Paediatric reference range for overnight urinary cortisol corrected for creatinine.

OBJECTIVES: Systemic activity of inhaled corticosteroids (ICS) may be assessed via urinary cortisol measurement. Overnight urinary free cortisol corrected for creatinine (OUFCC) has been extensively reported in adult studies. However, a paediatric mass spectrometric (MS) reference range for OUFCC is not established. MS methods for OUFCC avoid cross-reactivity with other steroid hormones and are thus preferable to immunoassays. The aim of the present study was to define an MS OUFCC normative range in children. METHODS: This was a cross-sectional study of healthy pre-pubertal children from 5 to 11 years. Children collected urine from 10 pm or bedtime, whichever was earlier, until 8 am. Urinary free cortisol was measured via a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay (Acquity UPLC with Xevo TQ-S Mass Spectrometer [Waters]) with in-house reagents. Urinary creatinine was measured using a commercial assay (Roche). RESULTS: Complete urine collections were obtained from 72 males and 70 females, mean age (SD) 8.6 (1.9) (range 5.0-11.8) years. The OUFCC 95% prediction interval was 1.7-19.8 nmol/mmol. Geometric mean OUFCC was 5.7; range 1.1-24.8 nmol/mmol. CONCLUSIONS: The obtained normative LC-MS/MS OUFCC reference data facilitate the use of mass spectrometry OUFCC assays in assessment of systemic activity of endogenous and exogenous corticosteroids in children.

Extra-fine particle inhaled corticosteroids, pharma-cokinetics and systemic activity in children with asthma.

During recent years, extra-fine particle inhaled corticosteroids with a median aerodynamic diameter ≤2 µm have been introduced in the treatment of asthma. The aim of this paper was to review pharmacokinetics and systemic activity of extra-fine particle hydroalkane pressurized metered dose inhaled (pMDI) ciclesonide and beclomethasone dipropionate in children. A literature review was performed. Systemic bioavailability of oral and pulmonary deposition of extra-fine ciclesonide and beclomethasone dipropionate was 52% and 82%, the half-life in serum 3.2 and 1.5 h and first-pass hepatic metabolism >99% and 60%, respectively. Secondary analyses of urine cortisol/creatinine excretion found no effects of ciclesonide pMDI between 40 and 320 µg/day or of beclomethasone dipropionate pMDI between 80 and 400 µg/day. Ciclesonide pMDI 40, 80 and 160 µg/day caused no effects on short-term lower leg growth rate as assessed by knemometry. Ciclesonide 320 µg/day was associated with a numerically short-term growth suppression equivalent to 30% which was similar to 25% and 36% suppression caused by beclomethasone dipropionate HFA and CFC 200 µg/day, respectively. Consistent with the differences in key pharmacokinetic features, beclomethasone dipropionate is associated with a systemic activity detected by knemometry at a lower dose than ciclesonide. Whether that correlates with a clinically important difference remains to be explored. Assessments of systemic activity of beclomethasone dipropionate <200 µg/day and of ciclesonide >180 µg/day as well as head-to-head comparisons are warranted. Preferably, such studies should apply the sensitive method of knemometry.

The 2014 Danish references from birth to 20 years for height, weight and body mass index.

AIM: To construct new Danish growth charts for 0- to 20-year-olds and to compare them with Danish references from 1982 and with World Health Organization (WHO) standards for children aged 0-5 years from 2006, by applying similar inclusion and exclusion criteria. METHODS: Anthropometric data from three contemporary Danish population-based studies were combined. References for height were based on healthy Caucasian children born at term. A total of 12,671 height measurements (8055 in boys and 4616 in girls) were included. Reference charts were developed using the generalised additive models for location, scale and shape. RESULTS: From prepubertal ages, a secular increase in height was observed for both genders. The differences were most pronounced in puberty, and final heights were increased by 1.4 cm in boys and 2.9 cm in girls compared to 1982 references. In boys, but not girls an upward shift in body mass index (BMI) above median levels was found. Reference curves for height were superimposable with standard curves based on the selective WHO criteria. Danish children were longer/taller and heavier and they had larger head circumferences than those reported in the recent multiethnic WHO standards. CONCLUSION: We recommend national implementation of these contemporary 2014 Danish references for anthropometric measurements.

