Wei-An Chang,1,2 Ming-Ju Tsai,1–4 Shu-Fang Jian,1 Chau-Chyun Sheu,1–4 Po-Lin Kuo1,5 1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 3Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 4Department of Respiratory Therapy, School of Medicine, College of Medicine, Kaohsiung Medical University, 5Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, TaiwanIntroduction: COPD is a chronic inflammatory disease of lung. The inflammatory response in COPD is associated with neutrophils, macrophages, T lymphocytes, and bronchial epithelial cells, and occurs mainly in the small airway, leading to irreversible airflow limitation.Methods: In order to investigate the microRNA–mRNA interaction in the microenvironment of the COPD airway, we used next-generation sequencing and bioinformatics in this study.Results: We identified four genes with microRNA–mRNA interactions involved in COPD small-airway bronchial epithelial cells: NT5E, SDK1, TNS1, and PCDH7. Furthermore, miR6511a-5p–NT5E interaction was found to be involved in small-airway bronchial epithelial cells, large-airway bronchial epithelial cells, and alveolar macrophages.Conclusion: Our results showed that miR6511a-5p–NT5E interaction plays an important role in COPD, which might be associated with cell–cell contact, activation of leukocytes, activation of T lymphocytes, and cellular homeostasis. These findings provide new information for further investigations of the COPD microenvironment, and may help to develop new diagnostic or therapeutic strategies targeting the bronchial epithelium for COPD. Keywords: bioinformatics, COPD, epithelium, miR6511a-5p, next-generation sequencing, NT5E