Pulmonary Edema and Biomarkers of Inflammation and Lung Epithelial Dysfunction Are Associated with Donor Smoking in the Ex Vivo Donor Lung

Abstract

Purpose Although smoking is common in organ donors and recipients of donor lungs from smokers have worse clinical outcomes, the mechanisms are unknown. We tested the association between donor smoking and the degree of pulmonary edema, the rate of alveolar fluid clearance (AFC) and biomarkers of lung epithelial injury and inflammation in the ex vivo donor lung. Methods and Materials Among 661 donors evaluated for the Beta-agonists for Oxygenation in Lung Donors (BOLD) study (albuterol vs. placebo), 301 had lungs resected without perfusion for physiologic studies, and were included. After transport at 4C, lungs were weighed for quantification of pulmonary edema and a BAL was done. Lungs were rewarmed to 37°C for measurement of AFC by airspace instillation of a 5% albumin solution. IL-8 and surfactant protein D (SP-D) were measured in BAL by ELISA. Results 130 (43%) donors were current smokers. Pulmonary edema assessed by lung weight was 7% higher in current smokers compared to non-smokers (441 ± 113g vs. 411 ± 115g, p = 0.03), and current smokers had poorer oxygenation at study enrollment compared to non-smokers (PaO2/FiO2 239 ± 133 vs. 279 ± 143, p = 0.016). AFC did not differ based on smoking status. BAL IL-8 was significantly higher in smokers while SP-D was lower ( Figure ). Conclusions Donor smoking is associated with more pulmonary edema in the resected lung, higher levels of the chemokine IL-8 and lower levels of surfactant protein D. Chronic exposure to cigarette smoke has important effects on inflammation, permeability and lung fluid balance in the organ donor that could potentially influence lung function in the lung transplant recipient.