Systemic activity of inhaled beclomethasone dipropionate: a double-blind comparison of volume spacers.

BACKGROUND: To which extent volume spacers may influence systemic activity of inhaled beclomethasone dipropionate (BDP) has not been evaluated. AIM: To assess whether the AeroChamber Plus™ spacer is equivalent to the Volumatic™ spacer for administration of inhaled hydroflouroalkane 134a propelled BDP in terms of lower leg growth rate (LLGR). PATIENTS AND METHODS: Prepubertal children with mild asthma (n = 26, aged 6-14 years) were included in a 3-time periods of 2 weeks duration randomized double-blind cross-over study with a single-blind placebo run-in and two washout periods. LLGR was measured with the knemometer. Interventions were inhaled BDP hydroflouroalkane 134a pressurized metered dose inhaler 100 µg and 200 µg b.i.d. with the AeroChamber Plus and 200 µg b.i.d. with the Volumatic spacer. RESULTS: Beclomethasone dipropionate 200 µg b.i.d. from the AeroChamber Plus was non-inferior to BDP 200 b.i.d. from the Volumatic spacer as the lower margin of confidence interval of the difference between treatments (-0.18 to 0.13 mm/week) was greater than the prespecified lower limit for non-inferiority (-0.20 mm/week). UFC/creatinine data showed no statistically significant variations. CONCLUSION: The systemic activity of BDP, via the Volumatic™, and AeroChamber Plus™ spacers is similar. The AeroChamber Plus spacer may be used in children without risk of increasing systemic activity of BDP.

Growth suppression caused by corticosteroid eye drops.

Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fluorometholone eye drops in a case series of five children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year.

Growth hormone treatment, final height, insulin-like growth factors, ghrelin, and adiponectin in four siblings with Seckel syndrome.

OBJECTIVE: To report on the effect of growth hormone (GH) treatment on final height (FH) and to describe the insulin-like growth factor (IGF) system, ghrelin, and adiponectin (ADPN) in children with Seckel syndrome. SUBJECTS AND RESULTS: Four severely growth-retarded Iraqi siblings (two girls and two boys) with Seckel syndrome were referred at ages 16.5, 14.4, 12.4, and 10.4 years. They were born at term, but their growth was retarded and birth weight ranged between 1 and 1.5 kg. The children were healthy and had a normal response to GH provocative test. Long-term GH treatment of the youngest brother and sister increased the FH by 7.2 and 3.4 cm, respectively, compared with their older brother and sister. At FH, body mass index standard deviation scores (BMISDS) ranged from -3.0 to -3.9. Serum levels of immunoreactive IGF-1, bioactive IGF-1, and IGF-binding protein 3 were all within normal to high range before GH treatment and increased after GH treatment. Fasting plasma ghrelin remained severely reduced. Despite low BMISDS, plasma ADPN was moderately reduced and showed an almost complete absence of the low-molecular-weight subform. CONCLUSION: This is the first report on the effect of GH treatment on FH in children with Seckel syndrome. GH may have increased FH. In addition to growth defects and reduced BMISDS, patients with Seckel syndrome are characterized by low fasting ghrelin levels, low total ADPN, and near deficiency of the low-molecular-weight ADPN subform. The possible significance of the hormonal changes requires further investigations.

A randomized trial of lower leg and height growth in children with asthma treated with inhaled budesonide from a new dry powder inhaler.

