Burden of corticosteroids in children with asthma in primary care: retrospective observational study
BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7350.1374 (Published 08 June 2002) Cite this as: BMJ 2002;324:1374All rapid responses
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Sir,
The article by Elkins-Daukes and colleagues (1) makes an attempt to identify a possible source of risk associated with the use of topical (inhaled and intranasal) steroids in children to treat co-existing asthma and rhinitis, in an impressive population sample. As some 70% of patients who have asthma also have rhinitis, this is an important issue. The possibility of patients receiving more than the total recommended dose, via different routes, for co-existing diseases is a clear concern but one which can be easily managed.
In re-calculating the apparent ‘’steroid load’’ received by the patients, in ‘BDP equivalents’, the authors have ignored (or failed to consider) a fundamental point about steroid safety and the differences between steroids.
The systemic bioavailability of the steroids is not the only predictor of likely systemic effect but it is the major factor. The systemic bioavailability of the different topical steroids used to treat asthma and rhinitis varies greatly, in some cases by almost 100 fold.
For example, BDP has a systemic bioavailability following inhalation of 62% and via the intranasal route 44% (2). In contrast Fluticasone propionate delivered to the lung via the DISKUS® has a bioavailability of 16% and Flixonase® delivered to the nose a bioavailability of 0.42% (3). Consequently, the potential for systemic effects can be substantially reduced by careful selection of the steroid used (4). The table below provides some details of the bioavailability of the more commonly used steroids administered to the lung and nose (5).
The more recently introduced steroids, such as fluticasone propionate and mometasone furoate have a substantially reduced systemic bioavailability, particularly via the nasal route, compared with some of the older steroids such as BDP, budesonide and triamcinolone.
Corticosteroid – Inhaled Route
Systemic
Bioavailability % Triamcinolone MDI 25 Beclomethasone dipropionate MDI 62 Budesonide Turbuhaler 38 Fluticasone propionate Diskus 16 Corticosteroid – Intranasal Route Triamcinolone aqueous nasal spray 46 Beclomethasone dipropionate aqueous nasal spray 44 Budesonide aqueous nasal spray 31 Mometasone furoate aqueous nasal spray 0.46 Fluticasone propionate aqueous nasal spray 0.42
The clinical significance of this observation has been shown, albeit in a small subset of patients from a larger study (6), in which patients receiving inhaled corticosteroids for asthma were also allowed to take additional steroids to treat concomitant rhinitis.
Corticosteroid for Asthma
FP BDP Mean Growth (cm/yr) No Added Intranasal steroid . 5.04 4.05 + Intranasal FP 5.02 4.24 + Intranasal BDP 4.42 3.65
The data demonstrates that when fluticasone propionate is given for asthma, there is no additional ‘steroid load’ when an additional dose is given for rhinitis. The converse is true when BDP is administered.
The importance of this is clear when one considers the available evidence from long term growth studies. In the case of BDP there are a number of studies which confirm a reduction in growth when it is used for treatment for asthma and there is likewise a clear but smaller growth reduction in children treated for rhinitis (alone) for 1 year (7). This is not the case for mometasone when administered for rhinitis (8) or fluticasone propionate, either when administered to treat asthma (9) or rhinitis (10).
The importance of appropriate treatment for rhinitis with corticosteroids cannot be over-emphasised. Recent evidence has shown that appropriate treatment with nasal corticosteroids can reduce the subsequent risk of asthma exacerbations and emergency room visits by patients with co-existing asthma and rhinitis (11,12).
In conclusion, the most effective treatments for asthma and rhinitis are the topically administered corticosteroids, by careful selection of the medication to treat both asthma and rhinitis, the possibility for systemic effects can be minimised, even though the total daily dose received may be increased. Consideration should also be given to allergen identification and avoidance which can reduce the need for medication.
Yours sincerely,
Dr GK Scadding,
Consultant Rhinologist,
Royal National Throat, Nose and Ear Hospital,
Grays Inn Road,
London, WC1X 8DA.
