Abstract
RATIONALE: Areas of increased lung attenuation visualized by computed tomography are associated with all-cause mortality in the general population. It is uncertain whether this association is attributable to interstitial lung disease (ILD). OBJECTIVES: To determine whether high-attenuation areas are associated with the risk of ILD hospitalization and mortality in the general population. METHODS: We performed a cohort study of 6,808 adults aged 45-84 years sampled from six communities in the United States. High-attenuation areas were defined as the percentage of imaged lung volume with attenuation values between -600 and -250 Hounsfield units. An adjudication panel determined ILD hospitalization and death. MEASUREMENTS AND MAIN RESULTS: After adjudication, 52 participants had a diagnosis of ILD during 75,232 person-years (median, 12.2 yr) of follow-up. There were 48 hospitalizations attributable to ILD (crude rate, 6.4 per 10,000 person-years). Twenty participants died as a result of ILD (crude rate, 2.7 per 10,000 person-years). High-attenuation areas were associated with an increased rate of ILD hospitalization (adjusted hazard ratio, 2.6 per 1-SD increment in high-attenuation areas; 95% confidence interval, 1.9-3.5; P < 0.001), a finding that was stronger among men, African Americans, and Hispanics. High-attenuation areas were also associated with an increased rate of ILD-specific death (adjusted hazard ratio, 2.3; 95% confidence interval, 1.7-3.0; P < 0.001). Our findings were consistent among both smokers and nonsmokers. CONCLUSIONS: Areas of increased lung attenuation are a novel risk factor for ILD hospitalization and mortality. Measurement of high-attenuation areas by screening and diagnostic computed tomography may be warranted in at-risk adults.