It is of interest to note that Loops 1, 2 and 4 play important but different roles in the CS-induced immune response in COPD progression as shown in Fig 12. The activation of Loop 1 results in a marked predominance of M1 over M2, thus responsible for the innate immune response [Fig 12(B)]. In this case, Tg is predominant over T8 or T17 [Fig 12 (C)]. The activation of Loop 4, as well as Loop 2 (data not shown), drives Th17 and CD8+ to predominate over Treg, responsible for the adaptive immune response [Fig 12(D)]. In this case, both M1 and M2 are relatively low [Fig 12(B)]. These results demonstrate that there exist different cellular and molecular mechanisms (endotypes) in COPD progression. In particular, these different endotypes (mechanisms) can lead to similar TD (CODP) outcomes, highlighting the heterogenous nature of COPD. This finding would be of particular importance in treatment of COPD using personalized medicine and target therapy  as discussed below.