The Journal of Allergy and Clinical Immunology
Volume 117, Issue 1 , Pages 45-52, January 2006

Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma

  • Robert S. Zeiger, MD, PhD

      Affiliations

    • From the Department of Pediatrics, University of California-San Diego
    • Department of Allergy, Kaiser Permanente San Diego
    • Corresponding Author InformationReprint requests: Robert S. Zeiger, MD, PhD, University of California, San Diego, Department of Pediatrics, and Kaiser Permanente, San Diego, Department of Allergy, 7060 Clairemont Mesa Blvd, San Diego, CA 92111.
    • ,
  • Stanley J. Szefler, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver
    • ,
  • Brenda R. Phillips, MS

      Affiliations

    • Department of Health Evaluation Sciences, Pennsylvania State University, Hershey
    • ,
  • Michael Schatz, MD, MS

      Affiliations

    • Department of Allergy, Kaiser Permanente San Diego
    • ,
  • Fernando D. Martinez, MD

      Affiliations

    • Arizona Respiratory Center, University of Arizona, Tucson
    • ,
  • Vernon M. Chinchilli, PhD

      Affiliations

    • Department of Health Evaluation Sciences, Pennsylvania State University, Hershey
    • ,
  • Robert F. Lemanske Jr., MD

      Affiliations

    • Clinical Science Center, University of Wisconsin, Madison
    • ,
  • Robert C. Strunk, MD

      Affiliations

    • Department of Pediatrics, Washington University, St Louis
    • ,
  • Gary Larsen, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver
    • ,
  • Joseph D. Spahn, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver
    • ,
  • Leonard B. Bacharier, MD

      Affiliations

    • Department of Pediatrics, Washington University, St Louis
    • ,
  • Gordon R. Bloomberg, MD

      Affiliations

    • Department of Pediatrics, Washington University, St Louis
    • ,
  • Theresa W. Guilbert, MD

      Affiliations

    • Arizona Respiratory Center, University of Arizona, Tucson
    • ,
  • Gregory Heldt, MD

      Affiliations

    • From the Department of Pediatrics, University of California-San Diego
    • ,
  • Wayne J. Morgan, MD

      Affiliations

    • Arizona Respiratory Center, University of Arizona, Tucson
    • ,
  • Mark H. Moss, MD

      Affiliations

    • Clinical Science Center, University of Wisconsin, Madison
    • ,
  • Christine A. Sorkness, PharmD

      Affiliations

    • Clinical Science Center, University of Wisconsin, Madison
    • ,
  • Lynn M. Taussig, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver
    • ,
  • for the Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute

      Affiliations

    • See Appendix E1 in the Online Repository of this article at www.jacionline.org for members of the Childhood Asthma Research and Education (CARE) Network involved in this study. The members of the Writing Committee were R. Zeiger (Chair), S. Szefler, B. Phillips, V. Chinchilli, R. Lemanske, F. Martinez, R. Strunk, M. Schatz, and G. Larsen.

Received 24 August 2005; received in revised form 3 October 2005; accepted 5 October 2005.

San Diego, Calif, Denver, Colo, Hershey, Pa, Tucson, Ariz, Madison, Wis, and St Louis, Mo

Background

Outcome data are needed to base recommendations for controller asthma medication use in school-aged children.

Objective

We sought to determine intraindividual and interindividual response profiles and predictors of response to an inhaled corticosteroid (ICS) and a leukotriene receptor antagonist (LTRA).

Methods

An ICS, fluticasone propionate (100 μg twice daily), and an LTRA, montelukast (5-10 mg nightly, age dependent), were administered to children ages 6 to 17 years with mild-to-moderate persistent asthma using only as-needed bronchodilators in a multicenter, double-masked, 2-sequence, 16-week crossover trial. Clinical, pulmonary, and inflammatory responses to these controllers were evaluated.

Results

Improvements in most clinical asthma control measures occurred with both controllers. However, clinical outcomes (asthma control days [ACDs], the validated Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV1/forced vital capacity, peak expiratory flow variability, morning peak expiratory flow, and measures of impedance), and inflammatory biomarkers (exhaled nitric oxide [eNO]) improved significantly more with fluticasone than with montelukast treatment. eNO was both a predictor of ACDs (P = .011) and a response indicator (P = .003) in discriminating the difference in ACD response between fluticasone and montelukast.

