丙卡特罗对支气管哮喘和喘息型支气管炎172例的研究

支气管哮喘119例和喘息型支气管炎53例,共172例(男性123例,女性49例,平均年龄41±s 10a),采用盐酸丙卡特罗治疗,50μg/次 po, bid,共1wk。总有效率分别为84.9％和70％。服药后30min,2h及1wk的FEV_1值和PEFR值(除后组1wk的FEV_1值改善不明显外)均有不同程度改善(P<0.01,P<0.05)。12例(7％)发生轻度肌肉震颤。值得采用该药治疗支气管哮喘和喘息型支气管炎。     

环孢素A气雾吸入对致敏大鼠气道高反应性的影响环孢素A气雾吸入对致敏大鼠气道高反应性的影响

目的评价环孢素A气雾吸入给药对致敏大鼠气道高反应性的影响。方法用氯化乙酰甲胆碱（Mch）诱导抗原攻击后的致敏大鼠气道阻力（raw）、肺动态顺应性（Cdyn）、PC50和PC25变化,观察环孢素A气雾吸入给药后的抗气道高反应性作用。结果环孢素A 5,20 g·L^-1气雾吸入给药,色甘酸钠20 g·L^-1气雾吸入给药和地塞米松 (0.5 mg·kg^-1, ip) 抑制Mch诱导的大鼠raw增高及Cdyn降低，增加raw PC50和 Cdyn　PC25值。结论环孢素A气雾吸入给药能预防Mch引起的大鼠气道高反应性，是其治疗哮喘的一个有效途径。     

Comparison of inhaled salbutamol powder and aerosol in asthmatic patients with low peak expiratory flow level

Summary The short-term bronchodilator effects of dry salbutamol powder and a pressurized salbutamol aerosol were compared in 22 patients with severe asthma, on 3 consecutive mornings, in a double-dummy cross-over study. Only patients with peak expiratory flow (PEF) rate lower than 250 l/min, were recruited. PEF measurement was employed to assess changes in ventilatory function induced by inhalation of the drugs. No significant difference was found between the PEF changes induced by the dry salbutamol powder (400 µg) and the pressurized aerosol (200 µg). Both forms of the drug produced a significant rise in mean PEF values. The study shows that even in asthmatic patients with poor ventilation, a dry powder inhaler and pressurized aerosol are effective means of drug delivery to the lungs.     

环孢素A气雾吸入对哮喘大鼠气道炎症的影响

目的研究环孢素A(CsA)气雾吸入对抗原诱导的大鼠过敏性气道炎症的作用。方法用卵白蛋白(OA)致敏大鼠,2周后气雾吸入CsA(5，10，20 g·L^-1),每天1次，连续7 d。大鼠致敏后d 20和d 21用OA(10 g·L^-1，每天1次)攻击，观察第2次OA攻击24 h后支气管肺泡灌洗液及外周血中嗜酸性粒细胞的数量和支气管肺组织病理学改变情况，测定支气管肺泡灌洗液中TNF-α含量。结果CsA气雾吸入能明显降低支气管肺泡灌洗液及外周血中嗜酸性粒细胞的数量，减轻肺组织中炎症细胞特别是嗜酸性粒细胞的浸润,减轻组织水肿及上皮损伤等气道炎症状况,降低支气管肺泡灌洗液中TNF-α含量。结论CsA气雾吸入对大鼠过敏性气道炎症具有抑制作用，其作用机制与细胞因子TNF-α释放减少有关。     

Effect of neutral endopeptidase inhibitor on airway function and bronchial responsiveness in asthmatic subjects

Summary We determined the effect of an inhibitor of neutral endopeptidase, acetorphan, on the skin responses to substance P and on the bronchostrictor effects of sodium metabisulphite aerosol in asthmatic subjects. One hour following ingestion of acetorphan (200 mg) or placebo tablets, cutaneous responses to substance P were performed in four subjects. In seven subjects, bronchial challenge with increasing concentrations of sodium metabisulphite solutions was performed and the concentration required to cause a 20% fall in baseline FEV₁ determined (PC₂₀).On the acetorphan day, there was a significant increase in the wheal and flare responses to substance P and to the diluent (0.9% NaCl) alone. However, there was no significant effect of acetorphan on the PC₂₀ metabisulphite.We conclude that metabisulphite airway challenge in vivo may not invoke the release of endogenous neuropeptides. However, the degree of inhibition of neuropeptide breakdown by the oral dose of acetorphan used may not have been optimal.     

