Fluticasone propionate in asthma: a long term dose comparison study.

BACKGROUND: Few dose ranging studies have investigated optimal dosing with inhaled corticosteroids in children with asthma. AIMS: To compare the efficacy and tolerability of fluticasone propionate 100 or 200 microg twice daily in children with moderate to severe asthma for one year. METHODS: One year, randomised, double blind, parallel group, multicentre study. Children aged 4-11 years (n = 528) with moderate to severe asthma who had previously received high dose inhaled corticosteroids were given fluticasone propionate 100 or 200 microg twice daily for the 52 week treatment period. Efficacy (exacerbations, lung function, and symptoms) and tolerability (adverse events and cortisol levels) were measured. RESULTS: There was a non-significant decreased risk of experiencing an exacerbation at any time with fluticasone propionate 200 microg twice daily compared with fluticasone propionate 100 microg twice daily. This difference reached significance among patients with more severe asthma (defined by previous inhaled corticosteroid dose >800 microg/day). Daily record card morning peak expiratory flow (PEF) in the total population improved significantly more with the higher dose of fluticasone propionate (between group difference, weeks 1-52: 11.4 l/min). Clinic visit mean PEF improved from baseline with both doses, but the response was significantly greater with the higher dose (between group difference, week 52: 17.8 l/min). Both doses were equally well tolerated and overnight urinary cortisol concentrations were unchanged or slightly increased during treatment with either dose. CONCLUSION: This long term dose comparison study shows that treatment with fluticasone propionate 200 micro g twice daily may offer benefits over a lower dose, particularly in children with more severe asthma.     

Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate

Aims: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. Methods: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250–750 µg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. Results: Eighteen asthmatic patients (10 boys, 8 girls), aged 7–17 years received inhaled fluticasone therapy at a median dose of 477 µg/m² per day for 5–16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2–3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. Conclusion: After therapy for asthma with inhaled fluticasone at approximately 500 µg daily for up to 16 weeks, half the children had evidence of adrenal suppression.     

Systematic review of the dose-response relation of inhaled fluticasone propionate

Aims: To examine the dose-response relation of inhaled fluticasone for both efficacy and adrenal function in children with asthma. Methods: Systematic review of double blind randomised dose-response studies of fluticasone in children of at least 4 weeks duration. Main outcome measures: FEV₁, morning peak expiratory flow, night awakenings, ß agonist use, major exacerbations, 12 or 24 hour urinary cortisol, peak plasma cortisol post-stimulation. Results: Seven studies of 1733 children with asthma met the inclusion criteria for efficacy. The dose-response curve for each efficacy outcome measure suggested that the response began to plateau between 100 and 200 µg per day with additional efficacy at the 400 µg per day dose shown in one study of severe asthmatics. Five studies of 1096 children with asthma met the inclusion criteria for assessment of adrenal function. The largest placebo controlled study of 437 children reported no difference in 24 hour urinary cortisol between placebo and fluticasone at doses of 100 and 200 µg per day. The non-placebo controlled study of 528 children reported significant suppression of overnight urinary cortisol levels with fluticasone at 400 compared with 200 µg per day. Conclusions: There is insufficient data to determine the dose-response of fluticasone in children at doses >400 µg per day. The dose-response curve for fluticasone appears to plateau between 100 and 200 µg per day for efficacy. There was additional efficacy at the 400 µg per day dose in children with severe asthma; however there was evidence of adrenal suppression at this dose.     

Effects of 2 inhaled corticosteroids on growth: results of a randomized controlled trial.

