Sheth, Safety of Intranasal Steroids in Treatment of Allergic Rhinitis 127 measure the HPA axis is beyond the scope of this article; however, they have been elegantly reviewed by Allen.12 Galant and colleagues performed a randomized, double- blind, placebo-controlled study to evaluate the effects of FP 200 mg daily on HPA axis function measured by 12- hour urinary free cortisol levels in children 2 to 3 years of age after 6 weeks of treatment.13 FP was equivalent to placebo with respect to effects on HPA axis function measured by 12-hour urinary free cortisol. Grossman and colleagues studied FP in 250 children aged 4 to 11 years with seasonal AR.14 They found that the morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the FP and placebo groups. Furthermore, Wilson and colleagues studied 20 patients in a single-blind, randomized, four-way crossover design and compared the systemic bioactivity of aqueous formulations of BUD, MF, and TAA in terms of adrenal gland, bone, and white blood cell markers.15 The individual treatments were separated by 7-day washout periods. After 5 days of treatment at steady state, serial blood and urine samples were taken for 24 hours. Collective and fractionated measurements (daytime, over- night, and 8 AM) were done on plasma cortisol and urine cortisol/creatinine excretion. Plasma osteocalcin and blood eosinophil counts were measured at 8 AM. The authors found that there was no significant difference between placebo and the active treatments with any of the markers of adrenal suppression. The newer INCs have also been studied with regard to HPA axis suppression and safety. In a 6-week study in children 2 to 5 years of age with perennial AR, daily doses of 200, 100, and 25 mg of CIC nasal spray were compared with placebo nasal spray.16 The CIC-treated groups had a numerically (but not statistically) greater decline in 24- hour urinary free cortisol and plasma cortisol compared with the placebo treated group. In a 12-week study in children 6 to 11 years of age with perennial AR, daily doses of 200, 100, and 25 mg of CIC nasal spray were compared with placebo nasal spray. The CIC-treated groups had a numerically (but not statistically) greater decline in 24- hour urinary free cortisol compared with the placebo- treated group. The mean morning plasma cortisol value did not show any consistent treatment effect with differences from placebo. Another newer-generation INCs, FF has also been evaluated with respect to HPA axis function. Allen and colleagues measured serum cortisol after a single dose of nasal FF and compared this with placebo.17 They reported a ratio of FF to placebo in serum cortisol. The ratios (95% confidence interval) for FF 50, 100, 200, 400, and 800 micrograms were 1.00 (0.89–1.13), 1.04 (0.94–1.16), 1.05 (0.96–1.14), 1.06 (0.95–1.19), and 0.92 (0.82–1.04), respectively. Tripathy and colleagues measured serum cortisol levels after 6 weeks of therapy with FF in children aged 2 to 12 years with perennial AR.18 The ratio of end of treatment to baseline was 0.98 in the placebo group and 0.94 in the FF-treated group. Patel and colleagues reported a similarly designed study in adults (age 12 years and above), which included an additional arm of prednisone 10 mg daily for the last 7 days of treatment.19 The ratio of end of treatment to baseline was 0.99 for placebo, 0.97 for FF, and 0.49 for prednisone 10 mg groups. These data suggest a minimal HPA axis effect with FF. The prescribing information for FF provides additional data on urinary cortisol levels from these studies. With the urinary cortisol data, there was a large degree of variability in the measured results.20 Likely owing to this variability in urinary cortisol values, a more conservative conclusion was reached by the US Food and Drug Administration (FDA). According to the FDA, ‘‘when the results of the HPA axis assessments described above are taken as a whole, an effect of intranasal FF on adrenal function cannot be ruled out, especially in pediatric patients.’’20 Ocular Safety Another potential safety concern is ocular side effects. Derby and Maier conducted a retrospective observational cohort study of cataract incidence among users of oral and INCs identified from the United Kingdom–based General Practice Research Database with a nested case-control analysis to control for confounding factors.21 The study population included 286,078 subjects aged less than 70 years old drawn from 350 general practices in England and Wales. Patients were classified as users of only INCs, users of only oral corticosteroids, and nonusers of either medication. They found that the incidence rate of cataract (1.0 per 1,000 person-years) among users of INCs was similar to the incidence rate among nonusers. However, oral corticosteroid users were at higher risk of cataract (2.2 per 1,000 person-years). In this study, approximately 70% of INC exposure was to BDP only; the event rate in this group was similar to that in the unexposed group. Cataract risk did not increase with the number of prior prescrip- tions for INCs. The authors concluded that the use of INCs was not associated with an increased risk of cataracts in this study population. Another ocular concern is development of glaucoma or increased intraocular pressure. Medication class warnings suggest that nasal and inhaled corticosteroids may result in