IMPORTANCE Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free.OBJECTIVE To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. DESIGN, SETTING, AND PARTICIPANTS Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV 1 ] to forced vital capacity >0.7 and FEV 1 Ն80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. MAIN OUTCOMES AND MEASURESPhysical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life.RESULTS One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P < .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV 1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. CONCLUSIONS AND RELEVANCELung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.

Purposes:To provide a new detailed visual assessment scheme of computed tomography (CT) for chronic obstructive pulmonary disease (COPD) by using standard reference images and to compare this visual assessment method with quantitative CT and several physiologic parameters. Materials and Methods:This research was approved by the institutional review board of each institution. CT images of 200 participants in the COPDGene study were evaluated. Four thoracic radiologists performed independent, lobar analysis of volumetric CT images for type (centrilobular, panlobular, and mixed) and extent (on a six-point scale) of emphysema, the presence of bronchiectasis, airway wall thickening, and tracheal abnormalities. Standard images for each finding, generated by two radiologists, were used for reference. The extent of emphysema, airway wall thickening, and luminal area were quantified at the lobar level by using commercial software. Spearman rank test and simple and multiple regression analyses were performed to compare the results of visual assessment with physiologic and quantitative parameters. Results:The type of emphysema, determined by four readers, showed good agreement (k = 0.63). The extent of the emphysema in each lobe showed good agreement (mean weighted k = 0.70) and correlated with findings at quantitative CT (r = 0.75), forced expiratory volume in 1 second (FEV 1 ) (r = 20.68), FEV 1 /forced vital capacity (FVC) ratio (r = 20.74) (P , .001). Agreement for airway wall thickening was fair (mean k = 0.41), and the number of lobes with thickened bronchial walls correlated with FEV 1 (r = 20.60) and FEV 1 /FVC ratio (r = 20.60) (P , .001). Conclusion:Visual assessment of emphysema and airways disease in individuals with COPD can provide reproducible, physiologically substantial information that may complement that provided by quantitative CT assessment.q RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup /suppl

Purpose To correlate currently available quantitative CT measurements for airway disease with physiological indices and the body-mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index in patients with chronic obstructive pulmonary disease (COPD). Materials and methods This study was approved by our institutional review board (IRB number 2778). Written informed consent was obtained from all subjects. The subjects included 188 current and former cigarette smokers from the COPDGene cohort who underwent inspiratory and expiratory CT and also had physiological measurements for the evaluation of airflow limitation, including FEF25–75%, airway resistance (Raw), and specific airway conductance (sGaw). The BODE index was used as the index of clinical symptoms. Quantitative CT measures included % low attenuation areas [% voxels ≤ 950 Hounsfield unit (HU) on inspiratory CT, %LAA−950ins], percent gas trapping (% voxels ≤ −856 HU on expiratory CT, %LAA−856exp), relative inspiratory to expiratory volume change of voxels with attenuation values from −856 to −950 HU [Relative Volume Change (RVC)−856 to −950], expiratory to inspiratory ratio of mean lung density (E/I-ratio MLD), Pi10, and airway wall thickness (WT), luminal diameter (LD) and airway wall area percent (WA%) in the segmental, subsegmental and subsubsegmental bronchi on inspiratory CT. Correlation coefficients were calculated between the QCT measurements and physiological measurements in all subjects and in the subjects with mild emphysema (%LAA−950ins <10%). Univariate and multiple variable analysis for the BODE index were also performed. Adjustments were made for age, gender, smoking pack years, FEF25–75%, Raw, and sGaw. Results Quantitative CT measurements had significant correlations with physiological indices. Among them, E/I-ratio MLD had the strongest correlations with FEF25–75% (r = −0.648, <0.001) and sGaw (r = −0.624, <0.001) while in the subjects with mild emphysema subsegmental WA% and segmental WA% had the strongest correlation with FEF25–75% (r = −0.669, <0.001) and sGaw (r = −0.638, <0.001), respectively. The multiple variable analyses showed that RVC−856 to −950 was an independent predictor of the BODE index showing the highest R2 (0.468) as an independent variable among the QCT measurements. Conclusion Quantitative CT measurements of gas trapping such as E/I-ratioMLD, correlate better with physiological indices for airway disease than those of airway such as WA% or LD. In mild emphysema, however, quantitative CT measurements of airway correlate better with the physiological indices. RVC−856 to −950 is a predictor of the BODE index.

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