The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Feb 2015
ReviewThe potential pharmacologic mechanisms of omalizumab in patients with chronic spontaneous urticaria.
In patients given a diagnosis of chronic spontaneous urticaria (CSU), there are no obvious external triggers, and the factors that initiate the clinical symptoms of wheal, flare, and itch arise from within the patient. Most patients with CSU have an autoimmune cause: some patients produce IgE autoantibodies against autoantigens, such as thyroperoxidase or double-stranded DNA, whereas other patients make IgG autoantibodies against FcεRI, IgE, or both, which might chronically activate mast cells and basophils. In the remainder of patients with CSU, the nature of the abnormalities has not yet been identified. ⋯ IgE and FcεRI engagement can also decrease the release threshold of mast cells and increase their sensitivity to various stimuli through either FcεRI or other receptors for the degranulation process. Furthermore, IgE-FcεRI engagement potentiates the ability of mast cells to store and synthesize de novo inflammatory mediators and cytokines. Administration of omalizumab, by virtue of its ability to deplete IgE, attenuates the multiple effects of IgE to maintain and enhance mast cell activities and hence reduces the ability of mast cells to manifest inflammatory mechanisms in patients with CSU.
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J. Allergy Clin. Immunol. · Feb 2015
ReviewAsthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care.
Traditionally, asthma and allergic diseases have been defined by broad definitions and treated with nonspecific medications, including corticosteroids and bronchodilators. There is an increasing appreciation of heterogeneity within asthma and allergic diseases based primarily on recent cluster analyses, molecular phenotyping, biomarkers, and differential responses to targeted and nontargeted therapies. These pioneering studies have led to successful therapeutic trials of molecularly targeted therapies in defined phenotypes. ⋯ This review shows that therapies targeting the canonical type 2 cytokines IL-4, IL-5, and IL-13 have shown consistent efficacy, especially in asthmatic patients with evidence of TH2/type 2 inflammation ("type 2 high"). As of yet, there are no successful trials of targeted therapies in asthmatic patients without evidence for type 2 inflammation. We conclude that further refinement of type 2 therapies to specific type 2 phenotypes and novel approaches for patients without type 2 inflammation are needed for asthma and allergic disease treatment.
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J. Allergy Clin. Immunol. · Feb 2015
ReviewAdvances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014.
This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2014. Studies on food allergy suggest worrisomely high rates of peanut allergy and food-induced anaphylaxis-related hospitalizations. Evidence is mounting to support the theory that environmental exposure to peanut, such as in house dust, especially with an impaired skin barrier attributed to atopic dermatitis (AD) and loss of function mutations in the filaggrin gene, is a risk factor for sensitization and allergy. ⋯ Studies have also provided insights into the prevalence and characteristics of anaphylaxis and insect venom allergy, such as suggesting that baseline platelet-activating factor acetylhydrolase activity levels are related to the severity of reactions. Advances in drug allergy include identification of HLA associations for penicillin allergy and a microRNA biomarker/mechanism for toxic epidermal necrolysis. Research identifying critical events leading to skin barrier dysfunction and the polarized immune pathways that drive AD have led to new therapeutic approaches in the prevention and management of AD.
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The application of recently developed sensitive, specific, culture-independent tools for identification of microbes is transforming concepts of microbial ecology, including concepts of the relationships between the vast complex populations of microbes associated with ourselves and with states of health and disease. Although most work initially focused on the community of microbes (microbiome) in the gastrointestinal tract and its relationship to gastrointestinal disease, interest has expanded to include study of the relationships of the airway microbiome to asthma and its phenotypes and to the relationships between the gastrointestinal microbiome, development of immune function, and predisposition to allergic sensitization and asthma. Here we provide our perspective on the findings of studies of differences in the airway microbiome between asthmatic patients and healthy subjects and of studies of relationships between environmental microbiota, gut microbiota, immune function, and asthma development. In addition, we provide our perspective on how these findings suggest the broad outline of a rationale for approaches involving directed manipulation of the gut and airway microbiome for the treatment and prevention of allergic asthma.
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J. Allergy Clin. Immunol. · May 2014
ReviewThe diagnosis and management of acute and chronic urticaria: 2014 update.
These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and ACAAI have jointly accepted responsibility for establishing "The diagnosis and management of acute and chronic urticaria: 2014 update." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. ⋯ In addition, before confirming the selection of a Work Group chairperson, the Joint Task Force will discuss and resolve all relevant potential conflicts of interest associated with this selection. Finally, all members of parameter workgroups will be provided a written statement regarding the importance of ensuring that the parameter development process is free of commercial bias. Practice parameters are available online at www.jcaai.org and www.allergyparameters.org.