A proof-of-concept study to assess the putative dose response to topical corticosteroid in persistent allergic rhinitis using adenosine monophosphate challenge

M. L. Barnes, D. Menzies, A. R. Nair, P. J. Hopkinson, B. J. Lipworth

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    Introduction: The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER). Methods: Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 µg or 400 µg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios. Results: Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 µg, and 12.9% (4.8-20.9, P=0.009) by FP 400 µg. The 400-100 µg difference was 12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 µg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal suppression was detected at either dose. Conclusion: FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER. © 2007 The Authors.
    Original languageEnglish
    Pages (from-to)696-703
    Number of pages8
    JournalClinical and Experimental Allergy
    Volume37
    Issue number5
    DOIs
    Publication statusPublished - May 2007

    Fingerprint

    Adenosine Monophosphate
    Nose
    Adrenal Cortex Hormones
    Nitric Oxide
    Quality of Life
    Allergic Rhinitis
    Signal-To-Noise Ratio
    Double-Blind Method
    Cross-Over Studies
    Hydrocortisone
    Fluticasone
    Creatinine
    Therapeutics
    Placebos
    Outcome Assessment (Health Care)
    Confidence Intervals

    Keywords

    • Adenosine Monophosphate
    • Adolescent
    • Adult
    • Aged
    • Androstadienes
    • Cross-Over Studies
    • Dose-Response Relationship, Drug
    • Double-Blind Method
    • Drug Monitoring
    • Female
    • Glucocorticoids
    • Humans
    • Male
    • Middle Aged
    • Nasal Provocation Tests
    • Quality of Life
    • Rhinitis, Allergic, Perennial
    • Treatment Outcome

    Cite this

    @article{f8647786a34e4a8587e8b6f3075a11da,
    title = "A proof-of-concept study to assess the putative dose response to topical corticosteroid in persistent allergic rhinitis using adenosine monophosphate challenge",
    abstract = "Introduction: The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER). Methods: Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 µg or 400 µg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios. Results: Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9{\%} (95{\%} confidence interval -7.1 to 9.0, P=NS) by FP 100 µg, and 12.9{\%} (4.8-20.9, P=0.009) by FP 400 µg. The 400-100 µg difference was 12.0{\%} U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 µg were 81{\%} for AMP challenge, 54{\%} for domiciliary PNIF, 53{\%} for miniRQLQ, 24{\%} for symptom scores and 18{\%} for nasal nitric oxide. No adrenal suppression was detected at either dose. Conclusion: FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER. {\circledC} 2007 The Authors.",
    keywords = "Adenosine Monophosphate, Adolescent, Adult, Aged, Androstadienes, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Drug Monitoring, Female, Glucocorticoids, Humans, Male, Middle Aged, Nasal Provocation Tests, Quality of Life, Rhinitis, Allergic, Perennial, Treatment Outcome",
    author = "Barnes, {M. L.} and D. Menzies and Nair, {A. R.} and Hopkinson, {P. J.} and Lipworth, {B. J.}",
    year = "2007",
    month = "5",
    doi = "10.1111/j.1365-2222.2007.02713.x",
    language = "English",
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    pages = "696--703",
    journal = "Clinical and Experimental Allergy",
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    }

    A proof-of-concept study to assess the putative dose response to topical corticosteroid in persistent allergic rhinitis using adenosine monophosphate challenge. / Barnes, M. L.; Menzies, D.; Nair, A. R.; Hopkinson, P. J.; Lipworth, B. J.

    In: Clinical and Experimental Allergy, Vol. 37, No. 5, 05.2007, p. 696-703.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A proof-of-concept study to assess the putative dose response to topical corticosteroid in persistent allergic rhinitis using adenosine monophosphate challenge

    AU - Barnes, M. L.

    AU - Menzies, D.

    AU - Nair, A. R.

    AU - Hopkinson, P. J.

    AU - Lipworth, B. J.

    PY - 2007/5

    Y1 - 2007/5

    N2 - Introduction: The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER). Methods: Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 µg or 400 µg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios. Results: Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 µg, and 12.9% (4.8-20.9, P=0.009) by FP 400 µg. The 400-100 µg difference was 12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 µg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal suppression was detected at either dose. Conclusion: FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER. © 2007 The Authors.

    AB - Introduction: The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER). Methods: Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 µg or 400 µg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios. Results: Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 µg, and 12.9% (4.8-20.9, P=0.009) by FP 400 µg. The 400-100 µg difference was 12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 µg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal suppression was detected at either dose. Conclusion: FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER. © 2007 The Authors.

    KW - Adenosine Monophosphate

    KW - Adolescent

    KW - Adult

    KW - Aged

    KW - Androstadienes

    KW - Cross-Over Studies

    KW - Dose-Response Relationship, Drug

    KW - Double-Blind Method

    KW - Drug Monitoring

    KW - Female

    KW - Glucocorticoids

    KW - Humans

    KW - Male

    KW - Middle Aged

    KW - Nasal Provocation Tests

    KW - Quality of Life

    KW - Rhinitis, Allergic, Perennial

    KW - Treatment Outcome

    U2 - 10.1111/j.1365-2222.2007.02713.x

    DO - 10.1111/j.1365-2222.2007.02713.x

    M3 - Article

    VL - 37

    SP - 696

    EP - 703

    JO - Clinical and Experimental Allergy

    JF - Clinical and Experimental Allergy

    SN - 0954-7894

    IS - 5

    ER -