Alpha-adrenergic blockers

alpha-Adrenergic blockers are important drugs in the treatment of hypertension and other cardiovascular and noncardiovascular disorders. The ability to selectively block alpha-receptor subtypes provides a greater margin of safety and efficacy for these drugs.     

Plasma catecholamine responses in acute severe asthma.

Twenty patients presenting to an A&E department with acute severe asthma were studied. Despite clinically severe airway obstruction few had raised catecholamine levels. However several patients with impending respiratory arrest had markedly elevated catecholamine levels, and relationships are demonstrated between these levels and other measures of disease severity.     

Alpha-adrenergic blockade in preventing posttransplant edema of lung allograft

Effect of alpha-adrenergic blockers on pulmonary edema in lung transplantation was studied with a rat model of syngeneic left lung transplantation. Prior to harvesting, 0.1 mg of Prazosin or 0.4 mg of Yohimbine was given to the donor. Pulmonary and systemic hemodynamics were measured under the right pulmonary arterial occlusion (RPAO) at different time points after grafting. Wet to dry weight ratio (W/D) of all transplants was also calculated. Same procedure was conducted in rats with normal and ischemic lung and in transplanted animals without any treatments. While RPAO did not increase W/D in normal lung with a significant elevation in pulmonary arterial pressure (PAP), both these values significantly increased in transplanted lung. Transplanted animals could not tolerate RPAO 24 hours after grafting, but were tolerable later than 48 hours with elevated W/D and PAP. On the contrary, animals given Prazosin or Yohimbine were all tolerable at 24 hours postsurgery. Yohimbine significantly improved W/D. Consequently, it was demonstrated that pulmonary edema of the graft reached its peak during first 24 to 48 hours after transplantation and was alleviated by the blockade of alpha-adrenergic receptor in the graft vessel.     

Cardiopulmonary responses to continuous positive airway pressure in acute asthma

The effects of nasal continuous positive airway pressure (CPAP) on expiratory flow, arterial blood gas tensions, cardiovascular status, and dyspnea were studied in 21 patients with acute asthma. Therapy consisted of the following CPAP sequence: 30 minutes at 5 cm H₂O, 20 minutes at 0 cm H₂O, 30 minutes at 7.5 cm H₂O, and 20 minutes at 0 cm H₂O. Six control patients were fitted with a CPAP mask but given no positive-pressure therapy. Significant reductions in respiratory rate occurred from a baseline of 22.0 ± 1.0 to 19.8 ± 3.8 breaths/min at CPAP 5 cm H₂O and to 19.4 ± 4.3 breaths/min at CPAP 7.5 cm H₂O (P < .05). No significant change occurred in forced expiratory volume in 1 second (FEV₁), heart rate, mean arterial blood pressure, or arterial blood gas tension with either level of CPAP. Dyspnea, as assessed by a breathlessness score, improved during CPAP therapy (P < .05). These levels of CPAP were tolerated without deleterious side effects. In comparison, the control group showed no change in heart rate, respiratory rate, or breathlessness score during the study period. These data show that application of CPAP in acute asthma reduces respiratory rate and dyspnea with no untoward effects on gas exchange, expiratory airflow, or hemodynamics.     

Sphingosine-1-phosphate in allergic responses, asthma and anaphylaxis

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many cellular processes, acting not only as an extracellular ligand to its specific G protein-coupled receptors, but also as a putative intracellular messenger with yet unidentified targets. Mast cells are tissue-dwelling pivotal early effectors of allergic responses, which produce and secrete S1P that can bind to its receptors present on mast cells to influence their activation and functions. In this review, we will first discuss the current knowledge of S1P production by two isozymes of sphingosine kinase (SphK). Mechanisms of SphK activation will be discussed, with an emphasis on experimental approaches developed to study their differential activation and biological roles in the context of mast cells. The relevance of mast cells in the etiology of allergic disorders, asthma and anaphylaxis is well established. In this review, this concept will be revisited, focusing on the contribution of S1P production and secretion to the symptoms associated with dysregulated inflammatory responses. To conclude, counteracting the proinflammatory effects of S1P could be envisioned as a therapeutic strategy to treat allergic disorders, exacerbated airway inflammation, and anaphylactic reactions, and various options will be discussed, such as the development of pharmacological tools to inhibit SphKs, S1P neutralizing monoclonal antibody, and S1P receptor antagonists.     

