Heterogeneity in Normal-Appearing Lung Tissue is Similar Between COPD and Smokers, and Predicts Morbidity and Progression in COPD.

BACKGROUND

Studies have identified important associations between computed tomography (CT) features of the normal-appearing lung tissue and patient outcomes, however, the heterogeneity of normal-appearing tissue has not previously been considered in chronic obstructive pulmonary disease (COPD).

METHODS

We aimed to quantify heterogeneity in normal-appearing lung tissue on inspiratory CT imaging and its relationship with lung function and clinical outcomes. We analysed data from 520 participants enroled in the COPDGene study, including never-smokers, current and former smokers without airflow obstruction, and COPD (GOLD1-4). Quadtree decomposition was used to derive spatially-connected heterogeneity metrics for medium (-900 to -750 HU) and low (< -900 HU) density tissues, and for all tissues combined. Medium density included tissue typically classified as normal-appearing by HU thresholding. Associations between heterogeneity, lung function, and respiratory morbidity were tested using multivariable regression.

RESULTS

Heterogeneity in medium-density tissue was similar between current and former smokers without airflow obstruction and COPD (0.15±0.05 cf. 0.16±0.06, p=0.11), and was significantly higher than in never-smokers (0.10±0.03, p<0.001). After adjusting for emphysema, age, sex, race, smoking status, and BMI, heterogeneity was independently associated with FEV1 % predicted, St. George's Respiratory Questionnaire score, modified Medical Research Council dyspnoea score, six-minute walk distance, and greater FEV1 decline at follow-up.

CONCLUSION

Heterogeneity of normal-appearing lung tissue is associated with respiratory morbidity and disease progression in COPD. This highlights the importance of detecting subtle early changes in tissue architecture in current and former smokers at risk for and with COPD.