Abstract

A major contributory factor to the development of chronic obstructive pulmonary disease (COPD) is the inflammatory response to cigarette smoke. However, when those with COPD stop smoking, a continuous cycle of inflammation can lead to continued decline in lung function. Understanding the role of inflammatory cells in COPD is difficult because it is a mixture of diseases - bronchitis, small airways disease and emphysema - that exhibit different patterns of inflammation and different pathology. Neutrophils and macrophages have been implicated in this process; they release proteolytic enzymes and generate oxidants, which cause tissue damage, as well as cytokines and chemokines, which can potentiate inflammation and trigger an immune response. Analysis of sputum and bronchoalveolar lavage fluid shows increases in both neutrophils and macrophages in respiratory secretions in COPD subjects; neutrophils are the predominant cell in the conducting airways, whereas macrophages are the major cell in secretions from the small airways and parenchyma. Airway tissue neutrophils are increased in the large and small airways during infection and exacerbations, whilst parenchymal neutrophil numbers are inversely related to alveolar wall destruction, suggesting that they are not involved in the progression of emphysema. Macrophages are increased throughout the respiratory tract airway lumen and epithelium in COPD and are positively related to severity of disease, airway obstruction and degree of alveolar wall damage in emphysema. Unactivated T-lymphocytes do not linger in lung tissue. Activated (eg due to antigenic stimulus) memory T cells home in to the lung and act as effector cells. CD-8+ T cell differentiation into memory cells is facilitated by CD4+ T cells. Binding of CD-8+ T cells to collagen stimulates proliferation and mediator production which may contribute to the inflammatory response. CD8+ cytotoxic/suppressor T cells release cytotoxic perforins and granzyme B which cause cell death and apoptosis, a feature of emphysema. Lung secretions contain only a small percentage of T cells; most Tlymphocytes reside in the subepithelial and smooth muscle region of the tissue. During COPD, there is either an increase in the CD8+/CD4+ ratio of T cells, or an increase in the in total numbers of both CD8+ and CD4+ T cells, in the tissue. Smoking status, smoking history, degree of airway obstruction and emphysema are all related to increased CD8+ cells and/or CD8+/CD4+ ratio. During severe emphysema requiring lung volume reduction surgery, there is a considerable increase in macrophages, neutrophils, eosinophils, CD4+ and CD8+ T cells which relates to the severity of the disease. Interestingly, the marked increase in luminal CD8+ cells results in an increased ratio of CD8+/CD4+ T cells that is not seen in the parenchymal tissue. The florid inflammation observed in severe emphysema is suggested to be related to latent viral infection.

Keywords: Neutrophilic Inflammation, sputum, Central Airways, parenchyma, proinflammatory cytokines, Macrophages