A large volume spacer significantly reduces the effect of inhaled steroids on bone formation.

Inhaled steroids are increasingly advocated as first line treatment for mild asthma. Some studies suggest that inhaled steroids suppress bone formation as reflected by a fall in plasma osteocalcin. Spacers have been shown to increase the proportion of inhaled aerosol that is deposited in the lungs and to reduce the amount swallowed. We measured plasma osteocalcin levels to determine the effect on bone formation of inhaled beclomethasone dipropionate (BDP) with and without a 750 ml spacer in a double-blind, randomised, placebo-controlled, cross-over study. Twenty-six healthy male volunteers took BDP 500 micrograms (two puffs of Becloforte) together with two puffs of placebo, inhaled twice daily for seven days. One inhaler was taken directly while the other was inhaled through a 750 ml spacer. After a two week washout period, the inhalers were exchanged so that BDP was taken by the alternate route for a further seven days. Fasting plasma osteocalcin levels were measured at 09.00 h before and at the end of each week. After a week of BDP taken directly (without a spacer), osteocalcin levels fell from 11.8 (SEM 0.6) ng/ml to 9.5 (SEM 0.5) ng/ml (p < 0.001). After a week of BDP taken through a spacer, osteocalcin levels fell from 12.1 (SEM 0.5) ng/ml to 11.1 (SEM 0.5) ng/ml (p < 0.001). The fall in osteocalcin when a spacer was used was significantly less than when BDP was taken directly (p < 0.005). This is likely to be because the systemic effects on bone are caused by swallowed rather than inhaled BDP, and this is limited by the use of a spacer. Spacers should be more widely prescribed with inhaled steroids. Further prospective studies are indicated to evaluate whether spacers protect bone mass.     

倍氯米松联合异丙托溴铵治疗慢性阻塞性肺疾病疗效观察

目的观察倍氯米松联合异丙托溴铵治疗中重度慢性阻塞性肺疾病的效果。方法采用随机、单盲、安稳剂对照方法，选择中重度稳定期COPD患者122例，随机分为两组，治疗组62例，对照组60例。对照组服用氨茶碱的缓释剂，必要时使用短效的β2受体激动剂，治疗组在以上常规治疗基础上予以异丙托溴铵加丙酸倍氯米松长期吸入治疗，检查患者6min行走实验、肺功能、生活质量的改善和不良反应发生的情况，共观察24个月。结果治疗后治疗组6-MWD在逐渐改善（P〈0．05），生活质量评分有改善（P〈0．05），肺功能有轻到中度的改善（P〈0．05），不良反应少，对照组上述指标改善不明显。结论倍氯米松联合异丙托溴铵治疗中重度稳定期COPD患者有较好的疗效，短期可改善肺功能。     

Treatment of 106 chronic obstructive pulmonary diseases with shou er kang pill and high dose beclomethasone dipropionate aerosol]

106 chronic obstructive pulmonary disease (COPD) cases were divided into two groups, 53 cases treated with Shou Er Kang (SEK) pill (Kidney-reinforcing regimen) and high dose beclomethasone dipropionate inhaler, and 53 cases in the control group with high dose beclomethasone dipropionate aerosol alone. 64 patients were suffering from bronchial asthma and 42 patients from asthmatic bronchitis, sufficiently severe to be treated with inhaled corticosteroids. The results showed that the total effective rate was 100% and 96.9% in asthmatic patients of both groups; the total effective rates for asthmatic bronchitis patients were 85.7% in the SEK group and 52.4% in the control group. The Synacthen test showed that after the treatment, the adrenal cortex reserve power and secretive ability of the SEK group not only was intact but also improved markedly under high dose exogenous steroids. The adrenocortical secretive ability and reserve power of the control group were damaged with the inhalation of the newer steroids. The difference between the two groups was very significant (P less than 0.001); the relapse rate in the SEK group was 26.9%, but 40% in the control group. The results suggested that there were some occult disorders in COPD patients, especially asthmatic bronchitis patients at different levels on hypothalamus-pituitary-adrenocortical axis.     

中西医并用治疗咳嗽变异性哮喘的临床研究

目的观察中西医并用治疗咳嗽变异性哮喘的疗效。方法治疗组用宣肺祛邪、解痉平喘中药与西药氨茶碱和必可酮气雾剂治疗,对照组用口服氨茶碱和吸入必可酮气雾剂。结果治疗组的临床综合改善率明显高于对照组(P<0.05),副作用明显低于对照组(P<0.05)。结论中药配合氨茶碱和吸入必可酮气雾剂治疗咳嗽变异性哮喘,疗效更显著。     

Safety and efficacy of long-term treatment with inhaled beclomethasone dipropionate in steroid-dependent asthma.

