Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease: a randomized trial
TS Lapperre, JB Snoeck-Stroband… - Annals of internal …, 2009 - acpjournals.org
TS Lapperre, JB Snoeck-Stroband, MME Gosman, DF Jansen, A van Schadewijk…
Annals of internal medicine, 2009•acpjournals.orgBackground: Inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) are used to
treat moderate to severe chronic obstructive pulmonary disease (COPD). Objective: To
determine whether long-term ICS therapy, with and without LABAs, reduces inflammation
and improves pulmonary function in COPD. Design: Randomized, placebo-controlled
trial.(ClinicalTrials. gov registration number: NCT00158847) Setting: 2 university medical
centers in The Netherlands. Patients: 114 steroid-naive current or former smokers with …
treat moderate to severe chronic obstructive pulmonary disease (COPD). Objective: To
determine whether long-term ICS therapy, with and without LABAs, reduces inflammation
and improves pulmonary function in COPD. Design: Randomized, placebo-controlled
trial.(ClinicalTrials. gov registration number: NCT00158847) Setting: 2 university medical
centers in The Netherlands. Patients: 114 steroid-naive current or former smokers with …
Background
Inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD).
Objective
To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD.
Design
Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847)
Setting
2 university medical centers in The Netherlands.
Patients
114 steroid-naive current or former smokers with moderate to severe COPD.
Measurements
Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months.
Intervention
Random assignment by minimization method to receive fluticasone propionate, 500 µg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 µg twice daily, and salmeterol, 50 µg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29).
Results
101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3+ cells (−55% [95% CI, −74% to −22%]; P = 0.004), CD4+ cells (−78% [CI, −88% to 60%]; P < 0.001), CD8+ cells (−57% [CI, −77% to −18%]; P = 0.010), and mast cells (−38% [CI, −60% to −2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV1 decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3+ cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV1 level.
Limitations
The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months.
Conclusion
ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects.
Primary Funding Source
Netherlands Organization for Scientific Research, Netherlands Asthma Foundation, GlaxoSmithKline of The Netherlands, University Medical Center Groningen, and Leiden University Medical Center.
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