Increased theophylline clearance in asthmatic patients due to terbutaline

Summary The pharmacokinetic mechanism of the theophylline-terbutaline interaction has been studied. Sustained release theophylline 200–400 mg b.d. was given with placebo or terbutaline 2.5 mg t.d.s. to six adult asthmatic patients.Terbutaline decreased the serum trough theophylline levels from 8.1 to 7.3 µg/ml, improved daily the clinical score from 1.51 to 1.26 and increased the peak expiratory flow rate from 316 to 370 l/min. In a single dose study following the chronic therapy, it was shown that there was no change in the peak theophylline concentration or in the timing of the peak, but the t_1/2 was reduced from 9.0 to 7.5 h, and the systemic clearance was increased from 20.2 to 24.8 ml·h^–1·kg^–1.Thus, terbutaline reduced the serum theophylline concentration by increasing its systemic clearance.     

Effect of carbocysteine on cough reflex to capsaicin in asthmatic patients

AIMS: Cough, one of the main symptoms of bronchial asthma, is a chronic airway inflammatory disease with functionally damaged bronchial epithelium. Recently, we established an animal model with cough hypersensitivity after antigen challenge and clearly showed the protective effect of carbocysteine in this model. This study was designed to investigate the clinical effect of carbocysteine for cough sensitivity in patients with bronchial asthma. METHODS: The effects of the two orally active mucoregulatory drugs, carbocysteine and ambroxol hydrochloride, on cough response to inhaled capsaicin were examined in 14 patients with stable asthma. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. RESULTS: Geometric mean values of the cough threshold at run-in (baseline) and after 4 weeks' treatment of placebo, 1500 mg day-1 of carbocysteine and 45 mg day-1 of ambroxol hydrochloride were 12.8 micro M (95% confidence interval [CI] 5.5, 29.6), 11.0 micro M (95% CI 4.4, 27.5), 21.0 micro M (95% CI 8.8, 50.2) and 11.6 micro M (95% CI 5.8, 23.3), respectively. The cough threshold for carbocysteine was significantly greater than those of ambroxol hydrochloride (P = 0.047) and placebo (P = 0.047), respectively. CONCLUSIONS: These findings indicate that carbocysteine administration may be a novel therapeutic option for asthmatic patients, especially with cough variant asthma.     

Pharmacokinetics of nebulized and oral procaterol in asthmatic and non‐asthmatic subjects in relation to doping analysis

The purpose of the present study was to investigate pharmacokinetics of procaterol in asthmatics and non‐asthmatics after nebulized and oral administration in relation to doping. Ten asthmatic and ten non‐asthmatic subjects underwent two pharmacokinetic trials. At first trial, 4 µg procaterol was administered as nebulization. At second trial, 100 µg procaterol was administered orally. Serum and urine samples were collected before and after administration of procaterol. Samples were analyzed by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Serum and urine concentrations of procaterol were markedly higher after oral administration compared to nebulized administration. After oral administration, serum procaterol concentration‐time area under the curve (AUC) was higher (P ≤ 0.05) for asthmatics than non‐asthmatics. Likewise, urine concentrations were higher (P ≤ 0.01) for asthmatics than non‐asthmatics 4 (47 ± 12 vs. 28 ± 9 ng/mL) and 8 h (39 ± 9 vs. 15 ± 5 ng/mL) after oral administration. Detection of serum procaterol was difficult after nebulized administration with 38 samples (27%) below limit of quantification (LOQ) and only trends were observed. No differences were observed between asthmatics and non‐asthmatics in the urine concentrations of procaterol after nebulized administration. In summary, our data showed that asthmatics had higher urine concentrations of procaterol than non‐asthmatics after oral administration of 100 µg, whereas no difference was observed between the groups after nebulized administration. For doping control purposes, our observations indicate that it is possible to differentiate therapeutic nebulized administration of procaterol from prohibited use of oral procaterol. Copyright © 2016 John Wiley & Sons, Ltd.     

Prevention with clodronate of osteoporosis secondary to inhaled corticosteroid treatment in patients with chronic asthmatic bronchitis

Steroid therapy is the third most common cause of osteoporosis, after loss of gonad function and senescence. The aim of the present study was to evaluate the protective action of clodronate on bone mass loss induced by steroid therapy. Sixty patients with bronchial asthma receiving either fluticasone (250 mg x 4/day) or beclomethasone (250 mg x 4/day) inhaled corticosteroid treatment were enrolled. Half the patients received combination treatment with clodronate (100 mg i.m./14 days), for a total period of 12 months. All patients were evaluated at baseline and at the end of treatment for bone mineral density (BMD) and calcium/phosphor metabolism parameters (kalemia, kaluria, phosphoremia, phosphaturia, alkaline phosphatase and hydroxyprolinuria over a 24-h period). The results of this preliminary study confirm the protective influence of clodronate on bone mass loss, as documented by the increment in mean values in BMD reported at the end of treatment compared with baseline values.     

