05/12/04 Lung Health StudySlide 1 of 6 Lung Health Study Heavy Smokers Experienced a Greater Benefit in the Reduction of the Decline Rate of their Pulmonary Function as a result of LHS Smoking Intervention Program among Males SoonYoung Jang John Connett

05/12/04 Lung Health StudySlide 2 of 6 Chronic obstructive pulmonary disease (COPD) Fourth leading cause of death in the US since 1978 An insidious disease, with a long course of considerable deterioration of pulmonary function before symptoms even develop Lung Health Study (LHS1) Purpose: To determine the effectiveness of an intensive smoking cessation program and the use of inhaled bronchodilator in reducing the rate of decline in pulmonary function Study Population: Smokers, aged 35 to 60 years, with mild obstructive pulmonary disease Randomized Clinical Trial Background i.Ten clinical centers located in North America ii.From October 1986 to April 1994 iii.3,926 participants Total, 64% men Results of the Previous Study Success of the smoking intervention program in slowing down the rate of decline of pulmonary function More rapid rate of decline in lung function for heavy smokers at baseline among continuous smokers High rate of sustained smoking cessation among heavy smokers in LHS Objective To assess whether the effect of the smoking intervention program on the rate of decline of pulmonary function is the same for heavy smokers at baseline and light smokers at baseline, among males.

05/12/04 Lung Health StudySlide 3 of 6 Dataset The first 317 male participants from the original LHS1 dataset Primary Outcome Measure The cumulative change in the percent post-bronchodilator FEV1(forced expiratory volume in 1 second) from baseline, measured at yearly follow-up over a 5 year period Factors of Interest Two levels of Intent-to-treatment group: SI / UC Participation in LHS Smoking Intervention Program (SI) or Usual Care (UC) regardless of bronchodilator therapy status in the original study Two levels of smoking rate group: Heavy / Light Divided according to the median (30 cigs/day) of the participants’ self-reported cigarettes per day consumed at baseline Data Summaries Baseline characteristics by four combination groups Descriptive and graphical summary of the primary outcome over a 5 year period by four combination groups Analysis Four-way mixed effect analysis of variance using repeated measures model multiple pairwise comparisons using Tukey’s adjustment A polynomial contrast to test time trend Pearson chi-sq test for homogeneity of changes in smoking status, determined at the final year, between heavy smokers and light smokers Method

05/12/04 Lung Health StudySlide 4 of 6 Results Missing Response(FEV1) Rate 14.9% (40 out of 1590) Baseline Characteristics Similar distribution of weight and baseline FEV1 across four combination groups Significantly different age between the two smoking rate groups (F(1,314)=9.36, p-value=0.002) Data Summary Observed the slowest decline rate of FEV1 (%) in the SI Heavy smokers group (2.98±0.85) in contrast to the most rapid decline rate of FEV1 (%) in the UC Heavy smokers group (9.80±1.15) Observed no substantial differences between the SI Light smokers and the UC Light smokers groups (5.47±0.83 vs. 5.82±0.94) Suggested a linear Trend of decline with different rate between SI and UC ( Figure 1) Observed slightly more sustained quitters among heavy smokers (30.77% vs %) For sustained quitters, the former heavy smokers found slightly longer time period before quitting compared to the former light smokers (Mean=2.1, sd=1.47 vs. Mean=2.2, sd=1.46) Analysis Results No evidence of nonlinear trend for all groups (p-value > 0.5) Significant interaction between the intent-to-treat factor and the year factor (F(4,1040)=3.5, p-value < 0.01)

05/12/04 Lung Health StudySlide 5 of 6 Analysis Results (Continued) Significantly different effect of LHS smoking intervention program on the mean % change in FEV1 by smoking rate group (F(1,301)=13.81, p-value = ) No significant effect of the baseline smoking rate group when averaged across the two intent-to-treatment groups (F(1,301)=0.60, p-value>0.4) The slowest decline rate was observed in the SI heavy smokers group (3.29±1.47), and it significantly differed from all others. Significant participant-to-participant variability (48.18±8.88)

05/12/04 Lung Health StudySlide 6 of 6 Discussion Hypothesis: Expect the same or more rapid decline for heavy smokers compared to light smokers in the smoking intervention program NOT TRUE !! Why ? Unanswered Similar distribution of Sustained, Intermittent & Continuous smokers determined at the end of the study Similar % of cigarettes/day reduction Participants in the program were similar in age Similar in baseline FEV1 despite different smoking rate => related to airway hyper-responsiveness ? Shortcomings Post-hoc analysis of clinical trials data Voluntary based recruitment in the original study Measurement (Self-reported smoking rate, Raw FEV1) Specific to the LHS smoking intervention program Summary Greater benefit of the smoking intervention program on reducing the decline rate of pulmonary function among heavy male smokers Practical Implication An intensive and effectively organized smoking intervention program could help male heavy smokers prevent or delay the advance of severe COPD.