Peribronchiolar Metaplasia: A Cigarette Smoke-Induced Small Airway Injury Associated with Interstitial Lung Abnormality, Interstitial Lung Disease and Emphysema

Background: Peribronchiolar metaplasia (PBM) is a non-specific reaction to bronchiolar injury, characterized by both proliferation of bronchiolar epithelium and fibrosis along the peribronchiolar wall. While an association of PBM with diffuse interstitial lung diseases (ILDs) is recognized, its clinical significance in emphysema and interstitial lung abnormalities (ILAs) remains unclear. Methods: : A retrospective review of a cohort (n=352) undergoing surgical resection for suspected lung nodule/mass at a tertiary medical center between 2017 and 2020 was completed to 1) determine the prevalence of PBM and 2) identify association with clinical, radiographic and histologic characteristics. A multivariate logistic regression analysis was performed. Results: The study cohort was elderly (mean age 66.15±10.19 years), predominantly female (57.1%), Caucasian and overweight (mean BMI 28.35±6.88). Ninety percent of patients were current or ex-smokers with a median pack year of 40 (IQR 32.5). Thirty-two patients (9.1%) were observed to have PBM as a histological finding. Clinical chronic obstructive pulmonary disease (COPD) was diagnosed in two-thirds of patients with PBM. Comorbid gastroesophageal reflux disease (GERD) was significantly associated with PBM. Conventional measures of pulmonary function tests were not significantly different between the groups with and without PBM. Radiologic and histologic emphysema were observed in all patients with histologic PBM. In addition, radiologic centrilobular ground-glass opacities (CL-GGO) of ILAs, specific ILD patterns, isolated traction bronchiectasis (iTB), histologic fibrosis, desquamative interstitial pneumonia (DIP), anthracosis and honeycomb changes were associated with PBM. A logistic regression model which included CL-GGO ILA, iTB, histologic fibrosis, DIP and anthracosis strongly predicted PBM in the cohort. Conclusion: A constellation of radiologic and histologic smoking-related abnormalities predicted PBM in our cohort. This supports a co-existence of tissue responses including small airway disease, fibrosis and emphysema as consequence of cigarette smoking. PBM can function as a histologic marker of small-airway injury in a smoking population.