Chronic Obstructive Pulmonary Disease Exacerbations in the COPDGene Study: Associated

MeiLan Han ,K. MD , MS Ella Kazerooni ,A. MD David ynch , LA. MD yrica L Liu ,X. MS Susan Murray ScD , Jeffrey Curtis , L. MD Gerard Criner MD J. , Victor Kim , MD Russell Bowler. MD P , Nicola Hanania ,A. MD Antonio Anzueto , R. MD Barry Make ,J. MD John Hokanson ,E. MPH , PhD James D. Crapo , MD Edwin Silverman ,K. MD , PhD Fernando Martinez ,J. MD , MS George W R.ashko , MD For the COPDGene Investigators Purpose: To test the hypothesis—given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)—that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease.Materials and Methods: This research protocol was approved by the institutional review board of each participating institution, and all par-ticipants provided written informed consent. One thou-sand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quan-titative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a 2950-HU threshold. An automated pro-gram measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements.Results: In a multivariate analysis adjusted for lung function, bron-chial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (