Role of macrolide therapy in chronic obstructive pulmonary disease

Figures & data

Figure 1 Molecular structure of 14 member macrolides (erythromycin, A), fifteen member compounds (azithromycin, B) and a 16 member compound (C) (Jaffe and Bush 2001).

Figure 2 Molecular targets of macrolides (Tsai and Standiford 2004).

Table 1 Anti-inflammatory and bacterial virulence effects of macrolide antibiotics

Author, Year	Effect
Inoue et al 1992; Oishi et al 1994; Takizawa et al 1997; Kohyama et al 1999; Kikuchi et al 2002; Takaki et al 2003; Desaki et al 2004; Reato et al 2004	Down regulates TNF-α, IL-1, IL-4, IL-8 expression by various cell types
Ishizawa et al 2005	↑ production of β-defensin-1 and β-defensin-2 by epithelial cells
Villagrasa et al 1997	↓ superoxide and elastase release from stimulated PMNs
Shimane 1997; Khan et al 1999; Suzaki et al 1999; Yamasawa et al 2004	↓ stimulated release of IL-1β, IL-6, GM-CSF, and TNF-γ
Hashimoto et al 2001; Kanai et al 2004	↓ matrix metalloproteinase-9 expression and activity
Motojima et al 1996	↓ IL-5-induced increases in eosinophil survival
Keicho et al 1994; Aoshiba et al 1995; Adachi et al 1996; Inamura et al 2000; Ogawa et al 2003; Kadota et al 2005	↑ neutrophil, lymphocyte, histiocyte and eosinophil apoptosis
Oda et al 1994; Tsai et al 2004	↓ neutrophil chemotaxis
Culic et al 2002; Yamasawa et al 2004	↓ neutrophil survival
Rubin et al 1997; Shimizu et al 2003; Imamura et al 2004	↓ mucus secretion
Laforce et al 1983; Fost et al 1999; Imamura et al 2005	↓ methylprednisolone elimination
Baumann et al 2001; Tsang et al 2003	↓ P. aeruginosa adherence and outer membrane function
Kobayashi 1995; Ichimiya et al 1996; Takeoka et al 1998; Tateda et al 2001; Nagata et al 2004; Gillis and Iglewski 2004; Wagner et al 2005	↓ alginate, biofilm formation and quorum sensing
Kawamura-Sato et al 2000	↓ flagellin

Abbreviations: IL, GM-CSF, TNF-α, PMN.

Figure 3 Potential beneficial effects of macrolides in COPD patient.

Table 2 Effect of 12 months of erythromycin therapy on common colds and AECOPDs in patients with COPD

Outcome	Treatment group		p value
	Control (riboflavin) (n = 54)	Erythromycin (n = 55)
Total common colds, N	245	67	0.0002
Total number of exacerbations, N	64	14	<0.0001
Mild/moderate exacerbations	53	14	0.0087
Severe	11	0	0.0007
Total patients with one or more exacerbations, N	30	67	<0.0001
Mild/moderate	20	6	0.0004
Severe	10	0	0.0004

Copyright © 2001. Reproduced with permission from Suzuki T, Yanai M, Yamaya M, et al. 2001. Erythromycin and common cold in COPD. Chest, 120:730–3.

Table 3 Effect of azithromycin prophylactic therapy in COPD patients at high risk of AECOPD and treatment failure

Outcome	Treatment group		p value
	Azithromycin (n = 54)	Control (n = 40)
Exacerbations/year	187	249	30.0001
Hospitalizations/year	22	45	30.05

Copyright © 2000. Reproduced with permission from Gomez J, Baños V, Simarro E, et al. 2000. Estudio prospective y comparative (1994–1998) sobre la influencia del tratamiento corto profilactico con azitromicina en pacientes con EPOC evolucionada. Rev Esp Quimioterap, 13:379–83.

Figure 4 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.

Figure 5 The effect of clarithromycin and placebo on sputum colony forming units (Cfu) numbers/bacterial (PPM) isolate. Cfu numbers are logged. Weighted bars indicate the mean for the whole group. There was no statistically significant difference between pre- and post-therapy Cfu numbers for both clarithromycin and placebo groups. NS indicates not significant. Copyright © 2004. Reproduced with permission from Banerjee D, Honeybourne D, Khair OA. 2004. The effect of oral clarithromycin on bronchial airway inflammation in moderate-to-severe stable COPD: a randomized controlled trial. Treat Respir Med, 3:59–65.

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