Epithelial activation in nocturnal asthma

Our laboratory has shown greater alveolar tissue inflammation in nocturnal asthmatics (NA) at night as compared to the large airways. We hypothesized that epithelial surface markers will also be increased in the distal airways of patients with NA at night. In an ongoing study, we evaluated nine patients, four with NA and five with non-nocturnal asthma (NNA) at 4 am and 4 pm. All patients underwent bronchoscopy at both time points with endobronchial brushing of the proximal airways under direct visualization and the distal airways under fluoroscopic guidance using a cytological brush. Epithelial cells were stained for: CD54 (ICAM-1), HLA-DR (activation marker), CD1lb (CR3 receptor), CD29 (β-1 integrin), CD51 (vitronectin receptor) and CD49b (VLA-2, collagen receptor). The % predicted FEV₁ was significantly reduced in the NA group as compared to the NNA group at 4 am (60.3 ± 2.1% vs. 81.6 ± 2.4%, p=0.001). The % of cells staining for CD51 and CD49b were increased in the NA group as compared to the NNA group, but only in the distal tissue (CD51: 43.0 ± 5.1% vs. 21.2 ± 4.6%, p=0.02; CD49b: 32.0 ± 4.1% vs. 15.4 ± 3.7%, p= 0.02). In the NA group alone, CD29 and CD51 were greater in the distal tissue at 4 am as compared to 4 pm (CD29; 88.0 ± 3.9% vs. 77.0 ± 6.5%, p=0.024; CD51: 43.0 ± 5.1% vs. 24.0 ± 3.5%, p=0.025). A significant relationship was present between the % predicted 4 am FEV₁ and the % of CD49b positive cells in the distal airways (r=0.74,p=0.05). There were no differences in the numbers of cells staining for any of the markers in the proximal airways at either time point. These preliminary findings suggest that markers of epithelial activation are increased at night in the distal airways of patients with NA.