Although cigarette smoking is the main risk factor for COPD, other factors can also play an important role in disease development and progression . For example, as almost every component of the immune system undergoes age-associated changes, aging is a risk factor for developing COPD . An exacerbation of COPD (ECOPD) is defined as an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication, responsible for substantial COPD mortality . Viral or bacterial infections are the main causes of ECOPD, leading to an acute flare-up of inflammation in the lung with stable COPD. Interestingly, mechanical forces of lung tissues have been shown to contribute to COPD progression by allowing rupture of tissue elements which directly leads to increased airspaces and this progression can go on even after smoking cessation . It is important to point out that our current network model focusing on CS-induced COPD does not take these factors into account. Elucidating the roles of these factors in COPD progression is beyond the scope of this article. Possible extensions of the present work to incorporate these factors into the network model will be investigated in future studies.