Fluticasone and N-acetylcysteine in primary care patients with COPD or chronic bronchitis.

Radboud University Nijmegen Medical Centre, Department of General Practice, Nijmegen, The Netherlands.
Respiratory medicine (Impact Factor: 2.92). 02/2009; 103(4):542-51. DOI: 10.1016/j.rmed.2008.11.003
Source: PubMed

ABSTRACT Increased oxidative stress and bronchial inflammation are important mechanisms in the pathophysiology of COPD.
To investigate whether treatment with the inhaled corticosteroid fluticasone propionate (FP) or the anti-oxidative agent N-acetylcysteine (NAC) are effective in primary care patients.
The study was a 3-year placebo-controlled randomised controlled trial preceded by a 3-month washout and 2-week prednisolone pre-treatment. Patients were (ex-)smokers with chronic bronchitis or COPD. Interventions were inhaled FP 500microg b.i.d., oral NAC 600mg o.d., or placebo. Exacerbation rate and quality of life measured with the Chronic Respiratory Questionnaire (CRQ) were the primary outcomes, FEV(1) decline and respiratory symptoms secondary outcomes.
286 patients recruited from 44 general practices were randomised. Exacerbation rate was 1.35 times higher for NAC (p=0.054) and 1.30 times higher for FP (p=0.095) compared with placebo. CRQ total scores did not differ between NAC (p=0.306) or FP (p=0.581) treatment compared to placebo. Annual postbronchodilator FEV(1) decline was 64mL [SD 5.4] for NAC [p=0.569 versus placebo], 59mL [SD 5.7] for FP [p=0.935], and 60mL [SD 5.4] for placebo.
No beneficial treatment effects for either high-dosed inhaled fluticasone propionate or oral N-acetylcysteine were observed in our study population of patients with COPD or chronic bronchitis.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a major public health problem in India. Although several International guidelines for diagnosis and management of COPD are available, yet there are lot of gaps in recognition and management of COPD in India due to vast differences in availability and affordability of healthcare facilities across the country. The Indian Chest Society (ICS) and the National College of Chest Physicians (NCCP) of India have joined hands to come out with these evidence-based guidelines to help the physicians at all levels of healthcare to diagnose and manage COPD in a scientific manner. Besides the International literature, the Indian studies were specifically analyzed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (a) definitions, epidemiology, and disease burden; (b) disease assessment and diagnosis; (c) pharmacologic management of stable COPD; (d) management of acute exacerbations; and (e) nonpharmacologic and preventive measures. The modified grade system was used for classifying the quality of evidence as 1, 2, 3, or usual practice point (UPP). The strength of recommendation was graded as A or B depending upon the level of evidence.
    Lung India 07/2013; 30(3):228-67. DOI:10.4103/0970-2113.116248
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a common and morbid disease characterized by high oxidative stress. Its pathogenesis is complex, and involves excessive oxidative stress (redox imbalance), protease/antiprotease imbalance, inflammation, apoptosis, and autoimmunity. Among these, oxidative stress has a pivotal role in the pathogenesis of COPD by initiating and mediating various redox-sensitive signal transduction pathways and gene expression. The protective physiological mechanisms of the redox balance in the human body, their role in the pathogenesis of COPD, and the clinical correlation between oxidative stress and COPD are reviewed in this paper. N-acetylcysteine (NAC) is a mucolytic agent with both antioxidant and anti-inflammatory properties. This paper also reviews the use of NAC in patients with COPD, especially the dose-dependent properties of NAC, eg, its effects on lung function and the exacerbation rate in patients with the disease. Earlier data from BRONCUS (the Bronchitis Randomized on NAC Cost-Utility Study) did not suggest that NAC was beneficial in patients with COPD, only indicating that it reduced exacerbation in an "inhaled steroid-naïve" subgroup. With regard to the dose-dependent properties of NAC, two recent randomized controlled Chinese trials suggested that high-dose NAC (1,200 mg daily) can reduce exacerbations in patients with COPD, especially in those with an earlier (moderately severe) stage of disease, and also in those who are at high risk of exacerbations. However, there was no significant effect on symptoms or quality of life in patients receiving NAC. Further studies are warranted to investigate the effect of NAC at higher doses in non-Chinese patients with COPD.
    International Journal of COPD 08/2014; 9:825-836. DOI:10.2147/COPD.S51057
  • [Show abstract] [Hide abstract]
    ABSTRACT: Current guidelines limit regular use of inhaled corticosteroids (ICS) to a specific subgroup of patients with chronic obstructive pulmonary disease (COPD) in whom the forced expiratory volume in 1 s is <60% of predicted and who have frequent exacerbations. In these patients, there is evidence that ICS reduce the frequency of exacerbations and improve lung function and quality of life. However, a review of the literature suggests that the evidence available may be interpreted to favour or contradict these observations. It becomes apparent that COPD is a heterogeneous condition. Clinicians therefore need to be aware of the heterogeneity as well as having an understanding of how ICS may be used in the context of the specific subgroups of patients with COPD. This review argues for and against the use of ICS in COPD by providing an in-depth analysis of the currently available evidence.
    British Journal of Clinical Pharmacology 08/2014; 78(2):282-300. DOI:10.1111/bcp.12334 · 3.69 Impact Factor


Available from
May 20, 2014