OBJECTIVE: To compare the long-term effect of treatment with fluticasone propionate or beclomethasone dipropionate on growth in asthmatic children. DESIGN: Prospective, multicenter, randomized, double-blind, parallel-group study. SETTING: Children requiring regular treatment with inhaled corticosteroids and with a sexual maturity rating of Tanner stage 1 (prepubertal). PATIENTS: Three hundred forty-three children aged 4 to 11 years with asthma. The growth population (excluding patients with protocol violations likely to affect growth measurements) included 277 patients. INTERVENTIONS: Fluticasone propionate or beclomethasone dipropionate, both at a dosage of 200 microg administered twice daily via a dry powder inhaler (Diskhaler) for 12 months. MAIN OUTCOME MEASURES: Growth velocity, lung function, and serum and urinary cortisol levels. RESULTS: The adjusted mean growth velocity in the fluticasone group was significantly greater than that in the beclomethasone group (5.01 [SE, 0.14] vs 4.10 [SE, 0.15] cm/y; difference, 0.91 cm; 95% confidence interval, 0.63-1.20 cm; P<.001). Both treatments improved lung function, with significant differences in favor of fluticasone. Adverse events were similar in both groups, and there were no significant differences in effect on serum and urinary cortisol levels. CONCLUSIONS: The more favorable risk-benefit ratio of fluticasone indicates that this agent is preferable to beclomethasone for the long-term treatment of children with asthma, especially if moderate doses are required.     

A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide

AIMS—To determine effects on short term growth and collagen turnover of adding formoterol (Eformoterol) to half the glucocorticoid dose in children with asthma, treated with inhaled budesonide (Pulmicort Turbuhaler).
DESIGN—A randomised double blind, placebo controlled crossover study with two six-week periods.
SETTING—Outpatient clinic in secondary referral centre.
SUBJECTS—A total of 27 prepubertal children aged 6-13 years.
INTERVENTIONS—Formoterol 12 µg and dry powder budesonide 100 µg twice daily in one period; placebo and dry powder budesonide 200 µg twice daily in the other.
OUTCOME MEASURES—Primary outcome measures were lower leg growth rate, and serum and urine markers of type I and type III collagen turnover. Secondary outcome measures were inflammation markers in serum, and parameters of asthma control.
RESULTS—During budesonide 200 µg twice daily treatment, mean lower leg growth rate was 0.14 mm/week (p = 0.02) lower than during the formoterol and budesonide period. Similar statistically significant effects on markers of collagen turnover were found, whereas inflammation markers and asthma control did not vary statistically significantly between the two periods.
CONCLUSIONS—In children treated with inhaled glucocorticoids, halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover, with no loss of asthma control.

     

The role of inhaled corticosteroids in children with asthma

Inhaled corticosteroids offer a wide range of anti-inflammatory activity and have consistently proved to be the most effective medication for the control of childhood asthma. The high efficacy of inhaled corticosteroids has led to their use in milder disease and younger children in the hope that permanent changes in lung function and airway remodelling may be prevented. However, evidence has emerged over the past six years that the first of the inhaled corticosteroids to become available, beclomethasone dipropionate, may cause growth deceleration at a dose of 400 microg per day. This is especially apparent in children with mild symptoms. The newest of the inhaled corticosteroids to be developed, fluticasone propionate, is equipotent to older compounds at half the dose and in low doses is superior in efficacy to sodium cromoglycate. Two recent studies have shown that fluticasone propionate 100-200 microg per day does not cause growth suppression in children with mild asthma. The long term outcome for children who wheeze in early life is difficult to predict. For this reason the use of inhaled corticosteroids in very young children is best reserved for those with severe symptoms or a strong family history of asthma, and evidence, from measurement of inflammatory markers, of airway inflammation.     

Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate.

AIMS: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. METHODS: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250-750 microg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. RESULTS: Eighteen asthmatic patients (10 boys, 8 girls), aged 7-17 years received inhaled fluticasone therapy at a median dose of 477 microg/m2 per day for 5-16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2-3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. CONCLUSION: After therapy for asthma with inhaled fluticasone at approximately 500 microg daily for up to 16 weeks, half the children had evidence of adrenal suppression.     

Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma.

This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36-42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma.     

Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma

This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36-42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma.     

Systematic review of the dose-response relation of inhaled fluticasone propionate.

