Late-onset non-allergic (LONA) asthma in obesity is characterized by increased peripheral airway closure secondary to abnormally collapsible airways. We hypothesized that positive expiratory pressure (PEP) would mitigate the tendency to airway closure during bronchoconstriction, potentially serving as rescue therapy for LONA asthma of obesity. The PC dose of methacholine was determined in 18 obese participants with LONA asthma. At each of 4 subsequent visits, we used oscillometry to measure input respiratory impedance (Z) over 8 minutes; participants received their PC concentration of methacholine aerosol during the first 4.5 minutes. PEP combinations of either 0 or 10 cmHO either during and/or after the methacholine delivery were applied, randomized between visits. Parameters characterizing respiratory system mechanics were extracted from the Z spectra. In 18 LONA asthma patients (14 females, BMI: 39.6±3.4 kg/m), 10 cmHO PEP during methacholine reduced elevations in the central airway resistance, peripheral airway resistance and elastance, and breathing frequency was also reduced. During the 3.5 min following methacholine delivery, PEP of 10 cmHO reduced A and peripheral elastance compared to no PEP. PEP mitigates the onset of airway narrowing brought on by methacholine challenge, and airway closure once it is established. PEP thus might serve as a non-pharmacologic therapy to manage acute airway narrowing for obese LONA asthma.