Airway inflammation and hypersensitivity induced by chronic smoking

Abstract

Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation.

MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity: A new perspective for the treatment

“…The environmental risk factors for AHR include exposure to cigarette smoke [3], bacterial [5] and viral infections [7,54]. These risk factors can lead to acute and chronic airway inflammation.…”

“…Environmental risk factors for AHR such as exposure to cigarette smoke [3,4], and bacterial [5] or viral infection [6,7] may lead to airway inflammation, which triggers production of pro-inflammatory mediators like tumor necrosis factor-␣ (TNF-␣), interleukins (ILs) and kinins. These pro-inflammatory mediators can result in activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-B) signal pathways that induce airway G-protein coupled receptor (GPCR) upregulation for kinins [8][9][10] and airway epithelium dysfunction [6,11].…”

Sensitization by Pulmonary Reactive Oxygen Species of Rat Vagal Lung C-Fibers: The Roles of the TRPV1, TRPA1, and P2X Receptors

“…Thus, sensitization of VLCFs by inflammatory mediators has been implicated in the pathogenesis of the airway hypersensitivity in asthma patients [2], [11]–[13]. To this end, three previous studies have provided indirect evidence indicating that there is a cause-effect relationship between ROS and the airway hypersensitivity.…”

Asymmetric dimethyl-arginine metabolism in a murine model of cigarette smoke-mediated lung inflammation

“…In addition to numerous other compounds, inhalation of CS also exposes the lung to high levels of free radicals present in the smoke. The exposure leads to the activation of endogenous oxidative processes, which in turn modulate the activity of redox-sensitive signal transduction pathways (Kou et al, 2011;Pacher et al, 2007). These pathways also include the transcription factor nuclear factor (NF)-B (Tamimi et al, 2012).…”