Development and validation of a predictive model of failed stepping-down of inhaled corticosteroids in adult asthmatics

BACKGROUND Asthma guidelines suggest stepping-down of inhaled corticosteroids (ICSs) when asthma is stable. OBJECTIVE To determine outcomes of stepping-down and prediction of outcome after stepping-down of ICSs in controlled adult asthma. METHODS We performed a retrospective study on 21-81 year-old hospital-based outpatients with asthma in Japan. Protocol for stepping-down of ICSs was performed according to the GINA guideline. Failure/success of stepping-down is judged as occurring exacerbation or not for stepping-down of ICSs. Multiple logistic regression analysis was used to develop a prediction model for failed stepping-down, and then was validated by the leave-one-out cross-validation method. Our model of prediction score was calculated using receiver-operating characteristic area under the curve (AUC) analysis. The Nelson-Aalen curve demonstrated time to failure of stepping-down of ICSs. RESULTS A total of 126 patients with asthma attempted the stepping-down of ICSs according to the guideline. Of patients with follow-up, 97 (77.0%) of stepping-down attempts were successful. Using multivariate logistic regression analysis, comorbidity with rhinitis/rhinosinusitis and phlegm grade were independent predictors of failed stepping-down of ICSs, with odds ratios of 3.8 (95% confidence interval, 1.04-13.3; P=0.04) and 1.3 (95% confidence interval, 1.01-11.5; P=0.04), respectively. These variables were then used to build a prediction score in terms of the prediction of failed stepping-down events. When the two variables were added to form the prediction score, the discriminative power of scores calculated by the prediction model using the AUC was 0.75 (range: 0.62-0.88) for naïve prediction and 0.72 (range: 0.60-0.86) after cross-validation. In the time-to-failure models, cumulative hazard ratio of failed stepping-down have fixed 1 year after stepping-down. CONCLUSION Our results suggest that comorbidity with rhinitis/rhinosinusitis and phlegm grade are imperative to predict failed stepping-down of ICSs in controlled patients with adult asthma.