Inhaled corticosteroids in children: use and effects of early treatment on asthma and lung function. Prevalence of asthma and the impact of severity in early life on later asthma in childhood

Introduction: The role of inhaled corticosterids (ICS) on disease progression in asthmatic children is not yet clear. Aims: This study was conducted (i) to determine how often ICS were used for treatment of obstructive airways disease (OAD) in early childhood; (ii) to assess if ICS treatment had an effect on lung function in young children with recurrent bronchial obstruction (rBO); (iii) to explore if early ICS treatment in children with OAD during the first 2 years of life can modify occurrence of current asthma in school children; (iv) to define a severity score for severity of OAD during the first 2 years of life and assess if the severity score can be used to predict asthma in school children; and (v) to investigate the prevalence of asthma in children in an urban population. Subjects and Methods: The present study is part of a 10‐year follow‐up of children in the prospective birth cohort (n = 3754), the Environment and Childhood Asthma study in Oslo. For aim 1, all children from the entire cohort who had completed follow‐up questionnaires as well as all children defined with rBO were assessed. For aim 2, 54 children with rBO (with and without ICS treatment) and 15 controls with tidal flow volume measurements upon presentation of the disease and 2 years of age were studied. For aims 3 and 4, 459 subjects (with and without rBO at 2 years of age) from the case control study who attended 10‐year follow‐up were studied. For aim 5, the 616 of 803 subjects who had lung function measurements performed after birth were reinvestigated at the age of 10 years. Results: A total of 2.1% of all the children in the cohort and 21% of children with rBO had received ICS treatment by 2 years of age. The mean difference of change in baseline tidal breathing (the ratio of time to peak expiratory flow to total expiratory time) was significantly higher in the ICS‐treated group only by 2 years of age and correlated significantly with duration of ICS treatment. However, in rBO children, the use of ICS treatment before 2 years of age was not associated with reduced risk of current asthma at 10 years of age. The risk (odds ratio, 95% confidence interval) of current asthma among rBO subjects with a severity score above five was 20.2, 9.9–41.3 compared to controls. In 10‐year‐old children, the lifetime prevalence of asthma was 20.2%. Conclusions: One‐fifth of young children with recurrent bronchial obstruction had received inhaled corticosteroids by age 2 years. Lung function appeared to improve in children using ICS from the start of symptoms of OAD until 2 years of age, mostly in children with the longest duration of treatment. However, use of ICS during the first 2 years of life in children with OAD did not reduce asthma present 8 years later. A scoring system based on severity and frequency of OAD during the first 2 years of life predicted current asthma at 10 years of age. One in five 10‐year‐old children in the city of Oslo at some time had asthma.     

Effect of inhaled steroids on lung function in young children: a cohort study.

The objectives of the present study were to determine the use of inhaled corticosteroids (ICS) for treating recurrent bronchial obstruction (rBO) in young children up to 2 yrs of age and to assess possible modifying effects of ICS on lung function in young children with rBO. From an observational, noninterventional birth cohort of 3,754 newborn children (3,697 with complete questionnaire data by 2 yrs of age), 306 children with documented rBO by age 2 yrs (cases) were identified along with 306 matched controls. Two tidal flow/volume measurements were taken, one at presentation of disease (children were steroid naive) and one at 2 yrs of age (mean age 11.2 and 25.6 months, respectively), from: 21 cases who subsequently received ICS (ICS+); 33 who did not (ICS-); and in 15 controls. The mean +/- SD duration of ICS treatment was 10.3 +/- 6.5 months. The main outcomes were treatment with ICS and baseline ratio of time to peak expiratory flow/total expiratory time (tPTEF/tE). From the entire cohort, 77 children (2.1%) and 21% of children with rBO had received ICS by 2 yrs of age. Baseline tPTEF/tE was significantly lower at the first visit only in ICS+ as compared to ICS- subjects, as well as in ICS+ and ICS- as compared to controls. The mean difference in baseline tPTEF/tE from first to second visit was borderline statistically significant in the ICS+ group only and correlated significantly with duration of ICS treatment. The present observational cohort study demonstrated that one-fifth of young children with recurrent bronchial obstruction had received inhaled corticosteroids. Early inhaled corticosteroid treatment improved lung function by age 2 yrs, mostly in those with the longest duration of treatment.     

