Benefits of high-dose i.v. immunoglobulin in patients with severe steroid-dependent asthma.

STUDY OBJECTIVE: To determine the efficacy of IV immunoglobulin (IVIg) in severe asthma to reduce steroid requirements. DESIGN: Pre- and posttreatment measurements were analyzed using Dunnett's multiple comparison procedure. SETTING: Hospital clinical research center. PATIENTS: Eleven adolescents and adults with severe, steroid-dependent asthma enrolled over a 14-month period. INTERVENTIONS: IVIg was administered at a dose of 2 g/kg every 4 weeks for a total of seven infusions. MEASUREMENTS AND RESULTS: Steroid requirements, pulmonary function including lung volumes, symptom scores, bone densitometry, and airway reactivity monitored by methacholine challenge were followed over the course of 7 months. A significant decrease in steroid usage was achieved. Despite substantial steroid reduction, the patients demonstrated improvement in their pulmonary function and symptom scores. The responses to methacholine challenge were unaffected by IVIg treatment. CONCLUSIONS: IVIg provides a potentially important adjunctive therapy in severe asthma, reducing oral steroid requirements and steroid side effects without deterioration of lung function.

Effects of glucocorticoids on lymphocyte activation in patients with steroid-sensitive and steroid-resistant asthma.

BACKGROUND: Glucocorticoids are important medications used to control the airway inflammation associated with asthma. Synthetic glucocorticoids vary in their binding affinity for the glucocorticoid receptor (GCR). METHODS: We compared hydrocortisone, beclomethasone dipropionate, triamcinolone acetonide, flunisolide, and budesonide with regard to their capacity to inhibit phytohemagglutinin-induced peripheral blood mononuclear cell proliferation from six patients with steroid-sensitive asthma and seven patients with steroid-resistant asthma. Peripheral blood mononuclear cell GCR binding affinities for dexamethasone and budesonide were also determined for both patient groups by using a radioligand binding assay and Scatchard analysis. RESULTS: Dose-dependent inhibition was demonstrated for all glucocorticoids in both patient groups, with the steroid-resistant group requiring approximately 2 log-fold more glucocorticoids for an equivalent degree of inhibition. The mean concentrations necessary to cause 50% inhibition of lymphocyte proliferation (IC50s) for the steroid-sensitive group ranged from 2 x 10(-10) mol/L for budesonide to 7 x 10(-8) mol/L for hydrocortisone, whereas the mean IC50s for the steroid-resistant group ranged from approximately 2 x 10(-8) mol/L for budesonide to greater than 10(-6) mol/L for hydrocortisone. In addition, a significant correlation was noted between the degree of inhibition of lymphocyte proliferation (IC50) and the binding affinity of dexamethasone to the GCR. Patients with steroid-resistant asthma have been shown to have a reduced GCR binding affinity. The GCR binding affinity for budesonide was significantly higher in both groups (i.e., lower dissociation constant) than that obtained for dexamethasone. CONCLUSION: These data suggest that glucocorticoids such as budesonide, by virtue of their high GCR binding affinities and greater ability to suppress lymphocyte proliferation, may therefore be beneficial in the management of difficult-to-control asthma.

Intravenous immune globulin: an alternative therapy in steroid-dependent allergic diseases.

A fundamental feature of asthma is abnormal airway function, now recognized to result from both acute and chronic inflammatory changes. Central to the development of these inflammatory changes may be the activation of T cells and the release of pro-inflammatory cytokines. In the skin, a similar cascade of events may underlie the pathogenesis of atopic dermatitis. Asthma and atopic dermatitis often share several features that may be important in their pathogenesis: T-cell infiltration of the tissues, elevated IgE levels, and a history of known triggers associated with positive immediate skin-test reactions. In both diseases, administration of intravenous immune globulin (IVIG) on a regular basis appears to reduce the need for systemic corticosteroids, reduce symptoms and for asthmatics, reduce hospitalization costs. Although the mechanism of action of IVIG in these disorders remains to be defined, it may be exhibiting significant anti-inflammatory activity. IVIG may be a potent alternative in the treatment of severe, steroid-dependent allergic disorders, reducing steroid dependency.

Latex: a new occupational hazard for physicians.

Identification of latex sensitive individuals can be life saving. The American College of Allergy and Immunology has put forth the following recommendations: 1) Just as patients are routinely asked preoperatively about allergy to medications prior to treatment, a careful history should be obtained from every patient prior to any procedure involving contact with latex. Any patient who has a history of rash, itching, hives, rhinitis, swelling, or eye irritation or asthmatic symptoms after touching a balloon, rubber glove or any latex containing object is at risk for anaphylaxis. Previous medical history, of unexplained allergic or anaphylactic reactions during a medical procedure, may indicate sensitization. 2) Health care providers or other workers who give a history of only mild latex-glove eczema rarely have anaphylactic events. However, a history of work-related conjunctivitis, rhinitis, asthma, or urticaria may indicate allergic sensitization and increased risk for more severe reactions in the future. 3) The utility of screening tests for predicting anaphylaxis remains controversial. Suitable reagents for skin prick tests for latex are not commercially available at this time. Inasmuch as prick testing appears to carry a substantial risk of inducing anaphylaxis, this test must be considered experimental and it should only be done by experienced physicians with resuscitative equipment and personnel immediately available. Serum tests for latex-specific IgE, currently performed on a research basis at several laboratories, may confirm a suspected diagnosis in many cases but presently lack sensitivity to identify all patients with true latex allergy.(ABSTRACT TRUNCATED AT 250 WORDS)