In conclusion, although the link that correlates the patterns of lung inflammation to the clinical outcomes, response to therapy, and prognosis of COPD patients is still very elusive, our study proposes a novel AIM2 inflammasome-dependent mechanism that could be involved in the failure of corticosteroid therapy, taking an important step forward and opening new horizons to alternative treatment strategies for COPD patients. Here, AIM2 is linked to chronic obstructive pulmonary disease.