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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01429896.

Keywords: Peanut; allergy; exercise and sleep deprivation; thresholds.

Figure 1. Consort diagram

*one was excluded after review on the grounds that it had been stopped prematurely, resulting in a full analysis population of 81 participants

Figure 2. Percentage change in threshold (logged) for each covariate.

Full-analysis population n=81. Visits 1-3 refer to the chronological order of post-baseline challenge days. LOAEL = lowest observed adverse effect level is the reactive threshold in mg peanut protein during baseline challenge

Figure 3. Threshold dose distribution model

Doses given in mg peanut protein, per challenge type, showing cumulative probability of reacting against dose in peanut protein in milligrams. Full analysis population, n=81

Figure 4. Eliciting dose estimates (mg peanut protein) derived from threshold distribution curve;

mean (95% CI) by challenge type for eliciting doses (ED) for 1, 5, 10, 50, 80 and 95% of the full analysis population, n=81 are shown.

Figure 5. Dose distribution curve for extended analysis population (n=123) with 95% confidence intervals.

Dose is mg peanut protein. Eliciting doses (ED) in mg with 95% CI for 1, 5, 10, 50, 80 and 95% of the extended analysis population are shown as an inset table.

Figure 6. Descriptive analysis of participants whose dose threshold increased, decreased or remained the same following exercise and sleep deprivation (n=66).

Numbers show percentage of participants in each group (of a total of n=66 who undertook an exercise and non-intervention challenge, or sleep deprivation and non-intervention challenge). This was a post –hoc analysis therefore no statistical test was applied.