Chronic Obstructive Pulmonary Disease Exacerbations in the COPDGene Study: Associated Radiologic Phenotypes

Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Radiology (Impact Factor: 6.87). 07/2011; 261(1):274-82. DOI: 10.1148/radiol.11110173
Source: PubMed


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.
This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a -950-HU threshold. An automated program 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.
In a multivariate analysis adjusted for lung function, bronchial 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 (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047).
Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes.

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    • "In addition, a variety of disease-related phenotypes have been studied related to imaging, exercise capacity, respiratory symptoms, and physiology. Computerized tomography (CT) imaging enables assessment of the severity and distribution of emphysema–the destruction of lung parenchyma–as well as thickening of airways [13-15]. The underlying assumption in our analysis is that these phenotypic variables are not independent, but, rather, interact to define distinct groups of patients (subtypes). "
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    ABSTRACT: Background The investigation of complex disease heterogeneity has been challenging. Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes. Results We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD). We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants. Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches. Conclusion Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease severity, and genetic mechanisms.
    BMC Systems Biology 06/2014; 8(1):78. DOI:10.1186/1752-0509-8-78 · 2.44 Impact Factor
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    • "The current finding that GERD is significantly associated with an exacerbation history also agrees with Hurst et al. [7], who found an association with similar strength, but who did not control for the effect of PPIs use. The consistent results from different research designs in different populations [7,30] point towards a significant relationship between GERD and COPD exacerbations, and provide a robust body of evidence to give strong consideration to this factor as a potential disease-modifying intervention. At least one small study has tested the concept of using PPIs in COPD patients with no reflux symptoms [31], and found a lower number of exacerbations after treatment with lansoprazole. "
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    ABSTRACT: Background The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes. Methods Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score. Results GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association. Conclusions In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.
    Respiratory Research 06/2014; 15(1):62. DOI:10.1186/1465-9921-15-62 · 3.09 Impact Factor
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    • "Compared to patients with COPD, overall emphysema severity was moderate in our cross-sectional study in children and mostly young adults with CF [29,45,46]. Values for EV and EI were on average less elevated in CF compared to the values previously reported for patients with advanced stages of COPD. "
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    ABSTRACT: Histopathological studies on lung specimens from patients with cystic fibrosis (CF) and recent results from a mouse model indicate that emphysema may contribute to CF lung disease. However, little is known about the relevance of emphysema in patients with CF. In the present study, we used computationally generated density masks based on multidetector computed tomography (MDCT) of the chest for non-invasive characterization and quantification of emphysema in CF. Volumetric MDCT scans were acquired in parallel to pulmonary function testing in 41 patients with CF (median age 20.1 years; range 7-66 years) and 21 non-CF controls (median age 30.4 years; range 4-68 years), and subjected to dedicated software. The lung was segmented, low attenuation volumes below a threshold of -950 Hounsfield units were assigned to emphysema volume (EV), and the emphysema index was computed (EI). Results were correlated with forced expiratory volume in 1 s percent predicted (FEV1%), residual volume (RV), and RV/total lung capacity (RV/TLC). We show that EV was increased in CF (457±530 ml) compared to non-CF controls (78±90 ml) (P<0.01). EI was also increased in CF (7.7±7.5%) compared to the control group (1.2±1.4%) (P<0.05). EI correlated inversely with FEV1% (rs=-0.66), and directly with RV (rs=0.69) and RV/TLC (rs=0.47) in patients with CF (P<0.007), but not in non-CF controls. Emphysema in CF was detected from early adolescence (~13 years) and increased with age (rs=0.67, P<0.001). Our results indicate that early onset emphysema detected by densitometry on chest MDCT is a characteristic pathology that contributes to airflow limitation and may serve as a novel endpoint for monitoring lung disease in CF.
    PLoS ONE 06/2013; 8(8):e73142. DOI:10.1371/journal.pone.0073142 · 3.23 Impact Factor
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