Statin Use Reduces Decline in Lung Function

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.

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

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

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

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

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

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

Results

 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.

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

Results (adjusted ) Effect by statin use Change in FEV 1(ml/yr) 95% CIChange in FVC (ml/yr) 95% CI Not using statins to to Using statings to to -5.9

Results (unadjusted)

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

Results (smoking)

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

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

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.

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

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.

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

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.

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.

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.

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