Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma

OBJECTIVE: To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast (MON) in 342 children (6 to 12 years of age) with persistent asthma. STUDY DESIGN: Randomized, double-blind, 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks. RESULTS: Compared with MON, FP significantly increased mean percent change from baseline FEV1 (forced expiratory volume in 1 second) (P=.002), morning PEF (peak expiratory flow) (P=.004), evening PEF (P=.020), and percent rescue-free days (P=.002) at end point, and it significantly reduced nighttime symptom scores (P <.001) and mean total (P=.018), and nighttime (P <.001) albuterol use. Withdrawals from the study were more frequent with MON (21%) than with FP (13%). Adverse events (69% vs 71%) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar. Parents and physicians were more satisfied with FP treatment than with MON (P=.006 and P=.016, respectively, at Week 12). Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ($1.25 vs $3.49). CONCLUSION: FP was significantly more effective than MON in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles. Parent- and physician-reported satisfaction ratings were higher with FP treatment, and asthma-related costs were lower.     

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.     

Efficacy and safety of inhaled steroid and cromone treatment in school-age children: A randomized pragmatic pilot study

In the treatment of asthma, inhaled steroids are more effective than cromolyn, whereas the latter offers extreme safety. The aim of the present pilot study was to evaluate, contemporarily, efficacy and safety aspects of different asthma treatment modalities. In 75 school‐age children (mean age 9.5 years; range 5.5–14.7 years), treatment of asthma was started with budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromones (CROM, n = 15). BUD was used at a dose of 800 µg/day during the first 2 months and at 400 µg/day thereafter. The respective FP doses were 500 and 200 µg/day. Efficacy of the treatment was assessed by measuring forced expiratory volume in 1 second (FEV₁) and by evaluating the use of bronchodilators. Side‐effects of the treatment were evaluated by following growth of the children and by performing low‐dose adrenocorticotropin (ACTH) testing. At 4 months FEV₁ had improved by a mean of 8.2% in the BUD group and by 5.4% in the FP group (p< 0.01 vs. baseline in both groups; NS between BUD and FP groups). The use of bronchodilators had decreased from five doses/week to one dose/week in the BUD group (p< 0.05), and from three doses/week to one dose/week in the FP group (p< 0.01) (NS between the groups). In the CROM group, the FEV₁ value and the use of bronchodilators did not change. The treatment was unsuccessful on the basis of FEV₁ decrease and increased bronchodilator use in, respectively, 30 and 15% of the BUD‐, 20 and 7% of the FP‐, and 50 and 47% of the CROM‐treated children. Therefore, to prevent one treatment failure in the CROM group, between three and five children would need to move to treatment with steroids. The treatment had measurable systemic effects on the basis of height standard deviation (SD) score decrease and minor adrenocortical suppression in, respectively, 60 and 30% of the BUD‐, 27 and 17% of the FP‐, and 20 and 0% of the CROM‐treated children. Therefore, to avoid systemic effects in one steroid‐treated child, three BUD‐ and six to 14 FP‐treated children would need to move to treatment with CROM. In conclusion, in school‐age children asthma should be treated first with inhaled steroids. It is probable that the best combination of efficacy and safety can be achieved by using low steroid doses.     

Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone.

BACKGROUND AND AIMS: Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose. METHODS: Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l). RESULTS: A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day. CONCLUSION: Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.     

Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study

OBJECTIVE: We tested the hypothesis that adding montelukast to budesonide would improve asthma control in children with inhaled glucocorticoid-dependent persistent asthma. STUDY DESIGN: In a multicenter, randomized, double-blind, crossover study, we compared the benefit of adding montelukast, 5 mg, or placebo once daily to budesonide, 200 microg, twice daily. RESULTS: After a 1-month run-in with budesonide, 200 microg, twice daily, 279 children were randomized to montelukast or placebo. The mean +/- SD age was 10.4 +/- 2.2 years, the mean forced expiratory volume in 1 second (FEV(1)) was 77.7% +/- 10.6% predicted, and reversibility was 18.1% +/- 12.9%. Compared with adding placebo to budesonide, adding montelukast produced significant improvements in mean percent change from baseline FEV(1) (P =.062 [P =.010 for per-protocol analysis]), mean absolute change from baseline FEV(1) (P =.040), mean increase from baseline in morning (P =.023) and evening (P =.012) peak expiratory flows, decrease in exacerbation days by approximately 23% (P <.001), decreased beta2-agonist use (P =.013), and reduced blood eosinophil counts (P <.001). The treatments did not differ significantly with regard to safety. CONCLUSIONS: Montelukast, 5 mg, added to budesonide improved asthma control significantly, indicated by a small additive effect on lung function and a clinically relevant decrease in asthma exacerbation days.     

