Use Of Inhaled Corticosteroids In Children Research Articles

Measurement of exhaled nitric oxide concentration in asthma: a systematic review and economic evaluation of NIOX MINO, NIOX VERO and NObreath.

High fractions of exhaled nitric oxide (FeNO) in the breath of patients with symptoms of asthma are correlated with high levels of eosinophils and indicate that a patient is likely to respond to inhaled corticosteroids. This may have a role in the diagnosis and management of asthma. To assess the diagnostic accuracy, clinical effectiveness and cost-effectiveness of the hand-held electrochemical devices NIOX MINO(®) (Aerocrine, Solna, Sweden), NIOX VERO(®) (Aerocrine) and NObreath(®) (Bedfont Scientific, Maidstone, UK) for the diagnosis and management of asthma. Systematic searches were carried out between March 2013 and April 2013 from database inception. Databases searched included MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Science Citation Index Expanded and Conference Proceedings Citation Index - Science. Trial registers such as ClinicalTrials.gov and the metaRegister of Controlled Trials were also searched in March 2013. All searches were updated in September 2013. A rapid review was conducted to assess the equivalence of hand-held and chemiluminescent FeNO monitors. Systematic reviews of diagnostic accuracy and management efficacy were conducted. A systematic review of economic analyses was also conducted and two de novo health economic models were developed. All three reviews were undertaken according to robust high-quality methodology. The rapid review (27 studies) found varying levels of agreement between monitors (Bland-Altman 95% limits of agreement up to ±10 parts per billion), with better agreement at lower FeNO values. Correlation was good (generally r > 0.9). The diagnostic accuracy review identified 22 studies in adults (all ages) and four in children. No studies used NObreath or NIOX VERO and seven used NIOX MINO. Estimates of diagnostic accuracy varied widely. FeNO used in combination with another test altered diagnostic accuracy only slightly. High levels of heterogeneity precluded meta-analysis. Limited observations included that FeNO may be more reliable and useful as a rule-in than as a rule-out test; lower cut-off values in children and in smokers may be appropriate; and FeNO may be less reliable in the elderly. The management review identified five randomised controlled trials in adults, one in pregnant asthmatics and seven in children. Despite clinical heterogeneity, exacerbation rates were lower in all studies but not generally statistically significantly so. Effects on inhaled corticosteroid (ICS) use were inconsistent, possibly because of differences in management protocols, differential effectiveness in adults and children and differences in population severity. One UK diagnostic model and one management model were identified. Aerocrine also submitted diagnostic and management models. All had significant limitations including short time horizons and the selective use of efficacy evidence. The de novo diagnostic model suggested that the expected difference in quality-adjusted life-year (QALY) gains between diagnostic options is likely to be very small. Airway hyper-responsiveness by methacholine challenge test is expected to produce the greatest QALY gain but with an expected incremental cost-effectiveness ratio (ICER) compared with FeNO (NObreath) in combination with bronchodilator reversibility of £1.125M per QALY gained. All remaining options are expected to be dominated. The de novo management model indicates that the ICER of guidelines plus FeNO monitoring using NObreath compared with guidelines alone in children is expected to be approximately £45,200 per QALY gained. Within the adult subgroup, FeNO monitoring using NObreath compared with guidelines alone is expected to have an ICER of approximately £2100 per QALY gained. The results are particularly sensitive to assumptions regarding changes in ICS use over time, the number of nurse visits for FeNO monitoring and duration of effect. Limitations of the evidence base impose considerable uncertainty on all analyses. Equivalence of devices was assumed but not assured. Evidence for diagnosis is difficult to interpret in the context of inserting FeNO monitoring into a diagnostic pathway. Evidence for management is also inconclusive, but largely consistent with FeNO monitoring resulting in fewer exacerbations, with a small or zero reduction in ICS use in adults and a possible increased ICS use in children or patients with more severe asthma. It is unclear which specific management protocol is likely to be most effective. The economic analysis indicates that FeNO monitoring could have value in diagnostic and management settings. The diagnostic model indicates that FeNO monitoring plus bronchodilator reversibility dominates many other diagnostic tests. FeNO-guided management has the potential to be cost-effective, although this is largely dependent on the duration of effect. The conclusions drawn from both models require strong technical value judgements with respect to several aspects of the decision problem in which little or no empirical evidence exists. There are many potential directions for further work, including investigations into which management protocol is best and long-term follow-up in both diagnosis and management studies. This study is registered as PROSPERO CRD42013004149. The National Institute for Health Research Health Technology Assessment programme.

P233 Long-term Impact Of Inhaled Corticosteroids On Bone Mineral Density And Fracture Risk In Patients With Asthma: Systematic Review And Meta-analysis

Background A recent meta-analysis of 16 randomised controlled trials (RCTs) and 7 observational studies demonstrated a modest but statistically significant increase in fracture risk with inhaled corticosteroid (ICS) use in chronic obstructive pulmonary disease. However, it is not clear whether ICS use has similar skeletal adverse effects in patients with asthma. We aimed to evaluate the association between ICS and fractures and changes in bone mineral density when used for >12 months in asthma. Methods We initially searched MEDLINE and EMBASE in July 2013, and performed an updated PubMed search in June 2014. We used a combination of search terms involving drug name and adverse effects of interest, and we also hand-searched reference lists of existing systematic reviews and trial reports. We selected RCTs and controlled observational studies of any ICS vs non-ICS control treatment for asthma (at least 52 weeks duration). Meta-analysis of odds ratios was conducted using RevMan 5.3 with the primary outcome measure being fracture events. We also analysed mean differences in bone mineral density (gram per cm squared) using inverse variance method. Heterogeneity was assessed using the I2 statistic. Results We selected nine RCTs and 11 observational studies for the meta-analysis. There was no significant association between ICS and fractures in children in one RCT, or in a pooled analysis of two observational studies, (OR 1.02, 95% CI 0.94–1.10). No significant fracture risk in adults was reported in 4 observational studies (pooled OR 1.09, 95% CI 0.45–2.62). Meta-analysis of bone mineral density at the lumbar spine did not show significant reductions with ICS use in children (three RCTs and three observational studies), or in adults (three RCTs and four observational studies). Similarly, meta-analysis of bone mineral density at the neck of femur in adults did not demonstrate significant reductions compared to control (three RCTs and four observational studies). Conclusion In our systematic review of 20 studies, use of ICS for >12 months in patients with asthma was not associated with statistically significant adverse effects on bone mineral density or fractures.