Short-term knemometry is a highly sensitive and accurate method for non-invasive assessment of systemic activity of inhaled corticosteroids in children with asthma. However, there are no randomized data available to elucidate the relation between inhaled corticosteroid suppressed short-term lower leg and height growth. The aim of the present study was to assess the relation between short-term lower leg and 1-yr height growth in children with asthma treated with inhaled budesonide from the new Pulairmax inhaler 200 µg once daily in the morning or montelukast 5 mg once daily. A total of 52 pre-pubertal children with asthma were included in a randomized open-label parallel group study. Length of the lower leg and height were measured by knemometry and stadiometry, respectively, at study entry and after 2, 4, 12, 20, 28, 36, 44 and 52 wks. Lower leg and height growth rates were significantly lower in the budesonide than in the montelukast group (p < 0.0001). Mean 2-wks lower leg growth rate was 0.17 mm/wk in the budesonide and 0.39 mm/wk in the montelukast treated children (p = 0.02). Mean 1-yr height growth rate was 5.51 cm/yr in the budesonide and 6.51 cm/yr in the montelukast group [95% CI: (0.20; 1.79)]. There was a strong linear correlation between lower leg and height growth in both groups, rho = 0.96 (budesonide) and 0.98 (montelukast). In conclusion, 1-yr height growth suppression of budesonide 200 µg administered via the Pulairmax inhaler once daily in the morning was indicated from suppressed short-term lower leg growth providing evidence that short-term knemometry is able to predict 1-yr height growth suppression of inhaled corticosteroids. Short-term knemometry should be performed as part of the safety assessments of new inhaled corticosteroids and inhalation devices in children with asthma before long-term height growth evaluations are initiated.

Telephone consultation as a substitute for face-to-face consultation during the COVID-19 pandemic.

INTRODUCTION: The health authorities have recommended that face-to-face consultations be substituted by telephone consultations to reduce the risk of virus transmission in out-patient clinics during the coronavirus disease 2019 (COVID-19) pandemic. The aim of the present study was to assess the frequency of such telephone consultations and families' evaluations of them in a paediatric outpatient clinic during the initial weeks of the COVID-19 pandemic lockdown. METHODS: During the period from 16 March to 23 April 2020, telephone consultations substituting face-to-face consultations in children and adolescents from 0 to 19 years of age were prospectively recorded. In subsequent telephone interviews, families were asked about their views on the telephone consultation. RESULTS: During the observation period, the clinic had 499 scheduled face-to-face appointments and 112 (22.4%) substitute telephone consultations. A total of 103 families participated in a telephone interview representing 87 (84.5%) children with atopic diseases and 16 (15.5%) with other conditions. A total of 100 (97.0%) of the families agreed or strongly agreed that they felt good about being offered a substitute telephone consultation; 14 (13.6%) said that a telephone consultation was not the best option, whereas 89 (80.4%) would not have preferred a face-to-face consultation; 98 (95.1%) felt that the telephone consultation was useful to them. CONCLUSIONS: A minority of planned face-to-face consultations was substituted by telephone consultations during the COVID-19 pandemic lockdown. Families were satisfied with substitute telephone consultations. FUNDING: none. TRIAL REGISTRATION: not relevant.

Anti-inflammatory treatment of asthma: differentiation and trial-and-error.

UNLABELLED: The relative lack of evidence for anti-inflammatory treatment of some phenotypes of asthma in children has been highlighted in recent guidelines and consensus reports specifically aiming at the paediatric population. Consequently, we are left with a need for defining treatment strategies in the clinical setting. The decision to initiate antiinflammatory treatment should be based on assessments of the individual child's age, the type of asthma, severity, heredity and atopic condition, adherence factors and sensitivity to systemic adverse effects of treatment options. Inhaled corticosteroids are potent anti-inflammatory agents that are effective in the whole spectrum of asthma in school age children. In toddlers with viral wheeze and in children with mild asthma oral leukotriene receptor antagonists or inhaled corticosteroids may be given on a trial-and-error basis. CONCLUSION: To treat all children with asthma equally effectively from infancy through adolescence does not mean that they should be treated identically and in some types of asthma a trial-and-error approach may be warranted.