David H Richards
GlaxoSmithKline R&D
Greenford Road,
Greenford,
Middx., UB6 0HE
References:
Elkins-Daukes S., Simpson CR., Helms PJ., et al. Burden of corticosteroids in children with asthma in primary care: retrospective observational study. British Medical Journal 2002; 324: 1374.
Daley-Yates PT., Price AC., Sisson JR., et al., Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Br J Clin Pharmacol 2001; 51:400-409
Daley-Yates PT., Kunka RL., Shen YY., et al. The Relative Systemic Exposure to Fluticasone Propionate (FP) and Mometasone Furoate (MF) Administered as Aqueous Nasal Sprays in Healthy Subjects. J Allergy Clin Immunol 2000; 105 (1): S201.
Richards DH., Daley-Yates PT. Choice of inhaled and intranasal steroids when used in combination for asthma and rhinitis in children. Allergy 2000; 55 (Suppl. 63): A185
Daley-Yates PT., Pierre LN. Pharmacokinetic (PK) and pharmacodynamic (PD) data for inhaled and intranasal corticosteroids (CS) reassessed using a physiological PK/PD model. Eur. Resp. J., 2001; 18(Suppl 33): 147S
Richards DH., Scadding GK. Inhaled and intranasal steroids –the differences explained in terms of potential for growth effects. Allergy 2000; 55 (Suppl. 63): A904
Skoner DP., Rachelefsky GS., Meltzer EO., et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics 2000; 105: e23
Schenkel EJ., Skoner DP., Bronsky EA., et al. Absence of retardation in growth in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics 2000; 105: e22
Allen DB., Bronsky EA., LaForce CF., et al., Growth in asthmatic children treated with fluticasone propionate. J. Pediatr. 1998; 132:472-7
Personal Communication – Dr EE Philpot, GlaxoSmithKline Inc., Raleigh, N.C., USA.
Crystal-Peters J., Neslusan C., Crown WH., Torres A. Treating allergic rhinitis in patients with comorbid asthma: the risk of asthma-related hospitalisations and emergency department visits. J. Allergy & Clin. Immunol. 2002; 109: 57-62
Intranasal steroids and the risk of emergency department visits for asthma. Adams RJ., Fuhlbrigge AL., Finkelstein JA., Weiss ST. J. Allergy & Clin. Immunol. 2002; 109: 636-42
Competing interests
GKS has been involved as a member of advisory panels, a lecturer and researcher on rhinosinusitis on behalf of many of the manufacturers of medications to treat allergy and asthma.
DHR is an employee of GlaxoSmithKline R&D.
Competing interests: Bioavailability % Triamcinolone MDI 25 Beclomethasone dipropionate MDI 62 Budesonide Turbuhaler 38 Fluticasone propionate Diskus 16 Corticosteroid – Intranasal Route Triamcinolone aqueous nasal spray 46 Beclomethasone dipropionate aqueous nasal spray 44 Budesonide aqueous nasal spray 31 Mometasone furoate aqueous nasal spray 0.46 Fluticasone propionate aqueous nasal spray 0.42
During the 4th Central and Eastern European Conference in Poland
professors from European and American Allergology societies disscused
these subjects. H. Nolte from University Hospital from Denmark said, that
immunotherapy should be offered for every patient from 6 years old with
proved allergy to pollens. If it is available of course.
Do you have any statistics for immunotherapy in your country?
It is very common in Germany and becomes quite common in Poland.
I would appreciate your answer.
Jaroslaw Gornicki
Competing interests: No competing interests
Asthma in pediatric age group if properly controlled by anti
inflammatory agents prevents remodelling of air ways
thus making adult life more comfortable.I think keeping this in
consideration our primary care physician should keep close watch on
symptoms and objective parameters like PEFR/FEV1.
Competing interests: No competing interests
Oral corticosteroids vs inhaled corticosteroids use in acute moderate to severe asthma - evidence based approach - an Indian experience.
Acute exacerbations of asthma defined as acute episodes of progressively worsening shortness of breath, cough, wheezing, chest tightness or a combination of these symptoms. Treatment of acute exacerbations includes inhaled beta 2 agonist, oxygen along with corticosteroids and anticholinergic drugs.
