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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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Molecular targets of macrolides (Tsai and Standiford 2004).
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f2-copd-3-331: Molecular targets of macrolides (Tsai and Standiford 2004).

Mentions: Macrolides exert broad-ranging immunomodulatory effects on mammalian cells in vitro and in vivo, as comprehensively reviewed by others and briefly summarized in Table 1 and illustrated in Figure 2 (Zalewska-Kaszubska and Gorska 2001; Labro 2004; Tsai and Standiford 2004). Among their many activities, macrolides have been shown to exert effects on a wide range of cells including nasal and bronchial epithelial cells, alveolar macrophages, monocytes, eosinophils, neutrophils and lymphocytes. The effect on signaling pathways including NF-κB and AP-1 (Desaki et al 2000, 2004, Kikuchi et al 2002) is evident in Figure 2. Macrolides exert a host of effects that collectively limit tissue damage by neutrophils. In addition to effects on chemoattractants, these include inhibiting their oxidant burst, impairing degranulation, and increasing the rate of neutrophil apoptosis. There is also evidence that macrolides decrease mucus viscosity (Tamaoki et al 1995), and suppress angiogenesis (Yasunami and Hayashi 2001). Importantly, all these immunomodulatory effects are evident at concentrations attainable clinically by low-dose administration, and are not seen using 16-member macrolides. Most immunomodulatory effects are shared by the 14- and 15-member agents, although in some cases the effects vary among the individual compounds. For example, roxithromycin appears to exhibit consistent effects in vitro and in vivo (Agen et al 1993; Scaglione and Rossoni 1998). Similarly, clarithromycin and azithromycin induce apoptosis of peripheral blood lymphocytes to a qualitatively greater extent than josamycin (Ishimatsu et al 2004). Hence, macrolides have many properties that could mitigate the neutrophilic inflammation central to airway damage, and might also improve aspects of airflow obstruction.


Role of macrolide therapy in chronic obstructive pulmonary disease.

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

Molecular targets of macrolides (Tsai and Standiford 2004).
© Copyright Policy
Related In: Results  -  Collection

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

f2-copd-3-331: Molecular targets of macrolides (Tsai and Standiford 2004).
Mentions: Macrolides exert broad-ranging immunomodulatory effects on mammalian cells in vitro and in vivo, as comprehensively reviewed by others and briefly summarized in Table 1 and illustrated in Figure 2 (Zalewska-Kaszubska and Gorska 2001; Labro 2004; Tsai and Standiford 2004). Among their many activities, macrolides have been shown to exert effects on a wide range of cells including nasal and bronchial epithelial cells, alveolar macrophages, monocytes, eosinophils, neutrophils and lymphocytes. The effect on signaling pathways including NF-κB and AP-1 (Desaki et al 2000, 2004, Kikuchi et al 2002) is evident in Figure 2. Macrolides exert a host of effects that collectively limit tissue damage by neutrophils. In addition to effects on chemoattractants, these include inhibiting their oxidant burst, impairing degranulation, and increasing the rate of neutrophil apoptosis. There is also evidence that macrolides decrease mucus viscosity (Tamaoki et al 1995), and suppress angiogenesis (Yasunami and Hayashi 2001). Importantly, all these immunomodulatory effects are evident at concentrations attainable clinically by low-dose administration, and are not seen using 16-member macrolides. Most immunomodulatory effects are shared by the 14- and 15-member agents, although in some cases the effects vary among the individual compounds. For example, roxithromycin appears to exhibit consistent effects in vitro and in vivo (Agen et al 1993; Scaglione and Rossoni 1998). Similarly, clarithromycin and azithromycin induce apoptosis of peripheral blood lymphocytes to a qualitatively greater extent than josamycin (Ishimatsu et al 2004). Hence, macrolides have many properties that could mitigate the neutrophilic inflammation central to airway damage, and might also improve aspects of airflow obstruction.

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