The Aging Immune System and Its Relationship to the Development of Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs that usually manifests late in life. Physiologic and immunologic changes that occur in COPD often mimic changes seen in the aging lung. This has led some to characterize COPD as an ''accelerated aging phenotype.'' At the molecular level, COPD and aging share common mechanisms and are associated with significant dysregulation of the immune systems. Aging and COPD are characterized by increases in proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-a, which are implicated in aging-related inflammatory diseases and correlate with degree of obstruction in COPD. There is an age-dependent decline in naïve T cells with oligoclonal expansion of CD8 1 CD28 null T cells from chronic antigenic stimulation. The increase in CD8 1 CD28 null T regulatory cells inhibits antigen-specific CD4 1 T cell responses, leading to a decline in adaptive immune response. To compensate for the decline in the adaptive immune function there is a paradoxical up-regulation of innate immune system resulting in a proinflammatory state. The dysregulated adaptive immune system with activated innate immune responses seen with aging results in recruitment and retention of neutrophils, macrophages, and CD4 1 and CD8 1 T cells in the lungs of smokers with COPD. Once the inflammation is triggered, there is a selfperpetuating cascade of inflammation and lung parenchymal damage. This review will focus on how the aging immune system may contribute to COPD development later in life in susceptible individuals.

Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation

“…Age-related alterations in respiratory mechanics including decreases in pulmonary elastance have previously been described in Sftpd Ϫ/Ϫ mice up to 13 wk of age (8). Our findings that lung inflammation and structural abnormalities continue to increase up to 80 wk of age are novel and in accord with reports that inflammation contributes to reduced pulmonary function (22,43).…”

Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD

“…14 Theories to explain the basis of the inflammation and other aspects of COPD such as tissue loss include accelerated ageing and autoimmunity, 15 and may vary by different COPD phenotypes that are beginning to be described.…”

Risk of herpes zoster among patients with chronic obstructive pulmonary disease: a population-based study

“…Systemic immune disturbances have been observed in patients with COPD. [17][18][19] For example, Prieto and colleagues 17 found that cytotoxic activity of peripheral blood natural killer cells and phagocytic activity of peripheral blood monocytes, macrophages and polymorphonuclear cells were significantly reduced in patients with COPD compared with healthy control patients. Systemic cell-mediated immunity has been found to be impaired in COPD and to be associated with acute respiratory tract infection among patients with COPD.…”

“…18 Further, recent data have shown that COPD and aging produce significant molecular similarities in immunologic alterations. 19 Immunosenescence in aging is a well-known risk factor for herpes zoster; 5 immune system changes in COPD may further render such patients more vulnerable to varicella-zoster virus reactivation than age-matched control patients. We found that risk for herpes zoster was increased among patients with COPD in all age groups.…”