Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease

BACKGROUND—Inhaled corticosteroids are known to bebeneficial for patients with asthma, but their role in treatingpatients with stable chronic obstructive pulmonary disease (COPD)remains controversial. A study was undertaken to determine whetherinhaled corticosteroids are of functional benefit in patients who didnot show improvement with a trial of oral corticosteroids.
METHODS—In phase I patients with stable COPD weregiven a two week course of oral placebo followed by two weeks ofprednisone 40 mg per day in a single blind manner to distinguishbetween responders and non-responders to oral corticosteroids. In phaseII a double blind, randomised, parallel group trial of inhaledbudesonide 1600 µg per day versus placebo was carried out in 79 non-responders to oral corticosteroids. The primary outcome measure wasforced expiratory volume in one second (FEV₁), andsecondary outcome measures were exercise capacity, dyspnoea withexertion, quality of life, peak expiration flow rate, and respiratory symptoms.
RESULTS—Randomisation allocated 39 subjects toinhaled corticosteroids and 40 to placebo. There was no difference inthe change in FEV₁ from baseline between the treatment andplacebo groups; mean difference -12 ml (95% CI -88 to 63) at threemonths and -4 ml (95% CI -95 to 87) at six months. The proportionof patients with a 15% or greater improvement was no higher amongthose receiving inhaled corticosteroids than in the placebo group atany of the follow up visits. Changes in secondary outcomes were also no different.
CONCLUSIONS—Inhaledcorticosteroids,even at high doses, were of no physiological or functional benefit inthese patients with advanced COPD.

     

Effects of theophylline and ipratropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease

BACKGROUND—The effects of theophylline oranticholinergic agents on exercise capacity in patients with chronicobstructive pulmonary disease (COPD) remain controversial. The aim ofthe present study was to compare the effect of an oral theophyllinewith an inhaled anticholinergic agent and to examine the effects ofcombined therapy on exercise performance using progressive cycle ergometry.
METHODS—Twenty one men with stable COPD anda mean (SD) forced expiratory volume in one second (FEV₁)of 1.00 (0.40) l were studied. Theophylline (600 or 800 mg daily),ipratropium bromide (160 µg), a combination of both drugs, andplacebo were given in a randomised, double blind, four period crossoverdesign study. Spirometric data, pulse rate, and blood pressure wereassessed before and at 90 and 120 minutes after inhalation. Symptomlimited progressive cycle ergometer exercise tests (20 watts/min) wereperformed 90minutes after each inhalation, and dyspnoea was measuredduring exercise using the Borg scale.
RESULTS—The mean (SD) serum theophyllineconcentration was 18.3 (6.3) µg/ml, and seven patients had sideeffects during treatment with theophylline. Theophylline andipratropium bromide produced greater increases in FEV₁,maximal oxygen consumption, maximal minute ventilation, and severaldyspnoea ratios than placebo. There were no differences betweentheophylline and ipratropium bromide except in maximal heart rate. Acombination of both drugs produced greater improvements in pulmonaryfunction and exercise capacity than either drug alone.
CONCLUSIONS—Both high dose theophylline and highdose ipratropium bromide improved exercise capacity in patients withstable COPD. Although data based on short term effects cannot bedirectly applied to long term therapy, theophylline added to an inhaledanticholinergic agent may have beneficial effects on exercise capacityin patients with COPD.

     

Clinical impact of levofloxacin inhalation solution in cystic fibrosis patients in a real-world setting

BackgroundLevofloxacin inhalation solution is the most recently approved inhaled antibiotic in Europe and Canada for adult cystic fibrosis patients. Its efficacy and safety have been assessed in randomized controlled trials. Our aim was to evaluate real life experience and outcomes in our treatment centre.MethodsWe evaluated the efficacy of inhaled levofloxacin solution in 86 patients with cystic fibrosis in terms of the following outcome parameters: changes in %-predicted forced expiratory volume in one second (FEV₁), body-mass index (BMI), and exacerbation rate. We conducted an intraindividual analysis of patients who received levofloxacin inhalation solution twice daily 240 mg for at least 4 weeks.ResultsChange in FEV₁% predicted for the treatment period was +2.27% (p=0.0027) after 4 weeks. There was no change in BMI for overall group, but exacerbation rate compared to one year before initiation of inhaled levofloxacin decreased significantly (p=0.0024) after 1 year of treatment (3.23 ± 1.39 versus 2.71 ± 1.58).ConclusionsIn patients with cystic fibrosis, inhaled levofloxacin solution has the potential to improve FEV₁ and to reduce the number of bronchopulmonary exacerbations.     

Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma

Background: Although inhaled corticosteroids have an established role in the treatment of asthma, studies have tended to concentrate on non-smokers and little is known about the possible effect of cigarette smoking on the efficacy of treatment with inhaled steroids in asthma. A study was undertaken to investigate the effect of active cigarette smoking on responses to treatment with inhaled corticosteroids in patients with mild asthma. Methods: The effect of treatment with inhaled fluticasone propionate (1000 µg daily) or placebo for 3 weeks was studied in a double blind, prospective, randomised, placebo controlled study of 38 steroid naïve adult asthmatic patients (21 non-smokers). Efficacy was assessed using morning and evening peak expiratory flow (PEF) readings, spirometric parameters, bronchial hyperreactivity, and sputum eosinophil counts. Comparison was made between responses to treatment in non-smoking and smoking asthmatic patients. Results: There was a significantly greater increase in mean morning PEF in non-smokers than in smokers following inhaled fluticasone (27 l/min v –5 l/min). Non-smokers had a statistically significant increase in mean morning PEF (27 l/min), mean forced expiratory volume in 1 second (0.17 l), and geometric mean PC₂₀ (2.6 doubling doses), and a significant decrease in the proportion of sputum eosinophils (–1.75%) after fluticasone compared with placebo. No significant changes were observed in the smoking asthmatic patients for any of these parameters. Conclusions: Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in mild asthma. This finding has important implications for the management of patients with mild asthma who smoke.     

Response of patients receiving high dose beclomethasone dipropionate

Costello, J. F. and Clark, T. J. H. (1974).Thorax, 29, 571-573. Response of patients receiving high dose beclomethasone dipropionate. Beclomethasone dipropionate was inhaled by 16 patients with asthma in a dose of 1 mg daily for periods up to 24 weeks. No evidence of adrenal suppression was found in these patients as judged by basal cortisol levels. A further group of five patients with asthma inhaled 2 mg daily of beclomethasone dipropionate for periods up to 10 weeks and no evidence of adrenal suppression was found. A separate group of five patients was found to respond to increasing doses of beclomethasone dipropionate by increasing their forced expiratory volume in the first second. The results suggest that increased doses of beclomethasone dipropionate may provide additional benefit while continuing to avoid unwanted systemic side effects.     

Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids.

BACKGROUND: Asthmatic patients taking low to moderate doses of inhaled topical corticosteroids have been shown to have lower bone density than those taking bronchodilators only. There is little information on bone density in asthmatic patients taking high dose inhaled corticosteroids. METHODS: Bone mass was studied in three age matched groups of asthmatic patients. These comprised: 17 asthmatic patients who had never taken inhaled or systemic corticosteroids (group 1); 20 patients who had taken beclomethasone diproprionate in a dosage of 1000-2000 micrograms daily for at least a year, who had also received courses of systemic corticosteroids in the past (group 2); and 20 patients who were taking both high dose inhaled corticosteroids and regular low dose prednisolone, at a median dose of 7 mg daily (group 3). Vertebral bone density was measured by quantitative computed tomography. Biochemical indices of bone formation and resorption were also measured. RESULTS: Mean bone density in group 2 (127.5(22.6) mg/ml) was similar to that in group 3 (114.5 (36.0) mg/ml). Bone density was significantly lower in both of these groups than in group 1 (160.4 (27.4) mg/ml). There were no significant differences between groups for any of the markers of bone formation and resorption. CONCLUSIONS: Asthmatic patients receiving high dose inhaled beclomethasone and intermittent courses of systemic corticosteroids have reduced vertebral bone density. The bone loss is similar in degree to that seen in patients taking high dose inhaled topical corticosteroids and continuous low dose systemic corticosteroids.     

