Reference values for high attenuation areas on chest CT in a healthy, never‐smoker, multi‐ethnic sample: The MESA study

BACKGROUND AND OBJECTIVE: Normative values for HAA-a quantitative, CT-based measure of subclinical ILD-in healthy adults are needed to improve interpretability in clinical and research settings. METHODS: HAA was measured on full-lung CT in 3110 participants in the MESA study. Clinical prediction models were developed using a healthy never-smoker subset with normal spirometry (n = 696). RMSE on cross-validation was used as the primary criterion for model selection. Parametric and non-parametric methods were considered. z-Scores were calculated for the entire study sample. Associations between z-scores and several ILD features were estimated. RESULTS: In the healthy never-smoker subset, the mean age was 69 years with a range of 54-93 years. The median HAA was 4.3% with a range of 2.7-17.8%. Linear regression had better predictive performance than other methods. The final model included race, height, weight, age and sex. The standard error of the estimate was 1.62 with a cross-validated RMSE of 1.64 and an adjusted R(2) of 0.139. z-Scores were associated with several ILD outcomes in adjusted models, including ILA (OR: 1.40 per z-unit; 95% CI: 1.30, 1.52), exertional dyspnoea (OR: 1.08 per z-unit; 95% CI: 1.02, 1.15) and FVC (expected increase per z-unit: -2.49; 95% CI: -2.95, - 2.03). CONCLUSION: We present a reference equation and z-scores to define expected values of HAA on full-lung CT to aid HAA interpretation in middle-aged and older adults.