Doses of systemic corticosteroids in hospitalised children with acute asthma: A systematic review

AIM: To present the doses of systemic corticosteroids reported by clinical trials in hospitalised children with acute asthma and to assess the possible relationship between doses of corticosteroids and clinical responses. METHODS: An electronic search of MEDLINE databases (January 1949-February 2005) and Cochrane Controlled Clinical Trials Register (February 2005) was undertaken using a combination of indexing terms related to systemic corticosteroids and acute asthma. Studies were selected if they met the following criteria: (i) randomized controlled trial; (ii) children aged 1-18 years and admitted to hospital for acute asthma; and (iii) treatment group consisting of systemic corticosteroids. RESULTS: Nine trials were included for this review. There was considerable variation between the reported doses of systemic corticosteroids. Only two trials assessed clinical responses to different doses of systemic corticosteroids. Both trials failed to show any therapeutic advantage of higher doses over lower doses. The results of the two trials were not suitable for pooling. CONCLUSIONS: Current data are not sufficient for establishing dose-response relationship of systemic corticosteroids in hospitalised children with acute asthma. Larger randomized trials are needed.     

The use of corticosteroids in syntomathic asthma in childhood

Corticosteroids (CS) have been used in the management of wheezing illnesses for several decades and have become the cornerstone of the management of childhood asthma. Inhaled corticosteroids are considered first-line treatment for frequent, persistent asthma in every guideline. Whilst undoubtedly they have provided enormous benefit to those asthmatics who would otherwise have been prescribed oral corticosteroids and so been at a high risk of side-effects, there is good evidence that inhaled corticosteroids are prescribed not only to too many asthmatic children but also to children who do not have asthma or who have other wheezing disorders. This review will assess the evidence for the benefit of corticosteroids, their use, and current prescribing practices in the common wheezing disorders of childhood.     

Randomised controlled trial of aminophylline for severe acute asthma.

OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol. RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group. CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment.     

Inhaled corticosteroids in childhood asthma: the story continues

Inhaled corticosteroids (ICS) are the most effective anti-inflammatory drugs for the treatment of persistent asthma in children. Treatment with ICS decreases asthma mortality and morbidity, reduces symptoms, improves lung function, reduces bronchial hyperresponsiveness and reduces the number of exacerbations. The efficacy of ICS in preschool wheezing is controversial. A recent task force from the European Respiratory Society on preschool wheeze defined two different phenotypes: episodic viral wheeze, wheeze that occurs only during respiratory viral infections, and multiple-trigger wheeze, where wheeze also occurs in between viral episodes. Treatment with ICS appears to be more efficacious in the latter phenotype. Small particle ICS may offer a potential benefit in preschool children because of the favourable spray characteristics. However, the efficacy of small particle ICS in preschool children has not yet been evaluated in prospective clinical trials. The use of ICS in school children with asthma is safe with regard to systemic side effects on the hypothalamic–pituitary–adrenal axis, growth and bone metabolism, when used in low to medium doses. Although safety data in wheezing preschoolers is limited, the data are reassuring. Also for this age group, adverse events tend to be minimal when the ICS is used in appropriate doses.     

A comparative trial of choline theophyllinate and controlled release aminophylline in chronic childhood asthma

A comparison of pharmacokinetics and therapeutic effects of a standard oral theophylline preparation (Choline Theophyllinate) and controlled release aminophylline (Phyllocontin) was made in two parallel double blind trials in 25 children with chronic asthma. Fourteen children entered a double blind cross-over trial; the remaining 11 were allocated to a parallel trial with no change of theophylline preparation throughout. Sustained plasma theophylline levels were observed with the controlled release preparation in contrast to the low morning levels obtained with Choline Theophyllinate. No significant differences were found for peak theophylline levels, morning or evening peak flow rates or required access to other bronchodilators. However nocturnal symptoms were significantly reduced and daytime activity scores improved (P less than 0.05) on the controlled release preparation. The sustained plasma theophylline levels found in children taking the controlled release aminophylline may have provided a small but useful therapeutic advantage over the standard preparation.     

