Inhaled corticosteroid dose response in asthma: Should we measure inflammation?

Abstract Background Inhaled corticosteroid (ICS) titration in asthma is primarily based on symptoms and pulmonary function. ICSs may not be increased on this basis despite residual airway inflammation. Objective To compare the dose-response relationships of ICSs on measures of pulmonary function, symptoms, and inflammation in patients with persistent asthma. Methods We performed a pooled post hoc analysis of 121 patients with mild to moderate asthma from 4 randomized clinical trials that incorporated an ICS dose ramp. Dose ramps were 0 to 200, 0 to 800, and 200 to 800 μg/d (beclomethasone equivalents). Outcome measures included spirometry, fractional exhaled nitric oxide, airway hyperresponsiveness (AHR), symptoms, serum eosinophilic cationic protein, and blood eosinophils. Results We found a plateau beyond a small improvement at 0 to 200 μg for forced expiratory volume in 1 second: 3.3% (95% confidence interval [CI], 2.0%–4.7%) at 0 to 200 μg vs 0.3% (95% CI, −0.8% to 1.4%) 200 to 800 μg ( P  = .001). A similar plateau was seen for symptom improvement beyond 0 to 200 μg. Inflammatory and AHR outcomes revealed further room for improvement beyond low-dose ICSs. There was dose-related suppression ( P P  = .03). AHR improved with all 3 dose ramps, with greater improvement at lower doses for indirect vs direct challenges. Conclusion ICS dose response may extend beyond low dose for inflammation and AHR but not symptoms or spirometry. Further study is required to identify whether this correlates with suboptimal longitudinal asthma control. Trial Registration ClinicalTrials.gov Identifiers: NCT00667992, NCT00995657, NCT01216579, NCT01544634.