AIMS: To examine the dose-response relation of inhaled fluticasone for both efficacy and adrenal function in children with asthma. METHODS: Systematic review of double blind randomised dose-response studies of fluticasone in children of at least 4 weeks duration. MAIN OUTCOME MEASURES: FEV1, morning peak expiratory flow, night awakenings, beta agonist use, major exacerbations, 12 or 24 hour urinary cortisol, peak plasma cortisol post-stimulation. RESULTS: Seven studies of 1733 children with asthma met the inclusion criteria for efficacy. The dose-response curve for each efficacy outcome measure suggested that the response began to plateau between 100 and 200 microg per day with additional efficacy at the 400 microg per day dose shown in one study of severe asthmatics. Five studies of 1096 children with asthma met the inclusion criteria for assessment of adrenal function. The largest placebo controlled study of 437 children reported no difference in 24 hour urinary cortisol between placebo and fluticasone at doses of 100 and 200 microg per day. The non-placebo controlled study of 528 children reported significant suppression of overnight urinary cortisol levels with fluticasone at 400 compared with 200 microg per day. CONCLUSIONS: There is insufficient data to determine the dose-response of fluticasone in children at doses >400 microg per day. The dose-response curve for fluticasone appears to plateau between 100 and 200 microg per day for efficacy. There was additional efficacy at the 400 microg per day dose in children with severe asthma; however there was evidence of adrenal suppression at this dose.     

Fluticasone propionate in children and infants with asthma]

The known efficacy of fluticasone propionate in adults, comparable at half-dosage of corticosteroids has been validated by the market authorization (MA) and by the national and international guidelines for beclomethasone. This could be partly explained by its pharmacological properties, affinity for glucocorticosteroid receptors, lung deposition and lipophilicity. The limited systemic adverse events is due to its low bioavailability, optimal hepatic clearance, high plasma protein binding. The efficacy in asthmatic children has been confirmed in clinical studies showing a "plateau" efficacy between 100 and 200 microg/d for the majority of children. Most children are controlled by such dosages: the added value of increasing posology on asthma control exists but is small. A high off-label posology does not allow more quickly asthma control and therefore is not justified. A twice daily dosing is more efficient, particularly for initiation of maintenance therapy, than a once daily dosing. A literature survey confirms that, at MA recommended daily doses in children (100-200 microg), fluticasone propionate has no clinically significant effect either on hypothalamic-pituitary-adrenal (HPA) axis (basal function or stimulation tests), bone or growth velocity. However, high daily doses (higher to 500 microg/day) for long periods expose to systemic adverse effects with measurable consequences on growth rate, bone density (decreasing biochemical makers of bone formation) and HPA function. Several cases of adrenal insufficiency that may have led to acute adrenal crisis have been reported in 4- to 10-year-old children receiving fluticasone propionate in doses between 500 to 2000 microg daily. In case of surgery or infection, a preventive treatment of adrenal insufficiency with hydrocortisone should be proposed for children treated for more than 6 months with such high daily doses. Such children need definitely an advice from paediatricians specialized in chest diseases as well as in endocrinology. It is important to recall that the clinical benefit of daily doses of inhaled corticosteroids higher than recommended is low and that the good use of inhaled corticosteroids particularly in children lays on the careful search of the minimal efficient daily doses.     

No effect of fluticasone propionate on linear growth in preschool children with asthma

Background: Eighty percent of asthmatic children develop asthma symptoms by the age of 5 years. Inhaled corticosteroids (ICS), depending on dosage, may cause linear growth reduction and adrenal gland suppression. There are few studies about linear growth of preschool children with asthma. The aim of the present study was to investigate whether there is any effect of fluticasone propionate (FP) on linear growth and adrenal gland function. Methods: Twenty‐eight children aged 18–52 months with persistent asthma receiving ICS FP 100–200 µg daily were studied for 1 year. Patients were divided into two groups according to clinical parameters: well (group 1) and poorly controlled (group 2). Height was measured every 3 months and expressed as height standard deviation score (SDS). Cumulative dose of FP expressed in mg was calculated for every patient. Early morning levels of serum adrenocorticotropic hormone (ACTH) and cortisol were assessed at the beginning and at the end of the study. Results: Patients took FP for an average of 11 months in group 1 and 16 months in group 2, which was not statistically significantly different. At the end of the study height SDS difference was ?0.0143 in group 1 and ?0.2000 in group 2, which was not statistically significantly different (t= 0.6072, P= 0.5489). There was also no statistically significant difference for average cortisol (P= 0.4381) or ACTH (P= 0.5845) concentration at the end of the study. Conclusion: FP 100–200 µg daily had no effect on linear growth or on the hypothalamic–pituitary–adrenal gland axis but further follow up is necessary.     