An open long-term trial of inhaled beclomethasone dipropionate was carried out in 32 asthmatic patients chronically dependent on systemic corticosteroids. Our objectives were to study the efficacy and safety of beclomethasone and to determine the proportion of patients in whom systemic steroids could be replaced by the new drug. All subjects had a clear history and physical findings of asthma as well as significant improvement in respiratory function after inhalation of salbutamol. Patients were followed for 4 to 8 years. Compared with a baseline period, patients receiving beclomethasone had reduced symptoms and needed less bronchodilator therapy, but their pulmonary function was unchanged. Bronchial biopsy specimens from seven patients who had been taking beclomethasone for as long as 8 years did not differ histologically from specimens from five asthmatic patients who had never taken the drug. Nine patients were able to stop taking systemic corticosteroids within 9 months, eight required them occasionally, and in eight the requirement was substantially reduced; the requirement did not change appreciably in the remaining seven. Inhaled beclomethasone is a safe and effective drug for chronic administration to asthmatic patients, and in 78% of our subjects the need for systemic steroids was substantially reduced or eliminated.     

吸入糖皮质激素及联用长效β_2受体激动剂在儿童哮喘中的应用

目的:观察四种方法治疗儿童哮喘的疗效。方法:符合入选条件的哮喘患儿随机分为四组。A组42例:吸入沙美特罗替卡松干粉剂,每日早、晚各1吸;B组45例:吸入布地耐德干粉吸入剂,每日早、晚各2吸并联用福莫特罗干粉吸入剂,每日早、晚各1吸;C组48例:应用布地耐德干粉吸入剂,每日早、晚各1吸;D组43例:应用丙酸氟替卡松气雾剂,每日早、晚各1喷借助筒式吸舒吸入。吸入时间均为24周。观察晨间最大呼气峰流速占预计值的百分数为主要疗效指标。结果:治疗后第1周及第4周与治疗前相比,吸入治疗无论单用糖皮质激素或糖皮质激素联用长效β2受体激动剂均有差异性(P<0.05)。治疗后第8周、第12周及第24周与第4周相比差异无显著性。而4组间的比较差异无显著性。而使用短效β2受体激动剂方面4组患儿组间及用药前后均无差异。结论:大部分儿童哮喘患儿可以单用吸入糖皮质激素就能达到治疗效果。如果病情较重或病程较长者治疗初期可以先试用联合制剂,待病情稳定后改为吸入糖皮质激素。     

雾化吸入布地奈德对哮喘儿童肺功能的影响

目的：探讨雾化吸入布地奈德福莫特罗粉加沙丁胺醇治疗儿童哮喘急性发作的疗效.方法：2006-01/2007-12我院儿科门诊哮喘患儿130例,随机分为3组：①A组（n=60）,用雾化器吸入布地奈德福莫特罗粉加沙丁胺醇混悬液;②B组（n=45）,使用贮雾罐和面罩,吸入布地奈德福莫特罗粉加沙丁胺醇气雾剂;③对照组（n=25）,不接受表面激素的吸入治疗.观察期为1a,在第4,12,24,48周随访,记录观察期的临床症状评分及哮喘急性发作时药物使用的情况.结果：与对照组相比,A组和B组明显降低了日间症状评分、夜间症状评分,有更多的无症状天数;显著减少了口服激素和吸入速效β2受体激动剂的需求,减少了哮喘的急性发作.而A组在观察期的第4,12周的治疗效果比B组更明显（P〈0.05）,两组在观察期的第24,48周的治疗指标的差异则无统计学意义.结论：雾化吸入布地奈德福莫特罗粉加沙丁胺醇治疗可以更好地减轻哮喘症状,更早地达到长期稳定,是婴幼儿哮喘的首选吸入方式.     

使用扩张剂后支气管扩张的气道反应性变化

目的:评价支气管扩张剂在支气管扩张治疗中的效果。方法:43例支气管扩张患者,每例患者在测定基础肺功能后,通过带贮雾罐的定量气雾吸入装置吸入400μg沙丁胺醇,30 min后测定肺功能。次日通过射流雾化器雾化吸入5 mg沙丁胺醇,30 min后测定肺功能。之后再分别评价定量气雾吸入溴化异丙托品40μg及经雾化器雾化吸入500μg对肺功能的影响。结果:支扩患者在吸入400μg及5 mg沙丁胺醇后,肺功能各参数均有提高,其中最大呼气峰值流速(PEF)分别提高8.4%和14.2%,第1秒钟用力呼气容积(FEV1)分别提高7.5%、13.0%,用力肺活量(FVC)分别增加8.9%、14.3%。吸入40μg及500μg溴化异丙托品后,PEF、FEV1及FVC分别增加7.3%与11.6%、5.5%与8.2%、6.9%与9.4%。18例患者(41.9%)在使用沙丁胺醇或溴化异丙托品后,肺功能有显著改善(FEV1提高>15%),其中,6例对沙丁胺醇和溴化异丙托品都有良好反应,9例仅对沙丁胺醇,另3例仅对溴化异丙托品有良好反应。对每例患者使用14种过敏原进行皮肤针刺试验,结果13例(30.2%)阳性。结论:许多支气管扩张患者对支气管扩张剂有良好反应。支气管扩张患者治疗前应当进行支气管舒张试验。     

羧甲司坦联合布地奈德治疗哮喘的临床研究

目的:观察羧甲司坦联合小剂量吸入性糖皮质激素治疗轻中度哮喘的临床效果。方法:将30例哮喘患者随机分为2组,实验组给与羧甲司坦联合小剂量二丙酸倍氯米松气雾剂,对照组给予大剂量二丙酸倍氯米松气雾剂联合安慰剂。治疗前后评价PEFRv、哮喘症状评分及不良反应。同时检测治疗前后诱导痰上清中IL-17及IL-8含量的变化。结果:羧甲司坦联合小剂量吸入性激素治疗轻、中度哮喘可显著降低PEFRv及改善症状评分(包括每日用沙丁胺醇气雾剂的喷数),两组间PEFRv改善百分比无明显统计学差异(P>0.05)。两组均可明显降低哮喘患者的诱导痰上清中IL-17及IL-8的水平,其中实验组治疗前后水平分别为:(168±43.2)vs(99±56.2)pg/mL,(542±121.4)vs(285±89.5)pg/mL。两组间毒副反应无明显差异。结论:小剂量吸入性激素联合羧甲司坦和大剂量吸入性激素对治疗轻中度哮喘的疗效相当,且安全性好。     

轻中度哮喘及吸入二丙酸倍氯米松对血糖及相关激素的影响

目的：探讨哮喘吸入二丙酸倍氯米松治疗哮喘时血糖和相关激素的改变及其，方法：将研究对象分成四组：正常对照组、哮喘组、短期吸入（二丙酸倍氯米松）、组和长期吸入（二丙酸倍氯米松）组，应用放射免疫法分别测定上述四组儿童的胰岛不，胰高血糖素水平，氧化法测定血糖水平并做糖耐量实验。结果：四组儿童的胰岛素、胰高血糖素和血糖之间差异无显性意义；糖耐量试验也证明，在哮喘和吸入二丙酸倍氯米松治疗的情况下血糖水平差异无显性。结论：轻中度哮喘患糖代谢基本正常，吸入小剂量糖皮质素不会引起机体糖代谢紊乱。     

布地奈德/福莫特罗吸入剂对支气管哮喘患者肺功能的影响

目的探讨布地奈德/福莫特罗吸入剂对支气管哮喘患者肺功能的影响。方法 60例支气管哮喘患者随机分为观察组（A组,n=30）和对照组（B组,n=30）。A组吸入布地奈德/福莫特罗干粉剂（160μg/4.5μg）/次,2次/d。B组吸入布地奈德干粉剂400μg/次,2次/d。观察并记录两组患者治疗前后日间、夜间哮喘评分、咳嗽评分及肺功能指标用力肺活量（FVC）、1s用力呼气容量（FEV1）、最大呼气峰流速（PEF）的变化。结果两组患者治疗后日间、夜间哮喘评分及咳嗽评分与治疗前比较差异均有统计学意义（P﹤0.01）;两组患者治疗后日间、夜间哮喘评分及咳嗽评分比较,A组优于B组（P﹤0.05）;两组患者治疗后FVC、FEV1、PEF与治疗前比较差异均有统计学意义（P﹤0.05或P﹤0.01）;两组患者治疗后FVC、FEV1、PEF比较,A组明显优于B组（P﹤0.05或P﹤0.01）。结论布地奈德/福莫特罗吸入剂能够减轻支气管哮喘患者的症状,改善其肺功能。     

