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Role of macrolide therapy in chronic obstructive pulmonary disease.

Martinez FJ, Curtis JL, Albert R - Int J Chron Obstruct Pulmon Dis (2008)

Bottom Line: In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors.Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis.Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, MI 48109-0360, USA. fmartine@umich.edu

ABSTRACT
Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide. The Global Burden of Disease study has concluded that COPD will become the third leading cause of death worldwide by 2020, and will increase its ranking of disability-adjusted life years lost from 12th to 5th. Acute exacerbations of COPD (AECOPD) are associated with impaired quality of life and pulmonary function. More frequent or severe AECOPDs have been associated with especially markedly impaired quality of life and a greater longitudinal loss of pulmonary function. COPD and AECOPDs are characterized by an augmented inflammatory response. Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identified pathogens in AECOPD and have been generally included in published guidelines for AECOPD management. In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors. Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis. Data in COPD patients have been limited and contradictory but the majority hint to a potential clinical and biological effect. Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.

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Levels of induced-sputum inflammatory markers in clarithromycin- and placebo-treated COPD patients before and after treatment. AT, after treatment; BT, before treatment; IL-8, interleukin-8; LTB4, leukotriene B4; TNF-α, tumor necrosis factor-α. *p < 0.05 before versus after treatment. Copyright © 2004. Reproduced with permission from Basyigit I, Yildiz F, Ozkara SK, et al. 2004. The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data. Ann Pharmacother, 38:783–92.
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f4-copd-3-331: Levels of induced-sputum inflammatory markers in clarithromycin- and placebo-treated COPD patients before and after treatment. AT, after treatment; BT, before treatment; IL-8, interleukin-8; LTB4, leukotriene B4; TNF-α, tumor necrosis factor-α. *p < 0.05 before versus after treatment. Copyright © 2004. Reproduced with permission from Basyigit I, Yildiz F, Ozkara SK, et al. 2004. The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data. Ann Pharmacother, 38:783–92.

Mentions: More recently, two groups have reported small controlled studies. Basyigit and colleagues (2004) randomized 30 stable male COPD patients (mean age ~69 yrs, FEV1~ 36% predicted) to clarithromycin (500 mg bid) or placebo for two weeks in addition to standardized bronchodilator therapy. Although no baseline differences were noted between the treatment groups, clarithromycin-treated patients experienced significantly improved sputum inflammatory markers (Figure 4), whereas physiologic studies did not change. The results of serum inflammatory markers were qualitatively similar in the two groups. In a second controlled study, 67 patients with moderate to severe COPD (mean age ~ 67 yrs, FEV1 ~43% pred) were randomized to three months of clarithromycin (500 mg of sustained release preparation daily) or placebo (Banerjee et al 2004). In contrast to the previous study, all patients were taking inhaled corticosteroids. Clarithromycin was associated with a significant improvement in the St. George’s Respiratory Questionnaire (SGRQ) symptom score (10.2 units) and the SF-36 Physical Function Score (12.9 units) but no difference in overall SGRQ score, shuttle walk distance, spirometry or CRP levels. During the relatively short time of follow-up there were five total AECOPDs (3 in the clarithromycin and 2 in the placebo group). No difference was seen in quantitative sputum cultures obtained in the stable state (Figure 5). In contrast to the previous study, sputum IL-8, TNF-α, or LTB4 levels did not differ between clarithromycin versus placebo treatment, although there was a modest macrolide-associated improvement in sputum neutrophil differential and neutrophil chemotaxis (Banerjee et al 2004).


Role of macrolide therapy in chronic obstructive pulmonary disease.

Martinez FJ, Curtis JL, Albert R - Int J Chron Obstruct Pulmon Dis (2008)

Levels of induced-sputum inflammatory markers in clarithromycin- and placebo-treated COPD patients before and after treatment. AT, after treatment; BT, before treatment; IL-8, interleukin-8; LTB4, leukotriene B4; TNF-α, tumor necrosis factor-α. *p < 0.05 before versus after treatment. Copyright © 2004. Reproduced with permission from Basyigit I, Yildiz F, Ozkara SK, et al. 2004. The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data. Ann Pharmacother, 38:783–92.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2629987&req=5

f4-copd-3-331: Levels of induced-sputum inflammatory markers in clarithromycin- and placebo-treated COPD patients before and after treatment. AT, after treatment; BT, before treatment; IL-8, interleukin-8; LTB4, leukotriene B4; TNF-α, tumor necrosis factor-α. *p < 0.05 before versus after treatment. Copyright © 2004. Reproduced with permission from Basyigit I, Yildiz F, Ozkara SK, et al. 2004. The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data. Ann Pharmacother, 38:783–92.
Mentions: More recently, two groups have reported small controlled studies. Basyigit and colleagues (2004) randomized 30 stable male COPD patients (mean age ~69 yrs, FEV1~ 36% predicted) to clarithromycin (500 mg bid) or placebo for two weeks in addition to standardized bronchodilator therapy. Although no baseline differences were noted between the treatment groups, clarithromycin-treated patients experienced significantly improved sputum inflammatory markers (Figure 4), whereas physiologic studies did not change. The results of serum inflammatory markers were qualitatively similar in the two groups. In a second controlled study, 67 patients with moderate to severe COPD (mean age ~ 67 yrs, FEV1 ~43% pred) were randomized to three months of clarithromycin (500 mg of sustained release preparation daily) or placebo (Banerjee et al 2004). In contrast to the previous study, all patients were taking inhaled corticosteroids. Clarithromycin was associated with a significant improvement in the St. George’s Respiratory Questionnaire (SGRQ) symptom score (10.2 units) and the SF-36 Physical Function Score (12.9 units) but no difference in overall SGRQ score, shuttle walk distance, spirometry or CRP levels. During the relatively short time of follow-up there were five total AECOPDs (3 in the clarithromycin and 2 in the placebo group). No difference was seen in quantitative sputum cultures obtained in the stable state (Figure 5). In contrast to the previous study, sputum IL-8, TNF-α, or LTB4 levels did not differ between clarithromycin versus placebo treatment, although there was a modest macrolide-associated improvement in sputum neutrophil differential and neutrophil chemotaxis (Banerjee et al 2004).

Bottom Line: In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors.Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis.Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, MI 48109-0360, USA. fmartine@umich.edu

ABSTRACT
Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide. The Global Burden of Disease study has concluded that COPD will become the third leading cause of death worldwide by 2020, and will increase its ranking of disability-adjusted life years lost from 12th to 5th. Acute exacerbations of COPD (AECOPD) are associated with impaired quality of life and pulmonary function. More frequent or severe AECOPDs have been associated with especially markedly impaired quality of life and a greater longitudinal loss of pulmonary function. COPD and AECOPDs are characterized by an augmented inflammatory response. Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identified pathogens in AECOPD and have been generally included in published guidelines for AECOPD management. In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors. Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis. Data in COPD patients have been limited and contradictory but the majority hint to a potential clinical and biological effect. Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.

Show MeSH
Related in: MedlinePlus