Subsensitivity of beta-adrenoceptor responses in asthmatic patients taking regular low dose inhaled salbutamol

Summary Tremor (Tr), chronotropic (HR) and metabolic (K, Glu) responses to cumulative doses of inhaled salbutamol (100 g to 4000 g) were compared in an age and sex matched group of 7 normal (N) and asthmatic (A) subjects.Comparison of regression lines between groups showed differences in HR and K. This was also reflected in attenuation of maximum responses in group A, for HR and K.These results show subsensitivity of chronotropic and hypokalaemic responses in patients with asthma, which may reflect tachyphylaxis from the effects of long term inhaled salbutamol therapy.     

Clinical and functional responses to salbutamol inhaled via different devices in asthmatic patients with induced bronchoconstriction

AIMS: This study aimed at evaluating changes in airway patency, lung volumes and perception of breathing discomfort intensity following salbutamol administration via the Diskus dry-powder inhaler (DPI) or a pressurized metered-dose inhaler with the Volumatic valved holding chamber (pMDI + Volumatic) in asthmatic patients with methacholine-induced bronchoconstriction. METHODS: On six different study days, 18 patients inhaled methacholine until forced expiratory volume in 1 s (FEV(1)) decreased by approximately 35% of baseline. Following placebo, 200 and 400 microg of salbutamol through the pMDI + Volumatic or the Diskus, changes in FEV(1), volume-adjusted mean forced expiratory flow from 25 to 75% of the forced vital capacity (isoFEF(25-75)), lung volumes and breathing discomfort intensity, assessed by visual analogue scale (VAS) score, were repeatedly measured over a 60-min observation period. RESULTS: Induced bronchoconstriction was accompanied by obvious reductions in lung volumes and increases in VAS score. After salbutamol administration, FEV(1) and VAS score changes were similar in all experimental conditions. However, following 400 microg salbutamol via pMDI + Volumatic, isoFEF(25-75) values increased up to 4.48 l s(-1) (95% confidence interval 4.06, 4.90), a significantly (P < 0.01) higher value than those attained in all other experimental conditions. Independently of the salbutamol dose, lung volumes rose to significantly (P < 0.01) higher levels in pMDI + Volumatic than in Diskus trials. The low salbutamol dose via the pMDI + Volumatic and the high dose via the DPI increased isoFEF(25-75) and lung volumes to similar extents. CONCLUSIONS: Salbutamol via the pMDI + Volumatic provides greater isoFEF(25-75) and lung volume increases in asthmatic patients with induced bronchoconstriction; salbutamol-induced changes in VAS scores poorly reflect those in small airway patency. The lack of differences in FEV(1) increases observed after 200 and 400 microg salbutamol may reflect attainment of the flat portion of the dose-response curve using either device.     

A comparison of the bronchodilator action of pseudoephedrine and ephedrine in patients with reversible airway obstruction

Summary A double-blind randomised cross-over study was performed on 12 subjects suffering from reversible airway obstruction (asthma) to determine the relative bronchodilator effects of oral pseudoephedrine 60 mg, pseudoephedrine 180 mg, ephedrine 25 mg and matched placebo. Spirometry was used to measure vital capacity and forced expired volume in 1 s, and whole body plethysmography was used to measure specific airway conductance. Measurements were recorded before each drug was given, and 1 h and 2 h after each drug. Reversibility of the airway obstruction on each day of the study was demonstrated by significant improvements in all parameters of lung function in response to 400 µg of isoprenaline inhaled after the 2-h measurement. No significant bronchodilator effect could be shown following the ingestion of pseudoephedrine 60 mg or 180 mg. Only a week bronchodilator effect was demonstrated after ephedrine 25 mg in that the percentage change in vital capacity at 2 h after ephedrine was greater than that following either dose of pseudoephedrine or the placebo. It is concluded that oral pseudoephedrine in single doses of 60 mg or 180 mg has no significant bronchodilator action in man, and that a single dose of up to 180 mg pseudoephedrine does not cause tachycardia or hypertension.     

A case series on lung deposition analysis of inhaled medication using functional imaging based computational fluid dynamics in asthmatic patients: effect of upper airway morphology and comparison with in vivo data

Context: Asthma affects 20 million Americans resulting in an economic burden of approximately $18 billion in the US alone (Allergies and Asthma Foundation 2000; National Center for Environmental Health (NCEH) 1999). Research studies based on differences in patient-specific airway morphology for asthma and the associated effect on deposition of inhaled aerosols are currently not available in the literature. Therefore, the role of morphological variations such as upper airway (extrathoracic) occlusion is not well documented.

