Alcohol and the Lung Ashish Mehta, Emory University David M Guidot, Emory University Journal Title: Alcohol Research Current Reviews Volume: Volume 38, Number 2 Publisher: Niaaa | 2017-01-01, Pages 243-254 Type of Work: Article | Final Publisher PDF Permanent URL: https://pid.emory.edu/ark:/25593/tdxw1 Final published version: https://www.arcr.niaaa.nih.gov/arcr382/article04.htm Copyright information: This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/). Accessed September 29, 2021 12:09 PM EDT ALCOHOL RESEARCH: Current Reviews Alcohol and the Lung Ashish J. Mehta, M.D., and David M. Guidot, M.D. Ashish J. Mehta, M.D., is an Assistant Professor of Medicine Among the many organ systems affected by harmful alcohol use, the lungs are in the Department of Medicine, particularly susceptible to infections and injury. The mechanisms responsible for Division of Pulmonary, Allergy, rendering people with alcohol use disorder (AUD) vulnerable to lung damage include alterations in host defenses of the upper and lower airways, disruption of alveolar epi- Critical Care & Sleep Medicine, thelial barrier integrity, and alveolar macrophage immune dysfunction. Collectively, Emory University, Atlanta, Georgia, these derangements encompass what has been termed the “alcoholic lung” and a Staff Physician at the phenotype. Alcohol-related reductions in antioxidant levels also may contribute to Atlanta VA Medical Center, lung disease in people with underlying AUD. In addition, researchers have identified Decatur, Georgia. several regulatory molecules that may play crucial roles in the alcohol-induced disease processes. Although there currently are no approved therapies to combat the David M. Guidot, M.D., is a detrimental effects of chronic alcohol consumption on the respiratory system, these Professor of Medicine in the molecules may be potential therapeutic targets to guide future investigation. Department of Medicine, Division of Pulmonary, Allergy, Critical Key words: Alcohol consumption; alcohol use disorder; alcoholic lung; lung; lung Care & Sleep Medicine, Emory disease; lung injury; respiratory system; pulmonary system; alveolar macrophage; University, Atlanta, Georgia, and antioxidant a Staff Physician at the Atlanta VA Medical Center, Decatur, Georgia. Few social practices have had a longer Guidot 2012). More than a century susceptibility to pneumonia through or more complicated history in human later, William Osler wrote that alcohol multiple mechanisms. The major fac- civilization than the consumption of abuse was the most important risk fac- tors include an increased risk of aspira- alcohol. As documented in academic tor for pneumonia (see Happel and tion, abnormalities in the way particles writings, but even more commonly in Nelson 2005; Mehta and Guidot 2012). are eliminated from the conducting art and music, humans have consumed As modern medicine evolved through- airways through the mucus (i.e., in alcohol for thousands of years, and out the 20th century, it became abun- mucociliary clearance), and impaired drinking is either a celebrated facet of dantly clear that alcohol use disorder activity of one branch of the immune social activities or a proscribed practice, (AUD) rendered people more suscep- system (i.e., innate immunity) within depending on the local moral or reli- tible to a wide variety of lung infec- the lower airways (for reviews, see gious views. Although alcohol intoxi- tions, including bacterial pneumonias Joshi and Guidot 2007; Mehta and cation has been described in various and tuberculosis, and increased mor- Guidot 2012). written recordings since antiquity, it bidity and mortality. In a now-classic Even more recently, researchers is only relatively recently that its true modern citation, Perlino and Rimland have identified an association between effects on lung health have been recog- (1985) coined the term “alcoholic leu- underlying AUD and acute respiratory nized. In the latter years of the 18th kopenic pneumococcal sepsis syndrome” distress syndrome (ARDS). ARDS century, the first Surgeon General of when they published a case series of is a severe form of acute lung injury the United States of America, Benja- patients with underlying AUD who that occurs as a complication of diverse min Rush (for whom the medical suffered from pneumococcal pneumo- insults, including sepsis, massive aspi- school in Chicago is named), noted nia and sepsis associated with leukope- ration, and trauma; it has a mortality that excessive alcohol consumption nia that was associated with a mortality rate of 30 percent to 50 percent, even was associated with pneumonia (see of more than 80 percent. Excessive with state-of-the-art modern medical Happel and Nelson 