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Background: Cow's milk (CM) is an increasingly common cause of severe allergic reactions, but there is uncertainty with respect to severity of reactions at low-level CM exposure, as well as the reproducibility of reaction thresholds., Objective: We undertook an individual participant data (IPD) meta-analysis of studies reporting double-blind, placebo-controlled food challenges in CM to determine the rate of anaphylaxis to low-level exposures and the reproducibility of reaction thresholds., Methods: We performed a systematic review and IPD meta-analysis of studies reporting relevant data. Authors were contacted to provide additional data and/or clarification as needed. Risk of bias was assessed using the National Institute for Clinical Excellence methodologic checklists., Results: Thirty-four studies were included, representing data from over 1000 participants. The cumulative ED 01 and ED 05 (cumulative doses causing objective symptoms in 1% and 5% of the at-risk allergic population) were 0.3 (95% confidence interval [CI], 0.2-0.5) and 2.9 (95% CI, 1.6-5.4) mg, respectively. At meta-analysis, 4.8% (95% CI, 2.0-10.9) and 4.8% (95% CI, 0.7-27.1) of individuals reacting to ≤5 mg and ≤0.5 mg of CM protein had anaphylaxis (minimal heterogeneity, I 2  = 0%). Then 110 individuals underwent repeat double-blind, placebo-controlled food challenges; the intraindividual variation in reaction threshold was limited to a ½-log change in 80% (95% CI, 65-89) of participants. Two individuals initially tolerated 5 mg CM protein but then reacted to this dose at a subsequent challenge, although neither had anaphylaxis., Conclusions: About 5% of CM-allergic individuals reacting to ED 01 or ED 05 exposure might have anaphylaxis to that dose. This equates to 5 and 24 anaphylaxis events per 10,000 patients exposed to an ED 01 or ED 05 dose, respectively, in the broader CM-allergic population. Most of these anaphylactic reactions would be mild and respond to a single dose of epinephrine., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: beta(2)-Adrenergic agonists are the most widely used bronchodilators for the treatment of asthma. On the other hand, there is concern that excessive use of beta(2)-agonists may contribute to the exacerbation of asthma. However, the mechanism of such adverse effects of beta(2)-agonists is not completely clear., Objective: The aim of this study was to assess the direct influence of beta(2)-agonists on airways by analyzing the effect of a beta(2)-agonist, fenoterol, on airway sensitivity in an animal model and on tachykinin neurokinin-2 receptor expression in bovine tracheal smooth muscle., Methods: We performed an acetylcholine challenge test on ovalbumin sensitized guinea pigs that were exposed to daily inhalation of ovalbumin and fenoterol. We also investigated the effects of fenoterol on neurokinin-2 receptor messenger RNA and density with Northern blot analysis and receptor binding assay., Result: The increase of airway responsiveness and the decrease of beta(2)-adrenergic receptors were found in guinea pigs that were treated with fenoterol. There were time- and dose-dependent increases of neurokinin-2 receptor mRNA and of density in tracheal smooth muscle that was treated with fenoterol., Conclusion: This increased airway responsiveness, increased neurokinin-2 receptor expression, and decreased beta(2)-adrenergic receptor density may be relevant to asthma exacerbation.

Background: Superantigenic exotoxins produced by Staphylococcus aureus and their specific IgE antibodies are thought to be important precipitating factors of atopic dermatitis (AD), but there are few reports evaluating these 2 factors at the same time., Objective: We examined whether the presence of the exotoxins sampled from the skin of patients with AD and the levels of anti-exotoxin IgE antibodies in their sera correlated with their severity of AD., Methods: Patients with mild-to-severe AD, 1 to 22 years of age, were evaluated by using Leicester's scoring system. Specific IgE antibodies against these exotoxins were determined by using ELISA. S aureus was isolated from 3 different areas of the skin. We examined whether the exotoxin (staphylococcal enterotoxin [SE]A, SEB, SEC, SED, and toxic shock syndrome toxin-1) could be detected., Results: The levels of SEB-specific IgE were correlated with the severity of AD. Five of 6 patients having very high SEB-specific IgE antibody titers were under 6 years of age, and SEB was most frequently isolated (41%). There was no difference in severity between patients with or without exotoxin-producing S aureus. The severity of 9 patients who had both exotoxin-producing S aureus on the skin and specific IgE antibody against the same exotoxin in sera was significantly higher than that of the other patients., Conclusions: Anti-SEB IgE titers correlate well with the severity of AD. The presence of exotoxin-producing S aureus may precipitate AD through its specific IgE antibody.