Inhaled aztreonam for chronic Burkholderia infection in cystic fibrosis: A placebo-controlled trial

BackgroundIndividuals with Burkholderia spp. infection have historically been excluded from efficacy trials of inhaled antibiotics, including aztreonam for inhalation solution (AZLI).MethodsA double-blind, placebo-controlled, 24-week trial of continuous AZLI/placebo treatment was undertaken in individuals with cystic fibrosis (CF) and chronic Burkholderia spp. infection. All subjects also received usual medical care (determined by their physicians). Additional antibiotic use was not restricted.ResultsBaseline FEV₁% predicted values ranged from 15.8% to 114.6%. No significant treatment differences (AZLI vs. placebo) were observed at week 24 for any endpoints, including FEV₁% predicted, number of respiratory exacerbations requiring systemic/inhaled antibiotics, or hospitalizations. Continuous AZLI administration was well tolerated. Burkholderia spp. susceptibility to antibiotics commonly used in CF therapy showed little change.Conclusions24-weeks of continuous AZLI treatment did not significantly improve lung function in CF subjects with chronic Burkholderia spp. infection. Non-study antibiotic use may have confounded any potential AZLI effects.     

Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease

BACKGROUND—Airwaysinflammation is a feature of chronic obstructive pulmonary disease(COPD), but the role of corticosteroids in the management ofclinically stable patients has yet to be established. A randomisedcontrolled study was carried out to investigate the effect of high doseinhaled beclomethasone dipropionate (BDP) administered for two monthsto patients with stable, smoking related COPD. Sputum induction wasused to evaluate bronchial inflammation response.
METHODS—34 patients(20 men and 14 women) were examined on three separate occasions. At theinitial clinical assessment (visit 0), spirometry and blood gasanalysis were performed. On visit 1 (within one week of visit 0) sputuminduction was performed and each patient was randomised to receiveeither BDP 500 µg three times daily (treated group) or nothing(control group). After two months (visit 2), all patients underwentrepeat clinical assessment, spirometry, and sputum induction.
RESULTS—There were nodifferences in sputum cell counts between the groups at baseline. Aftertwo months of treatment, induced sputum samples from patients in thetreated group showed a reduction in both neutrophils (−27%) andtotal cells (−42%) with respect to baseline, while the control groupdid not (neutrophils +9%, total cells +7%). Macrophages increased inthe treated group but not in the control group. The mean final value ofsputum neutrophils was 52% in the treated group and 73.3% in thecontrol group (95% confidence interval (CI) −27.2 to −15.4). Themean final value of sputum macrophages was 35.8% in treated group and19.3% in control group (95% CI 10.3 to 22.8). The differences betweenthe treated and control groups for neutrophils (−21.3%), macrophages (+16.5%), and total cells (−65%) were significant. Spirometry andblood gas data did not change from baseline in either patient group.
CONCLUSIONS—A twomonth course of treatment with high dose inhaled BDP reducessignificantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness ofinhaled steroids in COPD are needed to confirm the clinical importanceof this observation.

     

Consensus document on the overlap phenotype COPD-asthma in COPD

IntroductionAlthough asthma and COPD are different pathologies, many patients share characteristics from both entities. These cases can have different evolutions and responses to treatment. Nevertheless, the evidence available is limited, and it is necessary to evaluate whether they represent a differential phenotype and provide recommendations about diagnosis and treatment, in addition to identifying possible gaps in our understanding of asthma and COPD.MethodsA nation-wide consensus of experts in COPD in two stages: (1) during an initial meeting, the topics to be dealt with were established and a first draft of statement was elaborated with a structured “brainstorming” method; (2) consensus was reached with two rounds of e-mails, using a Likert-type scale.ResultsConsensus was reached about the existence of a differential clinical phenotype known as “Overlap Phenotype COPD–Asthma”, whose diagnosis is made when 2 major criteria and 2 minor criteria are met. The major criteria include very positive bronchodilator test (increase in FEV₁ ≥15% and ≥400 ml), eosinophilia in sputum and personal history of asthma. Minor criteria include high total IgE, personal history of atopy and positive bronchodilator test (increase in FEV₁ ≥12% and ≥200 ml) on two or more occasions. The early use of individually adjusted inhaled corticosteroids is recommended, and caution must be taken with their abrupt withdrawal. Meanwhile, in severe cases the use of triple therapy should be evaluated. Finally, there is an obvious lack of specific studies about the natural history and the treatment of these patients.ConclusionsIt is necessary to expand our knowledge about this phenotype in order to establish adequate guidelines and recommendations for its diagnosis and treatment.     

Does nedocromil sodium have a steroid sparing effect in adult asthmatic patients requiring maintenance oral corticosteroids?

