The role of alveolar macrophages and smoking in the development of postoperative pulmonary complications after lung cancer surgery.

Introduction: Postoperative pulmonary complications (PPC) including pneumonia and atelectasis are common after lung cancer surgery. Smoking is the biggest risk factor for PPC and has been shown to affect alveolar macrophages (AM) which have a key role in defending against infection and resolving inflammation. The role of the phenotype and function of the AM in the development of PPC has yet to be determined. Methods: Non-cancerous lung tissue was obtained from 50 patients undergoing lung surgery. Smoking status was self-reported and confirmed by exhaled carbon monoxide levels. AMs were isolated from the lung tissue and phenotyping using flow cytometry. AM efferocytosis was assessed using labelled apoptotic neutrophils from healthy donors. PPC was determined prospectively using the Melbourne Group Scale. Results: AM from smokers had increased expression of SIRPα and CD33, and reduced expression of CD206 and CD163 compared to long-term ex-smokers and never smokers (p<0.05). The efferocytosis index was lower in current/recent ex-smokers compared to long-term/never smokers (p<0.05). Patients with a PPC had lower efferocytosis and increased SIRPα levels compared to non-PPC patients (p<0.05). Higher SIRPα levels and lower efferocytosis index was associated with prolonged hospital length of stay (LOS). Conclusion: AM from smokers have altered phenotype including SIRPα expression, which is reduced in those who had stopped smoking after 1 month. SIRPα has an inhibitory role in efferocytosis, which was associated with PPC development and prolonged LOS. Further investigation is required to evaluate SIRPα as a potential target to rescue AM function to prevent PPC.