The health effects of e-cigarettes in patients with pre-existing lung disease are unknown. The aim of this study was to investigate whether aerosols from a fourth-generation e-cigarette produces similar in-vitro cytotoxic, DNA damage and inflammatory effects on bronchial epithelial cells (BECs) from patients with COPD, as cigarette smoke. BECs from patients with COPD who underwent surgery for lung cancer and comparator (immortalised 16HBE) cells were grown at air liquid interface (ALI). BECs were exposed to aerosols from a JUUL® e-cigarette (Virginia Tobacco and Menthol pods at 5% nicotine strength) or reference 3R4F cigarette for 30 min at ALI. Cell cytotoxicity, DNA damage and inflammation were measured. In response to the Virginia Tobacco and Menthol flavoured e-cigarette aerosols, COPD BECs showed comparable LDH release (cell cytotoxicity, p = 0.59, p = 0.67 respectively), DNA damage (p = 0.41, p = 0.51) and inflammation (IL-8, p = 0.20, p = 0.89 and IL-6, p = 0.24, p = 0.93), to cigarette smoke. 16HBE cells also showed comparable cellular responses to cigarette smoke. In airway cells from patients with COPD, aerosols from a fourth-generation e-cigarette were associated with similar toxicity to cigarette smoke. These results have potential implications for the safety of e-cigarette use in patients with lung disease. •E-cigarette aerosols cause similar adverse effects as cigarette smoke in bronchial epithelial cells from COPD patients .•Heightened cell cytotoxicity, DNA damage and inflammation was observed in in as little as 30  min of aerosol exposure.•E-liquid flavourings and their composition are an important source of toxicity.