Evening PEF Research Articles

Review of efficacy of ciclesonide for the treatment of asthma in children.

Background: Ciclesonide (CIC) is an inhaled corticosteroid (ICS) approved for the maintenance treatment of asthma in patients ages ≥ 12 years. The prodrug aspect of CIC is associated with a safety profile that may make it ideal for children. Objective: The objective was to summarize efficacy results from the eight phase III, randomized, double-blind, controlled trials in children with asthma conducted during CIC clinical development. Methods: Four trials compared CIC 40, 80, or 160 µg/day with placebo. Two trials compared CIC 160 µg/day with fluticasone propionate 200 µg/day, one trial compared CIC 80 or 160 µg/day with fluticasone 200 µg/day, and one trial compared CIC 160 µg/day with budesonide 400 µg/day. Results: The primary end point was met by at least two CIC doses versus placebo in the trials in which the primary end point was the change from baseline in lung function outcome (forced expiratory volume in 1 second [FEV1] % predicted or morning peak expiratory flow [PEF]). A trial that compared CIC with placebo did not meet the primary end point of superiority in time-to-first severe wheeze exacerbation or lack of improvement. The primary end point of noninferiority to the active control (fluticasone or budesonide) in the change from baseline in a lung function outcome (FEV1, morning PEF, evening PEF) was met with the CIC 160-µg dose in all active control trials. CIC generally demonstrated statistically significant improvements in forced expiratory flow at 25%-75% of forced vital capacity, asthma symptoms, rescue medication use, and asthma control when compared with placebo and noninferiority for these outcomes compared with fluticasone or budesonide. Conclusion: In children with asthma, once-daily CIC significantly improved large and small airway function, asthma symptoms, and asthma control, and reduced rescue medication use compared with placebo. CIC was comparable with other ICS used to treat asthma in children, which demonstrated its worth for the pediatric population.

Randomised trials of proton pump inhibitors for gastro-oesophageal reflux disease in patients with asthma: an updated systematic review and meta-analysis

ObjectiveAsthma often coexists with gastro-oesophageal reflux disease (GERD). The effect of proton pump inhibitors (PPIs) treatment on asthma concomitant with GERD was inconsistent. This study aimed to assess whether PPIs...

Acute respiratory effects of livestock-related air pollution in a panel of COPD patients

Living close to livestock farms has been associated with increased symptoms in patients with chronic obstructive pulmonary disease (COPD). The causes of these effects are still poorly understood. This panel study attempts to assess the acute effects of livestock-related air pollution in patients with COPD living in an area with intensive livestock farming in the Netherlands.Between February 2015 and July 2016, 82 participants took spirometry measurements twice daily (morning and evening) during a 3-month period, resulting in 12,672 FEV1 and PEF records. Participants also kept a diary on respiratory symptoms as well as livestock-related odor annoyance. Daily average ammonia (NH3) (a proxy for livestock-related air pollution) and fine particulate matter (PM10) levels were collected from monitoring stations in the area. Lung function was analyzed as decrements of >10% and >20% from their median as well as absolute values. Self-reported odor annoyance was analyzed as a dichotomous variable. All analyses were done using generalized estimated equations. We adjusted for humidity, temperature, linear trend, and took multiple testing into account.We found an odds ratio of 1.14 95%CI [1.05; 1.25] for decrements >20% in morning FEV1 per interquartile range (12 µg/m3) increase in NH3 concentration (lag 2). Odor annoyance was negatively associated with evening PEF (−4.46 l/min 95%CI [−7.59; −1.33]). Sensitivity analyses showed a stronger effect in participants with worse baseline lung function. No associations with symptoms were found.Our results show acute effects of livestock-related air pollution on lung function in COPD patients living in close proximity to livestock farms.

