Alcohol and Lung Disease

This combination increases your risk for several conditions and can aggravate symptoms of COPD. The same study found that people diagnosed with COPD, as well as other cardiovascular disorders, aren’t as likely to give up drinking because of the diagnosis. Similarly, people who are chronic tobacco users are four times more likely to be dependent on alcohol than the average population.

Also, as noted above, chronic alcohol ingestion interferes with Nrf2 signaling in alveolar macrophages (Mehta et al. 2011), thereby disrupting the expression of hundreds of genes that are crucial to combatting oxidative stress. Although the precise role of alcohol-mediated inhibition of the Nrf2–ARE pathway in mediating oxidative stress has not been completely clarified, this pathway represents a strategic target to direct future therapies. The potential influence of alcohol consumption on airway health and disease has been documented for a long time.

Reduced Antioxidant Levels

Importantly, alcoholics also are at increased risk for infections with Mycobacterium tuberculosis (Cook 1998). Following a brief overview of the well-known association between alcohol abuse and pneumonia, this article will discuss the newer clinical and experimental evidence linking alcohol abuse and acute lung injury and how systems biological approaches could be applied to identify novel therapeutic targets in the alcoholic lung. Although TB is treatable with antibiotics, the prevalence of multidrug-resistant tuberculosis (MDRTB) is on the rise and has been reported worldwide (WHO 2014). One of the main factors increasing the prevalence of MDRTB is noncompliance by patients who do not complete their is mary jane a drug normal 6-month treatment regimen, leading to the emergence of drug-resistant M. A recent study of MDRTB in South Africa reports that of 225 patients diagnosed with MDRTB, only 50 percent were cured or completed treatment. Other countries also report similar TB treatment defaults in individuals with AUD, resulting in poorer treatment outcomes and increased mortality rates (Bumburidi et al. 2006; Jakubowiak et al. 2007).

Potential Therapeutic Strategies for the Alcoholic Lung

Alcohol-induced suppression of G-CSF–driven neutrophil production combined with impaired bacterial clearance likely account for the high severity and mortality of bacterial infections among the alcohol-fed mice observed in these studies. The depletion of glutathione within the alveolar space of people with AUD explains many of the alcohol-related defects in the function of the alveolar epithelium as well as in the function of immune cells called macrophages (which will be discussed in the next section). Glutathione levels are affected by oxidative stress and inflammation; however, lungs of alcohol-exposed animals show no gross evidence of inflammation or injury at baseline, and otherwise healthy alcoholics likewise have no indication of lung inflammation or oxidative stress. Without evidence of an oxidant assault on the otherwise healthy alcoholic lung, the question remains why there is such overwhelming glutathione depletion.

1. In an attempt to explain some of these discrepancies, Breslin and colleagues (1973) compared the effects of exposure to different types of alcohol in a clinical study.
2. RSV is one of the most common lower respiratory tract viral pathogens and is a major cause of respiratory infections in children.
3. Heavy drinking means more than one drink a day for women or more than two drinks a day for men.
4. Originally described by Ashbaugh and colleagues (1967), ARDS is characterized by alveolar epithelial and endothelial barrier disruption, dysfunction of the lipoprotein complex (i.e., surfactant) coating the lung surfaces, and intense inflammation.
5. Therefore, the experimental findings to date implicate the pathophysiological sequence in the alcoholic lung shown in figure 2.

The Link Between Alcohol and COPD

When the animals were treated with recombinant GM-CSF, alveolar macrophage bacterial phagocytic capacity, GM-CSF receptor expression, and PU.1 nuclear binding were restored (Joshi et al. 2005). These studies offer the groundwork for understanding the importance of GM-CSF within the lung for the maturation and host immune function of the alveolar macrophage as well as the deleterious impact of chronic alcohol use on these processes. These phagocytic cells ingest and clear inhaled microbes and foreign particles from the lungs.

Additional studies using alveolar epithelial cell layers derived from these alcohol-fed rats found that this permeability defect was inhibited by neutralizing antibodies to TGF-β1 (Bechara et al. 2004). Together, these data suggest that prolonged alcohol intake increases TGF-β1 levels, which during inflammatory responses can be released and activated in the alveolar space, where it can directly impair epithelial barrier properties (Guidot and Hart 2005). ARDS is a severe form of lung injury characterized by fluid accumulation in the lung that is not related to heart problems (i.e., noncardiogenic pulmonary edema) as well as by flooding of the alveolar airspaces with protein-like (i.e., proteinaceous) fluid (Ware 2006; Ware and Matthay 2000).

Alveolar macrophages in alcohol-exposed animals also exhibit decreased production of important chemokines and mediators, which impairs their ability to recruit other cell types, namely neutrophils, during times of stress and infection (Happel et al. 2004). Although the majority of data focuses on the effects of chronic alcohol ingestion, experimental evidence further suggests that even acute exposure has similar detrimental effects on alveolar macrophage immune function, although these defects readily resolve (Libon et al. 1993). Taken together, these alcohol-mediated defects in alveolar macrophage function contribute to increased vulnerability to pulmonary infections.

Prolonged alcohol exposure alters the first line of the innate cellular defense, the mucociliary apparatus, against invading pathogens such as RSV. This defense system propels inhaled particles, microbes, toxins, and debris out of the lungs and airways with the help of the fine hairs (i.e., cilia) on the cells that line the respiratory tract. Another key function of the alveolar epithelium, namely the synthesis and secretion of surfactant—which is required to maintain alveolar integrity and gas exchange—also is impaired by chronic alcohol ingestion (Holguin et al. 1998). This impairment also is mediated by glutathione deficiency in the cells, and particularly in the mitochondria, and is reversible with dietary procysteine supplementation (Guidot and Brown 2000). Although these animal models provide convincing evidence implicating glutathione depletion as a mediator of alveolar epithelial barrier dysfunction, additional studies in humans are necessary to confirm these findings. As discussed in this review, genetic analysis has helped to identify potential candidate genes involved in alcohol-induced lung dysfunction that might explain the newly identified association between alcohol abuse and acute lung injury in humans.

Therefore, the experimental findings to date implicate the pathophysiological sequence in the alcoholic lung shown in figure 2. In addition to neutrophil recruitment to infected areas and reduced neutrophil-killing potential, production of these cells also is affected. In healthy individuals, the bone marrow produces approximately 120 billion neutrophils per fetal alcohol syndrome celebrities day (Cartwright et al. 1964; von Vietinghoff and Ley 2008). Moreover, bone-marrow neutrophil production is significantly increased 24 to 48 hours after a systemic bacterial infection (Melvan et al. 2011). Alcohol exposure suppresses neutrophil production by the bone marrow and other blood cell–producing (i.e., hematopoietic) tissues (Melvan et al. 2011; Raasch et al. 2010; Siggins et al. 2011).

As noted previously, alcohol-induced oxidative stress impairs multiple critical cellular functions within the lung. In particular, the critical barrier function within the alveolar epithelium is compromised. Under normal conditions, the alveolar epithelium is a tight barrier that allows the alveoli to remain air filled despite their close proximity to the lung’s small blood vessels (i.e., capillaries), through which the entire cardiac output courses. This dynamic barrier physically restricts the leakage of demi lovato first album fluid into the alveolar space but also actively transports sodium and fluid out of the alveolar space in order to maintain this gas exchange unit.