Introduction: Lung clearance index (LCI) is a measure of airway disease that has been shown to be abnormal in asthma. We hypothesized that LCI would be higher (worse) in children with severe therapy-resistant asthma (STRA) compared with difficult asthma (DA) and healthy controls and that LCI would fall in response to parenteral steroids in STRA. Methods: Sixty-four children with asthma who were prescribed high-dose asthma therapy (GINA steps 4 or 5) performed LCI and spirometry. Forty-three had STRA and 21 DA. Thirty-nine of forty-three STRA patients attended for a clinically indicated bronchoscopy during which an intramuscular injection of triamcinolone was given. LCI, spirometry, and fractional exhaled nitric oxide (FeNO) were performed on the day of the bronchoscopy and repeated 4 weeks later. Results: LCI was more abnormal in STRA (median: 7.40, range: 5.58-12.34) than in DA (6.55, 5.77-7.75), P =.0006, and healthy controls (6.53, 5.57-7.35), P =.005. In contrast to the first second forced expired volume (FEV1), LCI improved following systemic steroids; of 20 STRA patients with an abnormal LCI at baseline, 13 improved following triamcinolone. LCI and FeNO responses were concordant. Conclusions: There is a subgroup of children with STRA in whom LCI is elevated who improve following parenteral steroids. LCI may be a valuable additional domain in assessing steroid response in pediatric asthma.