Asthma and inflammation

Abstract

Allergic diseases affect approximately one-third of the general population, and asthma is a heterogeneous disorder, characterized by reversible airway obstruction and bronchial hyperresponsiveness, which is commonly associated with atopy [1,2]. Among the multiple factors that contribute to asthma are genetic predisposition, immunological aberration, and the possible involvement of noxious environmental factors [3]. Epidemiological studies, in particular, have suggested that worldwide increases in allergic and respiratory disease may be associated with environmental pollutants such as air pollution [4,5]. The major component of airborne particulate matter (PM) is diesel exhaust particles (DEPs), which can induce and enhance allergic responses [6] by entering cells as nanoparticles and directly and indirectly generating reactive oxygen species (ROS) [7,8]. The defensive response of the lung alveolar cells to ROS is mediated through nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and one of the primary cellular defenses to this reaction is mediated through glutathione S-transferases such as GSTM1 [9-11]. The GSTM1 null mutation is present in up to 50% of normal individuals and predisposes these individuals to a higher risk of acquiring environmentally related diseases, including some forms of cancer [11]. It has also been reported that individuals with the null mutation have a higher induction of IgE in response to DEP plus secondhand smoke exposure [12]. DEP increases inflammation and stimulates oxidant stress pathways in the normal bronchial epithelium, but asthmatics are more sensitive to the effects of DEPs, and individuals expressing GSTP1 ile/ile105 have higher histamine inductions when exposed to DEP and secondhand smoke [13,14]. In this chapter, the role of airborne PM predominated by diesel particles will be examined in light of their ability to increase oxidative stress and inflammation, which may be affected in many individuals by obesity, allergy, dietary antioxidants, and other bioactive substances.