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.     

A placebo controlled trial of fluticasone propionate in asthmatic children

Fluticasone propionate is a synthetic steroid for use by the inhaled route. It's high topical potency and low systemic bioavailability make it suitable for use in asthmatic children. A total of 258 children were randomised in a double-blind study to receive fluticasone propionate (50 g bd) as the dry powder formulation inhaled via a Diskhaler inhaler, or matched placebo (with current therapy) for 4 weeks throughout which time diary cards were completed. During clinic visits lung function and adrenal function were measured. Fluticasone propionate produced a significantly greater increase in morning peak expiratory flow rate (PEFR) (adjusted mean difference over days 1–28, 17 l/min (95% CI; 10, 24);P<0.001) and evening PEFR (adjusted mean difference over days 1–28, 16 l/min (95% CI; 9, 23);P<0.001). In addition, diary card symptom scores, beta₂-agonist rescue and clinic lung function improved significantly on fluticasone propionate. There were few adverse events and basal plasma cortisol remained within the normal range. In conclusion fluticasone propionate at 50 g bd is superior to placebo (current therapy) in the treatment of childhood asthma with no evidence of adverse effects.     

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 µg 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 µg 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 µg twice daily compared with fluticasone propionate 100 µg twice daily. This difference reached significance among patients with more severe asthma (defined by previous inhaled corticosteroid dose >800 µg/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 µg twice daily may offer benefits over a lower dose, particularly in children with more severe asthma.     

Growth and adrenal suppression in asthmatic children on moderate to high doses of fluticasone propionate

OBJECTIVE: Growth and adrenal suppression have been reported in asthmatic children using high-dose inhaled fluticasone propionate (FP). Inhaled FP, given at moderate doses (250-750 microg/day), has not been documented to be associated with growth or adrenal suppression in asthmatic children until recently. We report three cases illustrating these side effects. METHODS: Growth and adrenal suppression, after the introduction of inhaled FP, were observed in three prepubertal young asthmatic children referred to our asthma clinic and growth clinic. Growth centile and velocity were assessed by longitudinal stadiometry height measurements. Early morning plasma cortisol levels, and glucagon stimulation tests were used to assess the pituitary adrenal axis. RESULTS: Severe growth and adrenal suppression were noted in three children while they were on moderate doses of inhaled FP. Improvements in growth and adrenal function were observed following cessation or dose reduction of inhaled FP. CONCLUSIONS: Unexpected growth and adrenal suppression may occur in young asthmatic children using moderate doses of inhaled FP.     

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.     

The relation between adrenal function and the severity of bronchial hyperresponsiveness in children as measured by the methacholine provocation test

BACKGROUND: There is no satisfactory explanation why some individuals experience severe attacks of asthma, yet others, exposed to similar stimuli, have a milder form of the disease. OBJECTIVE: We tested the hypothesis that children with more severe disease may have relative adrenal insufficiency compared to the children with milder disease. PATIENTS AND METHODS: Sixteen children with chronic asthma aged 8-16 years old were studied. Adrenal function was evaluated by the 24-h excretion of urinary free cortisol (UFC) before and after ACTH stimulation, and by plasma cortisol levels before and 60 min after ACTH administration. The severity of bronchial hyperresponsiveness was evaluated by the methacholine provocation test. RESULTS: Nine children had 20% fall in forced expiratory volume in 1 sec (FEV1) after a provocative concentration (PC20FEV1) of methacholine > or =2.5 mg/ml and were considered as having mild-moderate bronchial hyperresponsiveness (Group A). Seven children had a PC20FEV1 of < or =1.25 mg/ml and were considered as having severe bronchial hyperresponsiveness (Group B). No significant difference was found between the peak plasma cortisol response to ACTH between the two groups (634+/-182 and 586+/-137 nmol/l, respectively). However, there was a significant statistical difference (p <0.01) in the 24-h UFC response to ACTH between the children from Group A (345+/-107 nmol/m2 ) and the children from Group B (161+/-125 nmol/m2). CONCLUSIONS: Based on the low levels of 24-h UFC secretion in severely asthmatic children in our study, we propose the encouragement of provision of a short course of inhaled steroids to be kept at home for the emergency therapy of those children identified as having high-risk asthma.     

