Effects of Smoking Intervention and the Use of an Inhaled Anticholinergic Bronchodilator on the Rate of Decline of FEV1 The Lung Health Study Nicholas R. Anthonisen, MD; John E. Connett, PhD; James P. Kiley, PhD; Murray D. Altose, MD; William C. Bailey, MD; A. Sonia Buist, MD; William A. Conway, Jr, MD; Paul L. Enright, MD; Richard E. Kanner, MD; Peggy O'Hara, PhD; Gregory R. Owens, MD; Paul D. Scanlon, MD; Donald P. Tashkin, MD; Robert A. Wise, MD; for the Lung Health Study Research Group Objective.\p=m-\Todetermine whether a program incorporating smoking interven- tion and use of an inhaled bronchodilator can slow the rate of decline in forced ex- piratory volume in 1 second (FEV1) in smokers aged 35 to 60 years who have mild obstructive pulmonary disease. Design.\p=m-\Randomized clinical trial. Participants randomized with equal prob- ability to one of the following groups: (1) smoking intervention plus bronchodilator, (2) smoking intervention plus placebo, or (3) no intervention. Setting.\p=m-\Ten clinical centers in the United States and Canada. Participants.\p=m-\A total of 5887 male and female smokers, aged 35 to 60 years, with spirometric signs of early chronic obstructive pulmonary disease. Interventions.\p=m-\Smoking intervention: intensive 12-session smoking cessation program combining behavior modification and use of nicotine gum, with continuing 5-year maintenance program to minimize relapse. Bronchodilator: ipratropium bro- mide prescribed three times daily (two puffs per time) from a metered-dose inhaler. Main Outcome Measures.\p=m-\Rate of change and cumulative change in FEV1 over a 5-year period. Results.\p=m-\Participants in the two smoking intervention groups showed signifi- cantly smaller declines in FEV1 than did those in the control group. Most of this dif- ference occurred during the first year following entry into the study and was attrib- utable to smoking cessation, with those who achieved sustained smoking cessation experiencing the largest benefit. The small noncumulative benefit associated with use of the active bronchodilator vanished after the bronchodilator was discontinued at the end of the study. Conclusions.\p=m-\An aggressive smoking intervention program significantly re- duces the age-related decline in FEV1 in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator results in a relatively small improvement in FEV1 that appears to be reversed after the drug is discontin- ued. Use of the bronchodilator did not influence the long-term decline of FEV1. (JAMA. 1994;272:1497-1505) From University of Manitoba, Winnipeg (Dr An- thonisen); University of Minnesota, Minneapolis (Dr Connett); National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Kiley); Case Western Reserve Uni- versity, Cleveland, Ohio (Dr Altose); University of Ala- bama at Birmingham (Dr Bailey); Oregon Health Sci- ences University, Portland (Dr Buist); Henry Ford Hospital, Detroit, Mich (Dr Conway); University of Ari- zona, Tucson (Dr Enright); University of Utah, Salt Lake City (Dr Kanner); University of Miami (Fla) (Dr O'Hara); University of Pittsburgh (Pa) (Dr Owens); Mayo Clinic, Rochester, Minn (Dr Scanlon); University of California\p=m-\ Los Angeles (Dr Tashkin); and The Johns Hopkins University, Baltimore, Md (Dr Wise). A complete list of the members of the Lung Health Study Research Group appears at the end of this article. Reprint requests to Lung Health Study, 2221 Univer- sity Ave SE, Suite 200, Minneapolis, MN 55414 (Dr Connett). CHRONIC obstructive pulmonary dis¬ ease (COPD) is a major cause of morbid¬ ity and mortality. It occurs almost exclu¬ sively in smokers, but affects only a mi¬ nority of them,1 indicating that other risk factors are important. It has a long course with considerable deterioration of lung function before symptoms develop.2 Ob¬ servational studies indicate that the age- related rate of decline of lung function is accelerated by smoking, and that spon¬ taneous smoking cessation is associated with a slowing of the rate of decline.2·3 However, spontaneous smoking cessation might imply a powerful selection bias in that people who decide to stop smoking may differ in other ways from people who do not, and these differences may influ¬ ence subsequent lung function. For editorial comment see 1539. A second risk factor for COPD that has received a great deal of attention is bron¬ chial hyperreactivity. According to the "Dutch hypothesis" of the development of COPD, smokers with hyperreactive airways develop symptomatic disease.4,5 This has been supported by several stud¬ ies showing more rapid decline of lung function in smokers with airways hyper¬ reactivity than in those without.6"8 In turn, this raises the question of whether therapy aimed at reducing airways reac¬ tivity or its presumed consequence, bron- chospasm, might alter the course of COPD. There is evidence that the rate of deterioration of lung function is reduced by bronchodilator therapy in COPD pa¬ tients who respond to bronchodilators.9 at University of Pennsylvania on February 7, 2011 jama.ama-assn.org Downloaded from