The results in this work demonstrate that CS-induced COPD development is a multi-step process involving both innate and adaptive immune responses. In the early acute phase of CS exposure, innate immune response predominates. During the transition from the innate to the adaptive immunity, if M1 predominates over M2, the system proceeds to high-grade chronic inflammation and eventually toward COPD where the adaptive immunity play a dominant role (Figs 2–4). However, when M2 (Treg) is predominant over M1 (Th17 and CD8+ T), the acute inflammation turns into the low-grade chronic inflammation, and COPD does not occur (Fig 5–7).