Abraham Resnick

A cluster of anaphylactic reactions in children with spina bifida during general anesthesia: Epidemiologic features, risk factors, and latex hypersensitivity

BACKGROUND Anaphylactic reactions (ARs) in high-risk pediatric patients undergoing general anesthesia, especially those with spina bifida, have been attributed to anesthetics, muscle relaxants, antimicrobials, ethylene oxide, and latex. METHODS To identify risk factors for AR during general anesthesia and to investigate the role of latex allergy, we studied epidemiologic and immunologic characteristics of patients with ARs during general anesthesia during a 13-month cluster of such reactions at Childrens Hospital of Wisconsin (case patients). Patients with AR were compared with patients with spina bifida undergoing uneventful general anesthesia during the same period (control patients). For each case patient and control patient, we conducted a chart review; a parental interview; skin prick testing with latex, anesthetics, aeroallergens, and banana extract; ELISA and RAST for latex-specific IgE; a total serum IgE; and an ELISA for IgE antibody to ethylene oxide. RESULTS Anaphylactic reactions occurred exclusively in patients with spina bifida (n = 10) or patients with a congenital urinary tract anomaly (n = 1). Case-patients were more likely than control patients to have a history of asthma (p = 0.002), rubber contact allergy (p = 0.001), food allergy (p = 0.001), rash caused by adhesive tape (p = 0.05), daily rectal disimpaction (p < 0.001), nine or more prior surgical procedures (p < 0.002), latex-specific IgE (p = 0.027), or elevated total serum IgE levels (p = 0.002). Multivariate analysis identified non-white race, rubber contact allergy, history of food allergy, and nine or more surgical procedures as significant independent risk factors. Logistic model equation identified the predicted probability of AR with a sensitivity, specificity, and positive predictive value of 82%, 97%, and 82%, respectively. CONCLUSIONS These findings demonstrate that atopy, especially symptomatic latex allergy, is associated with AR during anesthesia in patients with spina bifida. Until a standardized latex test is available, a medical history of immediate rubber contact allergy, non-white race, food allergy, or nine or more prior surgical procedures can identify patients with spina bifida at highest risk for ARs. A complete history, including rubber contact and food allergy, should be compiled on all patients with spina bifida before surgery.

Allergenic fungi and actinomycetes in smoking materials and their health implications

Street marijuana, commercial cigarettes and pipe tobaccos were studied for the presence of fungi and actinomycetes associated with hypersensitivity pneumonitis. Aspergillus species and thermophilic actinomycetes were isolated from the smoking materials. In addition, Aspergillus fumigatus spores were isolated from marijuana smoke, indicating the potential hazard involved in developing serious disease. Precipitin antibodies against fungi, particularly Aspergillus, showed a higher prevalence in marijuana smokers, whereas only very few cigarette smokers and nonsmokers demonstrated antibodies to fungi. Cigarette smokers and nonsmokers showed more or less similar prevelance of antibodies against thermophilic actinomycetes.

Latex Antigens Induce IgE and Eosinophils in Mice

Hypersensitivity to latex proteins has been reported with increasing frequency in recent years. Elevated levels of latex specific IgE have been detected in the majority of these patients. Severe anaphylaxis and death resulting from latex exposure has also been reported. Nevertheless, the immune mechanism of latex allergy is not fully understood. In this report, we describe a model of latex allergy developed in mice exposed to latex proteins. Animals exposed to latex proteins demonstrated enhanced levels of total IgE, peripheral blood and lung eosinophilia, and elevated levels of serum IL-4 and IL-5. mRNA transcripts of IL-4 and IL-5, but not IFN-gamma, could be demonstrated in spleen lymphocytes. Antibodies to latex belonging to all IgG subclasses were detected in the sera of mice exposed to latex antigens. The histology of the lung showed non-necrotizing granulomas and extensive interstitial chronic inflammatory infiltrates, particularly around bronchioles and small blood vessels. Although this model of latex allergy demonstrates a heterogeneous immunological response, the CD4-positive Th2 cell-mediated response predominated.

Role of Particulate Antigens of Aspergillus in Murine Eosinophilia

OBJECTIVE Allergic bronchopulmonary aspergillosis, a disabling hypersensitivity lung disease, results from inhalation of Aspergillus fumigatus antigens present in contaminated environments. A murine model has been developed to understand the immune mechanism involved in allergic bronchopulmonary aspergillosis. We have investigated the immunoregulatory role of different physical forms of A.fumigatus antigens, such as A.fumigatus spores, soluble antigens. and soluble antigen coupled inert particles, in the model. METHODS BALB/c mice were exposed to soluble A.fumigatus antigens, spores, or inert particles of comparable size to the spores coupled with A.fumigatus soluble antigens. Antibody and eosinophil response, pulmonary pathology, and cytokine expressions were studied. RESULTS Peripheral blood eosinophilia and pulmonary inflammation with influx of eosinophils into the lung was detected more in animals exposed to particulate antigens than in those exposed to soluble antigen. However, the total serum IgE and Aspergillus-specific IgG levels showed only a slight increase in the former groups as opposed to elevated levels in animals exposed to soluble antigen. The cytokine expression in in vitro antigen stimulated spleen cells showed a typical Th2 pattern in all antigen-exposed animals. IL-5 mRNA could be detected in the spleen cells cultured with antigen from all groups of antigen-exposed animals. CONCLUSION Particulate A.fumigatus antigens induced eosinophilia in mice prior to the elevation of serum IgE levels. This pattern of IgE and eosinophilia is reversed with the soluble antigen exposure in this model.

A partially purified glycoprotein antigen from Aspergillus fumigatus.

Culture filtrate antigens of Aspergillus fumigatus were fractionated by isoelectric focusing using a pH gradient of 4-6.5. Three fractions, namely, 18, 19 and 20 were pooled and subjected to immunochemical analysis. It contained a concanavalin A binding glycoprotein. Antibody raised against this component was used to prepare an affinity column of IgG-Sepharose and was used to purify crude culture filtrate antigens. This component produced three precipitin arcs in crossed immunoelectrophoresis using anti-A. fumigatus rabbit serum. This fraction has an isoelectric point of 6.5 and showed three components in two-dimensional electrophoresis with approximate molecular weights of 20, 40 and 80 kilo daltons. This antigen reacted with patient sera in the biotin-avidin linked immunosorbent assay and showed high levels of anti-A. fumigatus IgG and IgE antibodies in allergic bronchopulmonary aspergillosis and IgG antibodies in aspergilloma. Both controls and Aspergillus skin test positive asthmatics showed only low levels of specific antibodies. Because of the purity of this antigen, its potential use as a standardized antigen in the detection of antibody is discussed.