Effects of nebulized corticosteroids therapy on hypothalamic–pituitary–adrenal axis in young children with recurrent or persistent wheeze

Inhaled corticosteroids (ICS) are preferred drugs for the long-term treatment of all severities of asthma in children. However, data about the safety of ICS in infants is lacking. So, it is essential to do further clinical studies to examine the safety and efficacy of ICS in this population. In this study, the effects of nebulized budesonide and nebulized fluticasone propionate suspensions on hypothalamic–pituitary–adrenal axis is examined in infants with recurrent or persistent wheeze. Thirty-one children aged 6–24 months admitted to our hospital between January and December 2005 with symptoms of recurrent or persistent wheeze were included in the study. The patients were randomly allocated to receive 0.25 mg BUD or 0.25 mg fluticasone propionate twice daily for 6 wk and half dose for another 6 wk with a jet nebulizer at home. Blood samples for basal cortisol concentration, adrenocarticotropic hormone, glucose, HbA1c and electrolytes were obtained at the beginning and at the end of the study. Adrenal function assessment was based on changes in cosyntropin-stimulated plasma cortisol levels. The study was completed with 31 patients, 16 of whom received BUD and 15 FP. All patients except one had plasma cortisol concentrations above 500 nmol/l (18 μg/dl) or had an incremental rise in cortisol of >200 nmol/l after stimulation. Although nebulized steroids seem to be safe in infancy, we recommend that adrenal functions should be tested periodically during long-term treatment with nebulized steroids.     

Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom

Background: Until recently, only two cases of acute adrenal crisis associated with inhaled corticosteroids (ICS) had been reported worldwide. We identified four additional cases and sought to survey the frequency of this side effect in the United Kingdom. Methods: Questionnaires were sent to all consultant paediatricians and adult endocrinologists registered in a UK medical directory, asking whether they had encountered asthmatic patients with acute adrenal crisis associated with ICS. Those responding positively completed a more detailed questionnaire. Diagnosis was confirmed by symptoms/signs and abnormal hypothalamic-pituitary-adrenal axis function test results. Results: From an initial 2912 questionnaires, 33 patients met the diagnostic criteria (28 children, five adults). Twenty-three children had acute hypoglycaemia (13 with decreased levels of consciousness or coma; nine with coma and convulsions; one with coma, convulsions and death); five had insidious onset of symptoms. Four adults had insidious onset of symptoms; one had hypoglycaemia and convulsions. Of the 33 patients treated with 500–2000 µg/day ICS, 30 (91%) had received fluticasone, one (3%) fluticasone and budesonide, and two (6%) beclomethasone. Conclusions: The frequency of acute adrenal crisis was greater than expected as the majority of these patients were treated with ICS doses supported by British Guidelines on Asthma Management. Despite being the least prescribed and most recently introduced ICS, fluticasone was associated with 94% of the cases. We therefore advise that the licensed dosage of fluticasone for children, 400 µg/day, should not be exceeded unless the patient is being supervised by a physician with experience in problematic asthma. We would also emphasise that until adrenal function has been assessed patients receiving high dose ICS should not have this therapy abruptly terminated as this could precipitate adrenal crisis.     

