FOXO3 and chronic obstructive pulmonary disease: These reduced levels fail to control downstream transcription factors, such as FoxO3 and Nrf2, resulting in an abnormal immune response.400,401 Knockout of the SIRT1 gene in mouse airway epithelial cells induces a COPD phenotype.402 A variety of ncRNAs are involved in the pathogenesis of COPD.403,404