Characterization of within-subject responses to fluticasone and montelukast in childhood asthma

Stanley J. Szefler, Brenda R. Phillips, Fernando Martinez, Vernon M. Chinchilli, Robert F. Lemanske, Robert C. Strunk, Robert S. Zeiger, Gary Larsen, Joseph D. Spahn, Leonard B. Bacharier, Gordon R. Bloomberg, Theresa W. Guilbert, Gregory Heldt, Wayne J Morgan, Mark H. Moss, Christine A. Sorkness, Lynn M. Taussig

Research output: Contribution to journalArticle

431 Citations (Scopus)

Abstract

Background: Responses to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) vary among asthmatic patients. Objective: We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other. Methods: Children 6 to 17 years of age with mild-to-moderate persistent asthma were randomized to one of 2 crossover sequences, including 8 weeks of an ICS, fluticasone propionate (100 μg twice daily), and 8 weeks of an LTRA, montelukast (5-10 mg nightly depending on age), in a multicenter, double-masked, 18-week trial. Response was assessed on the basis of improvement in FEV1 and assessed for relationships to baseline asthma phenotype-associated biomarkers. Results: Defining response as improvement in FEV1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Compared with those who responded to neither medication, favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide, total eosinophil counts, levels of serum IgE, and levels of serum eosinophil cationic protein and lower levels of methacholine PC20 and pulmonary function; favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use, bronchodilator response, exhaled nitric oxide levels, and eosinophil cationic protein levels and lower methacholine PC20 and pulmonary function values. Conclusions: Response to fluticasone and montelukast vary considerably. Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy. Other children could receive either ICSs or LTRAs.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume115
Issue number2
DOIs
StatePublished - Feb 2005

Fingerprint

montelukast
Leukotriene Antagonists
Asthma
Steroid Receptors
Eosinophil Cationic Protein
Methacholine Chloride
Bronchodilator Agents
Lung
Adrenal Cortex Hormones
Nitric Oxide
Eosinophils
Immunoglobulin E
Biomarkers
Fluticasone
Inflammation
Phenotype

Keywords

  • Asthma
  • Biomarkers
  • Exhaled nitric oxide
  • Fluticasone propionate
  • Inhaled corticosteroids
  • Montelukast
  • Pulmonary response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Szefler, S. J., Phillips, B. R., Martinez, F., Chinchilli, V. M., Lemanske, R. F., Strunk, R. C., ... Taussig, L. M. (2005). Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. Journal of Allergy and Clinical Immunology, 115(2), 233-242. https://doi.org/10.1016/j.jaci.2004.11.014

Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. / Szefler, Stanley J.; Phillips, Brenda R.; Martinez, Fernando; Chinchilli, Vernon M.; Lemanske, Robert F.; Strunk, Robert C.; Zeiger, Robert S.; Larsen, Gary; Spahn, Joseph D.; Bacharier, Leonard B.; Bloomberg, Gordon R.; Guilbert, Theresa W.; Heldt, Gregory; Morgan, Wayne J; Moss, Mark H.; Sorkness, Christine A.; Taussig, Lynn M.

In: Journal of Allergy and Clinical Immunology, Vol. 115, No. 2, 02.2005, p. 233-242.

Research output: Contribution to journalArticle

Szefler, SJ, Phillips, BR, Martinez, F, Chinchilli, VM, Lemanske, RF, Strunk, RC, Zeiger, RS, Larsen, G, Spahn, JD, Bacharier, LB, Bloomberg, GR, Guilbert, TW, Heldt, G, Morgan, WJ, Moss, MH, Sorkness, CA & Taussig, LM 2005, 'Characterization of within-subject responses to fluticasone and montelukast in childhood asthma', Journal of Allergy and Clinical Immunology, vol. 115, no. 2, pp. 233-242. https://doi.org/10.1016/j.jaci.2004.11.014
Szefler, Stanley J. ; Phillips, Brenda R. ; Martinez, Fernando ; Chinchilli, Vernon M. ; Lemanske, Robert F. ; Strunk, Robert C. ; Zeiger, Robert S. ; Larsen, Gary ; Spahn, Joseph D. ; Bacharier, Leonard B. ; Bloomberg, Gordon R. ; Guilbert, Theresa W. ; Heldt, Gregory ; Morgan, Wayne J ; Moss, Mark H. ; Sorkness, Christine A. ; Taussig, Lynn M. / Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. In: Journal of Allergy and Clinical Immunology. 2005 ; Vol. 115, No. 2. pp. 233-242.
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AU - Szefler, Stanley J.

AU - Phillips, Brenda R.

AU - Martinez, Fernando

AU - Chinchilli, Vernon M.

AU - Lemanske, Robert F.

AU - Strunk, Robert C.

AU - Zeiger, Robert S.

AU - Larsen, Gary

AU - Spahn, Joseph D.

AU - Bacharier, Leonard B.

AU - Bloomberg, Gordon R.

AU - Guilbert, Theresa W.

AU - Heldt, Gregory

AU - Morgan, Wayne J

AU - Moss, Mark H.

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N2 - Background: Responses to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) vary among asthmatic patients. Objective: We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other. Methods: Children 6 to 17 years of age with mild-to-moderate persistent asthma were randomized to one of 2 crossover sequences, including 8 weeks of an ICS, fluticasone propionate (100 μg twice daily), and 8 weeks of an LTRA, montelukast (5-10 mg nightly depending on age), in a multicenter, double-masked, 18-week trial. Response was assessed on the basis of improvement in FEV1 and assessed for relationships to baseline asthma phenotype-associated biomarkers. Results: Defining response as improvement in FEV1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Compared with those who responded to neither medication, favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide, total eosinophil counts, levels of serum IgE, and levels of serum eosinophil cationic protein and lower levels of methacholine PC20 and pulmonary function; favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use, bronchodilator response, exhaled nitric oxide levels, and eosinophil cationic protein levels and lower methacholine PC20 and pulmonary function values. Conclusions: Response to fluticasone and montelukast vary considerably. Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy. Other children could receive either ICSs or LTRAs.

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KW - Biomarkers

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KW - Fluticasone propionate

KW - Inhaled corticosteroids

KW - Montelukast

KW - Pulmonary response

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