Inflammation and Structural Changes in the Airways of Patients with Atopic and Nonatopic Asthma

Abstract

The aim of the present study was to compare the cellular pattern and structural changes in the airway walls of atopic and nonatopic patients with asthma. Bronchial biopsy specimens were obtained from 13 atopic subjects with asthma, nine nonatopic patients with asthma, and seven healthy control subjects and investigated using immunohistochemical methods. The number of eosinophils increased in both asthma groups, but significantly more in the atopic group. The number of mast cells increased similarly in the two asthma groups, whereas the number of neutrophils increased only in the nonatopic asthma group. The number of T-lymphocytes (CD3-, CD4-, CD8-, CD-25-positive cells) was higher in patients with atopic asthma compared with nonatopic asthma. Interleukin-4 (IL-4) and IL-5-positive cells were more frequently found in the atopic asthma group, whereas cells staining for IL-8 were more frequent in the nonatopic group. The degree of epithelial damage was significantly higher in the atopic asthma group compared with the control subjects and the nonatopic asthmatics. The tenascin and laminin layer was significantly thicker in the atopic group compared with the group of nonatopic asthmatics. In the atopic group, there was a significant negative correlation between epithelial integrity (defined as the relative length of intact epithelium) and the eosinophil count and also between the number of CD25-positive cells and epithelial integrity. The number of mast cells correlated positively with the thickness of tenascin- and laminin-positive layers. In conclusion, we provide evidence of different patterns of involvement of inflammatory cells in atopic and nonatopic patients with asthma. There were also structural differences in the bronchial mucous membrane between atopic asthma and nonatopic asthma. This suggests that there are differences in the extent of the immunopathologic response of these clinically distinct forms of asthma.

Mast cell–derived TNF can promote Th17 cell–dependent neutrophil recruitment in ovalbumin-challenged OTII mice

“…The extent to which such mast cell-dependent mechanisms may influence the expression of IL-17-dependent immune responses in other settings remains to be determined, and may well vary according to the particular biological response examined. However, it is worth mentioning here that work in human subjects both has suggested that neutrophils may be potentially important contributors to airway pathology in certain subsets of patients with asthma, [41][42][43][44][45][46][47][48] and has identified IL-17 expression in the lungs of some subjects with this disorder. 32,[49][50][51][52][53] Therefore, it will be of interest to attempt to investigate whether the mechanisms that contribute to the mast cell-dependent enhancement of IL-17-dependent airway neutrophilia that have been revealed in our analyses of OTII mice have any bearing on the regulation of neutrophil recruitment that can occur in human asthma.…”

Neutrophilic airway inflammation and IL‐17

“…In asthma, the bronchial epithelial cell, the macrophage, the neutrophil and even the eosinophil bear the potential of contributing to neutrophil recruitment by producing IL-8 (41)(42)(43)(44)(45). In chronic bronchitis, the neutrophil itself may be an important producer of IL-8 (45).…”

Polymorphisms in interleukin 8 and its receptors (IL8, IL8RA and IL8RB) and association of common IL8 receptor variants with peripheral blood eosinophil counts

“…Increased levels of IL8 in sputum precede an exacerbation of asthma, and IL8-producing cells are more frequently found in non-atopic asthma patients. In addition, IL8 selectively inhibits IgE production in atopic patients (Amin et al 2000;Heinzmann et al 2004;Kurashima et al 1996). Recently, several studies have reported the association of the polymorphism -251T within the promoter of IL8 with respiratory syncytial virus (RSV) bronchiolitis in the UK, and juvenile idiopathic arthritis and asthma in Germany (Heinzmann et al 2004, Hull et al 2000.…”