The influence of serum theophylline concentration on the bronchodilating effect of salbutamol inhalation for bronchial asthma

To examine the effects of serum theophylline concentration on the bronchodilating effect of beta 2-stimulant inhalated by patients with bronchial asthma, 200 micrograms-Salbutamol inhalation test was performed on 30 patients with bronchial asthma (from 17 to 71 years old, averaging 49.7; 3 mild, 15 moderate, 12 severe), who had taken theophylline at various oral doses up to 6 hours before the test. Measurements of respiratory function, serum theophylline concentration, blood pressure, pulse rate and the plasma c-AMP and c-GMP concentrations before and one hour after inhalation revealed that inhalation of 200 micrograms salbutamol significantly increased FVC, FEV1.0, PEF and plasma c-AMP (p less than 0.001). No significant change was noted in plasma c-GMP, diastolic pressure or pulse rate. Systolic pressure significantly decreased (p less than 0.05). Furthermore, no significant correlation was noted between the rates of increase (%) in FVC, FEV1.0 and PEF and those in plasma c-AMP, c-GMP and c-AMP/c-GMP in one hour after inhalation. Inaddlition no significant correlation was noted between the rates of increase in FVC, FEV1.0 and PEF one hour after inhalation and serum theophylline concentrations (0-19.3 and 0-21.5 micrograms/ml before and one hour after inhalation, respectively). The above results suggest that the bronchodilating effect of salbutamol inhalated at dose of 200 micrograms is not influenced by the serum theophylline concentration both before and at one hour after inhalation of salbutamol. The bronchodilating effect of salbutamol seems to be ascribable to an increase of intracellular c-AMP level of bronchial smooth muscle.     

Asthma patients' perception of dyspnea during acute bronchoconstriction

The aim of this study was to analyze variations in the perception of acute bronchial obstruction among asthmatics in our practice and to try to define the variables that influence inter-individual differences. We studied 153 asthmatics in stable condition, using a Borg scale to measure dyspnea perceived during a histamine bronchial challenge test. To study individual perception we analyzed both absolute magnitude of perception of dyspnea on the Borg scale when forced expiratory volume in 1 second (FEV1) fell 20% (perception score 20-PS20) and the mathematical difference between PS20 and baseline dyspnea (change in Borg, CB). The results were as follows. 1) The factors that affected PS20 according to multiple linear regression were anxiety, baseline dyspnea and the provocative concentration required to produce a 20% fall in FEV1 (PC20). 2) Within each level of asthma severity, there were differences in dyspnea perception when FEV1 fell 20% (analysis of variance of repeated measures), such that patients with mild asthma and no bronchial obstruction perceived more change in dyspnea. 3) CB during the bronchial challenge test distinguished four ways of perceiving dyspnea: 15% were dysperceivers, 13% were hypoperceivers, 48% were normoperceivers and 24% were hyperperceivers. 4) Hypoperceivers and dysperceivers were at greater risk of severe exacerbation whereas hyperperceivers requested unnecessary medical consultations. 5) Subjects with poorer quality of life were usually dysperceivers; hyperperceivers were the second most common type among those with poorer quality of life. In conclusion, a large percentage of asthmatics do not appropriately perceive acute bronchial obstruction, and the simplest way to evaluate their perception is to calculate the change in dyspnea (on a Borg scale) during the bronchial challenge test. The manner of perceiving dyspnea can not be predicted beforehand, yet it has a significant impact on the use of medical resources and patient quality of life, among other aspects.     

Psychosomatic correlations in patients with bronchial asthma

Dyspnoea, anxiety are the main complaints of patients with bronchial asthma. The personality profile characteristic of bronchial asthma patients includes high levels of depression, anxiety and health preoccupation. Some of the negative aspects of mood correlate with degree of dysfunction. Studies involved 60 consecutive patients with bronchial asthma from light to severe. The author found some correlations between psychological and physiological symptoms. The levels of anxiety and depression were dependent on severity of symptoms (F = 4.54, df = 1.57, p = 0.04, F = 3.74, df = 1.57, p = 0.04). The correlation between the index of anxiety (according the Spielberger Questionnaire) and dyspnoea expressed: with Borg scale was (r = 0.63), with visual analogue scale was (r = 0.57). The intensity of anxiety and subjective feeling of dyspnoea was also correlated with pulmonary function tests results (PEF, FEV1). This suggests the relation between the psychosomatic parameters and severity of airway obturation.     

