Lung Function Decline and Disease Risk From Young Adulthood to Middle Age (CARDIA Lung)

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States, but markers that predict risk of developing disease outside of cigarette smoking have not been identified. Individuals with lung disease frequently have concurrent cardiovascular disease, but the reason for this is not well understood. In this study, we will identify markers that predict risk of future lung disease and evaluate the concurrent subclinical evolution of lung and heart dysfunction. This will allow for targeting of preventive strategies to stop the rising incidence of COPD and other lung diseases and provide insights into why heart and lung disease frequently occur together.

Study Overview

• Status: Completed
• Conditions: COPD; Restrictive Lung Disease; Lung Function; Heart - Lung Interaction
• Intervention / Treatment: Procedure: Lung spirometry; Other: CT scan analysis

Detailed Description

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. Although smoking is a major risk factor for COPD, only a minority of smokers develops COPD. Markers that predict risk of future COPD in young adults would be valuable to target risk reduction strategies and identify subclinical disease. Although COPD is classically defined by obstructive lung physiology, many individuals, including smokers, have spirometric restrictive physiology. Reduced lung function, whether manifesting as COPD or restriction, is associated with adverse cardiovascular outcomes. Our long-term goals are to identify subclinical manifestations of COPD and other lung disease and explore why heart and lung disease co-exist. This is an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study's year 30 examination. We will add pre- and post-bronchodilator spirometry to the exam and evaluate the lung parenchymal and vascular structure on cardiac CT scans from year 25. Informed by our preliminary data which documents that markers of systemic inflammation and endothelial dysfunction are associated with subsequent lung function decline in young adults, that lung function decline in young adults is associated with incident hypertension, and that there is a divergence in cardiac structure and function depending on the pattern of lung function decline, we propose the following specific aims: (1) To evaluate factors in young adults that predict incident COPD and/or restriction; (2) To determine whether incident COPD and incident restriction are associated with distinct cardiac structural and functional changes; and (3) To determine the lung structural and intrathoracic vascular changes associated with incident COPD and incident restriction. We will test the hypothesis that early life markers of systemic inflammation and endothelial dysfunction are associated with risk of subsequent lung disease and explore whether different inflammatory markers predict different lung phenotypes. We will then evaluate the cardiac structural changes associated with different lung phenotypes and evaluate the lung structural and pulmonary vascular alterations that may explain the concurrently evolving cardiovascular findings associated with developing lung disease. These studies will describe the subclinical manifestations of lung disease, identify markers that predict risk of future lung disease, and expand our understanding of heart-lung interactions as they evolve from health in young adults to disease in middle age.

• Study Type: Observational
• Enrollment (Actual): 3193

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants in the main Coronary Artery Risk Development in Young Adults (CARDIA) cohort study attending the year 30 examination

Description

Inclusion Criteria:

• Participation in the main CARDIA examination at year 30

Exclusion Criteria:

• Shortness of breath with pain in the chest within the past week
• Heart attack or stroke within the past month

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Obervational - CARDIA participants; CARDIA study participants will undergo lung function testing and have existing thoracic CT scans analyzed for lung structure.	Procedure: Lung spirometry; measurement of pulmonary function pre- and post-bronchodilator; Other Names: lung function; Other: CT scan analysis; Analysis of existing year 25 thoracic CT scans for lung and intrathoracic vascular structure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incident COPD	From cohort initiation, predictors of incident COPD	30 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incident restriction	From cohort initiation, predictors of incident restrictive lung physiology	30 years

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham; Brigham and Women's Hospital; Vanderbilt University; University of Minnesota; University of Kentucky; Kaiser Foundation Research Institute
• Investigators: Principal Investigator: Ravi Kalhan, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: September 17, 2014
• First Submitted That Met QC Criteria: September 17, 2014
• First Posted (Estimate): September 19, 2014

Study Record Updates

• Last Update Posted (Actual): August 22, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: STU00090966; R01HL122477 (U.S. NIH Grant/Contract)