Substitution of inhaled beclomethasone dipropionate for ingested prednisone in steroid-dependent asthmatics

The effect of inhaled beclomethasone dipropionate (dose, 400 μg daily) was investigated in 31 prednisone-dependent asthmatics. In a double-blind noncrossover study of 25 patients dependent on a daily prednisone dose of 17.5 mg or less, the dose of ingested prednisone was significantly diminished through the use of beclomethasone as compared with placebo (P < 0.001). In a subsequent single-blind study of the 12 patients who had received placebo, a similar decrease in prednisone dose was possible when these patients received beclomethasone. In all 25 patients the effect of beclomethasone was maintained for 2 years; 9 came to require less beclomethasone and 1 required more. In an additional single-blind study of six patients with severe asthma, dependent on prednisone in a dose of 20 to 25 mg/d, the response to beclomethasone was more variable and less significant (P < 0.01). However, at 2 years there was no significant benefit (P > 0.05) and there were two treatment failures.

In patients in whom reduction of dose or discontinuation of prednisone was possible plasma cortisol values before and after corticotropin administration increased significantly (P < 0.001). Prednisone reduction was associated with the appearance of mild musculoskeletal steroid-withdrawal symptoms of short duration in 15 patients, and recurrence of symptoms of rhinitis in 15 patients. Side effects of beclomethasone included episodes of hoarseness in 6 and easily treated oropharyngeal Candida albicans infection in 14.

     

吸入大剂量激素治疗重度哮喘的临床研究

观察大剂量激素吸入治疗慢性重度哮喘的临床疗效及副作用。方法选择３８例重度哮喘患者随机分为Ａ、Ｂ两组,级大剂量丙酸倍氯米松经储雾罐和不经储雾主治疗８－１４周。结论大剂量吸入激素可以明显改善病人症状及肺功能。     

喘乐宁与必可酮联合喷雾治疗小儿哮喘的疗效观察

[目的 ]比较喘乐宁及必可酮联合喷雾及一般疗法治疗小儿支气管哮喘的治疗效果 .[方法 ]将 5 0例支气管哮喘患儿随机分为 2组 ,即对照组 (采用吸氧、吸痰、控制感染及全身用氨茶碱和雾化吸入等 )和在吸氧、吸痰、控制感染基础上用喘乐宁与必可酮联合喷雾治疗组 .[结果 ]加用喘乐宁及必可酮组治疗效果明显优于对照组 ,两组相比具有显著性差异 .[结论 ]必可酮与喘乐宁合用治疗小儿哮喘急性发作效果显著     

The role of corticosteroids in the management of childhood asthma

Preventive treatment: * Inhaled corticosteroids are indicated in children with asthma who have more than mild persistent asthma or are unresponsive to non-steroidal medications after 2-4 weeks. * Initial administration of 400 microg/day of chlorofluorocarbon-beclomethasone dipropionate, or budesonide, or 200 microg/day of fluticasone propionate or hydrofluoroalkane-beclomethasone dipropionate, is suggested, with subsequent titration of the dose to achieve ongoing control with the lowest dose possible. * In situations where asthma control cannot be achieved with the above doses of inhaled corticosteroids, the addition of a long-acting beta2-agonist, theophylline or a leukotriene antagonist should be considered. * Specialist referral is recommended in children requiring high doses of inhaled steroids, regular oral steroids or in whom there is concern about possible steroid side effects. Treatment of acute asthma: * Systemic corticosteroid therapy is recommended for children with moderate to severe acute asthma or if there is incomplete response to beta2-agonists. * Initial administration of 1 mg/kg prednisolone (maximum, 50 mg) orally is suggested, and this may be repeated every 12-24 hours, depending on response. While a course of up to three days is generally sufficient, in more severe cases a prolonged course (with tapering) may occasionally be indicated. * The need for recurrent systemic corticosteroid therapy for acute episodes is an indication for reassessment of the child's interval therapy.     