Patient Education Provided to Asthmatic Children: A Historical Cohort Study of the Implementation of NIH Recommendations

NIH guidelines for treatment of childhood asthma emphasize educating both patients and family about avoiding triggers and providing information to support self-management of asthma. To determine the extent to which primary care providers had implemented these recommendations, we examined the patient education provided to a cohort of asthmatic children (n = 331) between January and December 1994.

During 1994 education of any type was documented for less than half the children. Provision of education was associated with asthma severity: An action plan for exacerbations was discussed with the majority with moderate or severe asthma (61%). Avoiding triggers (aOR: 2.38, 95% CI: 1.37-4.12) and treatment goals (aOR: 3.14, 95% CI: 1.46-6.75), were more likely to be discussed with children who were prescribed inhaled anti-inflammatory medication, after adjustment for asthma severity and age.

Limited implementation of the NIH recommendations by primary care providers in our study may have reduced their impact on the management of childhood asthma.     

A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children

BACKGROUND: Inhaled corticosteroids (ICS) may provide benefit in the therapy of acute asthma. The purpose of this study was to test the hypothesis that ICS are as effective as oral corticosteroids (OCS) in the management of acute childhood asthma. METHODS: A randomized, masked, placebo-controlled study was conducted in children aged 6 to 16 years seeking emergent care for an acute exacerbation of asthma. Patients were randomized into one of two groups: group 1 (OCS), oral prednisone, 2 mg/kg (maximum of 60 mg/d) for 7 days, and placebo pressurized metered-dose inhaler with valved holding chamber, four inhalations bid; and group 2 (ICS), flunisolide, four inhalations (1 mg) bid for 7 days, and daily placebo tablets. Spirometry (FEV(1)) was performed at baseline, day 3, and day 7 of the study. A symptom diary and twice-daily peak expiratory flow were recorded. RESULTS: A total of 58 subjects receiving ICS (n = 27) or OCS (n = 28) were enrolled. Baseline asthma severity, race, gender, and age were balanced between the two groups. chi(2) showed no significant difference in symptom severity between the two groups at any time during the study. FEV(1) percentage of predicted was lower in the ICS group on day 3 (65% vs 78%, p = 0.03) and on day 7 (77% vs 95%, p = 0.002). CONCLUSION: ICS were found to be useful in the management of acute asthma in children; however, spirometry data suggested a more rapid resolution of asthma with OCS.     

Asthma severity, psychiatric morbidity, and quality of life: correlation with inhaled corticosteroid dose.

OBJECTIVES: Psychiatric phenomena in asthma has been debated for some time. Inhaled corticosteroids (ICS) are a significant part of treatment. We attempted to quantify the prevalence of psychiatric morbidity relative to asthma severity, quality of life (QOL), and ICS dose. DATA SOURCES: Fifty asthmatic patients (18 > or = X < or =75 years) on ICS, attending an urban clinic had asthma and ICS dose stratified by symptom severity and preparation potency. Peak flow and forced expiratory volume in 1 second (FEV1) were measured. Patients completed general QOL and disease-specific QOL questionnaires, along with psychiatric rating scales. RESULTS: Patients (n = 50) clustered in the 40-59 year range (n = 27, 54%) and were predominantly female (n = 44, 88%) Hispanics (n = 30, 60%), with mild-moderate asthma (n = 18, 36%) and on low-dose ICS (n = 22, 44%). FEV1 ranged from 32 to 123 (mean 76.98, SE 3.01). Peak flow ranged from 210 to 590 (mean 407.83, SE 13.24). Prevalence of anxiety and depressive symptoms were higher than expected (Kendall's tau-c, n = 50, P < .01). Independently, high ICS dose and asthma severity correlated directly with all measures of psychiatric morbidity (Pearson's r0.781, P < .01). High ICS dose correlated inversely with SF-36 Mental Component Scale (Pearson's r0.681, P < .01) and directly with FEV1 and peak flow when age/sex adjusted (Spearman's rho: 0.660, P < .001). CONCLUSIONS: Psychiatric morbidity is more prevalent in this population and impacts negatively on QOL. Use of high-dose ICS benefited pulmonary function and "physical" QOL, yet may have negatively affected patients' mental well-being. Longitudinal follow-up, extension of sample size, and better study control would allow closer approximation of possible negative associations with ICS.     

Effect of aging on the relationship between asthma severity and bronchial hyperresponsiveness in children with asthma.

