David B Allen, MD  Journal of Allergy and Clinical Immunology 

Slides:



Advertisements
Similar presentations
Pharmacokinetic and Pharmacodynamic Studies for Systemic Exposure of Locally Acting Drugs Hartmut Derendorf, Ph.D. Günther Hochhaus, Ph.D. University of.
Advertisements

Food and Drug Administration Center for Drug Evaluation and Research Lessons Learned from Growth Studies with Orally Inhaled and Intranasal Corticosteroids.
Joint NDAC/DODAC Advisory Committee Meeting March 24, 2005 Rx Topical Corticosteroids and Testing for Adrenal Suppression Markham C. Luke, M.D., Ph.D.
Background Derma-Smoothe/FS ® (Fluocinolone acetonide ) Contains 0.01% fluocinolone acetonide in an oil base solution, Categorized as a low to medium potency.
Food and Drug Administration Division of Pulmonary and Allergy Drug Products Summary Comments - Orally Inhaled and Intranasal Budesonide and Fluticasone.
Systemic side effects of inhaled corticosteroids in patients with asthma Respiratory Medicine (2006) 100, 1307–1317 Department of Pulmonary & Critical.
Asthma and Small Airway Inflammation
Bronchial Hyperresponsiveness in the Assessment of Asthma Control
Bronchial Hyperresponsiveness in the Assessment of Asthma Control
The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5- year follow-up: Effectiveness of early intervention with budesonide in.
Adherence with montelukast or fluticasone in a long-term clinical trial: Results from the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial 
What effect does asthma treatment have on airway remodeling
Treating acute rhinosinusitis: Comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo  Eli O. Meltzer, MD, Claus Bachert,
Alalia Berry, MD, William W. Busse, MD 
Clinical outcomes and adverse effect monitoring in allergic rhinitis
Christine A. Sorkness, PharmD 
Safety and efficacy of mometasone furoate aqueous nasal spray in children with allergic rhinitis: Results of recent clinical trials  Javier Dibildox,
A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis  William R. Lumry, MD  Journal of.
Asthma diagnosis and treatment: Filling in the information gaps
Fluticasone furoate nasal spray: A single treatment option for the symptoms of seasonal allergic rhinitis  Harold B. Kaiser, MD, Robert M. Naclerio, MD,
David A. Khan, MD  Journal of Allergy and Clinical Immunology 
Effects of topical glucocorticoids on in vitro lactoferrin glandular secretion: Comparison between human upper and lower airways  Jordi Roca-Ferrer, MSa,
Comparison of once-daily ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, and placebo in the treatment of seasonal allergic rhinitis  Paul H. Ratner,
Bruce M. Prenner, MD, Bobby Q. Lanier, MD, David I
Safety and efficacy of mometasone furoate aqueous nasal spray in children with allergic rhinitis: Results of recent clinical trials  Javier Dibildox,
T lymphocytes in asthma: Bronchial versus peripheral responses
David P. Skoner, MD, Betty L
Knemometry is more sensitive to systemic effects of inhaled corticosteroids in children with asthma than 24-hour urine cortisol excretion  Bo Chawes,
Comparison of the efficacy of budesonide and fluticasone propionate aqueous nasal spray for once daily treatment of perennial allergic rhinitis  James.
Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth.
Adrenocorticosteroids
Rhinitis and asthma: Evidence for respiratory system integration
The impact of allergic rhinitis on bronchial asthma
Inhaled Corticosteroids
Clinical outcomes and adverse effect monitoring in allergic rhinitis
Peter M. Wolfgram, MD, David B. Allen, MD 
Allergic rhinobronchitis: The asthma–allergic rhinitis link
Michael Mellon, MD  Journal of Allergy and Clinical Immunology 
Peter König, MD, PhD  Journal of Allergy and Clinical Immunology 
H.William Kelly, PharmD  Journal of Allergy and Clinical Immunology 
Paul M. O’Byrne, MB, FRCPI, FRCP(C)a, Soren Pedersen, MD, PhDb 
Quality of life in adults and children with allergic rhinitis
Recruitment of T cells to the lung in response to antigen challenge
6. Asthma Journal of Allergy and Clinical Immunology
Synthetic responses in airway smooth muscle
Subjective and objective assessments in patients with seasonal allergic rhinitis: Effects of therapy with mometasone furoate nasal spray  Eli O. Meltzer,
Exercise-induced bronchoconstriction in children: Montelukast attenuates the immediate-phase and late-phase responses  Raul E. Melo, MD, Dirceu Solé,
Clinical need for a nebulized corticosteroid
Treating acute rhinosinusitis: Comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo  Eli O. Meltzer, MD, Claus Bachert,
H. William Kelly, PharmD  Journal of Allergy and Clinical Immunology 
A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma  Gordon D. Raphael, MDa, Robert.
Complications of allergic rhinitis
A placebo- and active-controlled randomized trial of prophylactic treatment of seasonal allergic rhinitis with mometasone furoate aqueous nasal spray 
Adherence with montelukast or fluticasone in a long-term clinical trial: Results from the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial 
Objective monitoring of nasal airway inflammation in rhinitis
Clinical effects of nedocromil sodium on challenges invoking neuronal mechanisms and on virally induced symptoms  Peter König, MD, PhD  Journal of Allergy.
Exercise-induced asthma: Is it the right diagnosis in elite athletes?
Erika von Mutius, MD  Journal of Allergy and Clinical Immunology 
Corticosteroids in the treatment of pediatric allergic rhinitis
Mometasone furoate administered once daily is as effective as twice-daily administration for treatment of mild-to-moderate persistent asthma  James P.
Efficacy and safety overview of a new inhaled corticosteroid, QVAR (hydrofluoroalkane- beclomethasone extrafine inhalation aerosol), in asthma  Jennifer.
Robert P. Schleimer, PhD  Journal of Allergy and Clinical Immunology 
David P. Skoner, MD  Journal of Allergy and Clinical Immunology 
Update on risk factors for food allergy
Systemic effects of local allergic disease
A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis  Warner Carr, MD, Jonathan Bernstein, MD, Phil Lieberman,
The correlation between allergic rhinitis and sleep disturbance
Normal diurnal variation in serum cortisol concentration in asthmatic children treated with inhaled budesonide  Benjamin Volovitz, MD, Arieh Kauschansky,
Clinical relevance of inhaled corticosteroids and HPA axis suppression
Desloratadine: A new, nonsedating, oral antihistamine
Presentation transcript:

