Chronic obstructive pulmonary disease (COPD) may be manifested by emphysematous destruction of the lung parenchyma and elevated measures of total lung capacity, conditions often associated with exposure to tobacco smoke. is increased awareness that smoking may also result in areas of increased lung density (interstitial lung ab-normalities) seen on high-resolution computer tomography (HRCT). Noting that there is scant evidence on the extent to which interstitial lung abnormalities are associated with a lesser amount of emphysema and lower measure of total lung capacity than anticipated based on knowledge of smoking exposure, researchers recently conducted a study to determine the relationship between interstitial lung abnormalities and HRCT measures of total lung capacity and emphysema. [N Engl J Med. [2011;364(10):897-906]. The study was designed to evaluate whether the associations between interstitial lung abnormalities and both total lung capacity and emphysema are modified by COPD status. The study cohort included non-Hispanic white and black smokers who had been recruited for the COPDGene Study. The researchers analyzed HRCT scans of 96% (n=2416) of the 2508 participants recruited from the 21 clinical centers taking part in the COPDGene Study. Of the 2416 participants, 48% (n=1171) were women, 25% (n=613) were black, 44% (n=1060) were active smokers, and 41% (n=1002) met the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD. Of the HRCT scans evaluated, 8% (n=194) showed interstitial lung abnormalities, 36% (n=861) were indeterminate, and 56% (n=1361) did not show interstitial lung abnormalities. There were 1421 HRCT scans evaluated by at least 2 readers. Of those, 63% (n=899) had concordant scores. Among the 522 scans for which evaluations were not concordant, 98% (n=510) involved 1 indeterminate reading. Discrepancies in the interpretation of HRCT scans with respect to the presence or absence of interstitial lung abnormalities were less common (2% [n=12]). After adjusting for relevant covariates, statistical models found that interstitial lung abnormalities were associated with reduced total lung capacity (−0.444 L; 95% confidence interval [CI], −0.596 to −0.292; P<.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of −950 Hounsfield units (−3%; 95% CI, −4% to −2%; P<.001) and −910 Hounsfield units (−10%; 95% CI, −12% to −8%; P<.001). Participants with interstitial lung abnormalities had a 47% decrease in their odds of having COPD; the strength of this association was influenced by GOLD stages 2 through 4 and interstitial lung abnormalities. Compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 0.37-0.76; P<.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<.02 for the interactions). Finally, interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. The specific interstitial abnormality most strongly associated with current smoking status was the presence of centrilobular nodules (odds ratio, 4.82; 95% CI, 2.47-9.44; P<.001). Study limitations included (1) the possibility that other conditions could mimic the changes on chest HRCT that were defined as interstitial lung abnormalities, (2) the possibility that measurements of total lung capacity were obtained by means of HRCT, and (3) because the study population included smokers with an oversampling of participants with COPD, the results may not be applicable to the general population.