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Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease
- Source :
- Annals of internal medicine, Scopus-Elsevier, Annals of Internal Medicine, 151(8), 517-527. American College of Physicians, Annals of internal medicine, 151(8), 517-527. American College of Physicians
- Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Male
medicine.medical_specialty
medicine.drug_class
Bronchi
Cell Count
Placebo
Gastroenterology
Fluticasone propionate
Drug Administration Schedule
Pulmonary function testing
Pulmonary Disease, Chronic Obstructive
Bronchodilator
Internal medicine
Forced Expiratory Volume
Administration, Inhalation
Internal Medicine
Medicine
Humans
Albuterol
Lung
Salmeterol Xinafoate
Fluticasone
Asthma
Aged
Inflammation
COPD
business.industry
Smoking
Sputum
General Medicine
Middle Aged
medicine.disease
Surgery
Bronchodilator Agents
Androstadienes
Treatment Outcome
Drug Therapy, Combination
Female
Salmeterol
Human medicine
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 00034819
- Volume :
- 151
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Annals of Internal Medicine
- Accession number :
- edsair.doi.dedup.....400201d08417b35cd94e9c5b9b5e6356