Clinical-physiologic correlations in acute asthma of childhood

Seventy-one patients who presented to the emergency room with acute asthma were evaluated to determine the relationship between common clinical signs and spirometric and transcutaneous arterial oxygen saturation (SaO2) measurements. Prior to treatment, a physical examination was performed, a clinical score assigned, and pulmonary function and SaO2 were measured. Although forced expiratory volume in 1 second (FEV1) and SaO2 had strong correlation with the overall clinical score (r2 = .47, .49 respectively), many patients with low clinical scores and apparent mild clinical disease had low FEV1 values (as low as 20% predicted). Of the individual components of the clinical score (ie, heart rate, respiratory rate, pulsus paradoxus, accessory muscle use, dyspnea, and wheezing), the degree of accessory muscle use correlated most closely with lung function followed by the degree of dyspnea and wheezing. Similarly, the degree of accessory muscle use correlated most closely with SaO2 followed by dyspnea and respiratory rate. Significant correlation (r2 = .59) was found between SaO2 and FEV1, although the range of SaO2 value for a given FEV1 was wide and some patients with low FEV1 values had normal SaO2 values. These results show that although clinically apparent severe disease and hypoxemia were always associated with low FEV1, their absence does not exclude the presence of airflow obstruction. It is concluded that for the optimal evaluation of acute asthma in children in the emergency room, clinical evaluation should be used in conjunction with objective laboratory measurements.     

Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial

A controlled double-blind trial was carried out to assess the effect of the early introduction of combined corticosteroid and beta-adrenergic drugs for the treatment of acute asthma in infants and toddlers. Seventy-four emergency room patients (aged 7 to 54 months) who were treated for acute asthma were studied. Treatment included, in addition to salbutamol inhalations, a single dose of intramuscular methylprednisolone (4 mg/kg) or normal saline as placebo. The patients were reevaluated 3 hours after initiation of treatment. At that time, patients were either admitted or discharged based on a clinical decision. Only 8 (20%) of 39 patients treated with steroids were admitted, compared with 15 (43%) of 35 in the placebo group (P less than .05). Sequential analysis of 33 pairs, matched by age and severity of symptoms, revealed statistically significant reduced admission rates in patients treated with steroids. In the younger patients (6 to 24 months), admission rate was significantly lower for those treated with steroids (18%) as compared with those treated without steroids (50%) (P less than .05). In the older group (24 to 54 months), the trend was similar but not statistically significant: 23% vs 31% in the steroid and placebo groups, respectively. These data indicate that corticosteroid treatment combined with an adrenergic agent, given early during an acute asthmatic episode, significantly reduces the hospital admission rate of infants and toddlers.     

Community-based randomized controlled trial of reduced osmolarity oral rehydration solution in acute childhood diarrhea.

OBJECTIVE: The standard oral rehydration solution (ORS) recommended by WHO and UNICEF does not reduce the volume or frequency of stools or the length of the episode. Hospital-based studies from developing and developed countries and intestinal perfusion studies suggest a beneficial effect on water and sodium absorption with reduced osmolarity ORS as compared with standard ORS. We conducted a community-based study comparing the efficacy of reduced osmolarity ORS (224 mmol/l) with standard ORS (311 mmol/l) in acute childhood diarrhea in a West African community. METHODS: Infants and toddlers age 0 to 30 months having 738 episodes of diarrhea identified by weekly household visits were randomly assigned to treatment with either standard ORS (n = 376) or reduced osmolarity ORS (n = 362). The children were followed by daily home visits to assess ORS intake and clinical characteristics. Duration of diarrhea was compared by proportional hazards regression analysis, the hazard ratio being interpreted as the relative recovery rate between the children receiving the two types of ORS. Because earlier reports have suggested that weaning status might be an important modifier for the performance of reduced osmolarity ORS, the effect was assessed overall and as an interaction between type of ORS and weaning status and age. Maternal satisfaction was assessed in a paired analysis among mothers whose children participated at least twice in the study. RESULTS: In the overall analysis reduced osmolarity ORS was as efficacious as standard ORS as assessed by duration of diarrheal episode and total number of stool evacuations on Days 1 and 2. Non-breast-fed toddlers (i.e. children ages 12 to 30 months) treated with reduced osmolarity ORS had significantly shorter diarrheal episodes [1.14 days vs. 1.78 days with standard ORS; hazard ratio, 1.50; 95% confidence interval (CI), 1.07 to 2.09] and lower total number of stool evacuations on Days 1 and 2 (3.9 stool evacuations vs. 5.0 stool evacuations with standard ORS; ratio of geometric means, 0.77; 95% CI 0.60 to 1.01). No significant difference was found for breast-fed toddlers or for infants. There was no statistically significant difference in the ORS intake between the two treatment groups. The odds ratio for the mother preferring reduced osmolarity ORS to standard ORS was 1.92 (95% CI 0.97 to 3.85). CONCLUSIONS: Reduced osmolarity ORS was as efficacious as standard ORS. Non-breast-fed children treated with reduced osmolarity ORS had significantly shorter diarrheal episodes and a tendency toward lower stool frequency. These findings may be of importance, especially in developing countries where early weaning is common.     