Acute respiratory effects of livestock related air pollution on a panel of COPD patients

GREEN, AIR, LMIC: PECHAKUCHA COMES TO ISEE! Johan Friso Foyer, Floor 1, August 27, 2019, 10:30 AM - 12:00 PM Living close to livestock farms has been associated with increased symptoms in patients with chronic obstructive pulmonary disease (COPD). The causes of these effects are still poorly understood. This panel study attempts to assess the acute effects of livestock related air pollution in patients with COPD living in an area with intensive livestock farming in the Netherlands. Between February 2015 and July 2016, 82 patients took spirometry measurements twice daily during a 3-month period, resulting in 12,672 FEV1 and PEF records. Patients also kept a diary on respiratory symptoms as well as livestock related odor annoyance. Daily average ammonia (NH3) (a proxy for livestock-related air pollution) and fine particulate matter (PM10) levels were collected from monitoring stations in the area. Lung function was analyzed as decrements of >10% and >20% from their median as well as absolute values. Self-reported odor annoyance was analyzed as a dichotomous variable. All analyses were done using generalized estimated equations. We adjusted for age, gender, height, humidity, temperature, linear trend, and took multiple testing into account. We found an odds ratio of 1.14 95%CI [1.05; 1.25] for decrements >20% in morning FEV1 per interquartile range (12µg/m3) increase in NH3 concentration (lag 2). Odor annoyance was negatively associated with evening PEF (-4.46 l/min 95%CI [-7.59; -1.33]). Sensitivity analyses comparing these associations between participants with different COPD definitions yielded no significant differences. No associations with symptoms were found. Our results show acute effects of livestock related air pollution on lung function in COPD patients living in close proximity to farms.

Efficacy of tiotropium in treating patients with moderate-to-severe asthma: A meta-analysis and systematic review based on 14 randomized controlled trials.

Background:The goal of the current meta-analysis and systematic review was to explore the efficacy of tiotropium in treating patients with moderate-to-severe asthma on the basis of qualified randomized controlled trials (RCTs).Methods:The following online electronic databases, such as Cochrane, PubMed, and Embase database were screened to identify qualified studies updated to January 2019 through the use of index words. Several literatures that were relevant to the present analysis were also included. To further analyze the main outcomes, we utilized the odds rations (OR), and mean difference (MD) along with its 95% confidence interval (95% CI).Results:A total of 14 RCTs with 4998 patients in the tiotropium group and 5074 patients in the control group were included in the present study. On the basis of the pooled results, tiotropium was significantly associated with improved morning PEF (SMD: 3.29, 95%CI: 2.03–4.55), evening PEF (SMD: 3.36, 95%CI: 2.24–4.48), peak FEV (SMD: 2.67, 95%CI: 1.47–3.88), and trough FEV (SMD: 1.90, 95%CI: 0.87–2.92) vs the control group. Nevertheless, no significant difference was observed in peak FVC (SMD: 0.77, 95%CI: −0.21–1.76), trough FVC (SMD: 0.67, 95%CI: −0.18–1.53), AE (RR: 0.98, 95%CI: 0.94–1.02) and serious AE (RR: 1.08, 95%CI: 0.77–1.52) between the 2 groups.Conclusions:In this review, we summarized the significant effect of tiotropium for the treatment of moderate-to-severe asthma, mainly in increasing morning PEF, evening PEF, peak FEV and trough FEV based on high-quality RCTs. Nevertheless, no significant difference in peak FVC, trough FVC, AE and serious AE was found between the 2 groups. A close comparison of the 2 groups revealed that more high-quality larger-sample RCTs are needed to gather more strong evidence on the therapeutic efficacy and safety of tiotropium for clinical practice.

Once-daily fluticasone furoate and vilanterol for adolescents and adults with symptomatic asthma: A systematic review with meta-analysis