Ability to learn inhaler technique in relation to cognitive scores and tests of praxis in old age

Clinical observations have shown that some older patients are unable to learn to use a metered dose inhaler (MDI) despite having a normal abbreviated mental test (AMT) score, possibly because of dyspraxia or unrecognised cognitive impairment. Thirty inhaler-naive inpatients (age 76–94) with an AMT score of 8–10 (normal) were studied. Standard MDI training was given and the level of competence reached was scored (inhalation score). A separate observer performed the minimental test (MMT), Barthel index, geriatric depression score (GDS), ideational dyspraxia test (IDT), and ideomotor dyspraxia test (IMD). No correlative or threshold relationship was found between inhalation score and Barthel index, GDS, or IDT. However, a significant correlation was found between inhalation score and IMD (r = 0.45, p = 0.039) and MMT (r = 0.48, p = 0.032) and threshold effects emerged in that no subject with a MMT score of less than 23/30 had an inhalation score of 5/10 or more (adequate technique requires 6/10 or more), and all 17/18 with an inhalation score of 6/10 or more had an IMD of 14/20 or more. The three patients with a MMT >22 and inhalation score <6 had abnormal IMD scores. Inability to learn an adequate inhaler technique in subjects with a normal AMT score appears to be due to unrecognised cognitive impairment or dyspraxia. The MMT is probably a more useful screening test than the AMT score in this context.     

小剂量氨茶碱联合丙酸倍氯米松在咳嗽变异性哮喘中的效果观察

目的探讨小剂量氨茶碱联合丙酸倍氯米松对咳嗽变异性哮喘的疗效。方法将90例咳嗽变异性哮喘患者随机分为3组,每组各30例。A组睡前吸入丙酸倍氯米松300μg/d,14d后减至200μg/d,1个月后减为100μg/d;B组使用小剂量氨茶碱睡前口服,开始0.2g/d,14d后减至0.1g/d,1个月后减为0.05g/d;C组联合应用氨茶碱和丙酸倍氯米松,用法用量与A、B两组相同。3组疗程均为2个月。观察3组患者咳嗽积分和肺功能变化。结果治疗后C组咳嗽症状积分明显低于A组和B组;肺功能检测指标一秒钟用力呼气量（FEV1）和最大呼气量（PEF）显著高于对照组。结论小剂量氨茶碱联合丙酸倍氯米松治疗咳嗽变异性哮喘具有协同作用,提高疗效,缩短病程,值得推广。     

影响干粉吸入剂雾化和沉积性能的制剂因素

干粉吸入剂是近年来肺部给药制剂研发的热点.随着微粉化技术不断成熟,新犁给药装置日益涌现,干粉吸人剂的应用范围越来越广.本文从微粉化的药物、载体和十粉吸人器等3个方面综述了干粉吸人剂的处方组成,并重点介绍了影响药物粉末雾化和沉积性能的几个关键因素.     

Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use.

OBJECTIVE--To examine the relationship between patterns of use of inhaled beclomethasone dipropionate and the risk of fatal and near-fatal asthma. DESIGN--Nested case-control analysis of a historical cohort; a further analysis. SETTING--The 12,301 residents of Saskatchewan aged 5 to 54 years who were dispensed 10 or more asthma drugs from 1978 to 1987. PATIENTS--The 129 persons who experienced asthma death (n = 44) and near-death (n = 85) and their 655 controls matched as to age and date of entry into the cohort, with the additional matching criteria of at least one hospitalization for asthma in the prior 2 years, region of residence, and having received social assistance. MAIN OUTCOME--Life-threatening attacks of asthma defined as death due to asthma or the occurrence of hypercarbia, intubation, and mechanical ventilation during an acute attack of asthma. RESULTS--After accounting for the risk associated with use of other medications and adjustment for markers of risk of adverse events related to asthma, subjects who had been dispensed, on average, one or more metered-dose inhalers of beclomethasone per month over a 1-year period had a significantly lower risk of fatal and near-fatal asthma (odds ratio, 0.1; 95% confidence interval, 0.02 to 0.6). CONCLUSION--These data support recent guidelines from several countries that recommend the use of inhaled corticosteroids in moderate and severe asthma.     

Ipratropium bromide: are patients treated with optimal therapy?

A double-blind crossover placebo controlled study was performed on 20 patients with stable chronic asthma, in order to obtain dose response data to ipratropium bromide (40, 80, 200 micrograms) given by metered dose inhaler. The use of the 200 micrograms dose gave a significantly greater peak effect and duration of action than the recommended standard therapeutic dose of 40 micrograms. There were marked individual variations in response to higher doses. Maximum response detected by spirometry occurred within 24 hours of inhalation, thus patients likely to gain clinical benefit are readily identified. The higher dose was well tolerated by most patients and may have clinical application in the treatment of patients who do not respond to the standard dose regime.