Effects of Exercise and Sleep Deprivation on Reaction Severity During Oral Peanut Challenge: A Randomized Controlled Trial.

BACKGROUND: The severity of allergic reactions to foods can vary markedly. Little is known of variations in reaction severity within or between individuals or the effects of cofactors. OBJECTIVE: We examined the effects of sleep deprivation and exercise and repeat challenges on the severity and patterns of allergic reactions to peanut. METHODS: In a randomized crossover study, adults with peanut allergy underwent 3 open peanut challenges in random order: with exercise after each dose, with sleep deprivation preceding challenge, and with no intervention. The primary outcome was eliciting dose, reported elsewhere. Reaction severity was a secondary outcome, evaluated using a weighted log-transformed numerical severity score. Analyses estimated the difference in severity between nonintervention challenge and challenges with exercise or sleep deprivation, adjusting for challenge order and using the highest dose tolerated by each individual across all their challenges. Symptom pattern reproducibility was assessed by comparing symptom sequences using pairwise sequence alignment to obtain a percentage match in symptom pattern. RESULTS: Eighty-one participants (mean age 25 y) completed at least 1 postbaseline challenge. Sleep deprivation, but not exercise, significantly increased severity score by 48% (95% CI 12%-84%; P = .009) compared with no intervention. A 38% increase in severity was observed between the first and the last postbaseline challenge (95% CI 1%-75%; P = .044). The average pairwise match of symptoms within individuals was 82.4% and across individuals was 78.3%. CONCLUSIONS: A novel severity score demonstrates that sleep deprivation and repeated challenges increase reaction severity. Understanding factors affecting severity is essential for effective risk management. We also show that symptom patterns in repeat peanut challenges are similar within and between individuals.

Effect of sleep deprivation and exercise on reaction threshold in adults with peanut allergy: A randomized controlled study.

BACKGROUND: Peanut allergy causes severe and fatal reactions. Current food allergen labeling does not address these risks adequately against the burden of restricting food choice for allergic patients because of limited data on thresholds of reactivity and the influence of everyday factors. OBJECTIVE: We estimated peanut threshold doses for a United Kingdom population with peanut allergy and examined the effect of sleep deprivation and exercise. METHODS: In a crossover study, after blind challenge, participants with peanut allergy underwent 3 open peanut challenges in random order: with exercise after each dose, with sleep deprivation preceding challenge, and with no intervention. Primary outcome was the threshold dose triggering symptoms (in milligrams of protein). Primary analysis estimated the difference between the nonintervention challenge and each intervention in log threshold (as percentage change). Dose distributions were modeled, deriving eliciting doses in the population with peanut allergy. RESULTS: Baseline challenges were performed in 126 participants, 100 were randomized, and 81 (mean age, 25 years) completed at least 1 further challenge. The mean threshold was 214 mg (SD, 330 mg) for nonintervention challenges, and this was reduced by 45% (95% CI, 21% to 61%; P = .001) and 45% (95% CI, 22% to 62%; P = .001) for exercise and sleep deprivation, respectively. Mean estimated eliciting doses for 1% of the population were 1.5 mg (95% CI, 0.8-2.5 mg) during nonintervention challenge (n = 81), 0.5 mg (95% CI, 0.2-0.8 mg) after sleep, and 0.3 mg (95% CI, 0.1-0.6 mg) after exercise. CONCLUSION: Exercise and sleep deprivation each significantly reduce the threshold of reactivity in patients with peanut allergy, putting them at greater risk of a reaction. Adjusting reference doses using these data will improve allergen risk management and labeling to optimize protection of consumers with peanut allergy.

Diagnostic Value of Tryptase in Food Allergic Reactions: A Prospective Study of 160 Adult Peanut Challenges.

BACKGROUND: Serum tryptase is useful in diagnosing drug and venom anaphylaxis. Its utility in food anaphylaxis is unknown. OBJECTIVE: The objective of this study was to determine whether tryptase rises in food allergic reactions, optimal sampling time points, and a diagnostic cutoff for confirming a clinical reaction. METHODS: Characterized peanut allergic patients were recruited and underwent up to 4 peanut challenges and 1 placebo challenge each. Tryptase was measured serially on challenge days both before (baseline) and during the challenge. The peak percentage tryptase rise (peak/baseline) was related to reaction severity. Receiver operating characteristic (ROC) curves were generated establishing an optimal diagnostic cutoff. RESULTS: Tryptase was analyzed in 160 reactive (9% anaphylaxis) and 45 nonreactive (placebo) challenges in 50 adults aged 18 to 39 years. Tryptase rose above the normal range (11.4 ng/mL) in 4 of 160 reactions. When compared with baseline levels, a rise was observed in 100 of 160 (62.5%) reactions and 0 of 45 placebo challenges. The median rise (95% confidence interval [CI]) for all reactions was 25% (13.3% to 33.3%) and 70.8% (33.3% to 300%) during anaphylaxis. Peak levels occurred at 2 hours and correlated with severity (P < .05). Moderate-to-severe respiratory symptoms, generalized erythema, dizziness, and hypotension were correlated with a higher peak/baseline tryptase (P < .05). ROC curve analysis demonstrated the optimal cutoff to identify a reaction as a 30% rise (sensitivity 0.53; specificity 0.85), area under the curve 0.72 (95% CI, 0.67-0.78). CONCLUSIONS: Serum tryptase measurement is valuable in food allergic reactions, and correlates with symptom severity. Comparing peak reaction levels at 2 hours with baseline is essential. A rise in tryptase of 30% is associated with food allergic reactions.

Anaphylaxis: current state of knowledge for the modern physician.

Anaphylaxis is a severe, potentially fatal, hypersensitivity reaction of rapid onset. It may trigger life-threatening cardiopulmonary compromise, often with skin and mucosal changes such as urticaria and angioedema. The prevalence of anaphylaxis is increasing and the number of cases of fatal anaphylaxis appears to be rising. Food, insect stings, and drugs are the most common triggers. Novel triggers are increasingly seen and include delayed anaphylaxis to red meat, food-dependent exercise-induced reactions and anaphylaxis to monoclonal antibodies. Anaphylaxis is usually IgE mediated, but other mechanisms also play a role for example direct mast cells activation. Differential diagnosis is discussed including asthma, syncope and shock; excessive endogenous histamine, food related syndromes, and some rare diagnoses. Intramuscular epinephrine is first line treatment. The role of other drugs is reviewed. Timed and serial serum tryptase measurements help to confirm the diagnosis. Long-term management is necessary to minimise the risk of recurrence and includes identification of the trigger(s), management of risk factors, education on avoidance and a formalised treatment plan with an epinephrine auto-injector if appropriate. Every patient who has experienced anaphylaxis should be referred to an allergy clinic for appropriate management. This is endorsed by many national guidelines (eg, UK NICE). Anaphylaxis is often misdiagnosed or miscoded as, for example, asthma or food allergy. Most doctors will encounter a patient with anaphylaxis in their career and should to be familiar with the clinical features, management and mechanisms of this potentially fatal condition.