BackgroundFluticasone furoate and vilanterol is a new inhaled corticosteroid (ICS) and long-acting β2-agonist (LABA) combination developed for once-daily administration via a dry powder inhaler. ObjectiveTo assess the efficacy and safety of fluticasone furoate–vilanterol in adolescents and adults with symptomatic asthma compared with ICS monotherapy or twice-daily ICS-LABA formulations. MethodsRandomized, placebo-controlled trials with longer than 8 weeks of treatment duration were included. Primary outcome was pulmonary function (forced expiratory volume in 1 second [FEV1] or peak expiratory flow rate [PEF]). ResultsSeven published randomized clinical trials were included (5,668 patients). Fluticasone furoate–vilanterol was associated with significant increases in trough FEV1 and morning and evening PEF compared with fluticasone furoate, 100 μg, monotherapy (90 mL, 20.1 L/min, and 18.9 L/min respectively). Fluticasone furoate–vilanterol reduced significantly the rate of severe asthma exacerbations (number need to treat for benefit = 24). Fluticasone furoate–vilanterol also produced significant increases in weighted FEV1 and morning and evening PEF (140 mL, 32.6 L/min, and 25.7 L/min, respectively) compared with fluticasone propionate, 500 μg twice daily. Fluticasone furoate–vilanterol presented a nonsignificant increase in the frequency of cardiac events (6.4% vs 1.8%) compared with fluticasone propionate. No differences were found between both available doses of fluticasone furoate–vilanterol (200/25 μg and 100/25 μg) in terms of efficacy. However, patients receiving fluticasone furoate–vilanterol, 200/25 μg, had a trend toward an increased risk of cardiac events. ConclusionFluticasone furoate–vilanterol combination was associated with an increase in trough FEV1 compared with fluticasone furoate–fluticasone propionate; however, observed differences may not be clinically significant. Studies comparing fluticasone furoate–vilanterol with fixed twice-daily ICS-LABA combinations are required.

Once daily nebulized beclomethasone is effective in maintaining pulmonary function and improving symptoms in asthmatic children

Compliance with long-term inhaled therapy in asthma is often poor, but it is likely to be improved with a simplified administration, once daily. The present study was designed to assess whether, in childhood asthma, a single dose of nebulized beclomethasone dipropionate once daily was as effective and safe as the same total daily dose administered twice daily. Asthmatic children, not treated with inhaled steroids for at least a month preceding the study and using short-acting bronchodilators more than once a week were enrolled in a double-blind, double dummy, randomised, multicentric study. After a two week run-in period on nebulised twice daily 400 mcg beclomethasone dipropionate, patients were randomly assigned to twelve weeks of treatment with 800 mcg nebulised beclomethasone dipropionate daily, either in single dose (o.d. group) or divided into two 400 mcg doses (b.i.d. group). 65 children (mean age 8.6 years, mean FEV1 81% of predicted), were valuable for intention to treat. During the run-in period, a significant improvement in FEV1, FVC, morning and evening PEF values and clinical scores was observed. Children then entered the randomised trial: 32 were included in the o.d. group and 33 in the b.i.d. group. During the twelve week treatment period, the observed improvement in pulmonary function parameters was maintained in both treatment groups. Morning and evening PEF showed a progressive slight increase as well as PEF diurnal variability showed a progressive reduction in the two treatment groups during the whole study period without reaching statistical significance. Moreover, in both treatment groups a similar progressive increase in symptom free nights and days and in the percentage of children achieving total asthma symptoms control was detected. Finally, no significant changes in urinary cortisol/creatinine ratio were observed throughout the study period and between groups. A daily dose of 800 mcg of beclomethasone, administered for twelve weeks with a nebuliser either once or twice daily provide similar efficacy in maintaining pulmonary function and symptoms of asthmatic children, with a good tolerability profile.

Ambient temperature and lung function in children with asthma in Australia

The association between ambient temperature and lung function in children with asthma is still uncertain. A panel of 270 children (aged 7-12 years) with asthma was recruited from six Australian cities. They performed three successive forced expiratory manoeuvres twice daily for 4 weeks. The highest peak expiratory flow rate (PEF) and forced expiratory volume in 1 s (FEV1) were stored for each session. During the same period, data were obtained daily on ambient temperature, relative humidity and air pollution. Mixed models were used to examine the effects of temperature on lung function, controlling for individual characteristics and environmental factors. Ambient temperature was negatively related to both morning and evening PEF and FEV1 for 0-3 days lag. In general, the effects of temperature were stronger in males than in females for evening PEF, while the effects were stronger in females for evening FEV1. Children with asthma living in southern cities were more sensitive to high temperature than those in the northernmost city. Higher ambient temperature is associated with lower lung function in children with asthma. Preventive health policies will be required to protect children with asthma from increasingly frequent high temperatures.