Inflammatory phenotypes in stable and acute childhood asthma

Asthma is a complex disease with a significant inflammatory component characterized by repeated episodes of exacerbation and inflammatory changes in both large and peripheral airways. The clinical course of childhood asthma varies substantially among individuals. The reasons why the clinical course of asthma displays persistence and even progression in some children but is intermittent in others remains unclear. Children with asthma are different from adults with asthma. Inflammatory involvement in children with asthma appears to be localised more in peripheral than central airways, and the inflammatory phenotype displays differences from adults. Children with acute asthma display a dominant eosinophilic inflammatory phenotype instead of the neutrophilic phenotype that is seen in adults with acute asthma. Corticosteroids do not alter the natural history of the disease and may not prevent progressive decline of lung function in the subset of severe asthma. The underlying inflammatory mechanisms involved in the decline of lung function remains to be elucidated. Non-invasive biomarkers for monitoring lung function and inflammation are needed in children to track and monitor pathological changes in the distal airways, as is the development of therapeutic strategies that effective to peripheral airway in this vulnerable population. This review summarises our present understanding of airway inflammatory phenotypes in children with asthma and factors determining disease severity in exacerbations of asthma, and focuses on studies evaluating relationships between clinical features and the dominant inflammatory phenotypes in disease prognosis in a variety of asthma populations. This presents the crucial steps for describing the strategies associated with improvements for paediatric asthma care.     

Loperamide in acute diarrhoea in childhood: results of a double blind, placebo controlled clinical trial

Fifty-three young children with acute diarrhoea were included in a hospital-based, double-blind trial of loperamide at two dose levels (0.4 and 0.8 mg/kg/day), given with standard oral rehydration therapy versus placebo plus oral rehydration therapy. The differences in the overall recovery rate were significant (P less than 0.05), the fastest being in the group given 0.8 mg/kg and slowest in the placebo group. Comparison between weights on admission and weights by day 3 showed that more children in the loperamide groups gained weight than in the placebo group (P less than 0.05). No serious side effects of loperamide were observed. The drug was withdrawn in one child because of excessive lethargy and sleep. The results indicate that loperamide in the doses employed is safe and may be a useful adjunct to oral rehydration in certain children.     

Efficacy of a home-made spacer with acute exacerbation of bronchial asthma : A randomized controlled trial

Metered dose inhaler (MDI) with spacer is the preferred method for administration of aerosolized medications in pediatric asthma. The expense of commercial spacers limits their use and indigenous alternatives have therefore been developed. Information on the clinical efficacy of home-made spacers is limited. This study was conducted to compare the efficacy of a valve-less home-made spacer with a commercial spacer in delivering salbutamolvia MDI in acute asthma. Asthmatic children aged 5–15 years who presented with an acute exacerbation to the pediatric chest clinic of a tertiary care hospital were enrolled in a single blinded randomized parallel group study. The study patients received 10 puffs of salbutamol (100(igJ puff)via MDI-home-made spacer or MDI-commercial spacer. Pre and post inhalation measurements of peak expiratory flow rate (PEFR), oxygen saturation (SaO2), respiratory rate (RR), pulse rate (PR) were made and compared. Sixty children were enrolled in the study, 31 were administered salbutamolvia the home-made spacer and 29via the commercial spacer. The median increase in PEFR was similar in both the groups (20.8% vs22.2%, p=0.4), clinical improvement being satisfactory in all patients. The valve-less home-made spacer is equally efficacious and cheaper than the commercial spacer in administering bronchodilators in acute exacerbations of asthma. Further studies on the efficacy of home-made spacer in delivery of inhaled steroids are needed.     

