Cigarette smoke, bacteria, mold, microbial toxins, and chronic lung inflammation

Abstract

Chronic inflammation associated with cigarette smoke fosters malignant transformation and tumor cell proliferation and promotes certain nonneoplastic pulmonary diseases. The question arises as to whether chronic inflammation and/or colonization of the airway can be attributed, at least in part, to tobacco-associated microbes (bacteria, fungi, and spores) and/or microbial toxins (endotoxins and mycotoxins) in tobacco. To address this question, a literature search of documents in various databases was performed. The databases included PubMed, Legacy Tobacco Documents Library, and US Patents. This investigation documents that tobacco companies have identified and quantified bacteria, fungi, and microbial toxins at harvest, throughout fermentation, and during storage. Also characterized was the microbial flora of diverse smoking and smokeless tobacco articles. Evidence-based health concerns expressed in investigations of microbes and microbial toxins in cigarettes, cigarette smoke, and smokeless tobacco products are reasonable; they warrant review by regulatory authorities and, if necessary, additional investigation to address scientific gaps.

Figure 1

A schematic view of an alveolus that depicts the effect of inhaled tobacco smoke on the terminal (respiratory) structure of the lung. Particulate matter “Tar” in tobacco smoke is inhaled deep into the lung where it is recognized by macrophages. The macrophages arise from the blood monocytes that migrate into the lung where they undergo differentiation and maturation. Macrophage phagocytosis of the chemical-rich “Tar” evokes the production of diverse proinflammatory mediators (for details, see Figure 1). Macrophages have toll-like receptors (TLR) that recognize diverse microbes and toxins (LPS is recognized by TLR-4). Shown in this illustration is the production of five proinflammatory cytokines: tumor necrosis factor, type alpha (TNFα), interleukin 1-beta (IL-1β), leukemia inhibitory factor (LIF), oncostatin M (OSM), and Interleukin-4 (IL-4). These soluble factors interact with other cells of the lung, and the response of these cells is thought to accelerate, amplify, and prolong pulmonary inflammation. The target cells may include T cells. The T cell that is depicted herein is representative of many different T cell subsets, including T helper cell subsets Th1, Th2, and Th17. Type I epithelial cells are the major cells lining the alveolar space, and facilitating O₂/CO₂. The type I cells are spread out and cover about 90 to 95% of the alveolar surface. The type II cells form only 5 to 10% of the surface but produce surfactant proteins. Polymorphonuclear leukocytes (PMN) mediate inflammation in multiple ways, including the production of an oxidative burst. Dendritic cells (DC) are professional antigen-presenting cells; they also mediate inflammation.