A randomised, double blind, placebo controlled trial of nedocromil sodium was undertaken to assess its corticosteroid sparing effect in 50 adults with asthma who had required an oral corticosteroid dose of (or equivalent to) at least 5 mg prednisolone a day continuously during the preceding year, in addition to inhaled beclomethasone dipropionate and bronchodilators. Patients having corticosteroids other than prednisolone were changed to prednisolone. A four week baseline period was followed by 20 weeks of inhaled nedocromil sodium (16 mg daily) or placebo. After four weeks of the treatment phase an attempt was made to reduce the oral prednisolone maintenance dose by 2.5 mg a fortnight until a dose of 5 mg daily was reached and thereafter by 1 mg a fortnight, provided that there was no significant clinical deterioration as judged by clinic assessments and daily diary cards. Of 50 patients recruited, 47 entered the treatment phase (age range 16-64 years), 24 receiving nedocromil sodium and 23 placebo. The total steroid reduction achieved was 2.5 mg in the nedocromil group and 3 mg in the placebo group, which did not differ significantly. There was no significant change in symptoms, lung function or inhaler use in either group during the study. The number of patient requiring short term upward adjustment of booster doses of oral prednisolone for exacerbations of asthma was similar in the two groups (26 with placebo, 28 with nedocromil). Thus nedocromil sodium does not appear to provide an oral corticosteroid sparing effect in chronic steroid dependent asthma.     

Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate.

One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a randomised, double blind, placebo controlled, crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day, both given for two weeks. One hundred and seven patients completed the study. Response was assessed as change in FEV1 and FVC measured on the last treatment day, and as change in mean peak expiratory flow (PEF) over the final seven days of treatment from home PEF recordings performed five times daily. A full response to treatment was defined as an increase in FEV or FVC, or an increase in mean daily PEF over the final seven days of treatment, of at least 20% from baseline values. An improvement in one measurement of at least 15%, or of 10% in any two measurements, was defined as a partial treatment response. Response to placebo showed a significant order effect, suggesting a carry over effect of active treatment of at least three weeks. Response to active treatment was therefore related to initial baseline values, and compared with placebo by considering responses in the first treatment phase only. A full response to oral prednisolone (16/38) was significantly more common than to placebo (3/35). The number of full responses to inhaled beclomethasone (8/34) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase, though full and partial responses to inhaled beclomethasone (12/34) were significantly more common than those to placebo (4/35). When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment, a response to prednisolone (39) occurring more frequently than to inhaled beclomethasone (26). Only 21 of the 44 responders showed a response to both forms of treatment. Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day, but better than placebo, in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction. It was, however, an effective alternative in over half of those showing a response to prednisolone.     

Randomised placebo controlled trial of β agonist dose reduction in asthma

BACKGROUND—Manypatients continue to take regular β agonists, often at high doses,contrary to national and international guidelines. Some studies havesuggested that this can worsen asthma control, but whether suchpatients can reduce their dose of β agonist and whether they wouldbenefit from this has not been determined. Reduction of β agonistdose was studied in a placebo controlled parallel group study.
METHODS—Followinga run in period, 33 subjects with asthma taking regular β agonistswere converted to an equivalent dose of terbutaline via a Turbohaler.Two weeks later terbutaline was continued at the same dose or changedto placebo in two stages a week apart. The change over period wascovered by an increased dose of inhaled steroid to attenuate anyimmediate effects of the change in dose. Subjects then attended weeklyfor six weeks for measurement of forced expiratory volume in one second(FEV₁) and the dose of methacholine that produced a 20%fall in FEV₁ (PD₂₀). Peak expiratory flow (PEF)and symptom scores were recorded twice daily throughout the study.Exacerbations, lung function, bronchial responsiveness, bronchodilatorresponse, β agonist use, and symptoms were compared before and sixweeks after reduction in the dose of βagonist.
RESULTS—Twenty five ofthe 33 subjects completed the study; three patients in each groupwithdrew due to an asthma exacerbation. The median terbutaline dosefell from 2500 to 500 µg/day in the βagonist reduction group andfrom 3000 to 2250 µg/day in the control group. There were smallnon-significant changes in FEV₁, PEF, symptom scores andPD₂₀ methacholine over the course of the study. TheFEV₁ response to a β agonist was greater in those whoreduced their β agonist dose than in the control group although thefinal FEV₁ achieved was the same.
CONCLUSIONS—Patientswith asthma taking high doses of β agonists can reduce the amount ofβ agonist they use without a significant change in their asthmacontrol. There was no evidence of improved asthma control with β agonist dose reduction.

