Inflammation and structural changes in the airways of patients with atopic and nonatopic asthma. BHR Group.

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.

[1]  L. Koenderman,et al.  Upregulation of formyl-peptide and interleukin-8-induced eosinophil chemotaxis in patients with allergic asthma. , 1993, The Journal of allergy and clinical immunology.

[2]  L. Fabbri,et al.  Bronchial epithelium and asthma. , 1989, The European respiratory journal. Supplement.

[3]  I. Virtanen,et al.  Tenascin is increased in airway basement membrane of asthmatics and decreased by an inhaled steroid. , 1997, American journal of respiratory and critical care medicine.

[4]  S. Durham,et al.  Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. , 1997, Journal of immunology.

[5]  S. Durham,et al.  IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against "intrinsic" asthma being a distinct immunopathologic entity. , 1996, American journal of respiratory and critical care medicine.

[6]  P. Venge,et al.  Human neutrophil lipocalin (HNL) is a specific granule constituent of the neutrophil granulocyte. Studies in bronchial and lung parenchymal tissue and peripheral blood cells , 1997, Histochemistry and Cell Biology.

[7]  D. Lúdvíksdóttir,et al.  Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjögren's syndrome , 2000, Allergy.

[8]  P. Howarth,et al.  Immunohistochemistry on resin sections: a comparison of resin embedding techniques for small mucosal biopsies. , 1993, Biotechnic & histochemistry : official publication of the Biological Stain Commission.

[9]  P. Jeffery.  Pathology of asthma. , 1992, British medical bulletin.

[10]  C. Kampf,et al.  Effects of TNF-alpha, IFN-gamma and IL-beta on normal human bronchial epithelial cells. , 1999, The European respiratory journal.

[11]  J. Virchow,et al.  Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. , 1992, The American review of respiratory disease.

[12]  M. Nieminen,et al.  Methacholine bronchial challenge using a dosimeter with controlled tidal breathing. , 1988, Thorax.

[13]  B. Sander,et al.  Assessment of Cytokines by Immunofluorescence and the Paraformaldehyde‐Saponin Procedure , 1991, Immunological reviews.

[14]  Mast cells and basophils. , 2000 .

[15]  S. Holgate,et al.  Adenosine bronchoprovocation: a promising marker of allergic inflammation in asthma? , 1997, Thorax.

[16]  C. Janson,et al.  Serum eosinophil cationic protein in relation to bronchial asthma in a young Swedish population , 1994, Allergy.

[17]  S. Durham,et al.  Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. , 1990, The American review of respiratory disease.

[18]  D. Lúdvíksdóttir,et al.  Exhaled nitric oxide and its relationship to airway responsiveness and atopy in asthma. BHR-Study Group. , 1999, Respiratory medicine.

[19]  S. Durham,et al.  Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. , 1991, The Journal of allergy and clinical immunology.

[20]  S. Wenzel,et al.  Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. , 1997, American journal of respiratory and critical care medicine.

[21]  S. Mattoli,et al.  Expression of the potent inflammatory cytokines, GM-CSF, IL6, and IL8, in bronchial epithelial cells of asthmatic patients. , 1992, Chest.

[22]  R. Todd,et al.  Sequential expression of transforming growth factors alpha and beta 1 by eosinophils during cutaneous wound healing in the hamster. , 1993, The American journal of pathology.

[23]  A. Wardlaw,et al.  Bronchial biopsies in asthma. An ultrastructural, quantitative study and correlation with hyperreactivity. , 1989, The American review of respiratory disease.

[24]  R. Dahl,et al.  Epithelial injury by human eosinophils. , 1988, The American review of respiratory disease.

[25]  P. Howarth,et al.  Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. , 1994, American journal of respiratory cell and molecular biology.

[26]  A. Frew,et al.  Position Paper: Allergen standardization and skin tests , 1993 .

[27]  S. Durham,et al.  Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. , 1992, The American review of respiratory disease.

[28]  A. Malmström,et al.  Eosinophil cationic protein alters proteoglycan metabolism in human lung fibroblast cultures. , 1992, European journal of cell biology.

[29]  P. Venge,et al.  Expression of laminins in the airways in various types of asthmatic patients: a morphometric study. , 1996, American journal of respiratory cell and molecular biology.

[30]  N. Flavahan,et al.  The eosinophil as a mediator of damage to respiratory epithelium: a model for bronchial hyperreactivity. , 1988, The Journal of allergy and clinical immunology.

[31]  D. Loegering,et al.  Toxicity of eosinophil cationic proteins for guinea pig tracheal epithelium in vitro. , 1989, The American review of respiratory disease.

[32]  B. Robinson,et al.  Eosinophils and major basic protein damage but do not detach human amniotic epithelial cells. , 1992, Experimental lung research.