Table 2.

Pathophysiological changes associated with smoking

Target of qualification	Biomarkers*	Articles
Microcirculatory system	Gingival blood flow (chronic effect ↓ and acute effect ↑, quit effect ↑) Number of vessels in inflamed site↓ (Gingival bleeding ↓) Oxygen sufficiency ↓ Pocket oxygen tension ↓ sICAM-1 ? (Serum ↑ and GCF ↓)	9-11 8 12 13 14, 15
Host immune inflammatory response systems	PMNs or neutrophil count ? (blood↑ and GCF↓) PMN function (chemotaxis, phagocytosis, and oxidative burst) ↓ Macrophage function ↓ T lymphocytes ? IgG2 ↓	16, 17 18 19** 17, 20, 21 22-27
Connective tissue and bone metabolism	IL-1a/β and IL-1ra ↓ IL-6 and IL-8 ↑, IL-4, and IL-10 ↓,TNF-α ↑ Elastase activity ? MMP-9 and MMP-3 in GCF ↑ MMP-8 ? (GCF ↑ and saliva ↓) α-2-Macroglobulin ↓ OPG ↓ and sRANKL/OPG ratio ↑ Prostaglandin E2 ↓ Free radicals ↑ Gingival fibroblast ↓ (Tissue repair and wound healing ↓)	16, 25, 28-31 25, 32-35 18, 36-38 39, 40 41, 42 43 44-46 36, 47-50 52 53

*↑: increase, ↓: decrease, ?: uncertain. **Lung macrophages

ICAM-1: intercellular adhesion molecule-1, GCF: gingival crevicular fluid, PMN: polymorphonuclear neutrophil, IgG: immunoglobulin G, IL: interleukin, TNF-α: tumor necrosis factor-α, MMP: matrix metalloproteinase, OPG: osteoprotegerin, RANKL: receptor activator of nuclear factor-κβ ligand