S7 Influence of Beta-2 Adrenoceptor Genotype on Response to Regular Racemic or Levosalbutamol in Steroid Treated Asthmatics

Background Asthmatic patients receiving inhaled corticosteroids often take frequent add-on therapy with albuterol despite on-demand prescription. We wished to evaluate trough methacholine airway hyper-responsiveness (the primary outcome) following regular treatment with racemic salbutamol and levosalbutamol compared to placebo, in steroid treated asthmatics stratified according to beta-2 adrenoceptor 16 genotype. Methods We performed a randomised, double-blind, placebo-controlled, triple crossover trial comparing 2 weeks of regular therapy with inhaled racemic salbutamol (200µg qid); levosalbutamol (100µg qid); or placebo on methacholine PC20 6 hours post dose in 30 persistent asthmatics (15 homozygous Arg16 and Gly16) receiving inhaled corticosteroids. Results There was no rebound worsening of trough airway hyper-responsiveness to methacholine after chronic exposure to either racemic (p=0.53) or levosalbutamol (p=0.84) compared to placebo; nor between genotypes - as doubling dilution (dd) difference in methacholine PC20 from placebo (Figure 1): salbutamol/Arg16= 0.36dd (95% CI: –0.43, 1.15); salbutamol/Gly16=0.01dd (95% CI: –0.47, 0.49); levosalbutamol/Arg16=–0.01dd (95% CI: –0.89, 0.87); levosalbutamol/Gly16=0.28dd (95% CI: –0.22, 0.77). Both active treatments improved morning PEF in Gly16 (p=0.04) but not Arg16 patients (p=0.50); while evening PEF improved in both Gly16 (p Conclusions Chronic exposure to either racemic or levosalbutamol added to inhaled corticosteroids did not cause rebound worsening of airway hyper-responsiveness at trough compared to placebo; with no difference seen between beta-2 adrenoceptor 16 genotypes.

Comparison of high‐dose salmeterol/fluticasone and moderate‐dose salmeterol/fluticasone plus low‐dose mometasone in patients with severe persistent asthma

The effects of adding a second inhaled corticosteroid with a different particle size, compared with using an increased dose of a single inhaled corticosteroid, were assessed in patients with persistent asthma. This was an open-label study of Japanese asthma patients over 20 years of age. After a 1-month run-in period, 36 patients with inadequate control while using salmeterol/fluticasone propionate 50/250 µg (SFC50/250) bd, were randomized to receive SFC50/500 bd or SFC50/250 plus mometasone 100 µg bd (SFC50/250/MF100) for 2 months. Both treatments resulted in improvements in morning and evening PEF. There were no significant changes in FEV(1) , maximum mid-expiratory flow, maximum expiratory flow rate at 50%, maximum expiratory flow rate at 25% or exhaled NO (FENO) in the SFC50/500 group. On the other hand, there were significant improvements in FEV(1) % (+12.2%, P = 0.0142), %maximum mid-expiratory flow (+28.9%, P = 0.0181), %MEF50 (+32.4%, P = 0.0206) and %MEF25 (+30.3%, P = 0.0113) in the SFC50/250/MF100 group. The changes in FENO (-23.2% (P = 0.0157) in the SFC50/250/MF100 group and -14.5% (not significant) in the SFC50/500 group) did not differ significantly between the groups. In patients with severe persistent asthma, addition of low-dose mometasone to SFC50/250 improved spirometric parameters, FENO and PEF, while an increase in dose from SFC50/250 to SFC50/ 500 only improved PEF.

Cochrane Review: Addition of long‐acting beta‐agonists to inhaled corticosteroids for chronic asthma in children

Cochrane Review: Addition of long‐acting beta‐agonists to inhaled corticosteroids for chronic asthma in children

Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children.

