The protein abundance of NOX isoforms NOX1, NOX2, NOX4, and NOX5 were all upregulated in end-stage COPD patients, indicating their roles in the late phase of the disease, while the results from ACS exposed mice support the mechanistic involvement of NOX1 and NOX4 in the early phase of COPD development using a model of ACS exposed mice. Here, NOX4 is linked to chronic obstructive pulmonary disease.