2005; Mehta and alcohol consumption seems to increase care in an intensive care unit (Villar et Alcohol and the Lung | 243 9012_NIAAA_ARCR_Journal_Organs_vol38_#2_TXT_v04_FINAL.indd 243 5/23/17 5:40 PM al. 2011; Wang et al. 2014; Ware which is reliably used as a surrogate to intoxication and the resulting decrease 2006; Ware and Matthay 2000). In quantify blood alcohol concentrations. in the level of consciousness promotes 1996, a seminal study demonstrated Interestingly, the alcohol vapor found aspiration of oral secretions into the for the first time that AUD inde- in the airways is not caused by inhala- lower airways because of diminished pendently conferred an approximately tion but is a result of the ready diffu- gag and upper-airway reflexes that twofold increase in risk of developing sion of alcohol from the airway blood would normally protect against this ARDS (Moss et al. 1996). A subse- supply across the airway epithelium phenomenon. These modifications in quent prospective study focusing only and into the airways themselves (George the upper airways seem to contribute on patients with severe sepsis revealed et al. 1996). This process explains why to the increased risk of lung infections, that the relative risk of developing alcohol vapor in the breath may be including those caused by more virulent ARDS was closer to fourfold higher in used to determine blood alcohol con- gram-negative organisms, in chronic those with an underlying AUD;1 this centration. The alcohol then is depos- heavy drinkers. effect was independent of factors such ited and metabolized in the airways. This risk further is exacerbated by as age, smoking, severity of illness, and This process leads to the formation of the negative effects of chronic alcohol nutritional status (Moss et al. 2003). reactive aldehydes (e.g., acetaldehyde), ingestion on the lower airways. In par- Other investigators have confirmed which in turn can interact and form ticular, animal models have established these associations (Iribarren et al. 2000; harmful adducts with proteins and that chronic excessive alcohol ingestion Licker et al. 2003; Spies et al. 1996; DNA (Sapkota and Wyatt 2015). The causes dysfunction of the mucociliary von Heymann et al. 2002). Taken formation of these adducts may dis- apparatus, an important host defense together, all of these findings indicate rupt normal cellular functions, induce mechanism responsible for clearing that drinking patterns that define inflammation, and impair healing. harmful pathogens and mucus from AUD are associated with a significantly Taken together, these findings demon- the lower airways (Happel and Nelson increased risk of serious lung infections strate that the airways—including the 2005). An early experimental study in and acute lung injury and thereby oral cavity and extending all the way to sheep investigating the effects of alcohol contribute to the deaths of tens of the alveolar space—are subjected to high on ciliary beat frequency (CBF) thousands of Americans every year, concentrations of alcohol and its delete- demonstrated a dose-dependent effect, and many more worldwide. rious metabolites during intoxication. such that low alcohol concentrations This review first will discuss key aspects Within the upper airways, chronic actually stimulated CBF, whereas high of the epidemiology and pathophysiology alcohol consumption leads to several concentrations impaired it (Maurer of AUD and lung health, before focus- alterations. First, chronic heavy drink- and Liebman 1988). Later mechanistic ing more in-depth on lung infections ing often is associated with poor tooth studies found that whereas short-term and acute lung injury, which comprise development and arrangement (i.e., alcohol exposure causes a transient the majority of alcohol-related lung dentition) as well as poor oral hygiene, increase in CBF, chronic exposure diseases. The article also will briefly and although these usually are attributed desensitizes the cilia so that they can- review some of the experimental thera- to poor nutritional and lifestyle choices, not respond to stimulation (Wyatt et pies that hold promise for decreasing clinical studies have established that al. 2004). Alcohol-induced failure of the enormous morbidity and mortality they also result, to some extent, from the mucociliary system could interfere caused by the “alcoholic lung” in the direct effects of alcohol exposure with the clearance of pathogens from our society. on the upper airway. Specifically, alcohol the airways and thereby may contrib- decreases saliva production in the sali- ute to the increased risk of pulmonary vary glands located in front of the ears infections in people with chronic heavy Alcohol