Chest
Volume 124, Issue 2, August 2003, Pages 449-458
Journal home page for Chest

Clinical Investigations
COPD
The Effect of Smoking Intervention and an Inhaled Bronchodilator on Airways Reactivity in COPD*: The Lung Health Study

https://doi.org/10.1378/chest.124.2.449Get rights and content

Background

The Lung Health Study (LHS), a 5-year, randomized, prospective clinical trial, studied the effects of smoking intervention and therapy with inhaled anticholinergic bronchodilators on FEV1 in participants who were 35 to 60 years of age and had mild COPD. Participants were randomized into the following three groups: usual care; smoking cessation plus inhaled ipratropium bromide; and smoking cessation plus placebo inhaler. This report evaluates the effects of these interventions, demographic characteristics, smoking status, and FEV1 changes on airway responsiveness (AR).

Methods and results

Of 5,887 participants, 4,201 underwent methacholine challenge testing both at study entry and study completion. All groups increased AR during the 5-year period. The increase in AR was greatest in continuing smokers and was associated with a greater FEV1 decline. An intent-to-treat analysis indicated no significant differences in AR changes among the three groups.

Conclusions

Changes in AR over a 5-year period in the LHS were primarily related to changes in the FEV1. The greater the decline in FEV1, the greater the increase in AR. Smoking cessation had a small additional benefit in AR beyond its favorable effects on FEV1 changes.

Section snippets

LHS Design

The study design, spirometric methodology, measurement of AR, and smoking intervention program all have been reported on in detail.3678 A total of 5,887 cigarette-smoking participants with an FEV1 of ≥ 50% of predicted and < 90% of predicted, and an FEV1/FVC ratio of < 0.70 were enrolled into the study and randomized into one of the following three groups: usual care (UC); smoking cessation plus a special intervention with an ipratropium bromide inhaler (SIA); and smoking cessation plus a

Demographics and Temporal Changes in Airways Reactivity

The clinical and demographic characteristics of the 4,201 participants in this study group are shown in Table 1. The reasons for the exclusion of the data for the remaining 1,686 LHS participants are given in Table 2. The study sample showed an overall increase in AR over the 5-year period, irrespective of treatment assignment, gender, or smoking status (Table 3). The increase in reactivity for the entire group was small, approximately 0.12 LMCR units. At randomization, 4.1% of the group

Discussion

The main finding of this study was that there was an overall tendency for AR to increase over a 5-year period in this group of long-term smokers with mild-to-moderate COPD. This increase in AR occurred in persons in all the analyzed subgroups except for those who quit smoking and subsequently improved their pulmonary function. Increasing AR was more pronounced in women, continuous smokers, and those participants with the largest declines in FEV1. The unifying theme of our analyses was that

Summary and Conclusions

In summary, we have found that a cohort of volunteers with mild-to-moderate COPD who enrolled in a clinical trial of smoking cessation and inhaled anticholinergic bronchodilator therapy showed continuing increases in AR. This progression was greater mainly in those who had the greatest decline in FEV1 but also occurred in older individuals and continuing smokers.

Appendix: List of Participants in the LHS Research Group

The principal investigators and senior staff of the clinical and coordinating centers, the National Heart, Lung, and Blood Institute, members of the Safety and Data Monitoring Board, and the Morbidity and Mortality Review Board are as follows.

References (24)

  • R Newcomb et al.

    Rebound hyperresponsiveness to muscarinic stimulation after chronic therapy with an inhaled muscarinic antagonist

    Am Rev Respir Dis

    (1985)
  • SAS

    SAS/STAT users guide: version 6

    (1990)
  • Cited by (66)

    • Serum bilirubin and disease progression in mild COPD

      2015, Chest
      Citation Excerpt :

      As the results of the more complex models (method two) were similar to the simple models, the primary analyses used method one. The response to methacholine challenge was measured at study enrollment, and the details of this have been described previously.11 Airway reactivity was quantified by the O'Connor two-point slope method.

    • The complex relationship of serum adiponectin to COPD outcomes

      2012, Chest
      Citation Excerpt :

      Additionally, 4,201 participants also underwent a methacholine provocation test at the baseline visit. The detailed method of these tests has been described previously.12 Airway reactivity was quantified by the O'Connor two-point slope method.

    View all citing articles on Scopus

    This research was supported by contracts NO1-HR46002 and NO1-46014 from the Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health. The following pharmaceutical companies supplied drugs used in this study: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (Atrovent and placebo inhalers); and Marion Merrell Dow Inc, Kansas City, MO (Nicorette). The Salt Lake City Center has been assisted by the Clinical Research Center, Public Health Research grant M01-RR00064 from the National Center for Research Resources.

    View full text