The alcoholic lung: epidemiology, pathophysiology, and potential therapies

Abstract

Epidemiological evidence gathered only in the past decade reveals that alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome by as much as three- to fourfold. Experimental models and clinical studies are beginning to elucidate the mechanisms underlying this previously unrecognized association and are revealing for the first time that chronic alcohol abuse causes discrete changes, particularly within the alveolar epithelium, that render the lung susceptible to acute edematous injury in response to sepsis, trauma, and other inflammatory insults. Recent studies in relevant animal models as well as in human subjects are identifying common mechanisms by which alcohol abuse targets both the alveolar epithelium and the alveolar macrophage, such that the risks for acute lung injury and pulmonary infections are inextricably linked. Specifically, chronic alcohol ingestion decreases the levels of the antioxidant glutathione within the alveolar space by as much as 80-90%, and, as a consequence, impairs alveolar epithelial surfactant production and barrier integrity, decreases alveolar macrophage function, and renders the lung susceptible to oxidant-mediated injury. These changes are often subclinical and may not manifest as detectable lung impairment until challenged by an acute insult such as sepsis or trauma. However, even otherwise healthy alcoholics have evidence of severe oxidant stress in the alveolar space that correlates with alveolar epithelial and macrophage dysfunction. This review focuses on the epidemiology and the pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments suggested by recent experimental findings.

Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats

“…Zinc also plays a role in the regulation of cellular glutathione (29) and protects cell membranes from oxidative damage (30). This is particularly intriguing, as we have published extensively on the role of oxidant stress and glutathione depletion in experimental models of chronic alcohol ingestion and in human subjects with alcohol abuse (5,7,(31)(32)(33)(34). Therefore, alcohol-induced zinc deficiency may play a central role in the oxidant stress and consequent cellular dysfunction that has been shown to characterize the alcoholic lung phenotype.…”

“…Our research group has determined that chronic alcohol ingestion in experimental animals as well as in otherwise healthy individuals has profound effects on airway epithelial and macrophage function (4)(5)(6)(7)(8)(9). Specifically, the epithelial barrier within the small gas-exchanging airways, the alveoli, is compromised.…”

Rusya'da Alkol ve Alkolizm: Politikalar ve Etkileri

“…[33][34][35] This is probably caused by smoking, aspiration of gastric contents and absence of public houses affordable for drinkers with low incomes, who loiter outdoors and can fall asleep in a cold place. Besides, derangements of pulmonary surfactant under the impact of alcohol consumption have been reported 36 . In this connection, it should be warned against application of invasive methods without evidence-based clinical indications 17 , e.g.…”

Alcohol, Signaling, and ECM Turnover

“…When these processes are impaired or fail the particulate matter enters into the alveoli, evoking a self resolving inflammatory response by the alveolar macrophage (AM). Alcohol abuse perturbs the mucociliary clearance of the pathogens by cilia, the AM recognition and phagocytosis of the stimuli, generation of chemical mediators, and the recruitment of auxiliary defenses, as well as the secretion of surfactant by lung epithelial cells (D'Souza ElGuindy et al, 2007;D'Souza et al, 1996;Gamble et al, 2006;Joshi and Guidot, 2007;Szabo and Mandrekar, 2009;Wyatt et al, 2004). These adverse effects of acute and chronic alcohol intoxication on the lung have been reviewed extensively elsewhere (Boe´et al, 2009;Happel and Nelson, 2005).…”

“…More recently, alcohol abuse has also been associated with increased incidence and severity of acute respiratory distress syndrome (ARDS) (Esper et al, 2006;Moss et al, 1996), increased risk for viral and fungal infections and, subsequent susceptibility to secondary bacterial infections (Fong et al, 1994;Jerrells et al, 2007). The increased susceptibility of alcohol abusers to a variety of lung infections is attributed largely to alcohol-mediated alterations in innate and adaptive immunity (Happel and Nelson, 2005;Joshi and Guidot, 2007;Szabo and Mandrekar, 2009). As is the case with other organs, the effects of alcohol on the lung may be direct or mediated via its metabolites (Sisson 2007).…”