Objective: Functional imaging based computational fluid dynamics (CFD) of the respiratory airways for five asthmatic subjects is performed in this study using computed tomography (CT) based patient-specific airway models and boundary conditions.

Methods: CT scans for 5 asthma patients were used to reconstruct 3D lung models using segmentation software. An averaged inhalation profile and patient-specific lobar flow distribution were used to perform the simulation. The simulations were used to obtain deposition for BDP/Formoterol^® HFA pMDI in the patient-specific airway models.

Results: The lung deposition obtained using CFD was in excellent agreement with available in vivo data using the same product. Specifically, CFD resulted in 30% lung deposition, whereas in vivo lung deposition was reported to be approximately 31%.

Conclusion: It was concluded that a combination of patient-specific airway models and lobar boundary conditions can be used to obtain accurate lung deposition estimates. Lower lung deposition can be expected for patients with higher extrathoracic resistance. Novel respiratory drug delivery devices need to accommodate population sub-groups based on these morphological and anatomical differences in addition to subject age.     

Adverse effects of a single dose of (+)-sotalol in patients with mild stable asthma

Aims To investigate the effect of (+)-sotalol, which is not thought to possess clinically significant β-adrenoceptor blocking activity, on airway responsiveness in subjects with mild asthma.
Methods A placebo controlled, double-blind, single dose, cross over study, evaluating the effects of oral (+)-sotalol 300  mg and oral (±)-sotalol 240  mg, on airway responsiveness, FEV₁, and heart rate in 18 asthmatic volunteers with quantifiable levels of airway responsiveness.
Results Compared with placebo, (+)-sotalol induced a significant increase in airway responsiveness, and a significant decrease in FEV₁, but there was no significant change in heart rate. Following (±)-sotalol there was no significant effect on airway responsiveness, but there were significant decreases in FEV₁ and heart rate. In one subject both (+)-sotalol and (±)-sotalol provoked a 49% decrement in FEV₁, and in another there were decrements of 20% and 18%, respectively.
Conclusions Despite theoretical considerations, it cannot be assumed that (+)-sotalol is safe in patients with asthma.     

Integration of dose counters in pressurized metered-dose inhalers for patients with asthma and chronic obstructive pulmonary disease: review of evidence

Introduction: An important factor responsible for suboptimal treatment in patients with obstructive airway diseases, which is often overlooked, is running out of medication. Addition of a dose counter to a pressurized metered-dose inhaler (pMDI) allows the patient to reliably track number of actuations, identify when the label claim number of actuations has been reached, and when a new inhaler needs to be purchased.

Areas covered: This article discusses the conventional methods for tracking doses in pMDIs, rationale of using dose counters, published evidence of studies, including performance and patient satisfaction with the use of pMDIs with dose counter. A section on the FDA guidance on dose counters and on Cipla’s dose counters is also included.

Expert opinion: It has been several years since the US FDA guidance on integration of dose-counting mechanisms into pMDIs and some time since pMDIs with dose counters have been available (albeit not with all pMDIs); but their importance has not been fully realized. This can be due to factors such as lack of adequate understanding about dose tracking, limited pMDIs being available with integrated dose counters and absence of a clear consolidation of the need, advantages, guidelines, types and characteristics of dose counters in published articles.     

长期吸入糖皮质激素哮喘患者肝脏B型超声检查结果分析

目的探讨长期吸入糖皮质激素（〉1年）的哮喘患者的肝脏B型超声检查异常情况及相关性。方法采用回顾性分析的方法,分析156例长期吸入糖皮质激素的哮喘患者的肝脏B型超声检查结果、血糖、血脂及身高、体质量值。结果肝脏B型超声检查阳性的共21例,总患病率为13．5％。男性患者B型超声阳性率〉女性,肝脏B型超声结果阳性者体质量指数、血脂、血糖均比B型超声阴性者高,差异均有统计学意义（P〈0．05）。结论长期吸入糖皮质激素对肝脏可能无明显影响。     

