Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
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Randomized Controlled Trial Clinical Trial
The effects of the novel SHIP1 activator AQX-1125 on allergen-induced responses in mild-to-moderate asthma.
SH2-containing inositol-5'-phosphatase 1 (SHIP1) is an endogenous inhibitor of the phosphoinositide-3-kinase pathway that is involved in the activation and chemotaxis of inflammatory cells. AQX-1125 is a first-in-class, oral SHIP1 activator with a novel anti-inflammatory mode of action. ⋯ AQX-1125, a novel oral SHIP1 activator, significantly reduces the late response to allergen challenge, with a trend to reduce airway inflammation. AQX-1125 was safe and well tolerated and merits further investigation in inflammatory disorders.
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The mechanisms by which mast cells in patients with unexplained anaphylaxis (UEA) are triggered remain elusive. Onset of episodes is unpredictable and often recurrent. The substantial overlap between the clinical manifestations of UEA and clonal mast cell disorders (CMD) suggests an association between these rare disorders. The two forms of CMD characterized to date are systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS). ⋯ The pathogenic mechanism underlying UEA could be explained by the presence of immunophenotypically aberrant mast cells with clonal markers in 47% of our subjects, indicating that clonal mast cell disorders are present in a substantial subset of these patients. Thus, the presence of CMD should be considered in patients with UEA if they have an elevated level of sBT (≥ 11.4 ng/mL) and cardiovascular symptoms such as syncope.
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In asthma, the airway inflammatory phenotype influences clinical characteristics and treatment response. Although induced sputum is the gold standard test for phenotyping asthma, a more accessible method is needed for clinical practice. ⋯ Blood eosinophil counts and derived ratios (ELR and ENR) can accurately predict eosinophilic asthma in patients with persistent uncontrolled asthma despite treatment. Blood neutrophil parameters are poor surrogates for the proportion of sputum neutrophils. Blood counts may be a useful aid in the monitoring of uncontrolled asthma.
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Randomized Controlled Trial Multicenter Study
Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics.
CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses. ⋯ Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders.
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Neuromuscular blocking agents (NMBAs) are a predominant cause of perioperative anaphylaxis in Europe. Diagnosis of NMBA allergy relies upon the careful review of the anaesthetic report complemented with skin tests. Additional diagnostic tests are quantification of specific IgE antibodies (sIgE) and basophil activation test (BAT). However, data on the predictive value of the skin tests, the BAT and the sIgE assays (drug-specific and substituted ammonium structures) are limited or not available, mainly because such exploration requires dangerous NMBA provocation tests. ⋯ Skin test and BAT have an excellent negative predictive value in our series. The uneventful re-exposure of rocuronium in patients with an isolated positive sIgE result to rocuronium calls into question the predictive value of this assay and suggests sIgE serology to be less clinically predictive than the functional investigations relying upon activation of mast cells or basophils. The presence of a positive sIgE to substituted ammonium structures such as morphine does not preclude further use of benzylisoquinolines.