Long-acting ss(2)- agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed in asthmatic children. To compare the safety and benefit of adding LABA to ICS with the same or an increased dose of ICS in children with persistent asthma. We searched the Cochrane Airways Group Asthma Trials Register (May 2008). We included randomised controlled trials testing the combination of LABA and ICS versus the same or an increased dose of ICS for minimum of at least 28 days in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included pulmonary function, symptoms, adverse events, and withdrawals. Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. A total of 25 trials representing 31 control-intervention comparisons were included in the review randomising 5572 children. Most of the participants were inadequately controlled on current ICS dose. We assessed the addition of LABA to the same dose of ICS and to an increased dose of ICS:(1) The addition of LABA to ICS was compared to same dose ICS, namely 400 mcg/day of beclomethasone or less in 16 of the 24 studies. The mean age of participants was 10 years and males accounted for 64% of the study populations. The mean FEV(1) at baseline was 80% of predicted or above in 10 studies; FEV(1) 61% to 79% of predicted in eight studies; and unreported in the remaining study. Participants were inadequately controlled before randomisation in all but seven studies. Compared to ICS alone, the addition of LABA to ICS was not associated with a significant reduction in exacerbations requiring oral steroids (seven studies, RR 0.92 95% CI 0.60 to 1.40). Compared to ICS alone, there was a significantly greater improvement in FEV1 with the addition of LABA (nine studies; 0.08 Litres, 95% CI 0.06 to 0.11) but no statistically significant group differences in symptom-free days, hospital admission, quality of life, use of reliever medication, and adverse events. Withdrawals occurred significantly less frequently with the addition of LABA.(2) A total of seven studies assessed the addition of LABA to ICS therapy compared with an increased dose of ICS randomising 1021 children. The mean age of participants was 8 years with 67% of males. The baseline mean FEV(1) was 80% of predicted or above in 2 of the 3 studies reporting this characteristic. All trials enrolled participants who were inadequately controlled on a baseline dose equivalent to 400 mcg/day of beclomethasone or less. There was no group significant difference in the risk of an exacerbation requiring oral steroids with the combination of LABA and ICS compared to a double dose of ICS (two studies, RR 1.5 95% CI 0.65 to 3.48). The increased risk of hospital admission with combination therapy was also not statistically significant (RR 2.21 95% CI 0.74 to 6.64). Compared to double dose ICS, use of LABA was associated with a significantly greater improvement in morning PEF (four studies; MD 7.55 L/min 95% CI: 3.57 to 11.53) and evening PEF L/min (three studies, MD 5.5 L/min; 95% CI 1.21 to 9.79), but there were insufficient data to aggregate data on FEV(1), symptoms, rescue reliever use, and quality of life. There was no statistically significant difference in the overall risk of all cause withdrawals (five studies; RR 0.71; 95% CI 0.42 to 1.20. There was no group difference in the risk of overall adverse effects detected. Short term growth was significantly greater in children treated with combination therapy compared to double dose ICS (two studies: MD 1.2 cm/year; 95% CI 0.72 to 1.7). In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but was superior for improving lung function compared to the same dose of ICS. Similarly, compared to a double dose ICS, the combination of LABA and ICS did not significantly increase the risk of exacerbations requiring oral steroids, but was associated with a significantly greater improvement in PEF and growth. The possibility of an increased risk of rescue oral steroids and hospital admission with LABA therapy needs to be further examined.

Benefits of fixed‐dose combination therapy with inhaled corticosteroids and long‐acting bronchodilators as initial maintenance therapy in the management of asthma

Revised Australian guidelines for asthma management were released by the National Asthma Council (NAC) in 2006. One area where clinical opinion and trial data have changed recently concerns the place of fixed-dose combination (FDC) therapy with inhaled corticosteroid (ICS) and long-acting beta(2)-agonists as initial maintenance therapy. A systematic review of the literature commissioned by the NAC and undertaken by the University of Tasmania addressed several questions, including whether there was evidence for the use of FDC therapy as first-line asthma treatment in steroid-naïve patients. Nineteen relevant studies were identified, from which 20 comparisons contributed to the analyses. The definition of steroid-naïve ranged from no ICS therapy over the preceding 1 month to no ICS therapy ever. FDC therapy was effective in subjects who were steroid-naïve and was more effective than an equivalent dose of ICS, irrespective of the definition of steroid-naïvety. Compared with ICS alone, FDC therapy increased mean FEV(1) by 140 mL, mean morning PEF by 21 L/min and mean evening PEF by 20 L/min. There was a mean increase of 9.8% in symptom-free days, associated with a greater reduction in rescue medication use of -0.12 puff/24 h. FDC therapy was not superior to ICS alone for prevention of withdrawals or exacerbations requiring systemic corticosteroids. Adverse events were similar for FDC therapy and ICS, whether ICS were administered at the same or an increased dose. FDC therapy is effective as first-line treatment in steroid-naïve subjects and is superior to ICS alone for most outcomes, irrespective of the period of time since last exposure to ICS.

