Control of airway inflammation maintained at a lower steroid dose with 100/50 μg of fluticasone propionate/salmeterol

Jarjour, Nizar N.; Wilson, Susan J.; Koenig, Steven M.; Laviolette, Michel; Moore, Wendy C.; Davis, W. Bruce; Doherty, Dennis E.; Hamid, Qutayba; Israel, Elliott; Kavuru, Mani S.; Ramsdell, Joe W.; Tashkin, Donald P.; Reilly, Donna S.; Yancey, Steven W.; Edwards, Lisa D.; Stauffer, John L.; Dorinsky, Paul M.; Djukanovic, Ratko

doi:10.1016/j.jaci.2006.03.043

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 118, Issue 1 , Pages 44-52, July 2006

Control of airway inflammation maintained at a lower steroid dose with 100/50 μg of fluticasone propionate/salmeterol

Nizar N. Jarjour, MD
- From the Pulmonary and Critical Care Medicine Section, the University of Wisconsin School of Medicine, Madison
Susan J. Wilson, PhD
- University of Southampton
Steven M. Koenig, MD
- Division of Pulmonary Medicine and Critical Care, University of Virginia, Charlottesville
Michel Laviolette, MD
- Laval Hospital and University, Montreal
Wendy C. Moore, MD
- Division of Pulmonary and Critical Care Medicine, Wake Forest University School of Medicine, Winston-Salem
W. Bruce Davis, MD
- Medical College of Georgia, Augusta
Dennis E. Doherty, MD
- University of Kentucky, Lexington
Qutayba Hamid, MD
- Meakins Christie Laboratories, McGill University, Montreal
Elliott Israel, MD
- Brigham and Women's Hospital, Harvard Medical School, Boston
Mani S. Kavuru, MD
- Cleveland Clinic Foundation
Joe W. Ramsdell, MD
- University of California at San Diego Clinical Trials Center
Donald P. Tashkin, MD
- University of California at Los Angeles
Donna S. Reilly, BS
- Respiratory Medicine Development Center, GlaxoSmithKline, Research Triangle Park
Steven W. Yancey, MS
- Respiratory Medicine Development Center, GlaxoSmithKline, Research Triangle Park
Lisa D. Edwards, PhD
- Respiratory Medicine Development Center, GlaxoSmithKline, Research Triangle Park
John L. Stauffer, MD
- Respiratory Medicine Development Center, GlaxoSmithKline, Research Triangle Park
Paul M. Dorinsky, MD
- Respiratory Medicine Development Center, GlaxoSmithKline, Research Triangle Park
Ratko Djukanovic, MD
- University of Southampton
- Reprint requests: Ratko Djukanovic, MD, Southampton General Hospital, Tremona Rd, Southampton, SO16 6YD United Kingdom.

Received 11 August 2005; received in revised form 23 March 2006; accepted 24 March 2006. published online 28 May 2006.

Madison, Wis, Southampton, United Kingdom, Charlottesville, Va, Montreal, Quebec, Canada, Winston-Salem and Research Triangle Park, NC, Augusta, Ga, Lexington, Ky, Boston, Mass, Cleveland, Ohio, and San Diego and Los Angeles, Calif

Background

Inhaled corticosteroids (ICSs) have been shown to reverse epithelial damage and decrease lamina reticularis thickness in patients with asthma.

Objective

This study investigated whether clinical asthma control and airway inflammation could be maintained after switching therapy from medium-dose fluticasone propionate (FP) to low-dose FP administered with the long-acting β₂-agonist (LABA) salmeterol.

Methods

Eighty-eight subjects (age, ≥18 years) who, during open-label screening, demonstrated improved asthma control after an increase from 100 μg of FP twice daily to 250 μg of FP twice daily were randomized to receive 100/50 μg of FP/salmeterol through a Diskus inhaler (GlaxoSmithKline, Research Triangle Park, NC) twice daily or continue 250 μg of FP twice daily through a Diskus inhaler for 24 weeks. Clinical outcomes were monitored, and bronchial biopsy specimens and bronchoalveolar lavage fluid were obtained before and after 24 weeks of treatment.

Results

There were no significant differences between treatments with respect to eosinophils in the bronchial mucosa and bronchoalveolar lavage fluid; mucosal mast cells, neutrophils, or CD3⁺, CD4⁺, CD8⁺, or CD25⁺ T lymphocytes; or concentration of mediators (GM-CSF, IL-8, and eosinophil cationic protein). The 2 treatments were not different with respect to lamina reticularis thickness. Consistent with the airway inflammatory measures, clinical and physiologic measures of asthma control were also similar.

Conclusion

This study demonstrates that control of asthma and airway inflammation is maintained over the 24-week treatment period when patients requiring a medium-dose ICS are switched to a lower-dose ICS with a LABA.

Clinical implications

A lower-dose ICS with a LABA is effective in controlling inflammation and providing clinical asthma control, confirming current guideline recommendations.

Key words: Fluticasone propionate, salmeterol, biopsy, bronchoalveolar lavage, eosinophils

Abbreviations used: BAL, Bronchoalveolar lavage, BALF, Bronchoalveolar lavage fluid, COPD, Chronic obstructive pulmonary disease, ECP, Eosinophil cationic protein, FP, Fluticasone propionate, FSC, Fluticasone propionate/salmeterol, ICS, Inhaled corticosteroid, IQR, Interquartile range, LABA, Long-acting β₂-agonist, PEF, Peak expiratory flow

Supported by GlaxoSmithKline, Research Triangle Park, NC.Presented in part at the American Thoracic Society Annual Meeting; May 21-26, 2004; Orlando, Fla.Disclosure of potential conflict of interest: P. M. Dorinsky, L. D. Edwards, and D. S. Reilly are all employed by GlaxoSmithKline. W. C. Moore, J. W. Ramsdell, and Q. Hamid have all received grant support from GlaxoSmithKline. S. W. Yancey and J. L. Stauffer are both employed by and own stock in GlaxoSmithKline. N. N. Jarjour has consultant arrangements with Asthmatax, has received grant support from GlaxoSmithKline, and is on the speakers' bureau for Schering-Plough. S. M. Koenig has received grant support from GlaxoSmithKline, AstraZeneca, and ONO and is on the speakers' bureau for Boehringer-Ingelheim, Pfizer, GlaxoSmithKline, AstraZeneca, Merck, and Schering-Plough. D. E. Doherty has received clinical trial funding from Altana, Boehringer-Ingelheim, GlaxoSmithKline, and Novartis. E. Israel has consultant arrangements with Asthmatax, Merck, Novartis, Protein Design Labs, Schering-Plough, and Wyeth; has received grant support from AstraZeneca, Genentech, Merck, Boehringer-Ingelheim, GlaxoSmithKline, and Wyeth; and receives lecture fees from Genentech and Merck. M. S. Kavuru has received grant support from and is on the speakers' bureau for GlaxoSmithKline and Genentech. D. P. Tashkin has received grant support from and conducted preceptorships for GlaxoSmithKline. R. Djukanovic has consultant arrangements with Aventis and Synairgen, owns stock in Synairgen, and has received grant support from GlaxoSmithKline and AstraZeneca. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(06)00860-8

doi:10.1016/j.jaci.2006.03.043

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 118, Issue 1 , Pages 44-52, July 2006

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