Airway responses to inhaled ouabain in subjects with and without asthma

Challenges with ouabain and histamine were performed a week apart in 10 patients with asthma and 5 normal subjects. Concentrations were increased cumulatively until specific airway conductance decreased by 30% or the maximal concentration of 1.0% was reached. At low concentrations, ouabain induced bronchodilatation in six patients who had asthma. Bronchodilatation gradually decreased with increasing concentrations and was followed by bronchoconstriction in two patients with asthma who had high airway sensitivity to histamine. Ouabain caused only bronchoconstriction in three patients with severe asthma. The normal subjects showed mild bronchodilatation or no response to ouabain. Several possible biochemical mechanisms may be responsible for the bronchodilatory response to low doses of ouabain, such as stimulation of adenylate cyclase or (Na+,K+)-adenosine triphosphatase. The absence of a bronchodilatory response to ouabain in patients with severe asthma suggests an impairment in the activity of these enzymes.     

Factors related to emotional responses in school-aged children who have asthma

A systematic review of the literature was performed to answer the following questions (a) What factors contribute to the emotional responses of school-age children who have asthma? (b) What are the potential gaps in the literature regarding the emotional responses of school-age children (ages 6-12) who have asthma? (c) Are children with a lower socioeconomic status (SES) and those who are minorities represented in the literature proportionate to their prevalence? Two main focus areas regarding emotional responses were identified: (a) factors related to children who have asthma and (b) factors related to caregivers of children who have asthma. Internalizing disorders were reported consistently for children and caregivers of children who have asthma. Negative consequences of asthma for children included panic and asthma attacks, missed school days, and behavioral problems. Issues for caregivers included higher levels of anxiety and depressive symptoms, asthma management deficits, and lower caregiver warmth and involvement. Gaps in the literature included separated studies for children ages 6-12, a lack of a standardized method to define SES, studies that were of a more experimental nature, and a disparate number of studies of minority children and caregivers relative to their asthma prevalence.     

Alpha-adrenergic blockade makes minimal contribution to ketanserin's hypotensive effect

Ketanserin is a selective (S2) serotonin receptor antagonist currently under investigation as an antihypertensive. It has been suggested that the antihypertensive action of ketanserin might be principally due to alpha-adrenergic receptor antagonism rather than its effect on serotonin receptors. We therefore determined the contribution of alpha-adrenergic blockade to the hypotensive effects of ketanserin in six patients with hypertension and compared that with the alpha-adrenergic blockade produced by prazosin, a known alpha 1-adrenergic antagonist. Each patient received placebo, ketanserin (40 mg every 8 hours), and prazosin (5 mg every 8 hours). Each agent was administered for 4 weeks in random order. Both ketanserin and prazosin lowered blood pressure significantly and to a similar extent. The extent of alpha-adrenergic blockade was determined from the ability to inhibit the hypertensive effect of phenylephrine infusions. The dose of phenylephrine required to raise the blood pressure by 20 mm Hg was significantly higher during both ketanserin (1.41 +/- 0.27 micrograms/kg/min; p less than 0.05) and prazosin (4.99 +/- 0.77 micrograms/kg/min; p less than 0.01) administration compared with placebo (0.85 +/- 0.15 micrograms/kg/min). However, the dose ratio was more than fourfold higher during prazosin treatment (7.38 +/- 1.99; p less than 0.05) than during ketanserin (1.69 +/- 0.21). Thus at equipotent hypotensive doses the extent of alpha-blockade produced by ketanserin was more than fourfold lower than that of prazosin, implying that mechanisms other than alpha-blockade must contribute to the antihypertensive actions of ketanserin.     