影响OSAHS患者CPAP治疗依从性的因素及医院内强化护理策略

目的分析影响阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者持续正压通气（CPAP）治疗依从性的因素,探讨提高OSAHS患者CPAP治疗依从性的医院内强化护理策略。方法入选2012年2月-2012年7月在我院鼾症诊治中心和呼吸科诊断为OSAHS并接受CPAP治疗的患者49例,在CPAP呼吸机治疗第2、3 d过程中给予医院内强化护理,观察强化护理对CPAP治疗效果和患者依从性的影响。结果强化护理前后AHI参数分别为（12.28±7.92）和（5.13±4.83）,平均漏气量分别为（0.62±0.45）和（0.37±0.25）L/s,平均SpO2分别为（92.57±1.61）%和（96.16±1.05）%,最低SpO2分别为（89.08±7.05）%和（95.42±3.41）%,SpO2〈90%的时间比例分别为（6.48±3.45）%和（0.19±0.36）%,且所有AHI参数强化护理前后均有统计学差异（P〈0.05）。医院内强化护理后出现呼吸机治疗不良反应的患者例数减少。结论医院内强化护理干预可提高OSAHS患者CPAP疗效,减少不良反应,提高患者依从性。     

布地格福吸入气雾剂治疗中、重度慢性阻塞性肺疾病患者的临床研究

目的 观察布地格福吸入气雾剂治疗中、重度慢性阻塞性肺疾病(COPD)患者的临床疗效与安全性.方法 将150例中、重度COPD患者随机分为对照A组50例、对照B组50例和试验组50例.对照A组给予噻托溴铵粉吸入剂每次18μg,qd,吸入治疗+沙美特罗替卡松每次300μg,bid,吸入治疗;对照B组给予布地奈德福莫特罗每次...     

吸入皮质激素治疗哮喘患者的骨密度、骨代谢变化及其危险因素

目的：探讨接受可吸入性皮质激素治疗-年以上的哮喘患者的骨质减少和骨质疏松的发病状况以及哮喘患者骨质减少和骨质疏松的危险因素。方法：自2007年8月到2011年7月,接受吸入性皮质激素治疗且治疗时间-年以上的哮喘患者为研究组,未接受吸入性皮质激素治疗的哮喘患者为对照组,哮喘患者年龄均在18岁以上。骨密度检测采用DEXA检测。骨质减少和骨质疏松采用WHOT—score评分。骨代谢指标包括血骨钙素以及碱性磷酸酶等,检测方法采用放免法进行。结果：研究对象共143名,其中研究组69例,对照组74例。研究组与对照组患者的血骨钙素水平分别为（3．8±2．4）、（2．7±1．4）μg／L,两组间无统计学差异（P=0．57）。两组患者的血碱性磷酸酶水平分别为（126±68）、（119±66）IU／L,两组间无统计学差异（P=0．37）。研究组和对照组患者的脊柱T—score评分均数分别为-0．72和-0．57（P=0．98）;股骨T—score评分均数分别为-0．60和-0．80（P=0．474）;髋骨T—score评分均数分别为0．19和0．06（P=0．275）。脊柱、股骨和髋骨T—score评分与年龄呈显著负相关,而与体重指数呈显著正相关。结论：哮喘患者骨质减少和骨质疏松危险因素是高龄和低体重指数,吸入皮质激素无累积效应。与对照组患者相比,吸入皮质激素治疗哮喘的患者没有其他的骨质减少和骨质疏松的危险因素。     

接受药师用药宣教后的慢性气道炎性疾病患者吸入剂用药依从性的影响因素分析

目的：了解用药宣教后慢性气道炎性疾病患者院外使用吸入剂依从性的情况，探讨其影响因素，为进一步开展针对性的用药宣教提供参考依据。方法：以2016年因慢性气道炎性疾病急性加重入院，出院后需规律使用长效吸入剂治疗的患者为研究对象（所有患者住院期间均经临床药师反复用药宣教），调查这类患者的人口学特征、家庭状况、患者自身患病情况及用药等现实情况，探讨其与吸入剂使用依从性关系，找出影响依从性的独立危险因素。结果：共有108例患者入组，在研究实施过程中因故死亡患者11例，实际患者97例，其中50例依从性好，47例依从性差。单因素分析示文化程度、1年内急性加重次数、对吸入剂治疗效果满意程度、方便取药程度、家庭关心、经济收入、合并用药种数、合并慢病种数、使用期间有无不良反应、1年随访次数对用药依从性有统计学意义（P<0.05）。多因素回归分析显示，1年急性加重次数（OR=20.394）、家庭关心（OR=40.442）、1年内随访次数（OR>999.999）为影响患者使用吸入剂依从性的独立因素（P<0.05）。结论：尽管住院期间进行了吸入剂使用的宣教，出院后定期随访督促，但仍有近一半患者未坚持规律使用吸入剂。临床药师必须采取更加积极的干预措施提高这类患者长期规范用药的依从性。