Salmeterol/fluticasone propionate vs. double dose fluticasone propionate on lung function and asthma control in children

There is a large body of data to support the use of an inhaled corticosteroid (ICS) plus a long‐acting β₂‐agonist vs. increasing the dose of ICS in adults, but less data in children. This double‐blind, parallel group, non‐inferiority study compared lung function and asthma control, based on Global Initiative for Asthma guidelines, in children receiving either salmeterol/fluticasone propionate (SFC) 50/100 μg bd (n = 160) or fluticasone propionate (FP) 200 μg bd (n = 161) for 12 wks. Change from baseline in mean morning peak expiratory flow increased following both treatments, but was significantly greater in the SFC group compared with FP [Adjusted mean change (s.e.) (l/min): SFC: 26.9 (2.13), FP: 19.3 (2.12); treatment difference: 7.6 (3.01); 95% CI: 1.7, 13.5; p = 0.012)]. Asthma control improved over time in both groups. Mean pre‐bronchodilator maximal‐expiratory flow at 50% vital capacity and percentage rescue‐free days showed significantly greater improvements in the SFC group compared with FP. All other efficacy indices showed comparable improvements in each group. Treatment with SFC 50/100 μg bd compared with twice the steroid dose of FP (200 μg bd), was at least as effective in improving individual clinical outcomes and overall asthma control, in asthmatic children previously uncontrolled on low doses of ICS.     

Safety of inhaled corticosteroids delivered by plastic and metal spacers

Methods: Thirty children (mean 4.3 (SD 0.3) years) received 200 µg budesonide twice daily by NC or AC, both with the mask provided, in a randomised, two month crossover trial. Twenty four hour urinary free cortisol (UFC) was determined as a measure of HPA suppression. Results: UFC decreased from 42.3 (7.8) nmol UFC/nmol creatinine control to 26.2 (2.4) (p = 0.06 v control) after AC, and to 24.5 (2.5) (p = 0.04 v control) after NC (p = 0.4 AC v NC). Conclusions: Despite a greater total dose delivered to the mouth, NC is not associated with greater HPA suppression when using 400 µg/day budesonide under real life conditions in young children.     

Intravenous immunoglobulin for cystic fibrosis lung disease: a case series of 16 children

Background and objective: Some children with severe cystic fibrosis (CF) lung disease develop chest tightness, recurrent dry cough, and intractable wheeze, often accompanied by deteriorating lung function and failure to expectorate sputum. In an attempt to reduce the use of regular oral corticosteroids, we treated a group of such children with monthly courses of intravenous immunoglobulin (IVIG). Methods: This is a retrospective case note review of 16 children, aged 3–16 years (median 13.0 years) who received 1–66 (median 7.5) courses of monthly IVIG, at a dose of 1 g/kg on two successive days for the first dose, followed by 1 g/kg monthly as a 12 hour infusion, with corticosteroid and antihistamine cover. Results: FEV₁ improved from a median (95% confidence interval (CI)) of 50% (39 to 61%) to 54% (48 to 66%), with a median (95% CI) difference of +7.5% (-1.5 to 14.5%; NS). FVC improved from 65% (60 to 77%) to 83% (70 to 89%), with a difference of +13% (4 to 22%, p = 0.01). The total daily dose/kg body weight of oral prednisolone was reduced from 0.6 (0.3 to 1.0) to 0 (0 to 0.1) mg/kg/day, with a reduction of -0.6 (-1.0 to -0.1, p = 0.006) mg/kg/day. The total daily dose of inhaled corticosteroid (budesonide equivalent) was a median (range) of 2000 µg (800–6000 µg), which was reduced to 1500 µg (0–3200 µg). The median (95% CI) difference was -400 µg (-1600 to 0 µg), p<0.05. IVIG was well tolerated and the regimen acceptable to all but one of the children. The following transient adverse reactions were seen in only one patient each: headache, fever, hypotension, aseptic meningitis, and chest tightness. Conclusion: We suggest that an n = 1 trial of IVIG in carefully selected patients with severe obstructive CF lung disease is worth considering, as for some it may lead to significant benefit.     