支气管哮喘与结核菌素反应相关性研究

目的研究支气管哮喘与结核菌素反应之间的关系.方法用ELISA法测定受试者IL-4、IgE、IFN-γ浓度,然后再与相时应的结核菌素反应结果比较.结果(1)支气管哮喘患者其结核菌素反应多为阴性,而结核痛患者多为阳性且常为强阳性.(2)结核菌素反应阳性者血清IL-4、IgE浓度明显低于阴性者,但血清IFN-γ浓度高于阴性者.结论支气管哮喘病人Th1细胞免疫功能低下,而其Th2细胞免疫功能增强.     

Secretory leukocyte protease inhibitor prevents allergen-induced pulmonary responses in animal models of asthma

Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways that exhibits broad spectrum inhibitory activity against mast cell and leukocyte serine proteases implicated in asthma pathology. To assess the potential therapeutic utility of SLPI in this disorder, its effects on antigen-induced pulmonary responses were evaluated. In Ascaris-sensitized sheep, SLPI (3 mg) administered by aerosol daily for 4 days, with the final dose 0.5 h before antigen challenge, reduced the areas under the curve for early- and late-phase bronchoconstriction (73 and 95%, respectively; p <.05 versus control responses). SLPI also inhibited the development of airway hyperresponsiveness to carbachol (84%, p <. 05 versus control response) measured 24 h after antigen challenge. In ovalbumin-sensitized guinea pigs, intratracheal administration of SLPI daily for 3 days, with the final dose 1 h before antigen challenge, inhibited the development of airway hyperresponsiveness to histamine with an ED50 of <0.05 mg/kg. Prolonged pharmacodynamic activity of SLPI was observed in both species. In a murine model of atopic asthma, SLPI inhibited leukocyte influx into the airways after chronic allergen challenge. SLPI administered to sheep by the predosing protocol described above also prevented the antigen-induced decrease of tracheal mucus velocity (p <.05). In addition, a single aerosol administration of SLPI (30 mg) to sheep 1 h after antigen challenge inhibited the subsequent late-phase bronchoconstriction and development of hyperresponsiveness and reversed the stimulated decrease in tracheal mucus velocity. These results suggest that SLPI may provide therapeutic intervention against the pathophysiology of asthma and its underlying pathology.     

Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma

What is known and Objective: Montelukast, a cysteinyl leukotriene receptor 1 antagonist, is safe and efficacious in patients with asthma. The mechanisms underlying the significant interpatient variability in response to montelukast are not clear but are believed to be, in part, because of genetic variability. Methods: To examine the associations between polymorphisms in candidate genes in the leukotriene pathway and outcomes in patients with asthma on montelukast for 4–8 weeks, we evaluated the changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV_1·0) and patients’ subjective symptom before and after montelukast treatment. DNA was collected from 252 Japanese participants. Results and Discussion: Two single‐nucleotide polymorphisms (SNPs) in the ALOX5 (rs2115819) and LTA4H (rs2660845) genes were successfully typed. There was no difference between members of the general population (n = 200) and patients (n = 52) in each genotype frequency. Significant associations were found between SNP genotypes in the LTA4H gene and changes in PEF and FEV_1·0. The PEF and FEV_1·0 responses to montelukast in the A/A genotypes (n = 4) for the LTA4H SNP were significantly higher than those in the G allele carriers (A/G+G/G) (n = 17). What is new and Conclusion: Despite the small sample size, our results suggest that genetic variation in leukotriene pathway candidate genes contributes to variability in clinical responses to montelukast in Japanese patients with asthma.     

