Exposure–Response Thresholds for Lung Diseases

This chapter pursues the possibility of generalizing some of the main qualitative insights from Chap. 9 to a wide class of exposure-related diseases: those that can be viewed as arising from destabilization of the physiological feedback control loops that normally maintain homeostasis. For example, several important heart (Eleuteri et al. 2009) and lung (Azad 2008) diseases are associated with oxidative stress caused by disruption of the normal balance between reactive oxygen species (ROS) and antioxidants. They include chronic lung inflammation, fibrosis, silicosis, and inflammation-mediated lung cancer. As detailed in Chap. 9, chronic obstructive pulmonary disease (COPD) involves failures to maintain protease/anti-protease and apoptosis/replacement balances in the alveolar epithelium and degradation/repair balance in the extracellular matrix, as well as oxidant–antioxidant balance in alveolar macrophages (AMs) and other lung cell populations. Chronic inflammation in the lung, heart, and other organs or organ systems arises from failure to maintain the normal balance between influx and clearance of inflammatory cells, such as neutrophils and macrophages, in the inflamed areas. Cancer reflects a loss of homeostatic control balancing proliferation and apoptosis rates in cell populations.