Acute exacerbations of asthma are an important cause of morbidity, school absenteeism and frequent hospital visits.
Anti-inflammatory property of corticosteroids accounts for their effectiveness in asthma. As there is airway inflammation which cause airway compromise in acute exacerbations, there are proven benefits of steroids in acute asthma in resolving the obstruction of the airways.
Corticosteroids have been used in the treatment of asthma for approximately five decades and their proven benefits in the emergency room in treatment of asthma exacerbations.
Corticosteroids are the first line drug therapies in the management of acute asthma exacerbations. Oral or parenteral corticosteroids have been effective equally but parenteral steroids are preferred for critically ill children.
Short-term use of high-dose steroids usually don’t have significant side effects, but may be associated with hyperglycemia, hypertension and other psychiatric problems.
A Cochrane review demonstrated improved outcomes for children who have received corticosteroids at the earliest in the emergency department. As there is difficulty to decide when steroids should be administered. It has been shown that steroids given for a short duration of 3-7 days in children, improve the symptomatology and reduce the chances of an early relapse.
Guidelines mention use of prednisolone 1-2 mg/kg/dose every 6 h for 24 h then 1-2 mg/kg/day in divided doses every 8-12 hours. The total duration of therapy can be 3-7 days depending upon the response. However 5-day courses of oral corticosteroids have not been shown to be superior to 3-day courses for outpatient management of acute exacerbations in children.In our setup we use 3 days of corticosteroid therapy.
Inhaled corticosteroids are very effective drugs in suppressing airway inflammation.
A Cochrane review did not find a significant reduction in the need for oral corticosteroids in school-aged children.
Intermittent inhaled did show symptomatic improvement and lower likelihood of requiring oral corticosteroids in preschoolers,
Inhaled corticosteroids treatment is generally considered generally safe in children. Inhaled corticosteroids are known to cause local and systemic adverse effects. Inhaled corticosteroids therapy should be started at its lowest effective dose because usually adverse effects are dose-dependent.Inhaled corticosteroids do not offer cure to asthmatic children. But there is proven role for inhaled corticosteroids in asthma exacerbations. There is less evidence to recommend that inhaled corticosteroids can replace systemic corticosteroids in emergency room for acute asthma exacerbations.
In our view as there are studies showing minimal side effects of inhaled corticosteroids which are better than oral corticosteroids in treatment of acute moderate to severe asthma. However, Inhaled medications are only effective if they are used precisely. Inhaled corticosteroids show improved clinical control and better airway responsiveness
Adherence to daily inhaled corticosteroid therapy is most important in control of asthma.
As asthma is not a curable disease but using good hygienic practices and creating awareness with appropriate controlling measures, child with asthma minimize the complications and hospitalizations.
References : 1)Elham Hossny,Nelson Rosario,Bee Wah Lee,Meenu Singh,Dalia El-Ghoneimy,Jian Yi SOH,Peter Le Souef. The use of inhaled corticosteroids in pediatric asthma: update.World Allergy Organization Journal20169:26 DOI: 10.1186/s40413-016-0117-0
2)Edmonds ML, Milan SJ, Camargo Jr CA, Pollack CV, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev. 2012;12, CD002308.
3) Sunil Saharan & Rakesh Lodha & Sushil K. Kabra.Management of Status Asthmaticus in Children.Indian J Pediatr (2010) 77:1417–1423 DOI
10.1007/s12098-010-0189-8
4) Chong J, Haran C, Chauhan BF, Asher I. Intermittent inhaled corticosteroid therapy versus placebo for persistent asthma in children and adults. Cochrane Database Syst Rev. 2015;7, CD011032.
5) Chang AB, Clark R, Sloots TP, et al. . A 5- versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised: a randomised controlled trial. Med J Aust. 2008;189(6):306–310 [PubMed].
6)Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001; (1): CD002178
7) Fanta CH, Rossing TH, McFadden ER. Glucocorticoids in acute asthma: A critical controlled trial. Am J Med 1983; 74: 845-851
Competing interests: No competing interests