Relationship between inflammatory cells and structural changes in the lungs of asymptomatic and never smokers: a biopsy study

Background: A study was undertaken to investigate the relationship between inflammatory cells and structural changes in the mucosa of the airways in an epidemiological sample of a group of asymptomatic smokers (smokers who had never sought medical attention for respiratory problems) and in non-smoking subjects. Methods: Bronchial biopsy specimens were taken from 29 smokers and 16 never smokers and stained with monoclonal antibodies HNL, EPO, AA1, CD68 in order to identify neutrophils, eosinophils, mast cells, and macrophages, respectively. The biopsy specimens were also stained with monoclonal antibodies to the cytokines interleukin (IL)-1β and IL-8. Structural changes were identified by staining the biopsy specimens with antibodies to tenascin and laminin and by evaluating the condition of the epithelial layer. Results: The numbers of all inflammatory cells and of cytokine staining cells were significantly increased in smokers. The thickness of the tenascin and laminin layers was increased in the smoking group and the integrity of the epithelial layer was significantly reduced. In smokers the epithelial integrity was negatively correlated with the number of eosinophils and macrophages. The thickness of the tenascin and laminin layers was positively correlated with AA1 and EPO positive cells only. Conclusion: High numbers of inflammatory cells are present in the bronchial mucosa of asymptomatic smokers which have a clear relationship with the impaired epithelial integrity. The increased thickness of the laminin and tenascin layers in these subjects was strongly related to the presence of eosinophils and mast cells, suggesting a role for these cells in tissue remodelling of the airways of smokers.

[1]  B. Bake,et al.  Measurement of closing volume with the single breath nitrogen method. , 1974, Scandinavian journal of respiratory diseases.

[2]  Y. Salorinne Single-breath pulmonary diffusing capacity. Reference values and application in connective tissue diseases and in various lung diseases. , 1976, Scandinavian journal of respiratory diseases. Supplementum.

[3]  A. Salsbury,et al.  Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy. , 1980, Thorax.

[4]  B. Bake,et al.  The single-breath N2-test and spirometry in healthy non-smoking males. , 1984, European journal of respiratory diseases.

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

[6]  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.

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

[8]  C. Dinarello Interleukin-1 and interleukin-1 antagonism. , 1991, Blood.

[9]  V. Lightner,et al.  Expression of human tenascin in synovitis and its regulation by interleukin-1. , 1992, Arthritis and rheumatism.

[10]  John I. Gallin,et al.  Inflammation: Basic Principles and Clinical Correlates , 1992 .

[11]  J. Bousquet,et al.  [Bronchial epithelium and asthma]. , 1992, Bulletin de l'Academie nationale de medecine.

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

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

[14]  J. Roca,et al.  Standardization of the measurement of transfer factor (diffusing capacity). Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. , 1993, The European respiratory journal. Supplement.

[15]  P. Venge,et al.  Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis. , 1993, The American review of respiratory disease.

[16]  L Wilhelmsen,et al.  Stressful life events, social support, and mortality in men born in 1933. , 1993, BMJ.

[17]  J E Cotes,et al.  Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. , 1993, The European respiratory journal. Supplement.

[18]  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.

[19]  J E Cotes,et al.  Lung volumes and forced ventilatory flows , 1993, European Respiratory Journal.

[20]  L. Fabbri,et al.  Airway eosinophilia in chronic bronchitis during exacerbations. , 1994, American journal of respiratory and critical care medicine.

[21]  D. Olivieri,et al.  Mast cells in the airway lumen and bronchial mucosa of patients with chronic bronchitis. , 1994, American journal of respiratory and critical care medicine.

[22]  L. Fabbri,et al.  Effect of smoking cessation on airway inflammation in chronic bronchitis. , 1995, American journal of respiratory and critical care medicine.

[23]  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.

[24]  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.

[25]  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.

[26]  P. Sterk,et al.  Chronic obstructive pulmonary disease: role of bronchiolar mast cells and macrophages. , 1997, The American journal of pathology.

[27]  R. Happonen,et al.  Effect of snuff and smoking on tenascin expression in oral mucosa. , 1997, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[28]  P. Jeffery,et al.  Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. , 1997, American journal of respiratory and critical care medicine.

[29]  J. Barberà,et al.  Interleukin-8 expression in bronchoalveolar lavage cells in the evaluation of alveolitis in idiopathic pulmonary fibrosis. , 1998, Respiratory medicine.

[30]  A. Sousa,et al.  Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease. , 1998, American journal of respiratory and critical care medicine.

[31]  O. Nilsson,et al.  A comparison of the expression of lymphocyte activation markers in blood, bronchial biopsies and bronchoalveolar lavage: evidence for an enrichment of activated T lymphocytes in the bronchoalveolar space. , 1999, Respiratory medicine.

[32]  C. Kampf,et al.  Effects of TNF-a, IFN-c and IL-b on normal human bronchial epithelial cells , 1999 .

[33]  P. Jeffery,et al.  Differences and similarities between chronic obstructive pulmonary disease and asthma , 1999, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[34]  T. Betsuyaku,et al.  Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema. , 1999, American journal of respiratory and critical care medicine.

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

[36]  F. Hargreave,et al.  Induced sputum, eosinophilic bronchitis, and chronic obstructive pulmonary disease. , 1999, American journal of respiratory and critical care medicine.

[37]  L. Fabbri,et al.  CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease. , 1999, American journal of respiratory and critical care medicine.

[38]  L. Fabbri,et al.  Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. , 2000, American journal of respiratory and critical care medicine.

[39]  D. Lúdvíksdóttir,et al.  Inflammation and structural changes in the airways of patients with atopic and nonatopic asthma. BHR Group. , 2000, American journal of respiratory and critical care medicine.

[40]  M. Traber,et al.  Tobacco-related diseases. Is there a role for antioxidant micronutrient supplementation? , 2000, Clinics in chest medicine.

[41]  A. Sousa,et al.  Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease. , 2000, The European respiratory journal.

[42]  F. Yamasawa,et al.  Increased expression of inflammatory mediators in small-airway epithelium from tobacco smokers. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[43]  U. Tylén,et al.  Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT. , 2001, Respiratory medicine.

[44]  L. Fabbri,et al.  Cellular and structural bases of chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[45]  L. Schwartz Mast cells and basophils. , 2002, Clinical allergy and immunology.

[46]  E. Gamble Cardioselective β blockers do not cause adverse respiratory effects in mild to moderate reactive airway disease , 2003 .

[47]  E. Salpeter,et al.  Cardioselective β-blockers in patients with reactive airway disease: a meta-analysis☆ , 2003 .

[48]  B. Weichman Inflammation: basic principles and clinical correlates , 1988, Agents and Actions.