Questionnaire about the risk of growth suppression of inhaled corticosteroids.

BACKGROUND: Inhaled corticosteroids are associated with a risk of growth suppression in children. The aim of the present study was to assess what children with asthma, lay people and paediatricians feel about the risk of growth suppression by inhaled corticosteroids. METHODS: A questionnaire was completed by seven populations consisting of 9-19 years old children and adolescents with asthma; 9-19 year olds with another chronic illness; healthy 9-19 year olds; parents to children with chronic conditions; parents to healthy schoolchildren; young adults; and paediatricians. RESULTS: A total of 1216 individuals completed the questionnaire. A total of 867 individuals (74.6%) would not worry about a risk of 1-year growth suppression in the range of 0.5-2 cm (range: 233 (63.3%) in parents to patients in a secondary referral centre to 59 (86.8%) in the group of paediatricians (χ 2 53.3, df 12, p<0.001; γ -223, error 0.042, p<0.001). A total of 745 individuals (64.3%) said that a loss in final height of 0.5-2 cm would not worry them (range: 34 (54.0%) in paediatricians to 119 (76.3%) in parents to healthy children (χ 2 49.5, df 12, p<0.001; γ -0.073, error 0.039, p=0.06). CONCLUSIONS: Most children with asthma, lay people and paediatricians do not worry about the risk of growth suppression of inhaled corticosteroids in the range up to 2 cm. Paediatricians worry less about the risk of 1-year growth suppression but more about final height suppression than children with asthma and other groups of children and adults. Paediatricians need to address the different concerns of some of their patients on this issue.

Molecular Allergy Diagnostics as an Adjunct to Conventional Diagnostics in a Secondary Pediatric Referral Center.

BACKGROUND: Several compositions for determination of specific molecular components in allergens have recently been patented. The role of Molecular Allergy (MA) diagnostics in suspected IgE mediated allergic conditions is currently debated. Guideline reports have concluded that population- based studies involving evaluation of the usefulness of MA diagnostics are needed. OBJECTIVE: To evaluate the usefulness of MA diagnostics in a secondary pediatric referral center. METHODS: A total of 961 children and adolescents aged 0.2-18.8 (mean 7.0) years was included in a prospective observational survey. Inclusion criterion was a suspected diagnosis of an IgE mediated condition based on history and clinical symptoms and signs. If a specific diagnosis could not be reached from conventional investigations suspected peanut allergy, birch pollen allergy and associated crossreactivity, insect allergy and triggering allergens for specific immunotherapy were assessed by MA diagnostics. RESULTS: Based on conventional work-up a diagnostic conclusion was established in 946 patients (98.4%). MA diagnostics were performed in 15 individuals (1.6%), 7 girls and 8 boys aged 3.2 to 17.8 (mean 10.6) years. In 8 cases a specific diagnosis was established based on MA diagnostics; in 7 cases MA diagnostics could not improve diagnosis. MA were most frequently (N = 7 (14%)) used in children with peanut allergy (N = 50). CONCLUSION: Most patients in a secondary pediatric referral center with suspected IgE mediated allergy can be managed by conventional diagnostic methods. MA diagnostics may be useful in small and selected subgroups as in patients with suspected peanut allergy, however, may not be helpful in all cases.

Differential effects of text message reminders on non-attendance and late cancellations in a paediatric outpatient clinic.