Maintaining asthma control in persistent asthma: Comparison of three strategies in a 6-month double-blind randomised study

In patients controlled with SFC250 Diskus bd, this double-blind, randomised 6-month study compared continuing SFC250 to stepping down to either SFC100 bd or FP250 bd. Six hundred and three patients previously using 1,000 microg BDP (or equivalent) daily +LABA and controlled according to investigator's judgement were recruited. Patients received SFC250 bd during an 8-week open run-in period. Four hundred and seventy six patients (mean age=43 years, mean FEV(1)=2.9+/-1.0) who fulfilled the randomisation criterion ('Well-controlled' asthma according to the GOAL weekly definition for the last 2 weeks of the run-in period) entered a 24-week treatment period. The statistical hypothesis was based on a non-inferiority of SFC100 or FP250 compared to SFC250. The main criterion was the change from baseline in morning PEF over weeks 1-12 in the per-protocol population. The non-inferiority limit was -15 L/min. At inclusion, the three treatment groups were well balanced. Mean morning PEF was 476, 470 and 465 L/min in the SFC250, SFC100 and FP250 groups, respectively. The adjusted mean change in morning PEF over weeks 1-12 was +1.76+/-2.43 L/min for SFC250, -3.07+/-2.32 L/min for SFC100 and -16.51+/-2.46 L/min for FP250. SFC100 was at least as effective as SFC250 (treatment difference -4.83 [-12.39; 2.72], p=0.151) whereas FP250 was not (treatment difference -18.27 [-26.05; -10.49], p<0.001). Similar results were observed over weeks 13-24 in morning PEF (SFC100-SFC250=-4.54+/-3.84, p=0.238; FP250-SFC250=-20.11+/-3.92, p<0.0001). Secondary endpoints showed a similar pattern. Over weeks 1-12, SFC250 was significantly more effective than FP250 on evening PEF, daily symptoms and bronchodilator use. There was no difference between SFC100 and SFC250. The mean annual rate of moderate exacerbations was 0.16 in both SFC 250 and SFC 100 groups, and 0.21 in FP 250 group (ns, Poisson analysis). All treatments were well tolerated. In patients achieving asthma control with SFC250, stepping treatment down with SFC100 was at least as effective on lung function and symptoms as continuing SFC250, whereas FP250 was not.

Efficacy and Safety of Formoterol in Japanese Patients with COPD

This study evaluated the efficacy and safety of the formoterol Turbuhaler at dosages of 4.5, 9 and 18 microg bid compared with placebo in Japanese patients with COPD. In this randomized, double-blind, placebo-controlled, multicenter study, 36 patients with a pre-bronchodilator FEV(1) value within 40 to 70% of the predicted value were randomized to receive formoterol at doses of 4.5, 9, and 18 microg bid, and placebo, for 1 week in a crossover fashion. The primary outcome variable, one hour post-dose FEV(1) on the last day of the one week treatment period, was significantly higher for all formoterol dosages compared with placebo (p<0.001 for all doses); adjusted g-means for formoterol 4.5, 9 and 18 microg bid, and placebo, were 1.510 L, 1.491 L, 1.520 L and 1.342 L, respectively. All three dosages of formoterol also provided significantly better improvements than placebo in the secondary variables FVC, inspiratory capacity (IC) and morning and evening PEF. Results for IC and PEF indicated a trend towards a larger improvement at higher dosages. Treatment with formoterol at dosages of 4.5, 9 and 18 microg bid showed significantly superior effects to placebo on FEV(1) in Japanese patients with COPD. The results for some of the secondary variables (IC and PEF) indicated a trend towards larger improvements at higher dosages. All dosages of formoterol were well tolerated in Japanese patients.

