Table 2.

Pathogenesis of Chronic Obstructive Pulmonary Disease: Potential Opportunities for Interactions With HIV

Population	Proposed Mechanism of Lung Inflammation/Tissue Destruction
All COPD	Inflammation is induced by tobacco smoke [26] ○ Lung tissue destruction due to influx of: ▪ Neutrophils ▪ CD8+ lymphocytes ▪ Macrophages
	Remodeled lung increases the risk for bacterial colonization [27] ○ Increased risk for repeated bacterial infection ○ Increased chronic inflammatory state within lungs
HIV infection and COPD	Independent influx of CD8+ lymphocytes [23, 28] Increased number of activated macrophages [29, 30] ○ Increased expression of matrix-metalloproteinase 9, a destructive enzyme [31] Oxidant-antioxidant imbalance ○ Increased oxidant stress from direct viral effects of HIV [32] ○ Decreased levels of antioxidants in the lung, including glutathione [33] HIV protein induction of apoptosis of lung endothelial cells [22, 34] Antiretroviral effects [14, 21, 24] ○ Direct effects ○ IRIS–type response to organisms in the lung Increased susceptibility to bacterial pulmonary infection [27] Increased susceptibility to Pneumocystis colonization after Pneumocystis infection ○ Primates with SHIV infection with Pneumocystis colonization develop airway obstruction over time [35] ○ Humans with HIV infection with Pneumocystis colonization show increased rates of airway obstruction after controlling for smoking [36]

Abbreviations: COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus; IRIS, immune reconstitution inflammatory syndrome; SHIV, simian/human immunodeficiency virus.