1. Statin Use Reduces Decline in Lung Function

2. Introduction  Lung function has been shown to predict both cardiovascular mortality and total mortality in patient with COPD  Higher decline rate association with increased mortality and hospital stay related to COPD  Inflammation and oxidative stress are considered important to the development of COPD.

3. Introduction  Statin has anti-inflammatory and antioxidant effects  Statins have been shown to reduce serum CRP level, reduce oxidative stress

4. Introduction  This study examines: 1.whether the use of statin affects the rate of lung function decline in the elderly. 2.whether smoking history modified this effect of statin

5. Method  Subjects in this study were part of the Veterans Administration Normative aging study.  Our study were 803/2280 whose lung function were measured 2-4 times during 1995-2005.

6. Method-study  Visit: overnight fasting and absence of smoking.  Exams: height and lung function( FVC, FEV 1 )  Pulmonary disorders indicated by questionnaire based on American Thoracic Society Division of Lung Disease 1978 questionnaire, including smoking habits and medication use  Confirmed by interviewers

7. Presentation  Choose the variables above and included them in all of our models.  Measurement of FVC and FEV 1 were taken 2-4 times for each subject.  Mixed linear model was used  P value <0.05 was considered significant

8. Presentation  Decline in lung function: Change in milliliters per year of FVC and FEV1 ∆yrs X (β+ 1.96 X SE) ∆yrs is change in years β is the estimated regression coefficient for time

9. Results

10.  1. statin users had more CAD than nonusers, but it differed little  2. lung function was lower. Because the statins use was increased over time. So it was measured at older age. Models with control of age or time are required for this  3. few subjects were black, same result with all white.

11. Results  The same results were got when excluding subjects(3%) using bronchodilator or steroid.

12. Results (adjusted ) Effect by statin use Change in FEV 1(ml/yr) 95% CIChange in FVC (ml/yr) 95% CI Not using statins -23.9 -27.8 to -20.1 -36.2 -41.5 to -30.8 Using statings -10.9 -16.9 to -5.0 -14.0 -22.2 to -5.9

13. Results (unadjusted)

14. Results (smoking)  1.divided smokers into four groups 1.never 2.longtime quitters(>10yrs) 3.recent quitters(<10 yrs) 4.current smokers.  2.changes in FEV1 and FVC

15. Results (smoking)

16.  Weakly suggest that longtime quitters and recent quitters may be able to benefit more from statin use than other groups.

17. Discussion  Suggest potential benefit of reducing decline in lung function related to statins users  Longtime and recent quitters seemed to benefit more from statin use. More study with current smoker is needed.  Pointing to a potential treatment of COPD in addition to stopping smoking.  Well designed clinical trial is needed to confirm the size of effect of statins

18. Discussion  An abstract publish for chest 2006 conference — reduces decline in FVC and FEV1 for the statin users, compared between current and former smokers.  Another study suggest that statin use in for lung transplantation recipients improved lung function and lower percentage of neutrophils and lymphocytes in BAL fluid.

19. Discussion  Animal study have found that statins reduce neutrophil level in lung tissue when lipopolysaccharides are used to induce inflammatory response of lung  Study on rat : statin protected against smoking-induced lung damage  Statins have been shown to suppress the concentration of Th1, IFN-r, NK cell, and IL-8 by human tissue

20. Discussion  Study showed that statin users have lower serum CRP level.  Inverse relationship between CRP and lung function. Increased CRP levels were associated with greater declines in FEV 1.  NADPH oxidase produce reactive oxygen species in lung to make oxidative stress. Statins have been shown to inhibit activation of NADPH oxidase in monocyte.

21. Discussion  Limitation of study: All elderly men, most were white Fewer current smoker and recent quitters  Non-randomized clinical trial Statins were used to lower cholesterol, Estimate decline in lung function by CAD instead of statin use=>no significant association

22. Discussion  Statin users may have more regular visit and more medication, especially steroid. The use was low, same estimates when Mx use was excluded.  Statin users may have engage in other health-conscious behavior.

23. Discussion  In table 1, lower FVC and FEV 1 were found in statin users 1.because of higher mean age. 2.higher level of heart Dx and HTN=> β -blocker use. Adding use of these Mx in our model did not change the estimated effect of statin.  Survivor bias: Very low lung function declines more slowly. Same data was obtained when excluding the lowest 5% of lung function.

24. Discussion  1. RCT is needed to confirm the effect of statin  2.The beneficial effect of statin seems to be present regardless of smoking history  3.This research indicate the positive effect of statin use beyond its cholesterol- lowering properties.

25. Thank you for your attention!!