An association between asthma and bronchial hyperresponsiveness (BHR) has been demonstrated. It is possible that the relationship between asthma severity and BHR in children with asthma is different in infants and in adolescents. The aim of this study is therefore to evaluate the effect of aging on the relationship between the severity of asthma and BHR in children with asthma. We measured BHR in 386 subjects ranging from 2 to 20 years of age. The subjects consisted of 323 children with asthma (boys:girls = 193:130, mean age 9.7 years) and 63 age-matched controls (boys:girls = 25:38, mean age 8.2 years). BHR was measured using the methacholine inhalation challenge by measuring the transcutaneous oxygen pressure (tcPO2) in children less than 6 years of age (Dmin-PO2) and by measuring the respiratory resistance (Rrs) in children 6 years of age and older (Dmin-Rrs). Throughout the whole age range, both the Dmin-PO2 and Dmin-Rrs in each asthma severity group were higher than those in the controls. In the asthmatics aged 2-5 years, the Dmin-PO2 levels in the mild asthma group were higher than those in the moderate and severe asthma groups (p < 0.001, p < 0.001, respectively), and the Dmin-PO2 levels in the moderate asthma group were also higher than those in the severe asthma group. This tendency was also found in the age ranges of 6-9 years and 10-13 years. In the asthmatics aged 14-20 years, the Dmin-Rrs levels were not significantly different among the three groups. Taken together, these data show that aging has an effect on the relationship between the severity of asthma and BHR during childhood and that BHR may not be the sole determinant for the severity of asthma in adolescence.     

Antibiotic use in infancy and the risk of asthma in Mexican American children

Objective: This study examined the associations of antibiotic use in infancy with lifetime doctor-diagnosed asthma and current wheeze among Mexican American children. Methods: In a population-based, cross-sectional investigation, parents of 2023 children 4–18 years of age completed a questionnaire/interview addressing respiratory conditions, antibiotic use, and covariates. Results: In adjusted analyses, among children without history of ear infections in infancy, children who used antibiotics ≥3 times and 1–2 times were more likely to report doctor-diagnosed asthma compared with their peers who did not use antibiotics in infancy [adjusted odds ratio (aOR)?=?5.14, 95% confidence interval (CI): 2.88–9.17, and aOR?=?2.15, 95% CI: 1.26–3.69, respectively, p trend < 0.0001]. The respective aORs for current wheeze were 3.67 (95% CI: 1.95–6.89) and 1.63 (95% CI: 0.91–2.95). Antibiotic use in infancy was not associated with asthma or current wheeze in children who had ear infections in infancy. In additional analyses, antibiotic use in infancy was associated with asthma in children without parental history of asthma or allergies (aOR?=?2.73, 95% CI: 1.70–4.39) but not in those with parental history of asthma or allergies. Among Mexico-born participants born in rural areas, antibiotic use in infancy was associated with a seven-fold increase in risk of asthma (aOR?=?7.21, 95% CI: 1.46–35.65), while the association was non-significant in Mexico-born children born in urban areas in Mexico. Conclusions: Antibiotic use in infancy may increase the risk of asthma and wheezing, but these associations were limited to subgroups of children.     

A pilot randomized trial of school-based administration of inhaled corticosteroids for at-risk children with asthma

Objective: To investigate whether high adherence to inhaled corticosteroids (ICS) among disadvantaged urban public school children on public insurance with persistent asthma is achievable by having school nurses administer morning doses on each day that school is in session. Design/methods: This was a pilot prospective randomized clinical trial of home versus school nurse-administered ICS among children on Medicaid enrolled in grades K-8. The primary outcome was the proportion of expected morning doses of ICS given to the intervention group in school over the 60-day treatment period. Secondary outcomes included the relative proportions of expected doses (morning, evening, and total), asthma-related morbidity, quality of life, and health-care utilization. Results: A total of 46 patients were enrolled (mean age 8.21 ± 2.45; 56.5% male; 91.3% non-Hispanic, African-Americans), and follow-up data were available for 44/46 (95.7%) patients. The groups did not differ in age, gender, race/ethnicity, or asthma severity. The intervention group received 91.7% of expected morning doses of ICS at school over the 60-day treatment period (95% CI [87.7, 95.5]). Intervention patients reported significantly less functional limitation (42.9% vs. 73.9%, p = 0.04), adjustment to family life (23.8% vs. 56.5%, p = 0.03), and sleep loss (1.7 vs. 4.1 nights in last 2 weeks, p = 0.035) than control patients at the end of the 60-days study period. There were no differences in unscheduled health-care utilization by group. Conclusions: These pilot data suggest that school-based administration of ICS has the potential to achieve high adherence to morning doses of ICS on school days among urban, disadvantaged, and largely minority children with asthma.     

