Poole, P. J. & Black, P. N. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. Br. Med. J. 322, 1271-1274

Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand.
BMJ Clinical Research (Impact Factor: 14.09). 05/2001; 322(7297):1271-4. DOI: 10.1136/bmj.322.7297.1271
Source: PubMed


To assess the effects of oral mucolytics in adults with stable chronic bronchitis and chronic obstructive pulmonary disease.
Systematic review of randomised controlled trials that compared at least two months of regular oral mucolytic drugs with placebo.
Twenty three randomised controlled trials in outpatients in Europe and United States.
Exacerbations, days of illness, lung function, adverse events.
Compared with placebo, the number of exacerbations was significantly reduced in subjects taking oral mucolytics (weighted mean difference -0.07 per month, 95% confidence interval -0.08 to -0.05, P<0.0001). Based on the annualised rate of exacerbations in the control subjects of 2.7 a year, this is a 29% reduction. The number needed to treat for one subject to have no exacerbation in the study period would be 6. Days of illness also fell (weighted mean difference -0.56, -0.77 to -0.35, P<0.0001). The number of subjects who had no exacerbations in the study period was greater in the mucolytic group (odds ratio 2.22, 95% confidence interval 1.93 to 2.54, P<0.0001). There was no difference in lung function or in adverse events reported between treatments.
In chronic bronchitis and chronic obstructive pulmonary disease, treatment with mucolytics is associated with a reduction in acute exacerbations and days of illness. As these drugs have to be taken long term, they could be most useful in patients who have repeated, prolonged, or severe exacerbations of chronic obstructive pulmonary disease.

Full-text preview

Available from:
  • Source
    • "The molecular mechanisms whereby inflammatory mediators are upregulated at exacerbation may be through activation of transcription factors such as nuclear factor (NF)-κB and activator protein-1 that increase transcription of proinflammatory genes (Erlandsen et al., 1993). Acute exacerbations have a direct effect on disease progression by accelerating loss of lung functional though the inflammatory response at exacerbation is variable and may depend in part on the etiologic agent (Poole, 2001; Troosters et al., 2010). Current therapies for COPD exacerbations are of limited effectiveness (Rennard et al., 2007). "

    Preview · Article · May 2015
  • Source
    • "These biochemical changes were accompanied by an improvement in the pulmonary function tests of these patients (Behr et al., 1997). In placebocontrolled trials, orally administered NAC (≥600 mg/day) has been shown to significantly improve the response to steroids, increase the general well-being, and decrease exacerbation rates, emergency room visits, days of illness, costs of hospitalization , and work time loss in patients with chronic lung diseases (Grandjean et al., 2000; Kasielski and Nowak, 2001; Poole and Black, 2001). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute lung injury (ALI) is a life threatening condition associated with hypoxemia, diffuse alveolar damage, inflammation, and loss of lung function. Lipopolysaccharide (LPS; endotoxin) from the outer membrane of Gram-negative bacteria is a major virulence factor involved in the development of ALI. The depletion of glutathione (GSH), an essential intra- and extra-cellular protective antioxidant, by LPS is an important event that contributes to the elevation in reactive oxygen species. Whether restoring GSH homeostasis can effectively ameliorate mitochondrial dysfunction and cellular apoptosis in ALI is unknown and therefore, was the focus of this study. In peripheral lung tissue of LPS-treated mice, hydrogen peroxide and protein nitration levels were significantly increased. Pre-treatment with GSH-ethyl ester (GSH-EE) prevented this increase in oxidative stress. LPS also increased the lactate/pyruvate ratio, attenuated SOD2 protein levels, and decreased ATP levels in the mouse lung indicative of mitochondrial dysfunction. Again, GSH-EE treatment preserved the mitochondrial function. Finally, our studies showed that LPS induced an increase in the mitochondrial translocation of Bax, caspase 3 activation, and nuclear DNA fragmentation and these parameters were all prevented with GSH-EE. Thus, this study suggests that GSH-EE supplementation may reduce the mitochondrial dysfunction associated with ALI.
    Full-text · Article · May 2012 · Frontiers in Physiology
  • Source
    • "This demonstrated a reduction in exacerbations of COPD compared with placebo. Six trial subjects required treatment with an oral mucolytic to prevent one exacerbation in the study period (range 2 months to 24 months) compared with placebo.59 A quantitative systematic literature review of the use of NAC specifically has also been carried out. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic obstructive pulmonary disease is a varied condition when examined from a number of different perspectives including factors which influence disease development, pathological process and clinical features. There may be a complex interaction between the degree by which each of these processes influences the development of COPD and the subsequent clinical phenotype with which the patient presents. The varied host response and subsequent clinical phenotype has generated much interest in recent years. It is possible that failure of treatment to impact on mortality and reverse the disease process is because of the heterogeneous nature of the condition. Identification and targeted treatment of clinical and pathological phenotypes within the broad spectrum of COPD may therefore improve outcome. This article will review previous work which has attempted to phenotype COPD and identify if specific treatment for these phenotypes has been shown to be of benefit. It will examine the work on pathological processes and clinical manifestations, both pulmonary and systemic, and will focus on pharmacological therapies.
    Preview · Article · Sep 2009 · International Journal of COPD
Show more