126 Allergy, Asthma, and Clinical Immunology, Volume 4, Number 3, 2008 use.5 In this study, 100 children aged 6 to 9 years of age were studied for 1 year to measure the effect of INCs on growth. One group (51 children) received BDP 168 mg twice daily and the other (49 children) a placebo nasal spray in a double-blind fashion. The children were prepubertal and had normal growth prior to the study. During the study, the children had their heights measured by stadiometry at months 1, 2, 4, 6, 10, and 12 of treatment. They also had their HPA axis assessed via 8 AM cortisol and cosyntropin stimulation testing. The results showed that the mean change in height was 5.0 cm/yr in the BDP group compared with 5.9 cm/yr in the placebo group (p , .01). The mean overall rate of growth was 0.14 mm/d for BDP versus 0.16 mm/d for placebo (p , .01). There were no differences in the 8 AM cortisol or response to cosyntropin stimulation. This study was one of the first to show a negative effect on growth in pediatric patients with INC use. In addition, the HPA axis was not affected in these patients. To date, this is the only study that shows an effect on growth with INC therapy. Subsequent studies with other INCs have not shown a similar effect on growth, suggesting that the effect with BDP was specific to that molecule, perhaps owing to its metabolite, beclomethasone monopropionate, with high systemic bioavailability or to the twice-daily dosing regimen. Murphy and colleagues examined the effect of once-daily therapy with budesonide (BUD) aqueous nasal spray on growth velocity in children with perennial AR.6 They studied 229 children ages 4 to 8 years. The mean growth velocity was 5.91 cm/yr in the BUD-treated children versus 6.19 cm/yr in the placebo-treated patients (p 5 not significant). Two newer-generation corticosteroids that have high first-pass metabolism and low systemic bioavailability have also been studied. Schenkel and colleagues examined the effect of intranasal mometasone furoate (MF) on growth.7 They studied 49 children treated with MF and 49 with placebo over 1 year. The children treated with MF had a mean change of 6.95 cm/yr versus 6.35 cm/yr in the placebo. Allen and colleagues did a similarly designed double-blind, parallel-group, multicentre study in children with perennial AR using the corticosteroid fluticasone propionate (FP).8 In this study, 74 children were treated with FP and 76 with placebo for 1 year. The children treated with FP had a mean change of 6.4 cm/yr versus 6.4 cm/yr in the placebo. Taken together, these studies are reassuring regarding a lack of any effect on growth with the newer-generation, low- bioavailability INCs in pediatric patients. Knemometry is an alternative way to measure growth in studies. It is more useful as a method to measure short- term growth and has been reported as being a more sensitive indicator of systemic bioactivity compared with urinary cortisol measurement. Appropriately used, it can measure changes as small as 0.1 mm over 1 week in lower leg length; however, the use of knemometry on final adult height or long-term (ie, greater than 6 months) growth has not been conclusively established. In addition, few studies have examined the correlation between short-term changes in knemometry and long-term changes in growth. Nonetheless, knemometry provides additional useful information regarding effects on growth. Skoner and colleagues examined growth as measured by knemometry in 49 pediatric patients treated with either placebo, triamcinolone acetonide (TAA) at doses of 110 mg and 220 mg, and FP 200 mg for 2 weeks in a four-way crossover study.9 The study predetermined that a 50% reduction in lower leg growth velocity was clinically significant. The magnitude of treatment effect was 219.6% for TAA 110 mg, 221.7% for FP, and 232.6% for TAA 220 mg. The authors concluded that there was no statistically significant difference in lower leg growth between any of the treatments and placebo. Owing to the short nature of the study and the large variability inherent in knemometry, these large treatment effects did not reach the predeter- mined values of 50% that the authors considered clinically significant. Newer-generation INCs have also been examined using knemometry. Gradman and colleagues studied fluticasone furoate (FF) over 2 weeks of treatment compared with placebo in 53 children and found the change in lower leg growth to be 0.42 mm/wk in the placebo group versus 0.40 mm/wk in the FF group.10 There was no statistical difference. Agertoft and Pedersen studied oral inhaled ciclesonide (CIC) at doses of 40, 80, and 160 mg in a similar design in 24 children.11 Note that this was an asthma medication inhaled into the lung; however, the data still provide useful information about medication safety. In this study, there was a trend toward an effect but no statistical significance. The placebo group grew 0.412 mm/wk, CIC 40 mg grew 0.425 mm/wk, CIC 80 mg grew 0.397 mm/wk, and CIC 160 mg grew 0.370 mm/wk. These short-term growth studies also provide the clinician with reassurance regarding a lack of effect on growth with newer-generation corticosteroids. HPA Axis Suppression of the HPA axis is one of the methods used to determine if steroids have potentially negative effects. Reviewing the types of studies and methods used to