Our global sensitivity analysis shows that the TD outcome is sensitive to a subset of parameters including k13, k14, and k15 and dTD in Eq 12. Fig 9 illustrates how variations in k13 affect the transitions from resistant, reversible to severely susceptible smokers. Here, the CS dose (S = 1.67) is the same as that in the case shown in Figs 2–4. While k13 is varied, dTD = 3.4×10−3 (1/day) and the values of the other parameters in Table A in S1 File are used. The results show that when k13 is less than 2.6×10−2 ml/(cell day),TD remains at a low-level (<30%), exhibiting a COPD resistant feature seen in Fig 9(A). While k13 lies in a value range of 2.6×10−2 and 0.31 ml/(cell day), COPD occurs but smoking cessation leads to TD decreasing to the baseline shown in Fig 9(B). In this case, COPD is reversible . When k13 is larger than 0.31 ml/(cell day), TD at the steady state is reduced to some extent but still remains at a high level (>30%) after smoking cessation at day 2500. A COPD patient in this case is severely susceptible . Interestingly, for a severely susceptible smoker whose k13 is relatively large, the M1-induced destruction of lung tissue predominates. In this case, M1 is sufficient for the progression of COPD, consistent with experiments in mice [24, 25].