Fine particles (particulate matter 2.5 μm [PM2.5]), a ubiquitous air pollutant, can deposit in the small airways that play a vital role in asthma. It appears to be unknown whether the use of a PM2.5 filtration device can improve small airway physiology and respiratory inflammation in children with asthma. To discover what pathophysiological changes in the small airways are associated with using a PM2.5-removing device in the bedrooms of children with asthma. Children with mild or moderate asthma were enrolled in this double-blind, crossover study. The participants used a true filtration device and a sham filtration device in their bedrooms in a random order for 2 weeks each with a 2-week washout interval. The study was conducted in a suburb of Shanghai, China, during a low-ozone season. Ozone and PM2.5 were measured inside bedrooms and outside a window. Impulse oscillometry, spirometry, and fractional exhaled nitric oxide were measured at the beginning and the end of each intervention. Peak expiratory flow was measured twice daily at home. Forty-three children (5-13 years old; 26 boys [60%]) participated. Outdoor 24-hour mean PM2.5 concentrations were moderately high, ranging from 28.6 to 69.8 μg/m3 (median, 53 μg/m3). During true filtration, bedroom PM2.5 concentrations were a mean (SD) of 63.4% (35.9%) lower than during sham filtration. Compared with sham filtration, true filtration was significantly associated with improved airway mechanics, reflected in a 24.4% (95% CI, 11.8%-37.1%) reduction in total airway resistance, a 43.5% (95% CI, 13.7%-73.3%) reduction in small airway resistance, a 22.2% (95% CI, 2.2%-42.2%) reduction in resonant frequency, and a 73.1% (95% CI, 0.3%-145.8%) increase in airway reactance. True filtration was also associated with significant improvements in fractional exhaled nitric oxide (a 27.6% [95% CI, 8.9%-42.4%] reduction) and peak expiratory flow (a 1.6% [95% CI, 0.8%-2.5%] increase). These improvements were significantly associated with bedroom PM2.5 reduction. Improvements in small airway function were nonsignificant (8.4% [95% CI, -1.4% to 18.3%]) in all participants but significant (13.2% [95% CI, 1.2%-25.1%]) in participants without eosinophilic airway inflammation at baseline. No improvements were observed for forced vital capacity, forced expiratory volume during the first second, and the ratio of these in all participants or subgroups. Per these results, indoor PM2.5 filtration can be a practical method to improve air flow in an asthmatic lung through improved airway mechanics and function as well as reduced inflammation. This warrants a clinical trial to confirm. ClinicalTrials.gov Identifier: NCT03282864.