Figures
- FIGURE 1.
Proposed pathogenesis of chronic obstructive pulmonary disease. ROS: reactive oxygen species; LPS: lipopolysaccharide; PAH: polyaromatic hydrocarbons; BEC: bronchial epithelial cell; IL: interleukin; TNF: tumour necrosis factor; GM-CSF: granulocyte-monocyte colony-stimulating factor; TGF: transforming growth factor; PMN: polymorphic neutrophil; MPO: myeloperoxidase; MØ: macrophage; MMP: matrix metalloproteinase; NE: neutrophil elastatse; TIMP: tissue inhibitors of metalloproteinase; αAT: α1-antitrypsin; VEGF: vascular endothelial growth factor; END: endothelial cell; CRP: C-reactive protein. #: denotes the site of action of statins.
- FIGURE 2.
Proposed pathogenesis of lung cancer. ECM: extracellular matrix; ROS: reactive oxygen species; LPS: lipopolysaccharide; PAH: polyaromatic hydrocarbons; HMG CoA: 3-hydroxy-3-methylglutaryl coenzyme A; GTPase; guanosine triphosphatase; SHH: sonic hedgehog homologue; NADPH: reduced nicotinamide adenine dinucleotide phosphate; EGFR: epidermal growth factor receptor; TGF: transforming growth factor; NF-κB: nuclear factor-κB; AP-1: activator protein-1; MMP: matrix metalloproteinase; MPO: myeloperoxidase; PMN: polymorphic neutrophil; FGF: fibroblast growth factor. #: denotes the site of action of statins.
- FIGURE 3.
Morbidity and mortality benefits with statin use in observational studies on a logarithmic scale. CVS: cardiovascular; COPD: chronic obstructive pulmonary disease. Data are presented as odds ratio (95% confidence interval), except hospital cohort which is presented as relative risk (95% confidence interval) and following COPD exacerbation which is presented as hazard ratio (95% confidence interval).
Tables
- Table. 1—
Summary of statin mediated pharmacological effects on pulmonary inflammation and remodeling
COPD pathway Study type Statin effect on pathogenic pathways [Ref.] Cytokine production MM, HM in vitro (liver cell line), HM in vivo (mononuclear cells) Reduce IL-6 induced CRP production by hepatocytes [52, 67, 68] HM in vitro (VSM cells and PBE cells) Reduce IL-8 production by VSM cells [69, 70] MM Inhibition of neutrophil accumulation and IL-8 and TNF-α concentration in BALF in rats [71] HM in vivo (serum), MM Reduce production of IL-β1 and TNF-α [52, 72] MM Reduced expression of IFN-γ TNF-α and MMP12 in whole lung [73] Matrix remodelling MM Reduced lung parenchymal destruction and MMP 9 activity in smoke exposed rat lung [74, 75] HM ex vivo (bronchial epithelial cells) Reduce release of MMP2 and MMP9 from bronchial epithelial cells from lung transplant patients [70] Neutrophil/macrophage influx HM ex vivo (bronchial epithelial cells), HM in vivo (PMN) Reduce neutrophil influx in lung transplant recipients by inhibiting release of IL-8 and GM-CSF from bronchial epithelial cells [70, 76, 77] HM in vitro (PMN), HM in vivo (serum) Reduce neutrophil endothelial adhesion and transendothelial migration [76, 78–80] MM Reduce neutrophil influx and inhibit the development of elastase induced pulmonary emphysema in mice [74, 75] MM, HM ex vivo (human monocytes) Reduce CRP-induced monocyte migration by inhibition of ICAM-1 in human monocytes [81] MM, HM in vitro (endothelial cells), HM in vivo (BALF) Reduced concentration of neutrophils and lymphocytes in BALF [74, 75] MM, HM in vitro Reduce chemokine and adhesion molecule expression to reduce migration of inflammatory cells into the airways [74, 81, 82] Epithelial/endothelial integrity MM Promotes alveolar cell regeneration and restores endothelial cell function [75] MM Reduce LPS-induced IL-6 gene expression leading to reduced lung vascular leak and pulmonary inflammation in mice lung [83] HM in vitro (endothelial and smooth muscle cells) Inhibition of VEGF in smooth muscle cells and endothelial cells [84] Apoptosis HM in vitro (macrophages and PMN) Enhances clearance of apoptotic cells in alveolar macrophages from patients with COPD [85] HM in vitro (endothelial cells), HM in vitro (endothelial and smooth muscle cells) Increase apoptosis in human vascular endothelial cells [84, 86] Oxidant response HM in vivo (PMN) Reduce IL-8 release from neutrophils and neutrophil derived reactive oxidant species [77] HM in vivo (serum), MM Strong anti-oxidant properties [87, 88] Mucus production MM Reduced LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5A induced mucus hypersecretion [71] CRP level HM in vitro (liver cell) Reduce CRP levels at the transcriptional level thorough Rac-1 mediated inhibition of STAT3 phosphorylation [67] COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; MM: murine model; HM: human model; VSM: vascular smooth muscle; PBE: primary bronchial epithelial; PMN: polymorphic neutrophil; BALF: bronchoalveolar lavage fluid; IL: interleukin; TNF: tumour necrosis factor; IFN: interferon; MMP: matrix metalloproteinase; GM-CSF: granulocyte-monocyte colony-stimulating factor; ICAM: intracellular adhesion molecule; LPS: lipopolysaccharide; VEGF: vascular endothelial growth factor.
- Table. 2—
Mortality benefit of statin use in the general population diagnosed with community acquired pneumonia
Cohort Subject n Risk reduction [Ref.] Retrospective cohort study in teaching hospital 787 0.36 (0.14–0.92) 64% reduction in 30-day mortality [102] Population based prospective cohort study 3415 0.78 (0.57–1.07) 22% reduction in mortality or admission to an ICU [103] Population based retrospective nested case–control 6089 0.47 (0.25–0.88) 53% reduction in fatal pneumonia [104] Prospective hospital based observational study 1007 0.46 (0.25–0.85) 54% reduction in 30-day mortality [105] Population based cohort study 29900 0.69 (0.58–0.82) 31% reduction in 30-day mortality [106] 0.75 (0.65–0.86) 25% reduction in 90-day mortality Retrospective national cohort study 8652 0.54 (0.42–0.70) 46% reduction in 30-day mortality [107] Population based case–control study 2235 0.81 (0.46–1.42) 19% reduction in risk of pneumonia (after excluding those with CAD) [108] Population based cohort study 3681 0.33 (0.19–0.58) 67% reduction in 30-day mortality [109] 0.45 (0.32–0.62) 55% reduction in long-term mortality Data are presented as odds ratio (95% confidence interval). Data for population based case–control study and cohort study are presented as hazard ration (95% confidence interval). ICU: intensive care unit; CAD: coronary artery disease.
Jump To
- Article
- Abstract
- PATHOPHYSIOLOGY OF COPD
- EPIDEMIOLOGY OF COPD
- CURRENT TREATMENT IN COPD
- COPD AND SYSTEMIC INFLAMMATION
- STATIN EFFECTS ON CLINICAL OUTCOMES IN COPD: AN OVERVIEW
- STATINS EFFECTS ON SYSTEMIC INFLAMMATION IN COPD
- STATIN EFFECTS ON PULMONARY INFLAMMATION IN COPD
- SUMMARY
- Statement of interest
- Provenance
- References
- Figures & Data
- Info & Metrics