Primary cell-mediated immune response in bronchial asthma. Relationship between primary in vitro and in vivo cell-mediated and antibody responses in patients with asthma and healthy controls

Eleven patients with asthma and ten sex and age matched healthy controls were immunized with the primary immunogen Helix pomatia Haemocyanin (HPH). The amplitude and the kinetics of in vitro cell-mediated immune response were measured by HPH-induced lymphocyte proliferation. Lymphocytes were also challenged in vitro with mitogens and recall antigens. In vivo cell-mediated immunity was determined by inducing delayed type hypersensitivity reactions with HPH. Anti-HPH antibody responses in the IgE, IgG and IgM classes were measured to gain an insight into the relation between cell-mediated and humoral immune responses in patients with asthma and healthy controls. The in vitro and in vivo cell-mediated response and the IgM antibody response did not differ between patients with asthma and controls. The IgE and IgG antibody responses, however, were increased in the patients. IgM antibody response correlated with both the in vitro and in vivo cell-mediated response (R = 0.45, P less than 0.05). IgE and IgG antibody responses however were not correlated with cell-mediated responses. These data suggest that the primary abnormality in immune regulation in patients with asthma concerns the control of the IgE and IgG class antibody responses.     

Hypnosis in asthma

Experimental and clinical evidence about posthypnotic amnesia are reviewed. Rather than postulate any single mechanism which might account for the phenomenon, two interpretations are contrasted which seem sharply opposed. First, posthypnotic amnesia may be seen as essentially like any other hypnotically suggested experience. It can be considered as an explicitly or implicitly administered posthypnotic suggestion. On the other hand amnesia can be viewed as a form of dissociation. One possible mechanism of such dissociation may be a basic difference of the structure of thought processes involved in hypnosis compared to those of normal waking experience. In this sense amnesia should occur independently of suggestion and be different in kind from most other hypnotic phenomena. The former mechanism may occur more frequently in experimental situations and the latter in clinical contexts.     

Corticosteroids in asthma

The use of corticosteroids in the treatment of asthma has significantly decreased the morbidity and mortality from this disease. However, corticosteroids have devastating side effects when given frequently or for prolonged periods. High doses of systemic corticosteroid preparations should be used only during bouts of acute bronchospasm, whereas the lowest possible dose needed to control symptoms is recommended for the treatment of chronic asthma. Aerosolized steroids offer an alternative to systemic preparations and have less associated morbidity. Various corticosteroid preparations have various potencies and durations of action that need to be considered. Patients with coexisting liver disease require preparations that do not need hepatic hydroxylation, whereas patients with congestive heart failure require preparations that minimize salt retention. When asthma and pregnancy coexist, it is vital that symptoms of bronchospasm are controlled to protect the fetus. During stressful situations, such as surgery, it is important to consider the possibility of hypothalamic-pituitary-adrenal axis suppression if the asthmatic patient has been previously treated with corticosteroids.     

儿童哮喘风险评分与哮喘预测指数用于预测反复喘息幼儿发生哮喘的临床研究

目的 探讨儿童哮喘风险评分（PARS）和哮喘预测指数（API）对反复喘息幼儿发生支气管哮喘（哮喘）的预测价值,为儿童哮喘的精准预测提供充分的证据。方法 收集100例1~3岁反复喘息儿童的临床资料,分别进行PARS和API评估,随访观察患儿是否发生哮喘,比较两者单独或联合应用的预测效能。结果 PARS预测反复喘息幼儿发生哮喘的灵敏度和特异度分别为54.55%和86.52%,ROC AUC为0.744 （95% CI 0.578~0.909）。API预测反复喘息幼儿发生哮喘的灵敏度和特异度分别为72.73%和52.81%,ROC曲线下面积为0.628（95% CI 0.460~0.796）。两者联合预测反复喘息幼儿发生哮喘的灵敏度和特异度分别为81.82%和44.94%,ROC曲线下面积为0.634（95% CI 0.474~0.794）。PARS预测反复喘息幼儿发生哮喘的ROC AUC略高于API及联合检测,但组间比较差异均无统计学意义（P均>0.05）。结论 PARS和API用于预测反复喘息幼儿发生哮喘的临床价值相当。     