Relationship between Exhaled Nitric Oxide and Exposure to Low-Level Environmental Tobacco Smoke in Children with Asthma on Inhaled Corticosteroids

Objectives. The relationship between exhaled nitric oxide (FeNO) and asthma severity or control is inconsistent. Active smoking lowers FeNO, but the relationship between passive smoking and FeNO is less clear. Children may be exposed to low-level environmental tobacco smoke (ETS) or thirdhand smoke, even if parents avoid smoking in the presence of their children. Our hypothesis was that FeNO is lower in children with asthma exposed to low-level ETS when compared with those who are not exposed. Methods. Children with stable asthma, 8-18 years of age, on low- or medium-dose inhaled corticosteroids (ICS) were enrolled. Spirometry, Asthma Control Questionnaire (ACQ), FeNO, exhaled breath condensate pH (EBC pH), and EBC ammonia were compared between children with and without ETS exposure as determined by urinary cotinine. Results. Thirty-three subjects were enrolled, of which 10 (30%) had urinary cotinine levels ≥1 ng/ml. There were no significant differences between the two groups in age, sex, BMI percentile, atopy status, FEV(1), EBC pH, or EBC ammonia. Median ACQ was 0.29 (IQR: 0.22-0.57) for those with cotinine levels <1 ng/ml and 0.64 (IQR: 0.57-1.1) for those with cotinine levels of ≥1 ng/ml, p = .02. Median FeNO (ppb) was 23.9 (IQR: 15.2-34.5) for unexposed subjects and 9.6 (IQR: 5.1-15.8) for exposed subjects, p = .008. Conclusions: Children with asthma on low to medium doses of ICS and recent low-level ETS exposure have lower FeNO levels when compared with non-ETS-exposed subjects. Exposure to low-level ETS or thirdhand smoke may be an important variable to consider when interpreting FeNO as a biomarker for airway inflammation.     

Efficacy and safety of the combination fluticasone propionate plus salmeterol in asthmatic preschoolers: An observational study

Background: Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta₂-agonists (LABA) are one of the available additional therapies but their use has rarely been studied among children younger than 5 years. Objective: The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age. Methods: A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records. Results: The children had previously received short-acting β₂-agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean duration of therapy with FP/SA was 12.45 ± 9.14 months. After adjusting for age, gender, and duration of treatment, a 89% reduction was recorded in annual hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy, p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs. after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after: 6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous treatment carry-on effect was observed. No major drug-related side-effects occurred in the study group. Conclusions: Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.     

Geographic variation in inhaled corticosteroid use for children with persistent asthma in Medicaid

Objective: Geographic variation in the rates of inhaled corticosteroid (ICS) use for children with persistent asthma in Medicaid has been reported, but the source of this variation is unknown. The objective of this study was to quantify the geographic variation in ICS use for children with persistent asthma in Medicaid that remains after adjusting for the characteristics of children in an area. Methods: Data from the 2005–2007 Medicaid Analytic eXtract files were used. Frequent fills of short-acting beta₂-agonist (SABA) were used to identify children 5–18 years of age with persistent asthma across the United States. A child was considered to have used an ICS if the child initially filled an ICS following frequent SABA use. Areas were determined using published methods, and the unadjusted ICS rate and the area treatment ratio for ICS, which adjusted for demographic and clinical characteristics, were calculated for each area. Results: Of 15,917 children, 13% used an ICS. The median unadjusted ICS rate for all areas was 10% but ranged from 0% to 64%. ICS use was less than expected for more than half of the areas based on the characteristics of the children in the area, but use was nearly five times what was expected in some areas. Areas with higher than expected ICS use were found contiguous to areas with lower than expected use. Conclusions: Geographic variation in ICS not attributable to the demographic and clinical characteristics of the children in an area exists and could prove useful in the struggle to reduce asthma exacerbation rates.     