Conclusions

The more favorable clinical, pulmonary, and inflammatory responses to an ICS than to an LTRA provide pediatric-based group evidence to support ICSs as the preferred first-line therapy for mild-to-moderate persistent asthma in children. eNO, as a predictor of response, might help to identify individual children not receiving controller medication who achieve a greater improvement in ACDs with an ICS compared with an LTRA.

Key words: Asthma control days, asthma control outcomes, Asthma Control Questionnaire, exhaled nitric oxide, fluticasone propionate, inhaled corticosteroids, leukotriene receptor antagonists, montelukast, pulmonary response

Abbreviations used: ACD, Asthma control day, ACQ, Asthma Control Questionnaire, AX, Area of reactance, CARE, Childhood Asthma Research and Education Network, eNO, Exhaled nitric oxide, FVC, Forced vital capacity, ICS, Inhaled corticosteroid, LTRA, Leukotriene receptor antagonist, NHLBI, National Heart, Lung, and Blood Institute, PC20, Methacholine dose required to reduce baseline FEV1 by 20%, PEF, Peak expiratory flow, R5, Resistance of the respiratory system at 5 Hz

 

 Supported by grants 5U10HL064287, 5U10HL064288, 5U10HL064295, 5U10HL064307, 5U10HL064305, and 5U10HL064313 from the National Heart, Lung, and Blood Institute. This study was carried out in part in the General Clinical Research Centers at Washington University School of Medicine (M01 RR00036) and National Jewish Medical and Research Center (M01 RR00051).

 Disclosure of potential conflict of interest: R. Zeiger has consultant arrangements with AstraZeneca, Genentech, GlaxoSmithKline, and Novartis and has received grants from AstraZeneca, Aventis, GlaxoSmithKline, and Merck. S. Szefler has consultant arrangements with AstraZeneca, Aventis, GlaxoSmithKline, and Merck and has received grants from the National Heart, Lung, and Blood Institute (NHLBI) Childhood Asthma Research and Education (CARE) network and AstraZeneca. M Schatz has received grants from GlaxoSmithKline and Sanofi-Aventis and is on the speakers' bureau for AstraZeneca and Merck. F. Martinez is on the advisory board for Merck, Genentech, and Altana Pharma; has patent licensing arrangements with Wisconsin Alumni Research Foundation; and is on the speakers' bureau for AstraZeneca. V. Chinchilli has consultant arrangements with Pfizer, Eli Lilly, and Insmed and has received grants from the NHLBI CARE Network. R. Lemanske has consultant arrangements with AstraZeneca, Aventis, GlaxoSmithKline, and Novartis/Genentech; has received grants from the NHLBI and the National Institute of Allergy and Infectious Diseases (NIAID); and is on the speakers' bureau for Merck, GlaxoSmithKline, and AstraZeneca. G. Larsen is on the advisory board for GlaxoSmithKline and Schering-Plough. J. Spahn has consultant arrangements with GlaxoSmithKline, has received grants from Merck, and is on the speakers' bureau for GlaxoSmithKline. L. Bacharier has received grants from the NHLBI and is on the speakers' bureau for GlaxoSmithKline, Merck, Genentech, and AstraZeneca. T. Guilbert has consultant arrangements with GlaxoSmithKline; has received grants from GlaxoSmithKline and Genentech; is on the speakers' bureau for GlaxoSmithKline, AstraZeneca, Soma Medical Education, Innovia Education Institute, Antidote; and is part of the Exchange Program Steering Committee that designs CMEs. C. Sorkness has consultant arrangements with GlaxoSmithKline and AstraZeneca, has received grants from GlaxoSmithKline, and is on the speakers' bureau for GlaxoSmithKline, AstraZeneca, and Genentech. L. Taussig has consultant arrangements with GlaxoSmithKline.

PII: S0091-6749(05)02267-0

doi:10.1016/j.jaci.2005.10.012

The Journal of Allergy and Clinical Immunology
Volume 117, Issue 1 , Pages 45-52, January 2006

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