     

64层螺旋CT低剂量双相扫描测定肺体积评价慢性阻塞性肺疾病患者肺功能

目的探讨64层CT低剂量双相扫描肺体积测量指标评估慢性阻塞性肺疾病(COPD)患者肺功能的价值。方法选择经临床肺功能检查确诊的36例COPD患者(COPD组)及30名健康体检者(正常对照组),采用64层CT行深吸气末、深呼气末全肺低剂量(50mAs)及常规剂量(100mAs)吸气末扫描,得出每次扫描的容积CT剂量指数(CTDIvol)和剂量长度乘积(DLP),并换算出有效剂量(ED)。以配对样本t检验比较两组间不同扫描剂量及不同呼吸状态下的CT-DIvol、DLP、ED;应用Fisher确切概率法比较CT图像质量。按扫描层数将全肺分为上、中、下3个肺区,应用Pulmo软件测量和计算COPD组与正常对照组的各体积指标:深吸气末体积(Vin)、深呼气末体积(Vex)、体积差(Vin-Vex)、体积比(Vex/Vin)、体积变化百分比(Vin-Vex)/Vin×100%。于CT检查前后3天完成PFT检查,对比研究指标为第1秒用力肺活量(FEV1)的实测值与预计值的比值(FEV1%)及FEV1与用力肺活量(FVC)的比值(FEV1/FVC)。结果所有图像均成功用于自动分割技术与数据处理。与正常对照组比较,COPD组除各肺区的Vin及上肺区Vin-Vex外,其余各体积指标差异均有统计学意义(P均<0.05);Vex、Vex/Vin、(Vin-Vex)/Vin×100%均与FEV1%、FEV1/FVC存在相关性(P<0.01)。结论 64层CT低剂量双相扫描肺体积指标可较好评价COPD患者肺功能,临床应用价值较高。     

Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

BACKGROUND: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids does not appear to be as effective as similar treatment of asthma. It seems that only certain subgroups of patients with COPD benefit from steroid treatment. A study was undertaken to examine whether inhaled fluticasone propionate (FP) had an effect on lung function and on indices of inflammation in a subgroup of COPD patients with bronchial hyperresponsiveness (BHR). METHODS: Twenty three patients with COPD were studied. Patients had to be persistent current smokers between 40 and 70 years of age. Non-specific BHR was defined as a PC(20) for histamine of 相似文献   

Effects of short-term and long-term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Dutch CNSLD Study Group.

BACKGROUND--Recent reports have suggested short-term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain. METHODS--Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long-term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 micrograms inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 micrograms beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2.5 years of treatment. RESULTS--In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids. CONCLUSIONS--No detrimental long-term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long-term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short-term studies with single serum parameters of bone metabolism, but well designed long-term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism.     

Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease

BACKGROUND: Combined treatment with inhaled corticosteroids and long acting beta2 agonists is approved for the treatment of chronic obstructive pulmonary disease (COPD), but little is known about the onset of effect of the combination. METHODS: Data were used from 1465 patients with COPD entered into a large 1 year double blind trial with daily measurements of peak expiratory flow (PEF) and symptom scores. RESULTS: PEF was significantly higher after 1 day in patients treated with salmeterol 50 microg twice daily or the salmeterol/fluticasone propionate combination 50/500 microg twice daily than placebo. In patients treated with fluticasone propionate 500 microg twice daily alone, PEF differed from placebo after 2 days. The differences after 2 weeks compared with placebo were 16 l/min (95% confidence interval (CI) 11 to 21), 11 l/min (95% CI 6 to 16), and 27 l/min (95% CI 22 to 33) for salmeterol, fluticasone propionate, and the salmeterol/fluticasone propionate combination, respectively. For all treatments the effect on PEF after 2 weeks was comparable to that seen at the end of the study. The difference between the salmeterol/fluticasone propionate combination and placebo after 2 weeks as a percentage of baseline was similar for PEF and clinic forced expiratory volume in 1 second (FEV1). Differences in breathlessness scores were statistically significant after 1 day for the group treated with salmeterol alone and after 2 days for the combination group. The 2 week change in FEV1 was only partly indicative of a long term response in individual patients. CONCLUSIONS: The effects of salmeterol and fluticasone propionate, alone or in combination, on PEF and breathlessness are seen within days and most of the obtainable effect on these parameters is reached within 2 weeks.     

