High-Attenuation Areas on Chest Computed Tomography and Clinical Respiratory Outcomes in Community-Dwelling Adults

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.

Keywords: epidemiology; hospitalizations; mortality; pulmonary fibrosis; subclinical interstitial lung disease.

Figure 1.

Continuous associations between high-attenuation areas (HAA) and (A) interstitial lung disease (ILD) hospitalization and (B) ILD mortality. Models are adjusted for total volume of imaged lung; percent emphysema; and generalized propensity score 2, which included age, sex, race/ethnicity, smoking status, cigarette pack-years, body mass index, waist circumference, height, educational attainment, study site/scanner, glomerular filtration rate, radiation dose, alcohol use, total intentional exercise (metabolic equivalent min/wk), coronary artery calcium, diabetes medication use, insulin use, fasting glucose, hypertension, antihypertensive medication use, systolic and diastolic blood pressures, cholesterol medication use, total and high-density lipoprotein cholesterol levels, C-reactive protein, d-dimer, and cancer history. Solid line is the overall effect estimate, and dashed lines are the 95% confidence bands. Each vertical hash mark in the rug plot along the x-axis represents one study participant.