Efficacy and safety of fluticasone propionate hydrofluoroalkane inhalation aerosol in pre-school-age children with asthma: a randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of fluticasone propionate (FP) hydrofluoroalkane (HFA) in children age 1 to < 4 years with asthma. STUDY DESIGN: Children were assigned (2:1) to receive FP HFA 88 mug (n = 239) or placebo HFA (n = 120) twice daily through a metered-dose inhaler with a valved holding chamber and attached facemask for 12 weeks. The primary efficacy measure was mean percent change from baseline to endpoint in 24-hour daily (composite of daytime and nighttime) asthma symptom scores. RESULTS: The FP-treated children had significantly greater (P < or = .05) reductions in 24-hour daily asthma symptom scores (-53.9% vs -44.1%) and nighttime symptom scores over the entire treatment period compared with the placebo group. Daytime asthma symptom scores and albuterol use were slightly more decreased with FP than with placebo; however, the differences were not statistically significant. Increases in the percentage of symptom-free days were comparable. The percentage of patients who experienced at least 1 adverse event was similar in the 2 groups. Baseline median urinary cortisol excretion values were comparable between the groups, and there was little change from baseline at endpoint. FP plasma concentrations demonstrated that systemic exposure was low. CONCLUSIONS: FP HFA 88 mug twice daily was effective and well tolerated in pre-school-age children with asthma.     

Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial

AIMS—To determine the role of formoterol in the treatment of children with bronchial asthma who are symptomatic despite regular use of inhaled corticosteroids.
METHODS—A randomised, double blind, parallel group, placebo controlled study to investigate the effects of inhaled formoterol (12 µg twice a day) in 32 children with moderate to severe bronchial asthma. The study consisted of two week run in periods and six week treatment periods, during both of which the patients continued their regular anti-inflammatory drugs. The efficacy parameters were symptom scores, bronchodilator use, daily peak expiratory flow rates (PEFR), methacholine hyper-reactivity, forced expiratory volume in one second (FEV₁), lung volumes, and airway conductance.
RESULTS—Formoterol treatment for six weeks decreased symptom scores, PEFR variability, and the number of rescue salbutamol doses, and increased morning and evening PEFR significantly. No adverse reactions were seen.
CONCLUSION—These findings suggest that inhaled formoterol is effective in controlling chronic asthma symptoms in children who are symptomatic despite regular use of inhaled corticosteroids.

     

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目的观察布地耐德(BUD)联用福莫特罗(FOM)与单用双倍剂量BUD干粉吸入疗法对轻度持续性哮喘患儿的有效性和安全性,探讨儿童轻度持续性哮喘的理想治疗方案。方法选取2005-01—2005-06在广州医学院附属第一医院呼研所专科门诊就诊的轻度持续哮喘患儿50例,采取开放、随机、平行对照方法把50例患儿分为两组,分别吸入BUD联用FOM(B+F组)或双倍剂量BUD(Double B组)8周,药物均用都保干粉吸入装置吸入。8周的观察期内由患儿或家长记录哮喘日记,包括日间和夜间症状评分、无症状天数、其它平喘药物(包括应急用速效β2-受体激动剂、长效缓释茶碱、口服长效β2-受体激动剂、全身用糖皮质激素)使用情况,同时以简易峰流速仪监测其呼气峰流速值(PEF)作为主要肺功能指标。结果B+F组和Double B组在治疗8周后,日间症状及PEF均较治疗前明显改善,无症状天数明显增加,差异具有统计学意义(均P<0.05);与治疗前比较,B+F组在治疗8周后夜间症状评分明显下降(P<0.05),而Double B组治疗前后比较差异无统计学意义(P>0.05);两组间日间症状评分、夜间症状评分、无症状天数及PEF治疗前及治疗后比较差异均无统计学意义(均P>0.05)。两组间病情反复发作次数、需联合应用速效β2-受体激动剂次数及口服强的松、长效缓释茶碱或口服长效β2-受体激动剂的天数均无统计学意义(均P>0.05)。结论低剂量吸入糖皮质激素(ICS)联用长效β2-受体激动剂(LABA)与单用双倍剂量ICS治疗儿童轻度持续性哮喘的疗效相当。但从减少或避免ICS潜在的全身性副反应方面考虑,联用低剂量ICS+LABA可能是更好的选择。