Allergy
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Hereditary angioedema (HAE) is a life-threatening, autosomal dominant disorder characterized by unpredictable, episodic swelling of the face, upper airway, oropharynx, extremities, genitalia, and gastrointestinal tract. Almost all cases of HAE are caused by mutations in the SERPING1 gene resulting in a deficiency in functional plasma C1 esterase inhibitor (C1EI), a serine protease inhibitor that normally inhibits proteases in the contact, complement, and fibrinolytic systems. Current treatment of HAE includes long-term prophylaxis with attenuated androgens or human plasma-derived C1EI and management of acute attacks with human plasma-derived or recombinant C1EI, bradykinin, and kallikrein inhibitors, each of which requires repeated administration. As an approach to effectively treat HAE with a single treatment, we hypothesized that a one-time intravenous administration of an adeno-associated virus (AAV) gene transfer vector expressing the genetic sequence of the normal human C1 esterase inhibitor (AAVrh.10hC1EI) would provide sustained circulating C1EI levels sufficient to prevent angioedema episodes. ⋯ A single treatment with AAVrh.10hC1EI has the potential to provide long-term protection from angioedema attacks in affected individuals.
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Randomized Controlled Trial
Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis.
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2-mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo-controlled, phase 2 trial (NCT01920893). ⋯ Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL-4Rα signaling suppresses IL-4-/IL-13-dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.
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Microbes in the airway have been shown to be associated with the pathogenesis of asthma. The upper airway microbiome influences the dysbiosis of the lower airway microbiome. However, to date, the influence of upper airway microbiome for adult and elderly asthma has not been fully elucidated. Here, the metagenome of upper airway microbiome of young adults and elderly was analyzed to identify their association with adult asthma. ⋯ These results suggest that the composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.
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Multicenter Study
The 2016 Melbourne thunderstorm asthma epidemic: Risk factors for severe attacks requiring hospital admission.
The world's most catastrophic and deadly thunderstorm asthma epidemic struck Melbourne, Australia, on November 21, 2016. ⋯ In epidemic thunderstorm asthma patients who presented to the ER, higher odds for hospital admission among patients with known asthma were further amplified by recent asthma admission, highlighting the vulnerability conferred by suboptimal disease control. Odds for hospital admission were lower in Asian patients born overseas, but higher in Asian patients born locally, than in non-Asian patients; these observations suggest susceptibility to severe thunderstorm asthma may be enhanced by gene-environment interactions.
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Allergen immunotherapy (AIT) is the only disease-modifying treatment option for patients with IgE-mediated inhalant allergies. Though used in clinical practice for more than 100 years, most innovations in AIT efficacy and safety have been developed in the last two decades. This expert review aimed to highlight the recent progress in AIT for both application routes, the sublingual (SLIT) and subcutaneous (SCIT) forms. ⋯ Potential clinical and nonclinical biomarkers are discussed. This review also focuses on potential future perspectives in AIT, such as alternative application routes, immune-modulating adjuvants, and recombinant vaccines. In conclusion, this state of the art review provides a comprehensive overview of AIT and highlights unmet needs for the future.