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??Objective To investigate the efficacy and safety of fluticasone propionate??FP?? inhalation solution compared with oral prednisone??PRE?? in Chinese pediatric and adolescent subjects??aged 4 to 16 years?? with an acute exacerbation of asthma. Methods This was a randomized?? double-blind?? double-dummy?? active-controlled?? parallel-group?? multi-center??non-inferiority study involving subjects??aged 4 to 16 years old??inclusive?? with an acute exacerbation of asthma??to compare the morning Peak expiratory flow??AM PEF??. Oral PRE once daily 2 mg/??kg·d????up to 40 mg/d for 4 d??then 1 mg/??kg·d?? or half of the original dose??up to 20 mg/d for 3 d?? for 7 d. The study comprised a 7-d treatment period and a 14-d follow-up period??. Results In terms of the primary efficacy endpoint mean AM PEF??the low limit of 95% CI was -9.64 L/min??which was above the pre-defined non-inferiority margin -12 L/min. Conclusion??FP inhalation solution was shown to be non-inferior to oral PRE in the treatment of acute exacerbation of asthma in Chinese pediatric and adolescent patients. FP inhalation solution demonstrates good safety.     

Efficacy of fluticasone metered-dose inhaler and dry powder inhaler for pediatric asthma.

BACKGROUND: For the treatment of bronchial asthma, two types of fluticasone inhaler devices are available, namely, metered-dose inhaler with spacer (MDI-S) and the dry powder inhaler (DPI). The former is recommended for young children with a low peak inspiratory flow (PIF) and the latter for adolescents and adults. But the difference in the therapeutic efficacy between them has been studied only rarely in adolescent patients. METHODS: In the present study, 21 post-elementary school-age patients with moderate persistent bronchial asthma (age 8-15 years, 10.3 +/- 2.1 years), who all had a sufficient PIF of 114 +/- 29 L/min, were examined in order to compare the two types of fluticasone inhalers. Eleven of 21 patients inhaled 200 microg/day Flutide using the MDI-S twice daily for 1 month in the first month, and the same dose using the DPI for the next month. The other 10 patients inhaled the opposite regimens. At the end of the each treatment, spirometry was examined. RESULTS: Measurements done before therapy and then at the end of MDI-S and DPI therapy, respectively, were as follows: forced expiratory volume in 1 s (FEV(1.0)), 72.4 +/- 18.2%, 91.5 +/- 18.2% and 84.1 +/- 16.3% (MDI-S vs DPI, P > 0.040); maximal mid-expiratory flow (MMEF), 62.0 +/- 23.6%, 88.7 +/- 26.5%, 79.3 +/- 33.4% (P > 0.044) and the peak expiratory flow (PEF) was 73.9 +/- 25.0%, 95.6 +/- 32.8%, and 90.5 +/- 29.5%, respectively (n.s.). MDI-S was thus found to be more effective in terms of %FEV(1.0) and in %MMEF. CONCLUSIONS: High therapeutic efficacy was obtained with the use of the MDI-S in fluticasone inhalation for post-elementary school-age patients with sufficient inspiration ability.     

Biochemical markers of bone metabolism in relation to adrenocortical and growth suppression during the initiation phase of inhaled steroid therapy

Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromone (CROM, n = 15) treatment groups. BUD dose was 800 microg/d during the first two months and 400 microg/d thereafter. The respective FP doses were 500 and 200 microg/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p < 0.001) and 15% (p < 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p < 0.01) and 21% (p < 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p = 0.12). In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p < 0.01) and 21% (p < 0.001), respectively. In those children who had no growth suppression, the changes were not significant: -4% in OC and +13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p < 0.01) than in those with normal adrenocortical function (10%, p = 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism.     

Effects of montelukast on symptoms and eNO in children with mild to moderate asthma

BACKGROUND: Asthma is a chronic inflammatory airway disease. Exhaled nitric oxide (eNO) is a marker reflecting airway inflammation. This study was conducted to investigate whether montelukast, a leukotriene receptor antagonist, could be used for the management of asthma and how fast the montelukast sodium decreased airway inflammation as demonstrated by eNO levels. METHODS: Twenty children aged 6-14 years (mean age: 9.2 +/- 2.4 years; mean weight 30 +/- 4.6 kg) with mild to moderate asthma were recruited for the study. They received montelukast plus an inhaled short-acting beta2 agonist as open and uncontrolled therapy. Asthma score (AS) and peak expiratory flow rate (PEFR) and eNO concentrations were measured at pretreatment (0 week) and post-treatment (1 and 2 weeks) as well as 2 weeks after withdrawal of therapy. RESULTS: In one week, the eNO levels (33.3 +/- 15.5 p.p.b. vs 14.8 +/- 8.6 p.p.b.; P < 0.05), and AS (4.2 +/- 1.3 vs 1.8 +/- 1.3; P < 0.05) decreased rapidly, and PEFR (206.9 +/- 69.7 L/min vs 236.2 +/- 69.8 L/min; P < 0.05) increased. Concurrent beta2 agonist use decreased from a mean +/- SD of 2.2 +/- 0.4-1.3 +/- 0.3 puffs per weeks (P < 0.05). After the withdrawal of treatment for 2 weeks, the eNO levels (29.2 +/- 16.1 p.p.b) rebounded again, although the improvements in AS (1.1 +/- 1.3) and PEFR (245.0 +/- 91.3 L/min) persisted. CONCLUSION: Oral montelukast sodium treatment of these children with mild to moderate asthma effectively improved asthmatic symptoms and suppressed airway inflammation in 1 week, suggesting that this leukotriene antagonist combined with short-acting beta2 agonists may provide effective treatment option in mild to moderate childhood asthma. Larger, controlled, and double-blinded studies are needed to confirm these preliminary open uncontrolled observations.     

