fluticasone and Growth-Disorders

Adverse events (AEs) associated with short-term corticosteroid use for respiratory conditions in young children.. Systematic review of primary studies.. Medline, Cochrane CENTRAL, Embase and regulatory agencies were searched September 2014; search was updated in 2017.. Children <6 years with acute respiratory condition, given inhaled (high-dose) or systemic corticosteroids up to 14 days.. One reviewer extracted with another reviewer verifying data. Study selection and methodological quality (McHarm scale) involved duplicate independent reviews. We extracted AEs reported by study authors and used a categorisation model by organ systems. Meta-analyses used Peto ORs (pORs) and DerSimonian Laird inverse variance method utilising Mantel-Haenszel Q statistic, with 95% CI. Subgroup analyses were conducted for respiratory condition and dose.. Eighty-five studies (11 505 children) were included; 68 were randomised trials. Methodological quality was poor overall due to lack of assessment and inadequate reporting of AEs. Meta-analysis (six studies; n=1373) found fewer cases of vomiting comparing oral dexamethasone with prednisone (pOR 0.29, 95% CI 0.17 to 0.48; I. Evidence suggests that short-term high-dose inhaled or systemic corticosteroids use is not associated with an increase in AEs across organ systems. Uncertainties remain, particularly for recurrent use and growth outcomes, due to low study quality, poor reporting and imprecision.

Topics: Acute Disease; Administration, Inhalation; Administration, Intravenous; Administration, Oral; Adrenal Cortex Hormones; Asthma; Bronchiolitis, Viral; Child, Preschool; Croup; Dexamethasone; Fluticasone; Glucocorticoids; Growth Disorders; Headache; Humans; Infant; Injections, Intramuscular; Pneumonia; Prednisone; Respiratory Sounds; Respiratory Tract Diseases; Respiratory Tract Infections; Tremor; Vomiting

Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth.. To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment).. We searched the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO; we handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases to look for potential relevant unpublished studies. The literature search was conducted in January 2014.. Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma.. Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child.. We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) [corrected] given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%.Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period.Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi² = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated li. Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Patient Dropouts; Pregnadienediols; Pregnenediones

Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians.. To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma.. We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014.. Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma.. Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation.. Among 22 eligible trials, 17 group comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X(2) = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, bone mass index and skeletal maturation reported with low quality of evidence due to imprecision.. In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Pregnadienediols; Pregnenediones; Randomized Controlled Trials as Topic

Fear of growth retardation may account for the underuse of inhaled corticosteroids in children with asthma, despite compelling evidence of their effectiveness. This fear may be reduced with newer agents with lower oral bioavailability if their theoretical advantage of fewer systemic adverse effects than the standard treatment of inhaled beclometasone is realized in practice. This review aims to determine if one of the newer agents, inhaled fluticasone, has less effect on the growth of pre-pubertal asthmatic children than inhaled beclometasone. The outcome measure was growth velocity. Two double blind, randomized controlled trials were identified. In one of the studies the mean growth velocity in the fluticasone group was 0.7 cm/year greater than in the beclometasone group. In the second, smaller study the mean growth velocity in the fluticasone group was 0.8 cm/year greater. There is therefore some evidence that fluticasone has less (if any) adverse effect on growth.

Topics: Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Fluticasone; Growth Disorders; Humans

Inhaled corticosteroids (ICS) reduce growth during the first year of treatment, but this growth suppressing effect does not continue during further treatment. Decreasing adherence may play a role in explaining this. The aim of this study was to examine the relationship between cumulative real exposure (with objectively assessed adherence) to ICS and height growth in children with asthma.. We investigated 99 prepubertal children with asthma, 2-13 years of age, who had been using ICS in guideline-recommended dosages for ≥3 months, and continued to do so during 1-year follow-up. ICS adherence was assessed by electronic monitoring devices, allowing calculation of true cumulative exposure to ICS. We analysed the relationship between cumulative ICS dose and height growth velocity (assessed as change in height SD score) over 1 year.. Median (IQR) adherence over 1 year was 84 (68-92) %. Mean cumulative fluticasone dose was 64.6 (SD, 27.8) mg, reflecting a daily dose of 167 (SD, 7) µg. The negative correlation between cumulative ICS dose and height growth velocity (r=-0.266; p=0.008) became non-significant after adjustment for age and sex in a multiple regression model (adjusted r=-0.188; p=0.066).. One year of ICS treatment in guideline-recommended dosages with high adherence did not result in significant or relevant growth suppression. Unaffected growth can be maintained for at least 1 year in children with asthma during ICS treatment with high adherence.

Topics: Administration, Inhalation; Adolescent; Anthropometry; Asthma; Body Height; Bronchodilator Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Fluticasone; Glucocorticoids; Growth Disorders; Humans; Male; Medication Adherence; Practice Guidelines as Topic

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Corticosterone; Fluticasone; Glucocorticoids; Growth Disorders; Humans; Infant; Male

Topics: Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Fluticasone; Growth Disorders; Humans

Topics: Administration, Intranasal; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asthma; Child, Preschool; Confidence Intervals; Data Interpretation, Statistical; Fluticasone; Growth; Growth Disorders; Humans

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Asthma; Bone and Bones; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Fluticasone; Growth Disorders; Humans; Male; Risk Assessment

We report the case of an atopic patient aged 16 with a perannual asthma. He has been treated since the age of 4 with inhaled corticosteroïds. His growth was regular until he was 14 when beclomethasone was replaced by fluticasone (both administered by pressurized inhaler) due to adrenal suppression. Growth inhibiting effects of different inhaled corticosteroids are discussed focusing mainly on their effect on collagen synthesis.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Collagen; Fluticasone; Growth Disorders; Humans; Male

Fluticasone propionate was introduced in 1993 in the UK as a potentially safer inhaled corticosteroid than those already in use. The efficacy and safety of fluticasone has been established at recommended doses of 200 micrograms/day, but not at higher doses that are often used.. Growth retardation was observed in six severely asthmatic children after introduction of high-dose fluticasone propionate treatment (dry powder). Assessment of cortisol response was by insulin-induced hypoglycaemia in three cases, by short tetracosactrin test in two, and by low-dose tetracosactrin and 24-hour urinary cortisol/creatinine ratio in one.. Six children with growth retardation noted after treatment with high-dose fluticasone propionate were found to have adrenal suppression. In one case the growth rate and cortisol response returned to normal 9 months after the fluticasone dose was reduced to 500 micrograms/day.. When high doses of fluticasone propionate are used, growth may be retarded and adrenal suppression may occur.

Topics: Administration, Topical; Adrenal Cortex; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Depression, Chemical; Female; Fluticasone; Glucocorticoids; Growth Disorders; Humans; Male

Topics: Administration, Topical; Adverse Drug Reaction Reporting Systems; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Fluticasone; Glucocorticoids; Growth Disorders; Humans; Pharmacists; Truth Disclosure

Topics: Administration, Topical; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Fluticasone; Glucocorticoids; Growth Disorders; Humans

Topics: Administration, Topical; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Fluticasone; Glucocorticoids; Growth Disorders; Humans