The Finnish national asthma programme: communication in asthma care--quality assessment of asthma referral letters

AIMS AND OBJECTIVES: The Finnish National Asthma Programme, which was launched in year 1994, considered the management of asthma as a community problem. The role of the primary health care in the management of asthma was emphasized. Optimal asthma management includes good communication between health care professionals. Referral letters are an accepted tool for evaluation of the communication process. The aim of this study was to assess the quality of asthma-related referral letters. METHODS: All non-acute referral letters (n=3176) to three pulmonary departments were screened in 2001 and all those related to asthma were included (n=1289). The 14 previously derived asthma-specific criteria were applied: occupation, smoking, known allergies, current medication, other diseases, onset of symptoms, wheezing, dyspnoea, specified dyspnoea, cough, specified cough, use of asthma medication, peak-flow follow-up or spirometry with bronchodilatation test as an attachment. The study group was prepared to accept the maximum of 30% of the referral letters to be of poor quality. RESULTS: Twenty-one per cent of the referral letters were graded good, 34% satisfactory and 45% poor. Information on wheezing, smoking habits and current medication was mentioned in 44%, 42% and 41% of asthma letters respectively. CONCLUSIONS: The Finnish National Asthma Programme calls for optimizing communication between doctors. The proportion of poor letters was 50% higher than the preset standard and clearly indicates a need for improvement. We found several issues, which need to be better communicated (smoking, lung function tests, wheezing, medication) when referring a patient with suspected asthma.     

儿童哮喘门诊规范化管理的实践

目的 开展儿童哮喘门诊规范化管理实践并探讨其效果。方法 采用方便抽样法,选取2016年12月-2017年2月在上海市某三级曱等儿童医院哮喘门诊就诊的哮喘患儿173例为研究对象,成立哮喘门诊规范化管理团队,干预措施包括流程优化、患儿档案建立、专业评估、规范诊疗、个性化的健康教育和干预措施的实施、示教药物吸入治疗、实时疾病监控、运用信息技术为哮喘患儿提供专业哮喘管理服务。结果 干预6个月后,173例患儿的儿童哮喘测试问卷评分由（19.24±3.49)分提升至（24.25±2.47)分;完全控制哮喘的患儿由61.8%上升到78.6%,未控制哮喘的患儿由11%下降至6.4% ;生存质量评分由（69.92±13.56)分上升至（76.37±9.44)分;医疗支出由[2519.04 (750.00,3750.00)]元/半年降低到[1338.00(643.75,1 718.75)]元/半年,差异均具有统计学意义（p<0.05)。结论 哮喘门诊规范化管理能有效提高哮喘患儿及家长的哮喘管理意识、知识和技术,在提高哮喘控制水平和生存质量的 同时,降低医疗支出,缓解家庭的经济压力。     

哮喘预测指数与哮喘预测评分对儿童哮喘的预测价值分析

目的 评估哮喘预测指数（API）和哮喘预测评分（APS）对儿童哮喘的预测价值。方法 分析266例年龄≥6岁既往有喘息患儿的问卷调查情况,调查表主要由API和APS的各项参数组成,包括患儿的一般情况、家族史、喘息情况、过敏情况和试验性治疗情况。利用腾讯问卷输入数据并进行整理,通过受试者工作特征（ROC）曲线下面积（AUC）评价API与APS对儿童哮喘的预测效能,通过Hosmer-Lemeshow检验评价校准度。结果 ROC曲线分析显示,API的宽松指标与严格指标的AUC分别为0.734与0.718,APS的AUC为0.975, APS的截断值为4.5分。Hosmer-Lemeshow拟合优度检验结果显示,2种哮喘预测工具的校准线图中的实测值与期望值贴合,校准度良好。结论 2种哮喘预测工具的校准度良好,APS对儿童哮喘的预测价值高于API。