Lung function in infants with chronic pulmonary disease after severe adenoviral illness.

OBJECTIVE: To evaluate pulmonary function and bronchodilator responses in young children with chronic pulmonary disease (CPD) after a severe adenoviral lower respiratory tract infection. METHODS: Pulmonary function tests were performed in 13 patients (mean age, 1.32 +/- 0.8 years) with CPD and were compared with a control group of 13 healthy infants (mean age, 1.16 +/- 0.4 years). RESULTS: Respiratory rate, peak tidal expiratory flow (PTEF), PTEF/tidal volume, absolute time up to PTEF, time percentage to PTEF, volume percentage for PTEF, and compliance and resistance of the respiratory system were significantly affected in the CPD group. Similarly, maximal flow at functional residual capacity (V'maxFRC) was 56.0 +/- 42 mL/s and 373 +/- 107 mL/s in the CPD and control groups, respectively (P =.001). No within-group differences with baseline values or between-group differences were noted in response to treatment with ipratropium bromide or albuterol. CONCLUSION: Young children with CPD caused by adenovirus have pulmonary function changes characterized by severe obstruction and diminished lung distensibility not responsive to the administration of inhaled ipratropium bromide or albuterol.     

Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone

Background and Aims

Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) >400 μg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose.

Methods

Children recorded as prescribed FP ⩾500 μg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m² intravenously) and was categorised as: biochemically normal (peak cortisol response >500 nmol/l); impaired (peak cortisol ⩽500 nmol/l); or flat (peak cortisol ⩽500 nmol/l with increment of <200 nmol/l and basal morning cortisol <200 nmol/l).

Results

A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6–19.3 years) were successfully tested. Of 194 receiving FP ⩾500 μg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of ⩾ 1000 μg/day.

Conclusion

Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving ⩾1000 μg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.     

Corticotropin releasing hormone stimulation test and nocturnal cortisol levels in normal children.

This study examined hypothalamic-pituitary-adrenal axis functioning in a group (n = 25) of very carefully screened normal children with considerable attention to issues of adaptation and procedural stress. The subjects (mean age 10.3 +/- 1.6 y) were selected as "supernormal" controls as a part of a large psychobiologic study of childhood depression. After careful acclimatization over 24 h, the subjects underwent all-night sampling of plasma cortisol every 20 min, then the following evening had a corticotropin releasing hormone (CRH) stimulation test (using human CRH). Human CRH resulted in a rapid stimulation of adrenocorticotropin and cortisol. Adrenocorticotropin levels increased from 6.8 +/- 3.5 (+/- SD) pmol/L (30.7 +/- 16.1 pg/dL) to a peak of 11.6 +/- 5.5 pmol/L (52.9 +/- 24.8 pg/mL) at 15 min with return to baseline levels by 60 min. Cortisol levels increased from 131.4 +/- 59.7 nmol/L (4.8 +/- 2.2 micrograms/dL) to a peak of 427.0 +/- 113.5 nmol/L (15.5 +/- 4.1 micrograms/dL) at 30 min with return to baseline by 120 min. The cortisol peak was significantly greater (p less than 0.05) in boys [474.6 +/- 129.7 nmol/L (17.2 +/- 4.7 micrograms/dL)] than in girls [366.9 +/- 52.4 nmol/L (13.3 +/- 1.9 micrograms/dL, p less than 0.05)]. Age, body mass index, and pubertal status were not significantly related to hypothalmic-pituitary-adrenal axis measures. Nocturnal cortisol reached a nadir at 160 +/- 60 min after sleep onset (0102 h) and a peak 480 +/- 60 min after sleep onset (0612 h). Nocturnal cortisol levels were significantly (positively) correlated with human CRH-stimulated cortisol (r = 0.56, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)     

Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma.

We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group. Conclusion: budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.