Systemic effects of intranasal steroids: An endocrinologist’s perspective  David B Allen, MD  Journal of Allergy and Clinical Immunology  Volume 106, Issue 4, Pages S179-S190 (October 2000) DOI: 10.1067/mai.2000.110038

Fig. 1 . The fate of intranasal steroids. The amount of intranasal corticosteroid that reaches the systemic circulation is the sum of nasal and oral bioavailable fractions. The majority of the drug is swallowed, and systemic bioavailability will be determined by the absorption from the gastrointestinal tract and the degree of first-pass hepatic inactivation. The absorption of the fraction that is deposited on the nasal mucosa varies from drug to drug and is influenced by solubility characteristics and other factors. NA, not available. Estimated percentages of systemic bioavailability are from the following sources: IN-FLU,15 IN-BDP,10 IN-BUD,10 IN-MF,17 and IN-FP.10,18 Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 2 . Short-, intermediate-, and long-term tests of the effects of corticosteroids administered to the airways on the HPA axis. Sensitivity for the detection of the systemic presence of INSs or ICSs is greatest with integrated studies of basal HPA axis function (eg, area-under-the-curve cortisol measurements); positive predictive value for risk of adrenal insufficiency is increased by the performance of dynamic tests of adrenal-gland responsiveness (eg, ACTH stimulation [relative predictive values of low-dose vs high-dose ACTH tests have not yet been determined]). AUC , area under the curve; UFC , urinary free cortisol. (Adapted from Allen DB. Limitations of short-term studies in predicting long-term adverse effects of inhaled cortico-steroids. Allergy 1999;54:29-34; © 1999 Munksgaard International Publishers Ltd, Copenhagen, Denmark. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 3 . Short-, intermediate-, and long-term tests of the effects of corticosteroids administered to the airways on growth. Highly sensitive knemometry is a poor predictor of long-term growth, which is more accurately assessed by intermediate-term or long-term whole body stadiometry. (Adapted from Allen DB. Limitations of short-term studies in predicting long-term adverse effects of inhaled corticosteroids. Allergy 1999;54:29-34; © 1999 Munksgaard International Publishers Ltd, Copenhagen, Denmark. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 4 . Mechanisms of growth suppression by corticosteroids (derived from both in vivo and in vitro studies). GHRH, growth hormone releasing hormone; GH, growth hormone; IGF-1, insulin-like growth factor-1. (From Allen DB, Julius JR, Breen TJ, Attie KM. Treatment of glucocorticoid-induced growth suppression with growth hormone. J Clin Endocrinol Metab 1998;83(8):2824-9; © The Endocrine Society. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 5 . Interaction of childhood growth and HPA axes. The commencement of nocturnal pulsatile growth hormone secretion normally coincides with the nadir in plasma cortisol concentrations. Consequently, the administration and absorption of airway corticosteroids at bedtime could theoretically have a disproportionate suppressing influence on growth, compared with early morning dosing. GH , growth hormone. Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 6 . Mean lower-leg growth rates during once-daily treatment with IN-MF 100 μg/d (0.58 mm/wk) or 200 μg/d (0.48 mm/wk), IN-BUD 400 μg/d (0.37 mm/wk), or placebo (0.35 mm/wk). Marked interindividual differences in growth velocity were observed during all 4 treatments. (Adapted from Agertoft L, Pedersen S. Short-term lower leg growth rate in children with rhinitis treated with intranasal mometasone furoate and budesonide. J Allergy Clin Immunol 1999;104:948-52. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 7 . Mean change in standing height from baseline over 1 year of treatment with IN-BDP 168 μg twice daily or placebo. (Adapted from Skoner DP, Rachelefsky GS, Meltzer EO, et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics [electronic pages] 2000;105:E23. Reproduced by permission of Pediatrics, © 2000.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 8 . Mean change in standing height from baseline over 1 year of treatment with IN-MF 100 μg once daily or placebo. (Adapted from Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics [electronic pages] 2000;105:E22. Reproduced by permission of Pediatrics, © 2000.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 9 . Mean change in standing height from baseline over 1 year of treatment with inhaled FP 50 μg or 100 μg twice daily or placebo. (Adapted from Allen DB, Bronsky EA, LaForce CF, et al. Growth in asthmatic children treated with fluticasone propionate. J Pediatr 1998;132:472-7. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 10 . Interaction of corticosteroids with bone metabolism, which contributes to the increased risk for osteoporosis. Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)