INTRODUCTION: SMS text appointment reminders reduce non-attendance rates in outpatient paediatric settings. The potential effect on late cancellation rates, however, has not been assessed. The aim of the present study was to assess if SMS text messaging reminders affect non-attendance and late cancellation rates in a secondary paediatric outpatient centre. METHODS: Non-attendances and late cancellations in children and adolescents aged 0-19 years of age were recorded prospectively during a year before and after the introduction of automatic SMS text messaging reminders. In a telephone interview, the families of late-cancelling patients were asked about the reasons for their cancellation. RESULTS: During the year before the introduction of SMS reminders, the clinic had 4,556 scheduled appointments in 1,466 patients (878 boys (59.9%) and 588 girls (40.1%); the year after the introduction, the clinic had 4,464 scheduled appointments in 1,424 patients (828 boys (58.1%) and 579 girls (41.9%). Before the introduction, 163 (4.3%) non-attendances and 162 (3.5%) late cancellations were recorded; after the introduction, 67 (1.5%) (p < 0.001) non-attendances and 177 (4.0%) (p = 0.28) late cancellations were recorded. During the no-SMS and SMS period, a total of 85 (52.5%) and 115 (65%) (p = 0.26), late cancelling families, respectively, said that that they had forgotten the appointment and could not manage to visit. CONCLUSIONS: SMS text reminders only improved the non-attendance rate; they did not influence the late cancellation rate. Most late cancellations were explained by forgetfulness. FUNDING: none TRIAL REGISTRATION: not relevant.

Suppressive effects of topical mometasone furoate and tacrolimus on skin prick testing in children.

Skin prick tests were performed in 12 children with atopic eczema before and after 2 weeks of treatment with topical mometasone furoate and tacrolimus. Both treatments significantly suppressed the allergen wheal size. Mometasone furoate reduced the histamine wheal size as well. Skin prick testing in children treated with topical glucocorticoids or tacrolimus is associated with a risk of false-negative test results.

Non-attendance in a secondary paediatric referral centre.

INTRODUCTION: Non-attendance in outpatient clinics may be associated with risks to patients' health, disturb the management of clinics and cause a waste of healthcare resources. The aim of the present study was to measure the non-attendance rate in a secondary paediatric outpatient centre and to assess reasons for non-attendance. METHODS: Non-attendance in children and adolescents aged 0-19 years were recorded prospectively during a year. In a telephone interview, the families of non-attending patients were asked about their reasons for non-attending. RESULTS: The number of scheduled attendances in 1,466 patients was 4,566. A total of 196 non-attendances (4.3%) were recorded in 167 patients (11.4%); 129 were boys (77.2%), 38 girls (22.8%). Patients aged 10-19 years had a higher frequency of non-attendance than patients in the 0-9-year age group (16% (115/715) versus 7% (52/751), respectively, p < 0.001). A total of 110 families (65.9%) stated that the reason for their non-attendance was that they had forgotten the appointment; 19 (11.4%) said that the family had decided not to show up because they had considered that their child had recovered. CONCLUSIONS: The non-attendance rate in the secondary paediatric referral centre studied was low. The majority of non-attendance may be explained by forgetfulness. FUNDING: none. TRIAL REGISTRATION: not relevant.

A Pilot Study of the Normative Range of Overnight Urinary Free Cortisol Corrected for Creatinine in Children.

BACKGROUND: For more than a decade, urinary free cortisol corrected for creatinine (OUFCC) has been used to assess the systemic bioactivity of inhaled corticosteroids in children with asthma. Paediatric normative ranges, however, have not been established. The aim of the present study was to define a preliminary range for OUFCC in Tanner stage 1 children. METHODS: A post hoc analysis was performed of 26 Tanner stage one children (aged 5-11 years) with mild asthma only requiring prn (pro re nata) treatment with short-acting ß2-agonists, who participated in a 3-way cross-over knemometry study. The study comprised a run-in, two washout periods and three treatment periods (2 weeks each). Urine was collected at the end of each period. A normative range was derived using the 95% prediction interval for the geometric mean OUFCC, calculated from run-in and washout periods. RESULTS: Twenty-six children contributed 41 OUFCC values. The geometric mean OUFCC was 9.0 nmol/mmol (95% PI: 3.6, 22.7 nmol/mmol). CONCLUSIONS: The OUFCC preliminary normative range was 3.6 to 22.7 nmol/mmol in Tanner stage one children. A larger study in healthy children is warranted to confirm these findings and to assess potential differences in OUFCC across developmental stages and age groups, and by gender and race. EUDRACT NUMBER: 2013-004719-32, CLINICALTRIALS. GOV IDENTIFIER: NCT02063139.

