unadjusted analyses showed significant BMI decreases in asthmatic (P = 0.002) and non-asthmatic (P = 0.001) participants and increases in cardiorespiratory function for asthmatic males and females (P = 0.003, P = 0.004) and non-asthmatic males and females (P < 0.001 for both). Asthmatic and non-asthmatic children both had improved exercise intensity (P = 0.033, P < 0.001). CONCLUSIONS: This program is both beneficial and practical for obese children with asthma for losing weight and improving cardiorespiratory function.

IL-5 production by bone marrow stromal cells: implications for eosinophilia associated with asthma.

BACKGROUND: Eosinophil infiltration of bronchial tissue is a hallmark of asthma. Recruitment of eosinophils into pulmonary tissue is dependent on the presence of IL-5. In addition, IL-5 plays a significant role in the differentiation, proliferation, and maturation of eosinophil progenitor cells in the bone marrow before recruitment into the lung. The contribution of bone marrow eosinophil production to eosinophilia associated with asthma is poorly understood. OBJECTIVE: The aims of this study were to determine whether bone marrow stromal cells produce IL-5 and to determine whether IL-5 production by stromal cells is upregulated by IL-1, an inflammatory cytokine associated with asthma. METHODS: IL-5 messenger (m)RNA from bone marrow stromal cells was amplified by RT-PCR and sequenced. Stromal cells were lysed, and IL-5 protein production was measured by ELISA. Upregulation of stromal cell IL-5 transcription, translation, and functional effect on eosinophil differentiation was evaluated after stimulation with recombinant IL-1alpha and IL-1beta and compared with untreated cells. RESULTS: Bone marrow stromal cells transcribe and translate IL-5. The nucleotide sequence of IL-5 mRNA from stromal cells was identical to that previously reported for murine T cells. IL-5 mRNA abundance in stromal cells increased with increasing cell confluence in culture. IL-5 mRNA and protein levels were upregulated by exposure of stromal cells to the inflammatory cytokines IL-1alpha and IL-1beta. Exposure of stromal cells to IL-1 resulted in increased eosinophil differentiation in coculture experiments with nonadherent bone marrow cells. CONCLUSION: The production of IL-5 mRNA and protein by bone marrow stromal cells is a novel finding that has implications for both normal eosinophilopoiesis and development of the accelerated eosinophil production associated with asthma.

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 child's home.

Tourette's syndrome mimicking asthma.

Tourette's syndrome is a neurological disorder consisting of chronic motor tics and involuntary vocalizations. Some of these vocalizations include coughing, grunting, and wheezing. We report two adolescents with a history of chronic coughing who presented for further evaluation of previously diagnosed asthma. A careful history suggested that Tourette's syndrome might be responsible for the patients' symptoms. Neurology evaluation confirmed the correct diagnosis of Tourette's syndrome for both patients. Treatment specific for this disease led to ablation of all symptoms. A history of repetitive coughing in adolescents may be the presenting symptom of Tourette's syndrome, thereby mimicking cough-equivalent asthma.

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 patient's 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.

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.

Laryngeal papilloma presenting as steroid-dependent asthma in a 3-year-old child without recurrent stridor.

Upper airway obstruction is well described as a cause of apparent asthma. However, it can be very difficult to diagnose in young children. This 3-year-old male presented with a 1-year history of severe recurrent wheezing with six emergency room visits in the previous 5 months. Cromolyn, inhaled corticosteroids, and frequent predinisolone bursts had not controlled the wheezing. There was no history of barky cough, croup, or stridor. His physical examination was notable for marked nasal obstruction. At initial presentation, his lungs were normal with no wheezing or stridor. Soft tissue neck X-ray films suggested the presence of a subglottic mass. A large solitary papilloma was found on bronchoscopy. After surgical removal, there was no further wheezing noted by either the parents or his physicians. Laryngeal papillomatosis may mimic asthma in the absence of symptoms of hoarseness, croup, or stridor. It should be particularly considered in 2 to 4-year-old children with recurrent wheezing that is poorly responsive to aggressive therapy including oral corticosteroids.

A bradykinin antagonist inhibits both bradykinin- and the allergen-induced airway response in primates.

Bradykinin is a mediator of bronchoconstriction and may play a role in the development of the asthmatic response after antigen challenge. Our objective was to study the effectiveness of NPC 17731 as a specific bradykinin beta 2-receptor antagonist and as an antagonist of the allergen-induced early phase of asthma. A primate model was used for all studies. Intracutaneous end-point titrations were performed with bradykinin. A shift of the bradykinin end-point titer was seen when NPC 17731 was injected by the intradermal route prior to performing the end-point titration. Using an aerosolized bradykinin or Ascaris suum antigen airway threshold challenge system, inhibition of the bradykinin or Ascaris airway response was evaluated after pretreatment with aerosolized NPC 17731. NPC 17731 proved to be a safe, effective specific bradykinin receptor antagonist in both cutaneous and airway challenges. NPC 17731 was able to inhibit the antigen-induced airway response in the primate. Bradykinin may play a larger role in mediating the early phase of the antigen-induced asthmatic response than previously was appreciated.

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.

Basement shower hypersensitivity pneumonitis secondary to Epicoccum nigrum.

Two children developed hypersensitivity pneumonitis after extensive exposure to an unventilated basement shower. Commercial precipitin panels were negative. After home inspection, individual mold species were isolated from the household and extracted. Precipitating antibodies to Epicoccum nigrum were found in both children. Resolution of the hypersensitivity pneumonitis occurred with avoidance and glucocorticosteroid therapy. E nigrum is a newly identified etiologic agent for hypersensitivity pneumonitis found in a mold-contaminated home.