Adherence to montelukast versus inhaled corticosteroids in children with asthma

Our objective was to compare adherence to montelukast with adherence to inhaled corticosteroids (ICS) in children with persistent asthma. In this retrospective study, we obtained data from a computerized hospital pharmacy database and medical records on 14l patients, 3-18 years of age, who received care for asthma at a military medical center. For each patient, we collected fill/refill data from a consecutive 6-month period and calculated an adherence rate, i.e., (# doses filled/# doses prescribed) x 100. We then determined whether the patient had "good adherence" (adherence rate, > or =70%) or "very poor adherence" (adherence rate, <50%). Eighty-one children were prescribed montelukast, and 104 took ICS; 44 of these children took both. The majority of patients had mild or moderate persistent asthma. There was no significant difference between mean adherence rates: 71% (95% CI, 65-77%) for montelukast vs. 67% (95% CI, 61-73%) for ICS. Fifty-one percent of patients taking montelukast had good adherence, compared to 41% in the ICS group (P = 0.27). Nineteen percent of the montelukast group and 26% of the ICS group had very poor adherence (P = 0.31). Using pharmacy refill data, we found that children with asthma were no more likely to take montelukast than inhaled corticosteroids. Adherence to both medications was suboptimal, even in a system that provides free and easy access to medications.     

Global Initiative for Asthma Strategy 2021. Executive Summary and Rationale for Key Changes

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes.GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting β₂-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS–formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA.Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS–formoterol as the reliever at all steps: as needed only in Steps 1–2 (mild asthma), and with daily maintenance ICS–formoterol (maintenance-and-reliever therapy, “MART”) in Steps 3–5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS–long-acting β₂-agonist (Steps 3–5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6–11 years, new treatment options are added at Steps 3–4.Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.     

The therapy of pre‐school wheeze: Appropriate and fair?

The current study aimed to assess prevalence and distribution of use of asthma medication for wheeze in pre-school children in the community. We sent a postal questionnaire to the parents of a random population-based sample of 4,277 UK children aged 1-5 years; 3,410 participated (children of south Asian decent were deliberately over-represented). During the previous 12 months, 18% of the children were reported to have received bronchodilators, 8% inhaled corticosteroids (ICS) and 3% oral corticosteroids. Among current wheezers these proportions were 55%, 25%, and 12%, respectively. Use of ICS increased with reported severity of wheeze, but did not reach 60% even in the most severe category. In contrast, 42% of children receiving ICS reported no or very infrequent recent wheeze. Among children with the episodic viral wheeze phenotype, 17% received ICS compared with 40% among multiple-trigger wheezers. Use of ICS by current wheezers was less common in children of South Asian ethnicity and in girls. Although a high proportion of pre-school children in the community used asthma inhalers, treatment seemed to be insufficiently adjusted to severity or phenotype of wheeze, with relative under-treatment of severe wheeze with ICS, especially in girls and South Asian children, but apparent over-treatment of mild and episodic viral wheeze and chronic cough.     

Survival of COPD patients using inhaled corticosteroids and long-acting beta agonists

We conducted a historical cohort study to examine the relationship between survival and use of inhaled corticosteroids (ICS) and/or long-acting beta agonists (LABA) in patients with chronic obstructive pulmonary disease (COPD). All COPD patients aged 40 years who were enrolled in one of two regional managed care organizations during 1995-2000, and who had 90 days use of an ICS and/or LABA (N=1288) or of a short-acting bronchodilator (N=397), were identified. Of patients treated with ICS and/or LABA, 14.4% died during the follow-up period, as compared to 28.2% of comparison patients (P<0.01). In a Cox proportional hazards model that controlled for age, sex, comorbidities, COPD severity, and asthma status, a reduced risk of death was found for ICS treatment (HR 0.59 [95% CI 0.46-0.78]), LABA (HR 0.55 [0.34-0.89]), and ICS plus LABA treatment (HR 0.34 [0.21-0.56]). A second model that excluded any patient who also had an ICD-9 code for asthma (N=840) still found improved survival among those using the combination of ICS plus LABA (HR 0.35 [CI 0.17-0.71]). Additional analyses that varied the exposure criteria also found a consistent treatment benefit. Inclusion of ICS or bronchodilator treatment during the follow-up period as a time-dependent function appears to negate the survival benefit; however, the underlying assumptions for valid time-dependent modeling are clearly violated in this situation. In conclusion, we found that COPD patients who used ICS alone or in combination with LABA had substantially improved survival even after adjustment for asthma and other confounding factors.     

Doubling daily inhaled corticosteroid dose is ineffective in mild to moderately severe attacks of asthma in adults

BACKGROUND: Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults. AIM: To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles. METHODS: A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects. RESULTS: From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV(1)) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 microg (three of 11, 73%) compared to 2000 microg or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%). CONCLUSIONS: Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.