title: Epidemiologic and Mechanistic Associations Between Smoking and Pancreatitis.
abstract: Alcohol has long been associated with pancreatitis. Although first described more than three decades ago, smoking has been widely accepted as an important risk factor for all forms of pancreatitis only in the past few years. Empiric data has confirmed smoking as an independent and dose-dependent risk for both acute and chronic pancreatitis. Smoking also increases the risk of recurrences and progression of established chronic pancreatitis. The effects of smoking are enhanced in the presence of alcohol consumption. Indirect evidence suggests that smoking cessation may be beneficial in preventing disease progression. Smoking cessation can therefore be an important strategy for primary as well as secondary prevention of pancreatitis. Therefore, in addition to alcohol, physicians should routinely counsel patients for the benefits of smoking cessation. The mechanisms through which cigarette smoke triggers pathological cellular events, resulting in pancreatitis, are unresolved. Although cigarette smoke contains greater than 4000 compounds, principally nicotine and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) have been broadly studied with regard to pancreatic diseases. Both nicotine and NNK have been shown to induce morphological changes in the pancreas consistent with those seen in pancreatitis. Furthermore, nicotine affects pancreatic secretion and NNK induces premature zymogen activation, two well-known features of pancreatitis. These cigarette toxins may mediate both pro- and anti-inflammatory pathways and can induce changes in pancreatic acinar cell function at the level of transcription, leading to conditions such as thiamin deficiency and mitochondrial dysfunction. Such circumstances could leave the pancreas prone to the development of pancreatitis. This review summarizes relevant research findings and focuses on the epidemiologic links between smoking and pancreatitis, and the cellular pathways that may be significant in induction and evolution of smoking-related pancreatitis.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, 200 Lothrop Street, M2, C-Wing, Pittsburgh, PA, 15213, USA.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Greer
authors.forename: Edwin
authors.initials: E
authors.lastname: Thrower
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Yadav