Allergy
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Review
An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions.
Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. ⋯ The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.
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Multicenter Study Clinical Trial
The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma.
Mepolizumab and omalizumab are treatments for distinct but overlapping severe asthma phenotypes. ⋯ After directly switching from omalizumab to mepolizumab, patients with uncontrolled severe eosinophilic asthma experienced clinically significant improvements in asthma control, health status, and exacerbation rate, with no tolerability issues reported.
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Although the complex disease of asthma has been defined as being heterogeneous, the extent of its endophenotypes remains unclear. The pharmacological approach to initiating treatment has, until recently, been based on disease control and severity. The introduction of antibody therapies targeting the Type 2 inflammation pathway for patients with severe asthma has resulted in the recognition of an allergic and an eosinophilic phenotype, which are not mutually exclusive. ⋯ Validation of these pathways contributes to defining endotypes and treatable mechanisms. Precision medicine approaches are necessary to link treatable mechanisms with treatable traits and biomarkers derived from clinical, physiologic and inflammatory features of clinical phenotypes. The deep molecular phenotyping of airway samples along with noninvasive biomarkers linked to bioinformatic and machine learning techniques will enable the rapid detection of molecular mechanisms that transgresses beyond the concept of treatable traits.
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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.