Fluticasone versus beclomethasone or budesonide for chronic asthma in adults and children.

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma. We searched the Cochrane Airways Group trial register (January 2007) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2006). Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1. Seventy-one studies (14,602 participants) representing 74 randomised comparisons met the inclusion criteria. Methodological quality was fair. Dose ratio 1:2: FP produced a significantly greater end of treatment FEV1 (0.04 litres (95% CI 0 to 0.07 litres), end of treatment and change in morning PEF, but not change in FEV1 or evening PEF. This applied to all drug doses, age groups, and delivery devices. No difference between FP and BDP/BUD were seen for trial withdrawals. FP led to fewer symptoms and less rescue medication use. When given at half the dose of BDP/BUD, FP led to a greater likelihood of pharyngitis. There was no difference in the likelihood of oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured frequently but data presentation was limited. Dose ratio 1:1: FP produced a statistically significant difference in morning PEF, evening PEF, and FEV1 over BDP or BUD. The effects on exacerbations were mixed. There were no significant differences incidence of hoarseness, pharyngitis, candidiasis, or cough. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing sore throat and when given at the same daily dose leads to increased hoarseness. There are concerns about adrenal suppression with Fluticasone given to children at doses greater than 400 mcg/day, but the randomised trials included in this review did not provide sufficient data to address this issue.

Comparison of twice-daily inhaled ciclesonide and fluticasone propionate in patients with moderate-to-severe persistent asthma

Objective To investigate the relative efficacy of ciclesonide and fluticasone propionate (FP) administered at comparable microgram doses in maintaining asthma control in patients with moderate-to-severe persistent asthma. Methods This randomized, open-label, parallel-group study enrolled patients aged 12–75 years with a ⩾6-month history of bronchial asthma. To enter a 2-week run-in period, patients had to have received FP 500–1000 μg/day or equivalent at a stable dose for ⩾4 weeks and have a forced expiratory volume in 1 s (FEV 1) ⩾80% of predicted. To enter the treatment period, patients had to have the following during run-in: FEV 1 ⩾80% of predicted; reversibility of ΔFEV 1 ⩾12% after 200–400 μg salbutamol; and ⩾1 day without asthma symptoms during the last 7 days. Patients were randomized to twice-daily ciclesonide 320 μg (ex-actuator) or twice-daily FP 330 μg (ex-actuator) for 6 months. Efficacy was assessed by lung function, asthma exacerbations, asthma symptoms and rescue medication use. Patients completed the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Adverse events (AEs), including local oropharyngeal AEs, were recorded. Results 528 patients were randomized (ciclesonide, n=255; FP, n=273). In both groups, FEV 1 was maintained from baseline to study end (mean increase: ciclesonide 11 mL, FP 24 mL; intention-to-treat [ITT] analysis). The least squares mean±standard error of the mean for the treatment difference was −13±29 (95% confidence interval [CI]: −70, 44) in the ITT analysis and −27±34 (95% CI: −93, 40) in the per-protocol (PP) analysis, demonstrating non-inferiority of ciclesonide to FP. Morning, evening and site-measured PEF improved significantly with both treatments (ITT and PP analyses: p<0.05). Six patients receiving ciclesonide and seven receiving FP (ITT analysis) experienced an asthma exacerbation requiring treatment with oral corticosteroids. Both treatments significantly decreased asthma symptom score sum (ITT and PP analyses: p⩽0.0001) and rescue medication use (ITT and PP analyses: p<0.05), with no significant difference between treatments. Both treatments significantly improved overall AQLQ(S) score (ITT and PP analyses: p<0.05). Significantly more patients experienced candidiasis and dysphonia with FP compared with ciclesonide ( p=0.0023). Conclusion Ciclesonide 320 μg and FP 330 μg administered twice daily over 6 months provided similar efficacy in patients with moderate or severe persistent asthma previously well-controlled by high doses of ICS at baseline. Ciclesonide was associated with fewer local AEs than FP.

Nedocromil sodium for chronic asthma in children.

