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N-Acetylcysteine Protection in COPDN-Acetylcysteine in COPD: An Alternative Mechanism of Action FREE TO VIEW

Wenxin Wu, PhD; Ahmed Awab, MD, FCCP; Jordan P. Metcalf, MD
Author and Funding Information

From the Division of Pulmonary and Critical Care, Department of Medicine, University of Oklahoma Health Sciences Center.

Correspondence to: Wenxin Wu, PhD, University of Oklahoma Health Sciences Center, Room 425, RP1, 800 N Research Pkwy, Oklahoma City, OK 73104; e-mail: wenxin-wu@ouhsc.edu


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(1):193-194. doi:10.1378/chest.13-2029
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To the Editor:

We read with interest the study by Tse et al1 in a recent issue of CHEST (July 2013). In their study, 1-year treatment with high-dose N-acetylcysteine (NAC) resulted in improved small airway function and decreased exacerbation frequency in patients with COPD. The authors proposed that the reduction in COPD exacerbations might be related to antioxidant and antiinflammatory effects of NAC, resulting in improved small airway function in COPD. Additionally, they proposed that NAC might reduce exacerbations by inhibiting bacterial adherence to ciliated epithelial cells and by NAC mucolytic effects.

Although we agree with these possibilities, one additional mechanism was not discussed. We propose that a major mechanism of NAC-mediated prevention of COPD exacerbations is through restoration of the normal antiviral innate immune response that is suppressed by cigarette smoking and perhaps in COPD.

Cigarette smoking is the major cause of COPD and predisposes patients to severe respiratory tract infections. Respiratory viral infections with rhinoviruses, influenza viruses, and respiratory syncytial virus are the main causes of COPD exacerbations, which are associated with disease progression and loss of lung function.2 Specifically, several studies have confirmed the relationship between cigarette smoking and the risk of influenza infection.3 Influenza infections are more severe, with more cough, acute and chronic phlegm production, breathlessness, and wheezing in smokers.4 The mechanism of increased susceptibility to infections in smokers is likely multifactorial but clearly includes an alteration of immunologic host defenses.

We have demonstrated that cigarette smoke extract (CSE) suppresses host antiviral activity in a human lung model.5 Thus, cigarette smoke exacerbates the susceptibility of the host to respiratory infectious diseases and the attendant pathology. We found that CSE treatment inhibited influenza-induced antiviral cytokine expression in our human model. This is associated with CSE-inhibited messenger RNA and protein expression of the major RNA virus sentinel RIG-I that is important in the antiviral host response. However, inhibition of viral-mediated RIG-I induction by CSE was prevented, and antiviral cytokine responses were restored by NAC.5 The interactions between host immune responses and influenza virus usually determine the outcome of infection. Restoration of these responses by NAC may have been a major mechanism in the decrease in exacerbations demonstrated by Tse et al1 in patients with COPD.

References

Tse HN, Raiteri L, Wong KY, et al. High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study. Chest. 2013;144(1):106-118. [CrossRef] [PubMed]
 
Sapey E, Stockley RA. COPD exacerbations. 2: aetiology. Thorax. 2006;61(3):250-258. [CrossRef] [PubMed]
 
Finklea JF, Sandifer SH, Smith DD. Cigarette smoking and epidemic influenza. Am J Epidemiol. 1969;90(5):390-399. [PubMed]
 
Kark JD, Lebiush M, Rannon L. Cigarette smoking as a risk factor for epidemic A(H1N1) influenza in young men. N Engl J Med. 1982;307(17):1042-1046. [CrossRef] [PubMed]
 
Wu W, Patel KB, Booth JL, Zhang W, Metcalf JP. Cigarette smoke extract suppresses the RIG-I-initiated innate immune response to influenza virus in the human lung. Am J Physiol Lung Cell Mol Physiol. 2011;300(6):L821-L830. [CrossRef] [PubMed]
 

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References

Tse HN, Raiteri L, Wong KY, et al. High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study. Chest. 2013;144(1):106-118. [CrossRef] [PubMed]
 
Sapey E, Stockley RA. COPD exacerbations. 2: aetiology. Thorax. 2006;61(3):250-258. [CrossRef] [PubMed]
 
Finklea JF, Sandifer SH, Smith DD. Cigarette smoking and epidemic influenza. Am J Epidemiol. 1969;90(5):390-399. [PubMed]
 
Kark JD, Lebiush M, Rannon L. Cigarette smoking as a risk factor for epidemic A(H1N1) influenza in young men. N Engl J Med. 1982;307(17):1042-1046. [CrossRef] [PubMed]
 
Wu W, Patel KB, Booth JL, Zhang W, Metcalf JP. Cigarette smoke extract suppresses the RIG-I-initiated innate immune response to influenza virus in the human lung. Am J Physiol Lung Cell Mol Physiol. 2011;300(6):L821-L830. [CrossRef] [PubMed]
 
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