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Introduction Extreme declines in forced vital capacity in one second (FEV1) during methacholine challenge testing (MCT), approaching double the usual termination threshold (>35%), are uncommon but clinically significant, with implications for patient safety and recovery time. These responses are difficult to predict. This study aimed to identify patient characteristics associated with extreme FEV1 decline during MCT.Methods A retrospective analysis was performed on 353 patients referred with suspected asthma who underwent MCT between July 2022 and May 2025. Testing used the 5-breath dosimeter method (MB3 Dosimeter, Pulmolink Ltd) with a saline-calibrated delivery dose of 0.0458 mg per stage. Methacholine (32 mg/mL; Stockport Scientific) was serially diluted using a quadrupling dose protocol, with dose doubling if FEV1 had fallen by ≥15% from baseline. A positive test was defined as PC2 0 <16 mg/mL. An extreme response was defined as an FEV1 decline ≥35% or ≥1 L from baseline. Demographic, clinical, and physiological variables were compared between extreme and non-extreme positive responses using appropriate parametric or non-parametric tests.Results Of the 353 patients, 138 (39.1%) had a positive MCT. Twenty-four patients demonstrated an extreme FEV1 response. Compared with those with non-extreme positive responses (20–34% decline), patients with extreme declines were significantly younger (median 33.4 [24.2 – 45.8] vs 47.1 [35.0 - 58.7] years, p=0.001) and had higher baseline FEV1 (3.26 [2.27 – 3.94] vs 2.37 L [1.98 – 2.95], p=0.002). There were no significant differences in sex, BMI, atopy, eosinophilic status, smoking history, suspected inducible laryngeal obstruction, or ethnicity.Conclusions Extreme FEV1 decliners during MCT were younger in age and had higher baseline FEV1. Awareness of these features may aid risk anticipation and enhance patient safety during bronchial challenge testing.