Lung volumes and emphysema in smokers with interstitial lung abnormalities

Abstract

Background: Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known.

Methods: We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema.

Results: Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As 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, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking.

Conclusions: In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

Figure 1. Four Major Radiographic Subtypes of Interstitial Lung Abnormalities

Each row of radiographs and reconstructions represents data from a single study participant. The images in Panel A are characteristic of centrilobular interstitial lung abnormalities; Panel B, subpleural interstitial lung abnormalities; Panel C, mixed centrilobular and subpleural interstitial lung abnormalities; and Panel D, radiographic interstitial lung disease. The images in the first two columns are three-dimensional reconstructions of an anterior-to-posterior view of the lungs (column 1) and a caudal-to-cephalad view (column 2). The translucent yellow–green represents the lung parenchyma; white, the tracheobronchial tree; opaque green, centrilobular opacities; and opaque orange, subpleural abnormalities. Columns 3 and 4 present axial high-resolution computed tomographic images of the chest, with images in column 3 approximately at the level of the carina and those in column 4 approximately at the level of the right inferior pulmonary vein.

Figure 2. Study Enrollment and Findings

Panel A divides the study participants into three groups according to the classifications established by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Each group is then broken down according to the subtype of interstitial lung abnormalities (ILA). Patients who could not be classified according to the GOLD criteria had a forced expiratory volume in 1 second (FEV₁) that was less than or equal to 80% of the predicted value and a ratio of FEV₁ to forced vital capacity (FVC) that was greater than or equal to 0.7. Those patients meeting the criteria for GOLD stages 0 to 1 had an FEV₁ that was 80% or more of the predicted value, and those meeting the criteria for GOLD stages 2 through 4 had an FEV₁ of less than 80% and a ratio of FEV₁ to FVC of less than 0.7. Panel B shows FEV₁ (percent of predicted value) plotted against the FEV₁:FVC (percent of predicted value) for participants with and those without ILA and classifies participants according to the GOLD criteria. Panel C is a frequency plot of total lung capacity as a percent of the predicted value in participants with and those without ILA. ILD denotes interstitial lung disease.