My NCBI Sign In
Jump to: Authorized Access | Attribution | Authorized Requests

Study Description

The 'Genome-Wide Associations Environmental Interactions in the Lung Health Study' at Johns Hopkins University aims to test for association between lung function decline as a primary outcome associated with chronic obstructive pulmonary disease (COPD) using banked DNA and phenotype data on 4,287 European Americans from the longitudinal, multicenter Lung Health Study (LHS). The broad goals of the LungGO/ESP-GO falls into two general categories: (i) discovery of all variants (i.e., common and rare) in all protein-coding regions of the human genome (i.e., the exome) conferring risk to complex pulmonary diseases including COPD, in a subset of the LHS cohort. The Johns Hopkins University LHS cohort offers a unique opportunity to elucidate genetic variants that cause COPD.

The Lung Health Study I was a randomized multicenter clinical trial with 5887 participants carried out from October 1986 to April 1994, designed to test the effectiveness of smoking cessation and bronchodilator administration in smokers aged 35 to 60 with mild lung function impairment. Participants were randomly assigned to one of three groups:

  • usual care, who received no intervention
  • smoking intervention with the inhaled bronchodilator ipratroprium bromide
  • smoking intervention with an inhaled placebo.
The effect of intervention was evaluated by the rate of decline of forced expiratory volume in one second (FEV1).

For the GWAS, only the subset of European American LHS participants for whom lung function data from three time points or more are available. Thus, the GWAS represents 73% of the 5,887 volunteers who participated in the LHS study. Importantly, LHS subjects included had similar demographics (including age, gender and BMI) and rates of lung function decline (mean annual change in FEV1% predicted: -0.96 %/yr vs. -0.99 %/yr, p=0.57) compared with those not included in the GWAS, reflecting little selection bias for our primary outcome. They were, however, more likely to have quit smoking after 5 years.

This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to lung function through large-scale genome-wide association studies of smokers enrolled in a multicenter clinical trial. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  • Study Weblink: Lung Health Study
  • Study Types: Longitudinal, Cohort
  • Number of study subjects that have individual level data available through Authorized Access: 4391

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

In the course of routine data cleaning and data analyses, investigators may incidentally identify genetic abnormalities that might influence the clinical care of an individual. These statements and recommendations have been developed to help investigators when they are informed of any such incidental findings.

  1. GENEVA Statement on Incidental Findings
  2. GENEVA Aneuploidy Reference Table
  3. GENEVA Pharmacogenetic Variants Reference Table

Study Inclusion/Exclusion Criteria

Inclusion criteria:

  • Male or Female
  • Any race or ethnicity
  • Ages 35 to 59
  • Smoker at time of screening visit
  • FEV1 between 55% and 90% of predicted (Crapo)
  • FEV1/FVC not greater than 70%

Exclusion criteria:

  • Life-threatening disease such as lung cancer, previous MI, gastric ulcer
  • Recent serious illness
  • Use of beta blockers
  • Narrow angle glaucoma
  • Diabetes
  • Major chest surgery
  • Pregnancy
  • More than 26 alcoholic drinks per week
  • Use of bronchodilators
  • Allergy to atropine or bromine
  • Overweight
  • DBP at second screening >95 and DBP >95 mm Hg at third screening
  • FEV1/FVC ≤75% at third screening

Women were included in all of the data collection protocols contributing to the Lung Health Study (LHS), and comprised approximately 37% of the enrolled subjects. Gender will be identified on the data in this initiative, but will not be an eligibility criteria. The contributing LHS protocols did not exclude subjects from any racial or ethnic background; however, only European Americans are included in this dataset. Children were excluded from the Lung Health Studies because the purpose of LHS was to test the efficacy of interventions for airway obstruction in adult smokers.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina Human660W-Quad_v1_A 592839 1048965
Study History

LHS was a multicenter (10 centers) in the US and Canada. Each center recruited 500-669 participants. Although enrollment into the LHS was open to participants regardless of ethnicity, only 4% of volunteers were non-white, and of those, only 225 were African American. The initial study population consisted of 5,887 men and women (63% male) who were smokers (aged 35-60) with spirometric evidence of mild to moderate lung function impairment. For the GWAS, only the subset of European American LHS participants for whom lung function data from three timepoints or more are available. Thus, the GWAS represents 73% of the 5,887 volunteers who participated in the LHS study. Importantly, LHS subjects included had similar demographics (including age, gender and BMI) and rates of lung function decline (mean annual change in FEV1% predicted: -0.96 %/yr vs. -0.99 %/yr, p=0.57) compared with those not included in the GWAS, reflecting little selection bias for our primary outcome. They were, however, more likely to have quit smoking after 5 years.

Participants were randomized with equal probability into three groups: (i) smoking intervention plus bronchodilator (ipratropium bromide); (ii) smoking intervention plus placebo; or (iii) no intervention. The primary outcome was rate of change and cumulative change in FEV1 over a 5 year period. Participants in the LHS were categorized as 'continuous smokers' or 'sustained quitters'. 'Intermittent smokers' (those quit at some annual visits but not at all) will be excluded from this analysis. Continuous smokers (N=2,231) were individuals who reported smoking at each annual visit. Sustained quitters (N=801) were those participants who had self-report of non-smoking (< 1 cigarette per week) which was validated with salivary cotinine assay and exhaled CO measurement as abstinent at every annual visit. The primary finding was that the use of the bronchodilator did not influence the long-term decline in FEV1. However, the aggressive smoking intervention programme significantly reduced the age-related decline in FEV1.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Other NCBI Resources
Authorized Data Access Requests
Study Attribution
  • Principal Investigator
    • Kathleen Barnes, PhD. Johns Hopkins University, Baltimore, MD, USA
  • Co-Investigator
    • Nadia Hansel, MD, PhD. Johns Hopkins University, Baltimore, MD, USA
  • Institute
    • Johns Hopkins University, Baltimore, MD, USA
  • Funding Source
    • HG004738. National Institutes of Health, Bethesda, MD, USA
  • Genotyping Center
    • Johns Hopkins University Center for Inherited Disease Research (CIDR), Baltimore, MD, USA
  • Funding Source for Genotyping
    • U01HG004438. NIH GEI grant "JH/CIDR Genotyping for Genome-Wide Association Studies". National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA