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Mite allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Enrique Fernández-Caldas, Leonardo Puerta, Luis Caraballo, Victor Iraola, Richard F. Lockey
As the complex nature of IgE synthesis became more evident, the discovery of “beyond MHC” immune response genes influencing IgE was more frequent. Polymorphisms in Th2 genes, for instance, those in the gene encoding interleukin 4 at the 5q31 locus [257,258] and the signal transducer and activator of transcription 6 (STAT6) [259], have been replicated in different populations. Associations with mite sensitization also have been reported with polymorphisms in the genes encoding interleukin-18 (IL-18) [260,261], leukotriene C4 synthase (LTC4S) [262], nitric oxide synthase 1 (NOS1) [263], interleukin-4 receptor alpha (ILR4A) [257], dendritic cell associated nuclear protein 1 (DCNP1) [264], interferon regulatory factor 1 (IRF-1) [265], CD14 [266,267], Janus kinase 2 (JAK2), GATA binding protein 3 (GATA3), CD40, and interleukin-5 receptor alpha (IL5RA) [268], all of them participating in any of the multiple steps of IgE synthesis. The significant associations with polymorphisms in innate immune genes suggest that genetic effects exert their influences at very early phases of the response. These loci include the complement component 3 (C3) associated with the specific IgE levels to D. pteronyssinus [269], the myeloid differentiation factor 2 (MD2) associated with the specific IgE levels to D. pteronyssinus and Der p 2 [270], and the nucleotide-binding oligomerization domain containing 1 (NOD1) associated with mite sensitization [268].
Principles of Treatment for Arthropod Bites, Stings, and Other Exposure
Published in Gail Miriam Moraru, Jerome Goddard, The Goddard Guide to Arthropods of Medical Importance, Seventh Edition, 2019
Gail Miriam Moraru, Jerome Goddard
In certain arthropod-related allergies (including asthma), such as dust mite or cockroach allergies, inhaled steroids, leukotriene antagonists, or cromolyn sodium may sometimes be used. For severe asthma, research has shown that anti-IgE products such as omalizumab can significantly reduce the number of days with asthma and allow reduction of inhaled steroid use.8,9 Other monoclonal antibodies such as benralizumab which targets an interleukin-5 receptor have shown benefit for persons with severe asthma.10 Cromolyn stabilizes mast cells against degranulation, thus preventing release of histamine, leukotrienes, and other pharmacological mediators. The use of epinephrine in severe or systemic hypersensitivity reactions acts to suppress (stabilize) mediator release from mast cells and basophils and reverses many of the end-organ responses to the pharmacological mediators of anaphylaxis, resulting in bronchodilation and relaxation of smooth muscle. The prompt use of epinephrine can often lead to complete resolution of the clinical manifestations of anaphylaxis within minutes.11
Diagnostic and therapeutic approaches for elderly asthma patients: the importance of multidisciplinary and multidimensional management
Published in Expert Review of Respiratory Medicine, 2023
Alida Benfante, Alessandra Tomasello, Enrico Gianquinto, Maria Noemi Cicero, Nicola Scichilone
Phase 3 studies confirmed the efficacy and safety of Benralizumab, a fully humanized afucosylated anti-eosinophil mAB binding the interleukin-5 receptor alpha submit (IL5-R), for adult patients with severe uncontrolled asthma with elevated blood eosinophils [72,73]. Differently from the most randomized clinical trials in which advanced age was an exclusion criterion, thus denying geriatric asthmatics access to interventional studies, in the SIROCCO and CALIMA studies the rate of elderly severe asthmatics (≥65–75 years) included was 12% and 14% respectively. Subgroup analyses of lung function and adverse events were performed by age (<18 yrs, 18 to <65 yrs, and ≥65 yrs) and age did not appear to influence the outcomes [74]. In addition, the treatment was well tolerated as demonstrated by the low discontinuation rate and safety profiles. In the ZONDA trial [75], the rate of elderly subjects (≥65–75 years) enrolled was 11% for placebo and Benralizumab Q4W group and 16% for Benralizumab Q8W group. For patients with asthma dependent on oral corticosteroids, Benralizumab during the 28 weeks of treatment was able to induce a significant reduction of oral corticosteroid dosage from baseline while maintaining disease control.
Multiple lung nodules, eosinophilia and severe asthma
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2022
Anurag Bhalla, Jean-Claude Cutz, Ehsan A. Haider, Michael Trus, Parameswaran Nair
Asthma is a chronic lung disease characterized by variable airflow obstruction and airway hyperresponsiveness and is associated with airway inflammation.1 About 40% of asthmatics demonstrate an eosinophilic inflammatory endotype, where eosinophils play a key role in disease pathophysiology.2,3 In uncontrolled patients, it is vital to consider medication adherence and conduct a thorough work-up to investigate for co-morbidities that may be contributing to worsening asthma control.4 Persistent eosinophilia may be associated with other pulmonary diseases that can occur concurrently with asthma, including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis and allergic bronchopulmonary aspergillosis.5 Other non-pulmonary causes of eosinophilia that must also be considered include drug reactions, allergic and mast cell diseases, parasitic infections, malignancy (both solid tumors and hematological malignancies), rheumatologic diseases and eosinophilic gastrointestinal disorders (highlighted in Table 1).6 We present a rare case of a patient with severe asthma, eosinophilia and pulmonary nodules and document their treatment response with an anti-interleukin-5 receptor alpha (anti-IL-5Rα) monoclonal antibody (mAb).
A drug safety review of treating eosinophilic asthma with monoclonal antibodies
Published in Expert Opinion on Drug Safety, 2019
Patrick Mitchell, Richard Leigh
Benralizumab is a targeted, humanized afucosylated, monoclonal antibody (IgG1, kappa) that binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα). The IL-5 receptor is expressed on the surface of eosinophils and basophils. The results of in vitro studies have also shown that the absence of fucose in the Fc domain of benralizumab results in much higher affinity binding for FcɣRIII receptors, which are expressed on immune effectors cells such as natural killer cells. This feature, unique to benralizumab in the anti IL-5 mAb class, induces apoptosis of eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). Benralizumab reduces eosinophilic inflammation through both effective depletion of IL-5 binding sites and enhanced ADCC. However, the exact mechanism of benralizumab action in asthma has not been definitively established.