1. The Use of Statins and Lung Function in Current and Former Smokers. Keddissi JI*, MD, FCCP, Younis WG*, MD, Chbeir EA, MD, Daher NN, MD, Dernaika TA, MD, and Kinasewitz GT, MD, FCCP Pulmonary and Critical Care Medicine The Oklahoma City VA Medical Center and the University of Oklahoma Medical Center, Oklahoma City, OK Journal conference Department of pulmonalogy R1 Jang Jeong Yoon Chest October 1, 2007 DOI:10.1378

2. Introduction Statin - treatment of patients with hypercholesterolemia. first line therapy for cardiovascular diseases effect lipid-lowering effects, anti-inflammatory, antioxidant, antithrombogenic, and vascular function.restoring actions. Smoking chronic inflammation.

3. Introduction  reducing inflammatory infiltration, and by inhibiting matrix metalloproteinase 9 (MMP-9) induction Simvastatin inhibits cigarette smoking induced emphysema and pul. HTN in rat lungs. Lee J-H, Lee D-S, Kim E-K, et al. Am J Respir Crit Care Med 2005;172:987.93. Statin use is associated with improved function and survival of lung allografts. Johnson BA, Iacono AT, Zeevi A, et al Am J Respir Crit Care Med 2003;167:1271.8. decreased incidences of mild-to-severe acute allograft and obliterative bronchiolitis, along with improved pulmonary function,

4. Purpose  statins on the decline in lung function, in a population at high risk for inflammatory lung disease smokers and former smokers.

5. Materials and Methods Oklahoma City Veterans Administration hospital in 2005, PFT : 6 months apart or longer Collected data included age, gender, race, smoking status (current or ex- smokers), and past medical history Medications, including statins, inhalers, cardiovascular and antiinflammatory agents ex-smokers if they quit smoking at least 6 months prior the last PFT.

6. Materials and Methods Satin and Control groups statin group FDA approved statins for at least 3 months To determine compliance with statin prescriptions: lipid profile data- within 60 days of the PFT Pulmonary function tests DLCO FVC,FEV1 Arterial blood gases A-a DO2 Primary endpoints :the annual decline in FEV1 and FVC Secondary endpoint :the need for respiratory related ED visits and/or hospitalizations.

7. Result 551 patients > 2 PFTs 418 patients 215 patients were on statins 137 patients : never smoked Hx. of asthma normal baseline spirometry average age : 66.8±9.3 years 271 Pts (65%) : ex-smokers 319 Pts (76%) :obstructive baseline spirometry 99 Pts (24%) : restrictive baseline spirometry

8. Result < < <

9. simvastatin (174 patients) lovastatin (25 patients) atorvastatin (12 patients) fluvastatin (4 patients)

10. Result

11. < >

14. p<0.0001 p=0.038 p =0.027 p<0.0001

15. Result

17. Discussion-Statin  Statin :↓LDL, ↑ HDL decrease mortality from cardiovascular disease and stroke  Antiinflammatory and immunomodulating activities 1 ) inhibiting leucocyte endothelial cell adhesion,cellular proliferation Brown RD, et al. Ann Rev Pharmacol Toxicol 2005;45:657.87. 2) induce apoptosis and reduce the level of oxidative stress Brown RD, et al. Ann Rev Pharmacol Toxicol 2005;45:657 ; 87.  Murine model of inflammatory lung injury 1) simvastatin : ↓vascular leak and lung inflammation ← lung neutrophil count and myeloperoxidase activity Jacobson JR, et al. Am J Physiol Lung Cell Mol Physiol 2005;288:L1026-32. 2) simvastatin : ↓ chronic hypoxic pul HTN,↓ hypoxia-induced muscularization of the alveolar arteries Girgis RE, et al. Am J Physiol Heart Circ Physiol 2003;285:H938.45.

18. Discussion-Statin  clinical studies of pul. effects of statins 1) in lung transplant patients: ↓incidence of acute rejection, ↑pulmonary function, ↑ patients- survival Johnson BA, et al. Am J Respir Crit Care Med 2003;167:1271-8. 2) IPF, no difference in median survival Nadrous HF,et al. Chest. 2004 Aug;126(2):438-46. 3) In a retrospective, cohort study of patients with COPD, a reduction in the rate of hospitalization and death was seen with the use of statins Mancini GB, et al. J Am Coll Cardiol. 2006 Jun 20;47(12):2554-60.

19. Discussion-Limitation 1. number of patients was relatively small 2. simvarstatin :classic statin or simvastatin 3. 6% LT inhibitors : asthmic feature 4. similar PFT between smoker vs ex-smoker -older in ex-smoker -smoking status -effect of smoking cessation 5. between statin and control group -interval between quit date, 1st PFT

20. Discussion  The slower lung function decline in statin users was observed in the obstructive, as well as the restrictive groups.  In patients with obstructive baseline spirometry, -lower incidence of respiratory related ED visits and/or hospitalizations in the statin group. --> did not influence the rate of lung function decline  slower decline in lung function in the statin group is due to a possible reduction in inflammation, rather than to a lower incidence of respiratory related ED visits and/or hospitalizations.

21. Conclusion  Statin may have a beneficial effect in inflammatory lung disease.