Impact of Preventive Treatment With Long-Acting β2-Adrenergic Agonists and Inhaled Corticosteroids on the Morbidity and Mortality of Severe Asthma Exacerbations in 1543 Patients

Background and objectivesRecent systematic reviews and meta-analyses examining long-acting β₂-adrenergic agonists (LABA) as maintenance treatment for asthma have shown surprisingly conflicting results. The aim of the present study was to determine the impact, in terms of efficacy and safety, of previous maintenance treatment on severe asthma exacerbations.Patients and methodsWe retrospectively evaluated the clinical characteristics of exacerbations experienced by 1543 patients with moderate persistent and severe persistent asthma. Drug therapy was as follows: a combination of inhaled LABAs and corticosteroids (493 patients), an inhaled corticosteroid only (456 patients), and no maintenance treatment (594 patients).ResultsAsthmatic patients taking LABAs did not show higher mortality, longer stay in the intensive care unit, longer hospital stay, lower pH, or worse airflow obstruction than the other 2 groups. On the contrary, they had a higher mean (SD) forced expiratory volume in 1 second at discharge (54% [16%]) than patients taking inhaled corticosteroids (48% [19%]) and patients taking no maintenance treatment (48% [20%]) (P=.009). Patients taking no maintenance treatment also had lower mean (SD) pH values (7.37 [0.11]) than patients taking LABAs (7.39 [0.09]) and patients taking inhaled corticosteroids (7.39 [0.08]) (P=.002), and more admissions to the intensive care unit (11.1% vs 6.5% and 7.7%; P=.002 and P=.018, respectively).ConclusionsThis study did not reveal higher morbidity or mortality in severe asthma exacerbations in patients with moderate persistent or severe persistent asthma who had received inhaled LABAs combined with inhaled corticosteroids. On the contrary, asthma patients who did not use maintenance treatment experienced more severe asthma exacerbations.     

Influence of intranasal steroids during the grass pollen season on bronchial responsiveness in children and young adults with asthma and hay fever

BACKGROUND: It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons. METHODS: In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment. RESULTS: In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly. CONCLUSIONS: Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.     

Time course of response to oral and inhaled corticosteroids in non-asthmatic chronic airflow obstruction.

One hundred and twenty one patients considered on clinical grounds to have non-asthmatic chronic airflow obstruction completed a double blind, crossover trial comparing oral prednisolone 40 mg per day with inhaled beclomethasone dipropionate 500 micrograms thrice daily, each given for 14 days, with a 14 day washout period between treatments. The time course of response was analysed for the 57 occasions where there was a significant increase in mean daily peak expiratory flow (PEF) over the treatment period. Mean daily PEF was still rising at day 14 on 12 occasions. After withdrawal of treatment mean daily PEF remained above pretreatments levels for more than two weeks in half the responses analysed. The peak response occurred earlier with inhaled beclomethasone (median 9.5 (range 3-14) days) than with oral prednisolone (median 12 (range 1-14) days), though both treatments produced a response that was sustained for a similar period. The results suggest that a trial of treatment with corticosteroids in this group of patients should last more than 14 days, and that in a study with a crossover design the washout period should be longer than two weeks.     

Twice daily beclomethasone dipropionate administered with a concentrated aerosol inhaler: efficacy and patient compliance.

The efficacy of twice daily inhaled beclomethasone dipropionate administered by a concentrated aerosol inhaler (one puff twice daily-500 micrograms/day) has been compared with that of treatment four times daily with a standard dose inhaler (two puffs four times daily-400 micrograms/day) in 21 patients with stable asthma. Double placebo inhalers were used in a randomised crossover fashion during two four week treatment periods. Mean peak expiratory flow (PEF), mean symptom scores, and number of extra salbutamol inhalations required were not significantly different between the two treatment periods. Local side effects were more common during treatment with the four times daily active preparation; overt oropharyngeal candidiasis, however, was not found in either group during the study. On completion of the crossover study patients were transferred to the twice daily regimen. At the three month follow up all patients had remained stable and the outpatient PEF was significantly higher (mean 382 (SD 26)l min-1) than at entry into the trial (mean 345 (24)l min-1) (p less than 0.05). Twice daily beclomethasone administered by a concentrated aerosol inhaler appears to be as effective as the standard four times daily regimen in controlling stable asthma.