05/12/04 Lung Health Study Slide 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

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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 Americaii. 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.

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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

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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. 24.69%)

• 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)

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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 = 0.0002)

• 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)

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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.