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Introduction In methacholine challenge testing (MCT), skipping a methacholine dose is suggested if FEV.sub.1 falls by 5%. Using a larger threshold may further shorten test duration, but data supporting this hypothesis is lacking. We evaluated the safety and consequences of using a 10% FEV.sub.1 fall as threshold to skip the next dose of methacholine in patients undergoing MCT. Methods We reviewed MCTs performed in our center in 2017-2018. A [less than or equai to] 10% FEV.sub.1 fall allowed the omission of the next methacholine dose. Patients of interest were those in which a dose was skipped after a previous FEV.sub.1 fall outside the usual range (5-10%, termed "skip.sub.5-10%"). Adverse events [AE; mild: > 1 nebulized salbutamol dose (2.5 mg) to reach basal FEV.sub.1, palpitations; severe: hypoxemia and/or need for medical attention or intervention] were compared in the skip.sub.5-10% group and others. Regression analysis was used to identify predictors of AE. Results 208 MCTs were analysed (135 males, age 52 [+ or -] 15 years). Skip.sub.5-10% occurred 111 times in 90 tests. Prevalence of AE was 5% and all were mild. Patients who developed AEs had lower FEV.sub.1, FVC and FEV.sub.1/FVC ratio, and higher lung volume values (all p 0.05), but similar prevalence of skip.sub.5-10% (36 vs. 44%, p = 0.64). Overall, MCTs in which at least one skip.sub.5-10% occurred had a lower mean number of doses (3.1 [+ or -] 0.6 vs. 3.5 [+ or -] 1.3 doses, p = 0.007). Baseline residual volume was independently related to the development of AEs (OR 1.05, 95% CI 1.01-1.10, p = 0.01), but not the presence of a skip.sub.5-10%, even when the skipped dose directly led to the reaching of PC.sub.20 (OR 5.40, 95% CI 0.73-39.22, p = 0.10). Conclusion Omitting a methacholine dose based on a [less than or equai to] 10% fall in FEV.sub.1 occurs frequently and has the potential to shorten test duration. AE are rare, but patients with worse baseline lung function and gas trapping are at increased risk of mild side effects. Keywords: Asthma, Methacholine challenge testing, Respiratory physiology