Randomised controlled trial of inhaled corticosteroids (fluticasone propionate) in cystic fibrosis

BACKGROUND: Controlling lung inflammation may be the key to improving morbidity and mortality in cystic fibrosis. OBJECTIVE: To assess the effects of inhaled corticosteroids on lung inflammation in cystic fibrosis. DESIGN: Double blind placebo controlled randomised sequence crossover trial. Fluticasone propionate (400 micrograms/day) was given as a dry powder inhaler for six weeks with a four week washout period before crossover. OUTCOME MEASURES: Sputum inflammatory markers (interleukin-8, tumour necrosis factor-alpha (TNF-alpha) and neutrophil elastase-both free and bound to alpha 1-antiprotease), sputum interleukin-10, lung function, and symptomatology. SUBJECTS: Twenty three children from a regional cystic fibrosis centre were enrolled into the study, with mean age 10.3 years (range 7 to 17 years) and mean baseline forced expiratory volume in one second (FEV1) of 64% (range 21% to 102%) predicted for sex and height. One patient was excluded for non-compliance to the study protocol. RESULTS: No significant benefit was shown for the use of fluticasone propionate in any of the outcomes. For sputum interleukin-8 there was an estimated true treatment median difference of 142 pg/ml (95% confidence interval (CI) 8 to 2866 pg/ml) in favour of placebo; while for maximal expiratory flow at 25% (MEF25%) remaining forced vital capacity predicted for sex and height there was a 15 percentage points (pp) (95% CI 4 to 26 pp) mean treatment difference in favour of placebo. Sputum interleukin-10 was undetected in any samples and unaffected by fluticasone propionate. Neither atopic status, baseline FEV1, nor concomitant DNase therapy had any effect on response to treatment. CONCLUSIONS: Lack of benefit from fluticasone propionate was most likely due to failure of the drug to penetrate the viscid mucus lining the airways. It is suggested a large multicentre trial with higher doses given for a longer time by a different delivery system is required to assess efficacy.     

Effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home

Many clinicians advise their patients to increase the dose of inhaled corticosteroids during acute asthma exacerbations, without strong clinical evidence supporting this treatment. This study investigates the effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home. The study population consisted of children with mild intermittent, mild and moderate persistent asthma aged 1 to 14 years who were treated in our outpatient clinic with inhaled budesonide for 1 year. After participating in an asthma education session, the parents were instructed to initiate treatment with inhaled budesonide at the first signs of asthma exacerbation, starting with 200 to 400 microg budesonide, in combination with beta-2 agonists 4 times a day and followed by a decrease in the dose in 4 to 8 days. Asthma status and peak expiratory flow rates were measured in the 3 monthly follow-up visits. Only children who complied with the treatment regimen and came for follow-up visits regularly were included in the final analysis. One hundred fifty children used our treatment protocol with inhaled budesonide to control their asthma attacks. Clinical improvement of asthma symptoms was achieved after a mean of 1.8 +/- 0.7 days from the beginning of treatment. The parents were able to control 94% of the 1,061 episodes of asthma exacerbation occurring during a cumulative follow-up period of 239 years. In the 3-month period before enrollment, 101 children (67%) had used oral corticosteroids to control their asthma attacks and 50 (33%) were hospitalized. During the entire follow-up period, only 11 children (7%) used oral corticosteroids, and none of the children were hospitalized. The present study demonstrates that children with asthma can control their exacerbations at home using inhaled corticosteroids (budesonide). Treatment, starting with relatively high doses followed by a rapid reduction in dose over 4-8 days, resulted in a decrease in the use of oral steroids and in hospitalization. To achieve good results, patient compliance is essential.