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Omalizumab has been shown to be effective in chronic urticaria (CU) patients in numerous reports. However, it remains unknown whether there are specific phenotypes of CU that are more responsive to omalizumab therapy. We sought to identify CU phenotypes responsive to treatment with omalizumab by characterizing patients and their response patterns. A retrospective chart review analysis of refractory CU patients unresponsive to high-dose H1-blockers and immunomodulators and subsequently treated with omalizumab at the University of Wisconsin Allergy Clinic was performed with particular focus on their autoimmune characteristics, response to therapy, and dosing parameters. We analyzed 19 refractory CU patients (16 patients failed or had toxic side effects to immunomodulators) treated with omalizumab with an overall response rate of 89% (17/19). Of these 19 patients, 9 patients (47%) had a complete response, 8 patients (42%) had a partial response, and 2 patients (11%) had no response. In comparing the response patterns to omalizumab, we found no statistically significant differences among "autoimmune positive" versus "autoimmune negative" patients. No statistically significant differences in responses were observed when comparing demographic parameters including age, gender, IgE levels, or dosing regimen. Our study shows that omalizumab has robust efficacy in refractory CU patients regardless of their autoimmune status, age, gender, IgE levels, or dosing protocol.

Over the past 2 decades, the prevalence of allergic respiratory diseases has increased, in part refl ecting changes in lifestyle and environment that promote a T-helper (Th) 2 cell phenotype. 1 It has been estimated that up to 20% of the US and Western Europe populations may be affl icted by allergic respiratory diseases. 2,3 A recent estimate of the total national medical expenditure attributable to adult asthma was reported as $18 billion, with the largest contributors being prescription drugs and inpatient hospitalizations. 4,5 Although allergen avoidance is an integral component and step of therapy, it is often impractical and insuffi cient. As a consequence, the mainstay of allergic disease management has been pharmacotherapy, especially antihistamines, bronchodilators, and inhaled/intranasal corticosteroids, which are targeted to regulate infl ammation of the upper and lower airways. Although these treatments are effective and, in most cases, safe, they offer no lasting benefi t once treatment is stopped and have limited intrinsic disease-modifying effects. Moreover, it has become apparent that allergic diseases are the result of immune dysregulation and refl ect an impairment in the natural tolerance that develops to allergens. 6,7 Immunotherapy has the potential to modify fundamental, underlying disease mechanisms and to have, Allergen-specifi c immunotherapy (SIT) involves the repeated administration of allergenic extracts to atopic individuals over a period of 3 to 5 years either subcutaneously (SCIT) or sublingually (SLIT) for the treatment of allergic respiratory diseases, including asthma and allergic rhinitis (AR). In studies, SCIT and SLIT have been shown to improve existing symptoms of asthma and AR and to also have the capability to cause disease-modifying changes of the underlying atopic condition so as to prevent new allergic sensitization as well as arrest progression of AR to asthma. Recent evidence suggests that immunotherapy brings about these effects through actions that use T-regulatory cells and blocking antibodies such as IgG 4 and IgA 2, which can then result in an "immune deviation" from a T-helper (Th) 2 cell pattern to a Th1 cell pattern. Numerous meta-analyses and studies have been performed to evaluate the existing data among these studies, with the consensus recommendation favoring the use of immunotherapy because of its potential to modify existing diseases. Signifi cant adverse reactions can occur with immunotherapy, including anaphylaxis and, very rarely, death. A primary factor in considering SIT is its potential to provide longlasting effects that are able to be sustained well after its discontinuation. Given the signifi cant burden these allergic diseases impose on the health-care system, SIT appears to be a cost-effective adjunctive treatment in modifying the existing disease state. CHEST 2012; 141(5):1303-1314Abbreviations: AR 5 allergic rhinitis; BHR 5 bronchial hyperresponsiveness; PEF 5 peak expiratory fl ow; SCIT 5 subcutaneous immunotherapy; SIT 5 allergen-specifi c...

House dust mites (HDM) are found in the environments where human habitation exists. Their density is dependent on environmental relative humidity; therefore higher populations are present in areas of the world with higher humidity levels e.g. coastal areas, tropics. To date 24 HDM allergens have been identified. Many of these represent digestive enzymes since HDM feces are the major source of allergen exposure. IgE- medicated sensitization to HDM allergens is an important factor in the pathogenesis of allergic diseases since it is the most common aeroallergen detected by skin testing or in vitro IgE assays. Sensitization to HDM allergens often occurs early in life and appears to play an important role in the progression from allergic rhinitis to asthma (the so-called “Allergic March”) in children. HDM sensitization is also associated with asthma across all age groups. Efforts to control environmental exposure to HDM allergens have often proven to be unsuccessful. While medications can improve symptoms, only immunotherapy currently provides disease modifying effects in allergic rhinitis and asthma. Several systemic reviews and meta-analysis indicate that both SCIT and SLIT are effective in the treatment of allergic rhinitis and asthma for HDM sensitivity. In this report we review recent studies and the evidence for the use of HDM SCIT and SLIT. Fundamental gaps in knowledge are identified which could lead to improved approaches to HDM allergy.

Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest.

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