Comparison and optimal use of fixed combinations in the management of COPD

Figures & data

Table 1 Effects of salmeterol/fluticasone and fluticasone propionate on inflammatory cell outcomes (fully published papers only)

Reference	Medication	Duration	Inflammatory cell outcomes
Barnes et al 2006	Salmeterol/fluticasone (SF) 50/500 μg (n = 55)	13 weeks	• SF significantly reduced the absolute numbers of biopsy (CD45+) leukocytes, CD8+ cells, and CD4+ cells.
	versus		• In biopsy SF significantly decreases cells expressing genes for TNF-α and IFN-γ.
	placebo (n = 69)		• No significant CD8:CD4 ratio differences or number of CD68+ cells.
Gizycki et al 2002	Fluticasone Propionate (FP) 500 μg bid (n = 14)	3 month	• Compared with baseline, FP treatment had no significant effects on the total number of inflammatory cells, lymphomononuclear cells, or macrophages in the airway mucosa.
	versus		• Compared with baseline and placebo FP did show a significant reduction in the number of mucosal mast cells.
	placebo (n = 10)		• Compared with placebo the FP group had significantly more neutrophils after treatment.
Hattotuwa et al 2002	Fluticasone propionate (FP) 500 μg bid (n = 16)	3 month	• No significant change in CD3+, CD8+, CD45, CD45Ro+ cells, neutrophils, macrophages, mast cells and eosinophils between baseline and end treatment.
	versus		• No significant reduction in neutrophils compared with placebo treatment. In comparison with placebo mast cells showed a 25% decrease in number in the subepithelium after FP (p = 0.04).
	placebo (n = 14)		• Significant reduction in the numbers of mucosal mast cells.
			• A reduction in the CD8:CD4 ratio in the epithelium and the numbers of subepithelial mast cells in the FP group.
			• CD4+ cells were significantly raised in the placebo group in both epithelium and subepithelium

Abbreviations: FP, fluticasone propionate; PF, ; SF, salmeterol/fluticasone.

Table 2 Inclusion criteria and definitions of studies using fluticasone propionate and salmeterol

	Treatment	Inclusion criteria	Exacerbation definition
Mahler et al 2002	Salmeterol/fluticasone versus fluticasone propionate, salmeterol or placebo	FEV1/FVC ≤ 70% FEV1<65% predicted normal and >0.70L	Exacerbation was defined by treatment and resulted in withdrawal from the study
Hanania et al 2003	Salmeterol/fluticasone versus fluticasone propionate, salmeterol or placebo	FEV1/FVC ≤ 70% FEV1<65% predicted normal and >0.70L	Moderate exacerbation: requiring treatment with. antibiotics and/or corticosteroids
			Severe exacerbation: requiring hospitalization
			Discontinuation after 1 exacerbation with inhaled or oral corticosteroids or hospitalization or 3 exacerbations treated with antibiotics
TRISTAN Calverley et al 2003a	Salmeterol/fluticasone versus fluticasone propionate, salmeterol or placebo	FEV1/FVC ≤ 70% FEV1 25%–70% predicted normal	Exacerbation: a worsening of COPD symptoms that required treatment with antibiotics, oral corticosteroids or both. Episodes that required corticosteroids treatment of hospital admission were noted separately.
		Reversibility after 400 μg salbutamol: <10% of predicted normal.
		At least one exacerbation per year in the last three years.
		At least one exacerbation in the year immediately before the trial entry requiring treatment with oral corticosteroids, antibiotics or both.
Dal Negro et al 2003	Salmeterol/fluticasone versus salmeterol or placebo	FEV1/FVC ≤ 70% FEV1 ≤ 80% predicted normal and >0,80L	Mild exacerbation: condition requiring salbutamol prn >2 occasions/24 h period on 2 or more consecutive days compared with the baseline mean of last 7 days of run-in;
		Reversibility after 400 μg salbutamol: ≤ 12% as a percent of predicted normal Regular treatment with 200 mg theophylline bid	Moderate exacerbations: condition requiring treatment with antibiotics and/or oral corticosteroids; Severe exacerbations: condition requiring emergency hospital treatment and/or hospitalization.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity

Table 3 Inclusion criteria and definitions of studies using budesonide and formoterol

	Treatment	Inclusion criteria	Exacerbation definition
Szafranski et al 2003	Budesonide/formoterol versus budesonide, formoterol or placebo	FEV1/FVC ≤70% FEV1≤50% predicted normal ≥1 severe COPD exacerbation within 2–12 month of first study visit.	Severe exacerbation: use of oral steroids and/or antibiotics and/or hospitalization due to respiratory symptoms.
Calverley et al 2003b	Budesonide/formoterol versus budesonide, formoterol or placebo	FEV1/FVC ≤70% FEV1 ≤50% predicted normal ≥1 COPD exacerbation requiring antibiotics and/or oral corticosteroids within 2–12 month of first study visit.	Exacerbations were defined by the required medical intervention: oral antibiotics and/or corticosteroids or hospitalization.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity.

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