Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease

Figures & data

Figure 1 CONSORT (consolidated standards of reporting trials) flow diagram.

Notes: ^aSamples not contaminated with squamous cells. The ITT population comprised all subjects who had evaluable sputum samples at baseline and who received at least a single dose of trial medication. The PP population comprised all subjects in the ITT population who also had an evaluable sputum sample at end point and no major protocol violations.
Abbreviations: AE, adverse event; COPD, chronic obstructive pulmonary disease; ITT, intent-to-treat; PP, per-protocol; SFC, salmeterol/fluticasone propionate.

Table 1 Summary of demographic characteristics (per-protocol population)

	SFC 250 N=26	Placebo N=26
Age (years)	64.7 (9.31)	62.2 (8.06)
Sex, n (%)
Male	25 (96%)	26 (100%)
Female	1 (4%)	0
Height (cm)	168.42	166.77
Weight (kg)	66.44	64.58
Concurrent medical conditions n (%)
Yes	23 (88%)	21 (81%)
No	3 (12%)	5 (19%)
Smoking history, n (%)	26 (100%)	26 (100%)
Current smoker, n (%)	12 (46%)	14 (54%)
Stopped smoking in last 6 months, n (%)
Yes	4 (29%)	3 (25%)
No	10 (71%)	9 (75%)
Number of pack years (years)	58.96 (34.028)	59.92 (29.425)
FEV1 (L) at baseline	1.983 (0.5797)	2.044 (0.4638)

Notes: N represents the number of subjects, including those with sputum samples contaminated with squamous cells. Results are expressed as n (%), mean, or as mean (SD).

Abbreviations: FEV₁, forced expiratory volume in 1 second; SD, standard deviation; SFC, salmeterol/fluticasone propionate.

Table 2 Statistical analysis of change from baseline in differential neutrophil count in induced sputum at week 12

Sputum differential neutrophils (%)	SFC 250 N=19	Placebo N=10
Raw median at baseline	48.50	38.25
Raw median at week 12	19.00	24.50
Raw median change from baseline	−7.90	−3.00
SFC 250 – placebo
Median difference	−9.95
95% CI	−25.000, 10.000
P-value	0.6269

Notes: Samples contaminated with squamous cells, and therefore of low quality, were excluded. N represents the number of subjects with samples not contaminated with squamous cells.

Abbreviations: CI, confidence interval; SFC, salmeterol/fluticasone propionate.

Table 3 Median difference at week 12, between SFC 250 and placebo, in the change from baseline in levels of biomarkers in sputum and serum (per-protocol population)

	Median difference (95% CI)	P-value
Sputum
Inflammatory cells, total count (cells ×10^5/mL)	0.380 (−1.9700, 2.6200)	0.5920
Sputum supernatant
IL-8 (pg/mL)	−62.0 (−1753.00, 582.80)	0.6561
MPO (ng/mL)	10.70 (−94.200, 291.600)	0.6207
SP-D (ng/mL)	10.00 (−10.100, 41.200)	0.5802
Serum
IL-6 (pg/mL)	−0.10 (−0.900, 0.700)	0.9747
IL-8 (pg/mL)	0.70 (−5.100, 3.700)	0.7655
hsCRP (ng/mL)	−17.5 (−336.00, 415.00)	0.8718
SP-D (ng/mL)	0.00 (−9.400, 10.700)	0.9632
CC-16 (ng/mL)	0.00 (−0.700, 0.200)	0.5798

Notes: Per-protocol population (placebo, n=26; SFC 250, n=26).

Abbreviations: CC-16, Clara cell 16; CI, confidence interval; hsCRP, high-sensitivity C-reactive protein; IL, interleukin; MPO, myeloperoxidase; SFC, salmeterol/fluticasone propionate; SP-D, surfactant protein-D.

Table 4 Median of % change from baseline neutrophils and IL-8, in sputum

	Placebo (N=10)	SFC 250 (N=19)	Differences (placebo – SFC 250)	95% CI lower	95% CI upper
Neutrophils	−1.3	−27.9	−26.6	−88.2	37.0
IL-8	48.3	−43.2	−85.0	−557.8	59.9

Notes: Bootstrap method (B=10,000). N represents the number of subjects with samples not contaminated with squamous cells.

Abbreviations: CI, confidence interval; IL-8, interleukin-8; SFC, salmeterol/fluticasone propionate.

Table 5 Statistical analysis of COPD pulmonary function tests at week 12 (per-protocol population)

	SFC 250 N=26	Placebo N=26
FEV1 (L)
Baseline mean (SE)	1.983 (0.1137)	2.044 (0.0910)
Adjusted change from baseline	0.078	0.053
SFC 250 – placebo
Mean difference (95% CI)	0.024 (−0.0524, 0.1009)
P-value	0.5266
FVC (L)
Baseline mean (SE)	3.445 (0.1532)	3.351 (0.1102)
Adjusted change from baseline	−0.214	−0.257
SFC 250 – placebo
Mean difference (95% CI)	0.043 (−0.2015, 0.2873)
P-value	0.7251

Notes: N represents the number of subjects including those with sputum samples contaminated with squamous cells.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SE, standard error; SFC, salmeterol/fluticasone propionate.