Limited Short-term Steroid Responsiveness Is Associated With Thickening of Bronchial Basement Membrane in Severe Asthma

Background: The clinical manifestations of bronchial remodeling in asthma and the potential impact of this process on lung function remain unclear. We aimed to determine whether the presence of pathologic features of airway remodeling in patients with asthma was associated with steroid responsiveness in the short term. Methods: Sixty-three consecutive patients with severe asthma with chronic airflow impairment (post-bronchodilator FEV1 < 80% predicted values) were recruited, clinically characterized, and had an initial bronchoscopy where endobronchial biopsy and BAL were performed. BAL cellular content was reported and reticular basement membrane (RBM) thickness was measured by validated repeated measures. Patients were then treated with 1 mg/kg/d of methyl prednisone, directly administered IV, for 10 days. A threshold of 15% FEV1 improvement was used to discriminate responsive (group 1) and refractory patients (group 2). Results: Thirty-eight patients had a steroid responsiveness > 15% (group 1) and a thinner RBM at the biopsy level (5.78 +/- 2.0 mu m vs 7.60 +/- 2.2 mu m; P = .001) compared with nonsteroid responsive group 2 patients as defined. The best predictors for being unresponsive were no long-term treatment with oral steroids and increased RBM thickness. The associated receiver operating characteristic curve indicated that RBM thickness could predict steroid responsiveness below 15% with an area under the curve of 0.747 (P = .0002) at a threshold of 7 mu m. Conclusions: Features of airway remodeling are associated with limited short-term steroid responsiveness in severe asthma. CHEST 2012; 141(6):1504-1511