Prednisolone Effects on Urine Cross-Linked N-Telopeptides of Type I Collagen (Ntx) Diurnal Rhythms in Children.

BACKGROUND: Recently, methods for mimicking endogenous cortisol rhythms hereby potentially reducing the risk of systemic adverse effects of exogenous corticosteroids have been patented. Methods for sensitive detection of adverse effects on bone turnover of various doses, administration routes and regimens of exogenous corticosteroids have been patented. Urine cross-linked Ntelopeptides of Type I collagen (Ntx) have been established as a sensitive bone resorption marker and urine levels of Ntx have been found to exhibit a distinct diurnal rhythm. OBJECTIVE: To assess whether the timing of administration of prednisolone affects the diurnal rhythm of Ntx in urine. METHODS: Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV were studied in an open randomized 2-periods cross-over trial, with a 1-day run in, and two 4-day periods of 5mg prednisolone in the morning and in the evening, respectively, separated by a 3-week washout period. At run in and on the last day of each treatment period, the first sample of urine was collected from 24.00 to 08.00h in the morning of the day of investigation. Thereafter, urine was collected in 4~hour intervals until 24.00 and in another 08.00h interval from 24.00 to 08.00h. RESULTS: Compared to run in and morning prednisolone treatment urine Ntx levels were suppressed from 24.00 to 8.00h during treatment with prednisolone in the evening (P < 0.01 for both comparisons) and no statistically significant circadian rhythm was observed. During morning prednisolone treatment Ntx trough and peak levels occurred from 16.00 to 20.00 and 24.00 to 08.00h, respectively, and the Ntx levels were significantly reduced from 12.00 to 20.00h as compared to run in (P < 0.005) and prednisolone treatment in the evening (P < 0.01). CONCLUSIONS: Depending on the time of administration, prednisolone interferes with diurnal rhythms in urine Ntx.

Gender differences of oligomers and total adiponectin during puberty: a cross-sectional study of 859 Danish school children.

CONTEXT: Pubertal stages have been shown to influence total adiponectin (ADPN) levels. Furthermore, testosterone has been shown to alter the isomer distribution of ADPN. OBJECTIVE: The goal of this study was to investigate whether pubertal stages and testosterone levels influenced total serum ADPN levels and the distribution of ADPN isomers. DESIGN: This is a cross-sectional study. PATIENTS: The study included 859 children and adolescents (396 males) aged 6-20 yr. MAIN OUTCOME MEASURES: Total ADPN and ADPN isomers were measured using a validated in-house immunofluorometric assay. Fractioning of the ADPN into the three major molecular fractions was performed in representative subgroups of pre- and postpubertal males and females (n = 40, 10 in each group) using a validated fast protein liquid chromatography method. RESULTS: Total ADPN levels before puberty were 13.4 (11.1-15.9) mg/liter (median and interquartile range) and 14.7 (12.3-18.1) mg/liter (P = not significant), in males and females, respectively. After puberty, ADPN levels were significantly reduced in males, 9.7 (8.2-12.0) mg/liter but remained unchanged in females, 12.1 (9.7-15.3) mg/liter (P < 0.0001). Concomitantly, a reduction was seen in the ratio of high-molecular-weight (HMW) isomers to total ADPN (HMW ratio) when comparing prepubertal and postpubertal males. Also, postpubertal males had lower HMW ratios than corresponding females (P = 0.038). Finally, a negative correlation was seen between HMW ratio and testosterone (r = -0.430, P = 0.007). CONCLUSION: Serum total ADPN levels decrease through puberty in males. Also, a reduced HMW ratio is seen in males at the onset of puberty. We speculate that the suppression of HMW ADPN may be caused by testosterone.