Study of employees with anhydride-induced respiratory disease after removal from exposure.

The purpose of this study was to determine clinical and immunologic status of hexahydrophthalic anhydride (HHPA) employees who have had immunologic respiratory disease and who have been removed from exposure for at least 1 year. In a retrospective study, 16 consecutive employees with HHPA-induced immunologic respiratory disease who had been removed from exposure for more than 1 year were evaluated. Eleven had asthma, allergic rhinitis, or both; five had hemorrhagic rhinitis. Respiratory symptoms were obtained by physician-administered questionnaire. Physical examination, spirometry, and chest film were obtained. Antibody against HHPA conjugated to human serum albumin (HHP-HSA) was determined by enzyme-linked immunosorbant assay. Symptoms, signs, and pulmonary functions were normalized in all employees. There was a decline in antibody titers for both IgE and IgG against HHP-HSA. There were no chest film findings attributable to HHPA. In this group, there appeared to be no evidence of permanent anatomic sequelae after removal from exposure for at least 1 year. Specific antibody was still present, but titers were lower at follow-up than at presentation for a substantial proportion of the sample.

Value of antibody level in diagnosing anhydride-induced immunologic respiratory disease.

The objective of this study was to determine whether immunologic anhydride-induced respiratory disease could be predicted on the basis of the level of specific immunoglobulin E (IgE) or immunoglobulin G (IgG) antibody. Eight-one anhydride-exposed employees in one plant were studied. Fourteen had disease and 67 did not. Immunologic studies were performed by enzyme-linked immunosorbent assay and expressed as titers. When optimal discriminant analysis was used, IgE < 1:5 and IgG < or = 1:10 were found to be the optimal titers for separating employees with and without immunologic respiratory disease caused by anhydrides. When IgG < or = 1:10 was used, 62 of 81 workers were correctly classified; the sensitivity was 100%, the positive predictive value was 45%, the specificity was 75%, and the negative predictive value was 100%. When IgE < 1:5 was used, 73 of 81 workers were correctly classified; the sensitivity was 86%, the positive predictive value was 67%, the specificity was 91%, and the negative predictive value was 97%. In conclusion, anhydride disease status can be predicted on the basis of specific IgG or IgE antibody level.

Idiopathic anaphylaxis. An attempt to estimate the incidence in the United States.

BACKGROUND: Idiopathic anaphylaxis has been described and classified, and increasing numbers of cases are being seen in the United States and abroad. Treatment regimens have been shown to be effective in prophylactic management. There is no available information about the number of cases in the United States. METHODS: We attempted to determine the number of cases of idiopathic anaphylaxis in the United States by mailing a questionnaire to all graduates (for the last 31 years) of the Northwestern University Allergy-Immunology Fellowship training program. RESULTS: Response to the questionnaire was 100%, and 633 cases were reported by this survey of 75 allergists. The current total number of identified cases of idiopathic anaphylaxis from all reports of cases in the United States is 1020. CONCLUSIONS: By extrapolation of the cases of idiopathic anaphylaxis reported by the allergists surveyed to the approximately 4000 allergists in the United States, the estimated number of cases in the United States is between 20,592 and 47,024. Idiopathic anaphylaxis is potentially fatal, represents a source of major medical health care costs, causes anxiety to patients and families, occurs in pediatric and adult populations, and is controlled by appropriate regimens. The estimated number of cases emphasizes the need for careful attention to idiopathic anaphylaxis by physicians.

Effectiveness of early therapy with corticosteroids in Stevens-Johnson syndrome: experience with 41 cases and a hypothesis regarding pathogenesis.

Evaluation of therapy for Stevens-Johnson syndrome was initiated as a retrospective analysis and then extended to a prospective series of patients treated with corticosteroids. This report extends the initial prospective study of patients with Stevens-Johnson syndrome treated with corticosteroids and evaluates the total series of 41 patients relative to outcome and the presumptive etiology. We propose that management of Stevens-Johnson syndrome requires corticosteroid therapy and that the survival of patients with Stevens-Johnson syndrome may depend on this therapy. No fatalities or adverse effects due to corticosteroids were noted. Stevens-Johnson syndrome due to a drug, a drug metabolite or viral infection may mimic a graft-versus-host reaction in which the patient rejects skin, mucous membrane, kidney or liver cells to which the drug, drug metabolite, or virus has bound. Corticosteroids suppress the inflammatory rejection until the activating agent has been eliminated.

A naturally occurring model of immunoglobulin E antibody-mediated hypersensitivity in laboratory animals.

A naturally occurring model of immunoglobulin E (IgE) antibody-mediated hypersensitivity in canine and rhesus monkey species to environmental allergens is described. Cutaneous responses to a dust mite mix (Dermatophagoides farinae/pteronyssinus) and to four storage mite extracts (Aleuroglyphus ovatus, Blomia tropicalis, Chortoglyphus sp., Lepidoglyphus destructor) occurred in the canine species. Rhesus monkeys had IgE antibody-mediated hypersensitivity to dust mite on cutaneous challenge, but to a lesser degree than the canine species. Biologic relevance was verified by eliciting positive airway challenges in both species. The IgE antibody-mediated basis of these responses was confirmed by passive transfer technique. Demonstration of dust mite allergy provides a naturally occurring model of IgE antibody-mediated hypersensitivity in the canine and rhesus monkey species. Storage mite IgE antibody-mediated hypersensitivity exists in the canine species.