Penicillin Allergy Evaluation: A Prospective, Multicenter, Open-Label Evaluation of a Comprehensive Penicillin Skin Test Kit.

BACKGROUND: Ten percent of the population claims an allergy to penicillin, but 90% of these individuals are not allergic. Patients labeled as penicillin-allergic have higher medical costs, longer hospital stays, are more likely to be treated with broad-spectrum antibiotics, and develop drug-resistant bacterial infections. Most penicillin skin test reagents are not approved by the Food and drug Administration or readily available to evaluate patients labeled penicillin-allergic. OBJECTIVE: To determine the negative predictive value (NPV) of the Penicillin Skin Test Kit containing the major allergenic determinant (penicilloyl polylysine), a minor determinant mixture (penicillin G, penicilloate, penilloate), and amoxicillin, produced according to Food and Drug Administration standards. METHODS: This was a prospective, multicenter, open-label investigation of penicillin skin testing using the Penicillin Skin Test Kit. Skin test-negative subjects were challenged with 250 mg amoxicillin, whereas skin test-positive patients were not challenged. The primary end point was NPV of the Penicillin Skin Test Kit, defined as the percentage of subjects with negative skin test results who did not experience an IgE-dependent reaction within 72 hours of amoxicillin challenge. RESULTS: In total, 455 patients with a history of penicillin allergy underwent skin testing and 63 (13.8%) had 1 or more positive test results; 65% of the positive test results were to the minor determinant mixture and/or amoxicillin alone. In the per protocol group of 373 skin test-negative subjects, 8 developed potential IgE-dependent reactions following oral amoxicillin challenge, translating to an NPV of 97.9% (95% CI, 95.8-99.1; P < .0001). All but 1 of the reactions was mild or moderate, and most subjects who required treatment received only antihistamines. CONCLUSIONS: The Penicillin Skin Test Kit, containing all relevant penicillin allergenic determinants, demonstrated very high NPV. Removal of a penicillin allergy label in a large majority of currently mislabeled patients has substantial personal and public health implications.

The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells.

BACKGROUND: Nuclear factor kappaB (NF-kappaB) plays a key role in the pathogenesis of asthma, being linked to the production of inflammatory cytokines that drive inflammation. A recently described anti-inflammatory protein, glucocorticoid-induced leucine zipper (GILZ), interferes with NF-kappaB-mediated gene transcription in T cells and macrophages. OBJECTIVE: We sought to analyze the regulation of GILZ expression in airway epithelial cells and determine whether GILZ mediates part of the anti-inflammatory effect of corticosteroids. METHODS: GILZ expression was assessed by means of PCR and immunoblotting in human epithelial cells at baseline and after stimulation with dexamethasone or cytokines (IL-1beta, TNF-alpha, and IFN-gamma). The effect of GILZ on LPS-, IL-1beta-, and polyinosinic:polycytidylic acid-induced NF-kappaB activation was assessed in BEAS-2B cells overexpressing GILZ. The requirement for GILZ in the inhibitory action of dexamethasone was assessed by knocking down GILZ expression by means of small interfering RNA (siRNA) technology. RESULTS: GILZ is constitutively expressed by human airway epithelial cells, and its levels are increased by dexamethasone and decreased by inflammatory cytokines. Overexpression of GILZ in BEAS-2B cells significantly inhibited the ability of IL-1beta, LPS, and polyinosinic:polycytidylic acid to activate NF-kappaB, whereas knockdown of GILZ inhibited the ability of dexamethasone to suppress IL-1beta-induced chemokine expression. CONCLUSION: This study demonstrates the expression of GILZ in human airway epithelial cells, its induction by dexamethasone, its suppression by inflammatory cytokines, and its role in mediating the anti-inflammatory effects of dexamethasone. CLINICAL IMPLICATIONS: Therapeutic upregulation of GILZ may be a novel strategy for the treatment of asthma.

Eosinophilic disorders in children.

Many pediatric diseases demonstrate blood or tissue eosinophilia. Included among these disorders are common atopic diatheses such as asthma as well as the rarer conditions of hypereosinophilic syndrome and eosinophilic gastrointestinal disorders. Eosinophil trafficking and activation in target organs leads to tissue damage and ongoing reparative attempts that can ultimately result in changes in organ structure and function. Recent treatment with biologic agents such as tyrosine kinase inhibitors and anti-interleukin-5 has offered new therapeutic options in certain eosinophilic disorders. Eosinophilic disorders such as eosinophilic esophagitis are increasingly being diagnosed in children, but many lessons in disease pathogenesis, diagnosis, optimal treatment, and natural history continue to be learned.

Biologic therapies for the treatment of asthma.

Asthma is a chronic disease of the airway whose pathogenesis involves the complex interplay between many cell types and inflammatory mediators. The mainstays of therapy, inhaled bronchodilators and corticosteroids, do not target the asthmatic airway specifically and therefore are associated with untoward side effects. Anti-IgE (omalizumab) is the only biologic therapy to have transitioned completely from bench to bedside. Other candidate therapies, such as those that alter the T-helper 1/T-helper 2 cytokine balance, interfere with inflammatory cell trafficking, or modify normal intracellular signaling cascades involved in inflammatory gene transcription, have had only limited success in human clinical trials. This article describes several potential novel biologic therapies that have been or could be investigated.