A 2-week, crossover study to investigate the effect of fluticasone furoate nasal spray on short-term growth in children with allergic rhinitis.

BACKGROUND: It is essential to assess potential growth effects of any newly developed corticosteroid. Fluticasone furoate is a recently approved, enhanced- affinity intranasal corticosteroid with low systemic bioavailability and proven efficacy in treating allergic rhinitis. OBJECTIVE: The aim of the current study was to assess whether treatment with fluticasone furoate nasal spray affected the short-term lower-leg growth rate in children with allergic rhinitis. METHODS: Prepubertal children with seasonal or perennial allergic rhinitis of at least 1 year's duration were included in this single-center, randomized, double-blind, placebo-controlled, crossover study. The study consisted of 4 periods, each of 2 weeks' duration screening, then 2 treatment periods separated by a washout). Study medications were fluticasone furoate nasal spray 110 microg and placebo nasal spray, both administered QD in the morning. The primary end point, lower-leg growth rate (measured in millimeters per week), was assessed by knemometry. Adverse events were also assessed. RESULTS: Fifty-eight patients were randomized to the study and comprised the intent-to-treat (ITT) population (mean [SD] age, 9.1 [1.4] years; 39 males, 19 females). Five patients were excluded from the ITT group due to protocol violations; thus, 53 patients (mean [SD] age, 9.0 [1.4] years; 35 males, 18 females) comprised the growth population (a de facto per-protocol group). In the growth population, the adjusted mean lower-leg growth rate was 0.40 and 0.42 mm/wk with fluticasone furoate and placebo, respectively. The difference in adjusted mean lower-leg growth rate between fluticasone furoate and placebo was -0.016 mm/wk (95% CI, -0.13 to 0.10). Fluticasone furoate was noninferior to placebo, as the lower boundary of the 95% CI was above the prespecified noninferiority margin of -0.20 mm/wk. These results were supported by the ITT analysis. Fluticasone furoate nasal spray was well tolerated and had an adverse-event profile similar to that of placebo nasal spray. Nasopharyngitis (placebo, 4; fluticasone furoate, 1) and headache (placebo, 3; fluticasone furoate, 1) were the most frequent adverse events during the treatment periods. CONCLUSION: In this study, fluticasone furoate nasal spray 110 microg QD for 2 weeks had no effect on lower-leg growth rate in these prepubertal children with allergic rhinitis.

Placebo-controlled study of montelukast and budesonide on short-term growth in prepubertal asthmatic children.

BACKGROUND: Inhaled corticosteroids and anti-leukotriene agents are widely used in the treatment of pediatric asthma. Although data on the effect of corticosteroids on growth are available, there are few such data on anti-leukotriene agents. The aim of this study was to assess the influence of montelukast on short-term lower leg growth rate (LLGR) in prepubertal children with asthma. METHODS: Forty-two boys (6- to 12-year old) and 29 girls (6- to 11-year old) with mild asthma were randomized to 1 of 2 crossover arms, with two treatment sequences per arm: montelukast 5 mg once daily/placebo or inhaled dry powder budesonide 200 microg twice daily/placebo. Budesonide was used as a positive control to ensure that the method was sensitive enough to detect a suppression of LLGR. The 3-week double-blind treatment period was followed by a 3-week washout. Primary outcome was LLGR over the 3-week treatment, measured by knemometry. RESULTS: Ninety-four percent of patients completed the study. Mean LLGR was similar between patients receiving montelukast and placebo treatments: mean difference, -0.02 mm/week [95% confidence interval -0.14, 0.11]. Mean LLGR in patients receiving budesonide was significantly less than for those receiving placebo (difference of -0.16 mm/week [-0.25, -0.06], P = 0.002). Mean LLGR was similar for patients taking placebo in the two arms (0.43 and 0.44 mm/week). CONCLUSION: Montelukast 5 mg did not significantly affect short-term LLGR in prepubertal children.