Does Use of Inhaled Corticosteroid for Management of Asthma in Children Make Them Shorter Adults?

The purpose of this review is to discuss the effect of daily inhaled corticosteroids (ICSs) on the height of children with asthma. The effect of ICSs on growth and height is dependent on the dose and the therapeutic index of the ICS; however, the effect on final adult height was not clear until recently. New data suggest that if growth suppression occurs with the use of ICSs in children, it is sustained, but not cumulative over the years. The observed reduction in the final adult height is small and does not outweigh the benefits of ICSs, and the growth effect may be minimized by use of newer ICSs and other approaches for management of asthma in children with mild to moderate asthma.

Inhaled corticosteroids for subacute cough in children.

Cough is the most common symptom presenting to primary healthcare services. Cough in children is associated with significant morbidity for both children and their parents. While inhaled corticosteroids (ICS) can potentially reduce cough associated with airway inflammation and airway hyper-reactivity, use of ICS in children is not without potential adverse effects. Therefore, it would be beneficial to clinical practice to evaluate the evidence for the efficacy of ICS in reducing the severity of cough in children with subacute cough (defined as cough duration of two to four weeks) systematically. To evaluate the efficacy of ICS in reducing the severity of cough in children with subacute cough. The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles were searched. The latest searches were performed in November 2011. All randomised controlled trials (RCTs) comparing ICS with a control group in children with subacute cough were considered for inclusion. Search results were reviewed against pre-determined criteria for inclusion. Two sets of review authors independently selected, extracted and assessed the data for inclusion. Study authors were contacted for further information where required. Data were analysed as 'intention to treat'. The search identified 1178 potentially relevant titles; however, there were no published studies that were specifically designed to answer this question. Two studies met criteria for inclusion in the review and 98 children were included in the meta-analysis. There was no significant difference between groups in the proportion of children 'not cured' at follow-up (primary outcome measure), with a pooled odds ratio (OR) of 0.61 (95% confidence interval (CI) 0.24 to 1.55). However, the included studies were limited in their ability to answer the review question by the fact that all participants were infants, post acute bronchiolitis illness, and cough duration at the start of study medication was ill-defined. There is currently no evidence to support the use of ICS for treatment of subacute cough in children. However, this systematic review is limited by the small number of studies available for analysis and the size, quality and design of these studies. Further well-designed RCTs are required to support or refute the efficacy of treatment with ICS in children with subacute cough.

Breathe easy: Updates on asthma management

Several asthma trials have been published in recent months evaluating key treatments such as long-acting beta-2 agonists (LABAs), inhaled corticosteroids (ICSs), and tiotropium (Spiriva— oehringer Ingelheim, Pfizer). Studies have questioned the recommendation to discontinue LABAs; compared the efficacy of intermittent, symptom-based ICS use with scheduled inhalations in adults with mild to moderate persistent asthma; evaluated the effects of ICS use in children on their adult height; and evaluated the role of tiotropium in the management of uncontrolled asthma.

High agreement between parental reported inhaled corticosteroid use and pharmacy prescription data

This study was conducted to assess the validity of parental reported use of inhaled corticosteroids (ICS) in children. ICS users were identified within the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and the PIAMA pharmacy sub-cohort which is nested within the PIAMA study. Complete medication histories were available for the first 8 years of life for children within the PIAMA pharmacy sub-cohort. Parental reported ICS use was measured by using data from questionnaires. ICS use in the pharmacy records was determined by using the Anatomical Therapeutic Chemical (ATC) codes. The proportion of overall agreement and kappa statistics with their corresponding 95% confidence intervals were calculated to quantify agreement between self-reported medication use and pharmacy prescription data. At all ages overall agreement was very high (>97%) and Cohen's kappa's ranged from 0.80 to 0.88 which also reflects excellent agreement between parental reported use of ICS and pharmacy prescription data. Our finding suggests that parental report of medication use is a reliable source of data to asses ICS use in children. The questionnaire-based medication data collected within the PIAMA study can be used to study asthma medication use in a large group of children.

Inhaled corticosteroids in childhood asthma: growing concerns.

Inhaled corticosteroids (ICS) are an established treatment for asthma in childhood. Recent data bring to light growing concerns that ICS may have significant effects on growth velocity in children. The Food and Drug Administration (FDA) recently convened a joint meeting to review these data, and to release new class labelling for ICS that notes this potential adverse effect. Additional concerns regarding ICS are also discussed, including other potential adverse effects, difficulty of use, noncompliance, and patient and parental concerns with the safety of ICS. The aim of this article is as follows: to describe the rationale for the use of ICS in children with asthma; to delineate the association of ICS with potential growth suppression in children; to discuss recent FDA class labelling for use of ICS in children; to describe other potential long term effects of ICS in children; and to detail compliance issues in children with asthma treated with ICS.