The growth of children and adolescents receiving orally inhaled corticosteroids, including QVAR, should be monitored routinely (., via stadiometry). If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect should be considered. The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including QVAR, each patient should be titrated to his/her lowest effective dose [see Dosage and Administration ( )] .
The other option for estimating low-dose changes, using an empirical dose–response model fit to high-dose data on the intermediate response, has the same drawbacks as with apical responses. Although mechanistic information may indicate that a particular intermediate step is a key step toward toxicity, that information normally does not specify the form of the dose response for the intermediate variable. Consequently, dose–response modeling of that variable will be empirical, and the dose response for the apical effect will be determined by the empirical dose response assumed for the intermediate biological variable (., Crump 1994a ). For example, if a single intermediate variable is dose related and that variable is modeled as varying linearly, quadratically, or threshold-like at low doses, the apical response will likewise vary linearly, quadratically, or threshold-like at low doses. Thus, dose–response modeling will still be empirical, and different empirical dose–response models will fit the data on the intermediate variable equally well and yet predict widely different risks of an apical response from the same low exposures.
The optimal treatment for mild asthma is uncertain. We assessed the effects of adding a long-acting inhaled beta-agonist, formoterol, to low doses of an inhaled corticosteroid, budesonide, for 1 yr in subjects with mild asthma, receiving no or only a small dose of inhaled corticosteroid. The 698 corticosteroid free patients (Group A) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus microg formoterol, or placebo. The 1,272 corticosteroid-treated patients (Group B) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus microg formoterol, 200 microg budesonide, or 200 microg budesonide plus microg formoterol. The main outcome variables were time to the first severe asthma exacerbation and poorly controlled asthma days. In Group A, budesonide alone reduced the risk for severe exacerbations by 60% and poorly controlled days by 48%; adding formoterol increased lung function with no change in other end points. By contrast, in Group B, adding formoterol reduced the risk for the first severe exacerbation and for poorly controlled days by 43 and 30%, respectively. Thus, in corticosteroid-free patients, low dose inhaled budesonide alone reduced severe exacerbations and improved asthma control, and in patients already receiving inhaled corticosteroid, adding formoterol was more effective than doubling the corticosteroid dose.