Guidelines for monitoring systemic effects of Glucocorticoids in children with a diagnosis of asthma

• Summary of Guideline
• Aims
• Background
• Diagnosis
• Investigation
• Treatment / Management

Summary of Guideline

The majority of children with a diagnosis of asthma can achieve good symptom control with low dose inhaled steroids. There is a small group of children in whom symptom control can only be achieved with high dose inhaled and/or oral steroids in addition to maximal add-on therapies. These children will be investigated to determine that they have true high steroid requirements (severe asthma) rather than difficult to treat asthma as research has shown that 40% of children referred as severe asthma had modifiable factors[1] . Our aim is to achieve symptom control on the lowest dose of inhaled (and oral) steroid possible for each

individual however there are those who will require high dose treatment. In these children monitoring of the potential side effects of high dose steroids is necessary and will be outlined in this guideline.

Definition of high dose steroids is age dependent and this depends on the guidelines followed:

According to NICE a high dose for children under 16 years would be over 400micrograms budesonide or equivalent(2)BTS/SIGN guidance 800micrograms/day beclomethasone diproprionate or budesonide are classed as medium dose and Fliotide Evohaler 125micrograms 2 puffs twice a day also as medium dose(3) The GINA guidance classes Beclomethosone diproprionate CFC (chlorofluorcarbon propellant) over 400micrograms/day in children 6-11 years and over 1000micrograms/day as high dose in adults and adolescents.(4)

The main potential side effects of steroids are on height velocity and suppressed adrenal function due to effects on the hypothalamic-pituitary-adrenal (HPA) axis. The rate of associated side effects continues to be high in those on high doses of steroids and has been underappreciated previously[3]. One study in children found a prevalence of adrenal axis suppression of 9.3% in those on inhaled corticosteroids(ICS) for asthma[4] where as other studies have reported incidences as high as 40%.

A recent study found cumulative steroid dose to have a correlation with effect on the HPA axis[5]. The peak cortisol level was significantly associated with the cumulative steroid dose but did not correlate with inhaled steroid dose alone regardless of how high the dose was. This evidence supports the need for investigation in children on inhaled steroids in whom multiple courses of oral steroids have been used increasing the cumulative steroid dose. BTS/SIGN guidance states that adrenal insufficiency is more likely to occur at doses over 800micrograms BDP or equivalent (medium dose according to their algorithm).(3)

The potential effects on bone mineral density are less clear. In adult studies[5] there has been shown to be an effect from steroids on bone mineral density and osteoporosis however this effect has not been shown in studies in children. Two large cohort studies of children with asthma found differing results with regard to effect on bone mineral density. The CAMP study[6] found that bone mineral density was affected in children with a low serum vitamin D level and high cumulative doses of ICS whereas the Helsinki study [7]found a reduction in bone mineral density which was greatest in the first 6 months of treatment and that height velocity can be used to determine if bone mineral density may be affected. There is no evidence for increased fracture rate in children associated withsteroid use.

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Aims

To improve monitoring for potential significant side effects in asthmatic children requiring high dose steroids.

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Background

In children with a diagnosis of asthma, adequate symptom control is achieved in the majority using low and safe doses of inhaled steroids. There is a small sub- group of children who require maximal conventional therapy including high dose inhaled steroids, long acting beta agonists and leukotriene receptor antagonists. It is this second group of children who need particular close monitoring for the potential side effects of glucocorticoids.

Inhaled corticosteroids have been found to result in adrenal suppression in up to

40% of children on treatment.(8) This includes those on treatment doses up to those recommended in guidelines. Close monitoring and consideration of the possible side effects is therefore essential.

Children seen in the tertiary asthma clinic will have adherence to treatment thoroughly investigated to ensure that they are concordant with treatment and appropriate doses of steroids are prescribed.

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Diagnosis

Diagnosis of asthma - at least one of the following criteria must be met

• Documented wheeze by a healthcare professional
• Documented bronchodilator reversibility
• Airway hyper-responsiveness (confirmed by direct or indirect challenge)
• Recorded evidence of spontaneous variation in FEV1 (≥12%) or peak flow
  (≥12%) in the past year
  Average diurnal peak flow variation over 13%

Exclusion of other diagnoses if there are features atypical of asthma. Confirming the correct diagnosis is essential to ensure that increasing doses of potentially harmful medications are not used in a situation where they will be of

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Investigation

Growth

• At every clinic visit every child will have his/her height and weight checked and plotted on a growth chart regardless of treatment regimen.

Further investigations should be considered after 12 months of treatment with high dose steroids or if the threshold for number of courses of oral steroids has been reached.

Low Dose Synacthen Test (1micrograms)

Monitoring for adrenal suppression should be performed in children who meet one or more of the criteria

• Inhaled steroids >800micrograms Beclomethosone daily equivalent (Fluticasone
  400micrograms/day) in 12-18 year olds, >500micrograms Beclomethosone daily
  equivalent in children <12years
• Multiple courses of oral steroids - >4 courses in 12 months
• Regular Prednisolone - alternate days (see below for guidance)  plan to wean and test when on less than 8mg/m2 . (Also plan to increase to daily steroids to cover duration of any acute illness)
• Those on continuous steroids in whom there is a plan to wean off steroids

When to do the test if on regular oral Prednisolone

• A Synacthen test is not indicated when on high dose Prednisolone
• The aim is to wean to just below maintenance adrenal dose before testing
• Adrenal steroid replacement dose is around 8mg/m²/day of
  Hydrocortisone split in 2/3 doses
• Prednisolone 1mg = Hydrocortisone 4mg

Eg: If child is on Prednisolone 10mg alternate days and has surface of 1.5m².
Daily Pred dose is 5mg = Hydrocortisone 20mg /day = 13.3mg/m²/day - defer test
Daily Pred dose is 2.5mg = Hydrocortisone 10mg /day = 6.7mg/m²/day - test now

Bone mineral density

Investigation of bone mineral density is not routinely considered. There is little evidence for effects in children with asthma with inhaled corticosteroids Investigations for bone mineral density should be considered in children

• requiring regular daily/alternate day oral steroids (at least 6 months of treatment)
• with confirmed adrenal suppression
• Low vitamin D levels
• Decreased height velocity on centiles 

For those on regular oral corticosteroids:
Give advice about diabetes risk and check for Glycosuria in clinic
BP monitoring in clinic
Optician review in community if prolonged steroids

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Treatment / Management

Low Dose Synacthen Test (1micrograms) test result

• Normal initial cortisol level with rise in cortisol to >500 - normal result with no further intervention required
• Low initial cortisol with rise to >500
  • No intervention required
  • Consider repeat morning ACTH and cortisol if clinically indicated
• Cortisol rise to 450 - 500
  • Consider normal if no symptoms of adrenal insufficiency (eg prolonged recovery from illnesses)
• Cortisol rise to between 350-450
  • Give steroid card (if not already supplied)
  • Steroid replacement with Hydrocortisone when unwell or
    undergoing surgery
  • May need daily Hydrocortisone if symptomatic
  • Discuss with Endocrine team
• Cortisol rise <350
  • Abnormal result requiring endocrine team review and treatment
• Low ACTH and low / undetectable baseline cortisol
  • Discuss with endocrine team

Low bone mineral density

• Check levels of Vitamin D - consider Vit D replacement
• Discuss with endocrine team

All children on high dose inhaled steroids and/or regular oral corticosteroids should carry a steroid card.

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