Pulmonary Function in Former Alcoholics

Emirgil, Cemil; Sobol, Bruce J.

doi:10.1378/chest.72.1.45

Cited by 29 publications

(28 citation statements)

References 14 publications

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“…Furthermore, since CYP2E1 is induced by chronic ethanol intake [32][33][34], our data would predict the increase in theophylline clearance observed in alcoholics by Jusko et al [35]. This is of particular relevance, as up to 50% of alcoholics have evidence of chronic obstructive pulmonary disease [36] and require theophylline therapy.…”

Section: Theophyine 4mm)mentioning

confidence: 51%

Metabolism of theophylline by cDNA‐expressed human cytochromes P‐450.

Ha¹,

Chen²,

Freiburghaus³

et al. 1995

Brit J Clinical Pharma

154

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1 Theophylline metabolism was studied using seven human cytochrome P-450 isoforms (CYPs), namely CYPlAl, 1A2, 2A6, 2B6, 2D6, 2E1 and 3A4, and microsomal epoxide hydroxylase (EH), expressed in human B-lymphoblastoid cell lines. 2 At a high theophylline concentration of 10 mm four CYPs (lAl, 1A2, 2D6, 2E1) catalyzed the metabolism of theophylline. 3 Theophylline had the highest affinity (apparent Km range 0.2-1.0 mM) for the CYPIA subfamily and the kinetics of metabolic formation mediated by CYP1A2indicated substrate-inhibition (K1 range 9-16 mM). 4 CYP1A2 catalyzed the demethylation of theophylline as well as its hydroxylation, and was associated with the highest intrinsic clearance (1995 1 h-' per mol CYP) to 1,3-dimethyluric acid (DMU). Therefore, this isoform can be considered to be the most important enzyme involved in theophylline metabolism in vitro. 5 CYP2El was responsible for a relatively high intrinsic clearance by 8-hydroxylation (289 1 h-' per mol CYP). The apparent Km value of this reaction was about 15 mm, suggesting that CYP2E1 may be the low-affinity high-capacity isoform involved in theophylline metabolism. 6 The affinity of theophylline for CYPlAl was comparable with that of its homologue 1A2. When induced, the participation of CYPlAl in theophylline metabolism may be important. 7 CYP2D6 played only a minor role and CYP3A4 was not active in the in vitro metabolism of theophylline. 8 Our findings confirm the major role of CYP1A2 in theophylline metabolism and explain why in vivo the elimination kinetics of theophylline are non-linear and in vitro theophylline metabolism by human liver microsomes does not obey monophasic kinetics. 9 The data suggest also that not only tobacco smoking but also chronic alcohol intake may influence theophylline elimination in man as ethanol induces CYP2E1.Keywords theophylline metabolism CYP1A2 CYP2E1 in vitro cDNA expressed microsomes

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Section: Theophyine 4mm)mentioning

confidence: 51%

Metabolism of theophylline by cDNA‐expressed human cytochromes P‐450.

Ha¹,

Chen²,

Freiburghaus³

et al. 1995

Brit J Clinical Pharma

154

View full text Add to dashboard Cite

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“…The findings were confirmed by Emirgil and correlated to symptoms of chronic bronchitis and shortness of breath in a similar group of alcoholics (Emirgil et al, 1974). A later study by Emirgil in 1977 studied pulmonary function in 44 abstinent members of Alcoholics Anonymous and found that 64% had airflow obstruction and 16% and 17% exhibited significant air trapping and/or impaired diffusion, respectively (Emirgil and Sobol, 1977). Airflow obstruction could not be accounted for on the basis of current smoking status or previous infection.…”

Section: Clinical Studies Of Alcohol and Copdmentioning

confidence: 77%

Alcohol and airways function in health and disease

Sisson

2007

Alcohol

142

136

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The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The impact of alcohol on lung airway functions is dependent on the concentration, duration and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation and probably attenuates the airway inflammation and injury observed in asthma and COPD. Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management and likely worsens outcomes including lung function and mortality in COPD patients. Non-alcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase type 2 (ALDH2). The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation and the interaction with other airway exposure agents, such as cigarette smoke, represent opportunities for future investigation.

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“…Although it is increasingly recognized that alcohol consumption alters many lung responses (12,22,43), the effect of alcohol in allergic asthma is poorly understood and may have important clinical implications.…”

Section: Discussionmentioning

confidence: 99%

Alcohol reduces airway hyperresponsiveness (AHR) and allergic airway inflammation in mice

Oldenburg

Poole

Sisson

2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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There is very limited knowledge about the effects of alcohol on airway hyperresponsiveness and inflammation in asthma. Historical accounts of alcohol administration to patients with breathing problems suggest that alcohol may have bronchodilating properties. We hypothesized that alcohol exposure will alter airway hyperresponsiveness (AHR) and pulmonary inflammation in a mouse model of allergic asthma. To test this hypothesis, BALB/c mice were fed either 18% alcohol or water and then sensitized and challenged with ovalbumin (OVA). AHR was assessed by means of ventilation or barometric plethysmography and reported as either total lung resistance or enhanced pause, respectively. Airway inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluid (BALF), cytokine levels in BALF, lung histology, and serum immunoglobulin E (IgE) levels. Alcohol feeding significantly blocked methacholine-induced increases in AHR compared with water-fed controls. Alcohol feeding significantly reduced total cell numbers (64%) as well as the number of eosinophils (84%) recruited to the lungs of these mice. Modest changes in lung pathology were also observed. Alcohol exposure led to a reduction of IgE in the serum of the EtOH OVA mice. These data demonstrate that alcohol exposure blunts AHR and dampens allergic airway inflammation indices in allergic mice and suggest that there may be an important role for alcohol in the modulation of asthma. These data provide an in vivo basis for previous clinical observations in humans substantiating the bronchodilator properties of alcohol and for the first time demonstrates an alcohol-induced reduction of allergic inflammatory cells in a mouse model of allergic asthma.

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Pulmonary Function in Former Alcoholics

Cited by 29 publications

References 14 publications

Metabolism of theophylline by cDNA‐expressed human cytochromes P‐450.

Metabolism of theophylline by cDNA‐expressed human cytochromes P‐450.

Alcohol and airways function in health and disease

Alcohol reduces airway hyperresponsiveness (AHR) and allergic airway inflammation in mice

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