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AND THE ANSWERS ARE . . .

  1. Almost all of the ICS dose reaching the lungs is then absorbed systemically.
    True
  2. The delivery system used does not affect how much of a dose of the ICS is absorbed systemically.
    False
  3. There is commonly suppression of growth velocity during the first year moderate dose ICS therapy in asthmatics.
    True
  4. Untreated persistent asthma does not reduce growth velocity.
    False
  5. The mean height is lower than predicted in asthmatic children after treatment for several years with moderate dose ICS.
    False

Discussion
There is considerable uncertainty and some misconceptions about the effects of chronic ICS therapy in children with persistent asthma. The potential for adverse systemic effects of chronic ICS therapy is related to the 1) amount deposited in the oropharynx and swallowed and 2) the amount reaching the lower airways and lungs. The percentage of swallowed ICS agents which reaches the systemic circulation varies among different ICS agents (e.g. – <1% for fluticasone ;11% for budesonide; 41% for beclomethasone) depending on the degree of first pass inactivation of the ICS in the liver. The percentage of ICS reaching the lungs varies with the delivery system (e.g. – MDI with an HFA propellant 30-60%; Turbular – 30%; dry powder inhaler – 8%). That portion of the ICS which reaches the lungs is almost completely absorbed systemically. Therefore, when a greater portion of a dose of the ICS reaches the lower airways, not only is there greater anti-inflammatory action in such airways, a larger amount of the ICS is subsequently absorbed systemically (assuming that almost all the swallowed portion of that ICS is inactivated in the liver). However, when almost all the ICS absorbed from the lungs is completely bound to plasma proteins, (as in the case of the ciclesonide metabolite), the risk for adverse systemic effects are markedly reduced.

A number of studies have shown a transient decrease in the growth velocity of pre-pubertal children during the first year of daily ICS treatments. However, longer follow-up studies have shown no reduced height (when compared to that predicted by a reliable formula) in asthmatic children treated daily with ICS in doses such as budesonide 400 mcg/day or fluticasone propionate 200 mcg/day.

Studies of these ICS effects are complicated by the fact that persistent uncontrolled asthma of moderate to severe degree itself may reduce growth velocity, possibly by stimulation of cytokines and other factors which can inhibit osteoblast activity and increase bone resorption rates.

References

1. J Allergy Clin Immunol 2003;112 (Suppl):S1-S40
2. Chest 2003;124:2329-2340
3. J Allergy Clin Immunol 2003;112:469-78
4. Am J Respir Crit Care Med 2003;168:779-82



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