Currently inhaled corticosteroids are the main stay in the maintenance treatment of chronic asthma in children. Although inhaled corticosteroids play a crucial role in the management of childhood asthma, the long-term side effects of inhaled corticosteroids used in the management of chronic asthma in children are not clearly known. The objective of this review is to compare the safety and efficacy of inhaled nedocromil sodium with placebo in the treatment of chronic asthma in children. We searched the Cochrane airway group trials register, Cochrane controlled trials register, Current contents, review articles, reference lists of articles. We also contacted the drug manufacturer and primary authors for additional citations. We also searched abstracts of major respiratory society meetings. The last search was carried out in October 2004 Randomised placebo controlled trials comparing nedocromil sodium to placebo in the treatment of chronic asthma in children (0 to 18 years). Both authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Fifteen trials (twelve parallel group studies; three crossover trials recruiting 1422 children (837 males and 585 females)) were included. The studies were generally of good methodological quality. Two large long term studies used nedocromil for six months and four to six years and showed conflicting results in symptom free days. Short term studies (duration between 4 weeks to 12 weeks) showed that nedocromil sodium produced some improvement in a number of efficacy measures compared to placebo including FEV(1), FVC, FEV(1) % predicted, PC20 FEV(1), evening PEF and symptom scores. The parent's assessment of efficacy was in favour of nedocromil (odds ratio (OR) 0.5 (95% CI 0.3 to 0.8). Nedocromil sodium has a good safety profile. The only significant side effect observed was unpleasant taste. There was little evidence for a clinically dose response effect and only a few studies recruited participants with severe asthma. A limited number of small studies have shown that nedocromil is of benefit in improving lung function and some measures of symptoms, but the evidence with regard to the primary outcome of the review was conflicting. Two long-term trials did not show consistent effects on lung function outcomes, whereas several small short-term trials have shown benefit in these outcomes. Differing severities at baseline may explain this difference with milder participants experiencing less benefit, although the discrepancy between study findings may also reflect publication bias. Nedocromil sodium is associated with a very good safety profile with no significant short term or long- term adverse side effects. Although nedocromil may have advantages over inhaled corticosteroids in terms of side effects, there is a need for head to head trials of nedocromil and inhaled corticosteroids to establish whether asthma control is similar, especially in mild asthma. It is not yet clear where nedocromil should sit in relation to other therapies in the treatment of asthma in children.

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Long-acting beta2-agonists as an inhaled corticosteroid-sparing agent for chronic asthma in adults and children.

The addition of a long acting beta agonist (LABA) to inhaled corticosteroid (ICS) therapy can improve asthma symptoms and reduce exacerbations. The addition of LABA may also have an ICS-sparing effect and permit a reduction in ICS maintenance dose. To determine the efficacy of adding LABA to maintenance ICS therapy in reducing the requirement for ICS while maintaining control of chronic asthma. We searched the Cochrane Airways Group trials register and reference lists of articles. Date of last search: November 2004 Parallel RCTs that compared reduced dose ICS in combination with LABA vs ICS alone in asthmatics requiring daily ICS. Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. Trials were analysed according to the following ICS dose comparisons: a fixed moderate/high dose or a reduced/tapering dose of the same ICS. 19 publications describing 10 trials of adults were included in the review. Studies that compared reduced dose (mean 60% reduction) ICS/LABA combination to a fixed moderate/high dose ICS found no significant difference in severe exacerbations requiring oral corticosteroids (RR 1.0, 95%CI 0.76 to 1.32), withdrawal due to worsening asthma (RR 0.82, 95%CI 0.5 to 1.35) or airway inflammation. There were also significant improvements in FEV1 (change from baseline WMD 0.10, 95%CI 0.07 to 0.12), morning & evening PEF and percent rescue free days with LABA. Two studies provided outcomes for a reduced/tapering ICS dose comparison. More participants receiving the LABA/reduced ICS combination achieved a reduction in ICS dose reaching significance in one study. A significant reduction of 253 mcg BDP was achieved in one study. In adults with asthma, using moderate to high maintenance doses of ICS, the addition of LABA has an ICS-sparing effect. The addition ofLABA permits more participants on minimum maintenance ICS to reduce ICS. The precise magnitude of the ICS dose reduction requires further study.