CS inhalation has been considered the major risk factor for COPD, but only about 20–30% chronic smokers develop the disease, suggesting that cigarette smokers have different levels of COPD susceptibility [1, 9]. Our simulations disclose that there exist three types of smokers according to their COPD susceptibilities, i.e., resistant, reversely susceptible and severely susceptible smokers. While long-term CS inhalation can cause just low levels of chronic inflammation in resistant smokers but without COPD, susceptible smokers can develop COPD eventually under the same CS exposure conditions as shown in Fig 9. After cigarette smoking cessation, COPD can be prevented in reversible susceptible smokers, but the disease cannot be fully reversed in severely susceptible smokers (Fig 9). The sensitivity analysis in this work has identified a subset of parameters in the model that govern the dynamical behaviors of COPD and describe the different disease susceptibilities of different smokers as shown in Fig 9 and Figures D-F in S1 File.