Allergen Immunotherapy for Asthma.

Allergen immunotherapy is a disease-modifying treatment for IgE-mediated allergies reducing disease burden and symptoms in patients with allergic rhinitis, with or without asthma. The growing evidence that allergen immunotherapy also has the potential to facilitate achieving asthma control in patients with allergic asthma resulted in its acknowledgment by international bodies (Global Initiative for Asthma and European Academy of Allergy and Clinical Immunology) as add-on treatment for mild/moderate asthma. Although there have been promising developments in biomarkers for patient selection and for allergen immunotherapy efficacy evaluation in patients with asthma, a lot more data are still required.

Identifying Low-Risk Beta-Lactam Allergy Patients in a UK Tertiary Centre.

BACKGROUND: There are marked geographical as well as temporal differences in patient sensitization profiles to ß-lactams (BL). OBJECTIVE: To determine the utility of skin test reagents and identify a cohort of patients where skin testing can be safely omitted in a cohort of patients referred to a UK tertiary referral center. METHODS: A retrospective study of the clinical characteristics of 1092 patients referred for BL allergy testing was analyzed using multivariate regression analysis. The effectiveness of skin test reagents was also evaluated. RESULTS: Multivariate logistic regression identified that a history of anaphylaxis (odds ratio [OR] 10.98, P = .001) and the patients' recall of the index drug (apart from ampicillin and meropenem, OR 3.51-12.43, P < .05) were independent predictors of type I BL allergic status and a time of less than 1 year elapsed since index reaction significantly increasing the odds of a patient with a history of anaphylaxis, having a type I BL allergy (OR 38.66, P = .003). An absence of anaphylactic severity, unknown name of the index drug and a reaction occurring more than 1 year before testing, has a negative predictive value (NPV) of 98.4%, which was similar to the NPV of skin testing of 98.9% for type I BL allergy. The NPV of skin testing with benzylpenicillin + amoxicillin ± index BL was similar with (98.9%) or without (98.1%) the use of benzylpenicillin polylysine and minor determinant for type I BL allergy. CONCLUSION: We identified a "low risk" cohort of patients where the history is of similar reliability to skin testing in predicting nonallergic status for BL allergy.

Omalizumab reduces bronchial mucosal IgE and improves lung function in non-atopic asthma.

Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE and inflammation and preserves/improves lung function when disease is destabilised by staged withdrawal of therapy.18 symptomatic, non-atopic asthmatics were randomised (1:1) to receive omalizumab or identical placebo treatment in addition to existing therapy for 20 weeks. Bronchial biopsies were collected before and after 12-14 weeks of treatment, then the patients destabilised by substantial, supervised reduction of their regular therapy. Primary outcome measures were changes in bronchial mucosal IgE+ cells at 12-14 weeks, prior to regular therapy reduction, and changes in lung function (forced expiratory volume in 1 s) after destabilisation at 20 weeks. Quality of life was also monitored.Omalizumab but not placebo therapy significantly reduced median total bronchial mucosal IgE+ cells (p<0.01) but did not significantly alter median total mast cells, plasma cells, B lymphocytes, eosinophils and plasmablasts, although the latter were difficult to enumerate, being distributed as disperse clusters. By 20 weeks, lung function declined in the placebo-treated patients but improved in the omalizumab treated patients, with significant differences in absolute (p=0.04) and % predicted forced expiratory volume in 1 s (p=0.015).Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE+ mast cells and improves lung function despite withdrawal of conventional therapy.

Audit of nasal lysine aspirin therapy in recalcitrant aspirin exacerbated respiratory disease.

BACKGROUND: Aspirin - exacerbated respiratory disease can prove difficult to control. Oral aspirin desensitization is effective, but has adverse effects and may not be cardio-protective at the high doses needed. OBJECTIVE: To examine the effectiveness of aspirin administered in lower doses via the nose. METHODS: An audit of 121 patients with aspirin exacerbated respiratory disease (AERD), 105 of whom were treated with intranasal lysine aspirin in gradually increasing doses following positive lysine aspirin challenge. RESULTS: Treatment was associated with subjective symptomatic improvement or stabilization in 60 of 78 patients at 3 months and 19 of 27 at 12 months. Nasal inspiratory peak flow, olfaction, exhaled and nasal nitric oxide levels were significantly improved (p < 0.05 for all). Patients with positive skin prick tests and those with later onset (>40 years) AERD improved more than non-atopics and those with early onset AERD. Asthma outcomes over 1 year were assessed by questionnaire in 22 patients on lysine aspirin and in 20 who were positive on challenge but who either refused treatment or took it only briefly (less than or equal to 3 months). There was a significant decrease in emergency visits (p = 0.0182), hospitalization (p = 0.0074) and oral steroid use (p = 0.004) in those on nasal lysine aspirin for a year. Gastrointestinal side effects occurred in 3.8%, lower than those reported for oral aspirin therapy. Conclusions and Clinical Relevance This form of therapy might reduce the need for expensive monoclonal antibodies in AERD patients.

"Auto-anti-IgE": naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation.

BACKGROUND: Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood. OBJECTIVE: Address the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation. METHODS: IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FcεRI. RESULTS: IgG autoantibodies binding to both free and FcεRI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen. CONCLUSION: Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma.

Airway epithelium in atopic and nonatopic asthma: similarities and differences.

Asthma is an inflammatory disorder of the airways, and the airway epithelium has the central role in its pathogenesis. In general, the airway inflammation is characterised by the infiltration of the epithelium and submucosa by a range of inflammatory cells driven largely by Th-2 lymphocytes, eosinophils, and mast cells. The pathogenic mechanisms of nonatopic asthma in comparison to its atopic counterpart have always been a subject of debate. Although clinically are two distinct entities, more similarities than differences have been observed between the two in terms of immunopathogenesis, underlying IgE mechanisms, and so on. in a number of previous studies. More information has become available in recent years comparing the ultrastructure of the epithelium in these two types of asthma. A comparison of airway epithelium in atopic and nonatopic asthma is presented here from the available information in the literature. Similarities outnumber the differences, until we unravel the mystery surrounding these two important phenotypes of asthma in more detail.