Relationship between the perception of dyspnoea and airway inflammatory markers

Poor dyspnoea perception in asthmatic patients seems to be associated with increased risk of asthma exacerbation. We have studied the relationship between basel ne dyspnoea perception and inflammatory markers in sputum in eight patients with mild asthma and in 13 patients with moderate to severe asthma.The perception of dyspnoea was scored on the Borg scale. Eosinophilic cationic protein (ECP) was measured by fluoroimmunoassay and by an interleukin (IL)-5 sandwich ELISA. The baseline Borg score was significantly higher in patients with severe asthma than in patients with mild to moderate asthma (4.1 +/- 0.29 vs. 2.28 +/- 0.28, P<0.05).The proportion of eosinophil and ECP levels in the sputum were significantly higher in patients with moderate to severe asthma. IL-5 in sputum was significantly increased in moderate to severe asthmatic patients compared to mild asthmatic patients. A significant relationship was found between the baseline perception score and FEV1/FVC (r = -0.53, P<0.01), sputum eosinophils (r = 0.70, P<0.01) and sputum ECP (r = 0.62, P<0.01).These findings suggest that the baseline perception score is related to inflammatory markers in sputum, and that the perception of dyspnoea as well as airway inflammatory markers may be considered to evaluate asthma severity.     

Effects of anti-asthma therapy on dyspnea perception in acute asthma patients

Blunted perception of dyspnea may predispose patients to fatal asthma attacks. To examine whether this impaired perception of dyspnea in patients with acute asthma could be corrected by anti-asthma therapy, the medical records of 104 consecutive asthma patients who had been hospitalized as a result of asthma attacks were analyzed retrospectively. During the course of treatment with conventional asthma medications, the forced expiratory volume in 1s (FEV1) and the Borg scale-based dyspnea perception scores during breathing through an inspiratory muscle trainer were measured at least twice. The baseline Borg score measured just before discharge was significantly lower than from that measured initially, regardless of improvement in FEV1. In contrast, the Borg score at the highest resistance (HR; 3.12+/-0.26 vs. 5.03+/-0.53; P<0.01) and the HR-induced DeltaBorg score (1.68+/-0.20 vs. 4.47+/-0.54, P<0.001) were increased significantly in the Poor Perceivers (Borg score 5 at HR and HR-induced DeltaBorg score 3). Patient age (r=0.363, P<0.001), blood eosinophil counts (r=-0.285, P<0.01), and serum total IgE levels (r=-0.213, P<0.05), but not FEV1, were significantly related to the effect of the treatment on the HR-induced DeltaBorg scores. These findings suggest that anti-asthma treatments decrease dyspnea even without a concomitant improvement in lung function and correct the impaired perception of inspiratory resistive load in acute asthma, and that age and allergy influence the effect of treatment on impaired perception.     

Do subjects with asthma have greater perception of acute bronchoconstriction than smokers with airflow limitation?

OBJECTIVE: Smokers who develop chronic airflow limitation (CAL) do not usually present for medical attention until their lung disease is well advanced. In contrast, asthmatic subjects experience acute symptoms and present for care early in the course of their disease. The aim of this study was to determine whether subjects with asthma differ from smokers with CAL in their ability to perceive acute methacholine-induced bronchoconstriction. METHODOLOGY: Thirteen subjects with diagnosed asthma and 10 current smokers with CAL, defined as forced expiratory volume in 1 s (FEV1) < 75% predicted and FEV1/forced vital capacity < 80%, with no previous diagnosis of asthma, were challenged with methacholine. Symptom severity was recorded on a Borg scale. Lung volumes were measured before challenge and after the FEV1 had fallen by 20%. RESULTS: After methacholine falls in FEV1 were similar in the asthmatic subjects and smokers. The regression lines relating change in FEV1 to symptom score were significantly steeper in asthmatic subjects than smokers (0.13 +/- 0.04, 0.03 +/- 0.04, respectively, P < 0.01). At 20% fall in FEV1 there were no significant differences between asthmatic subjects and smokers in the magnitude of change of lung volumes. CONCLUSIONS: In asthmatic subjects, symptoms are closely related to change in FEV1. In smokers with CAL, symptoms change little during bronchial challenge despite large changes in FEV1. The differences in perception between the two subject groups are not due to differences in acute hyperinflation during challenge. We propose that heavy smokers may adapt to poor lung function, or may have damaged sensory nerves as a result of prolonged cigarette smoking.     

Serum interleukin-5 measurements for monitoring acute asthma in children.

Cytokine-mediated interactions among the inflammatory cells may play a role in the pathogenesis of bronchial asthma. Interleukin-5 (IL-5) is a major cytokine in the recruitment of neutrophils to the area of inflammation. Serum IL-5 is a marker of disease activity and treatment efficacy in bronchial asthma. To understand the role of IL-5 in disease activity in acute asthma, changes in serum concentrations of IL-5 elaborated by activated eosinophil before and after prednisolone therapy with clinical improvement were determined in the present study. Circulating levels of IL-5 in 16 normal control subjects and in sera from 22 allergic asthmatic children with acute exacerbation and in stable condition were determined by using commercially available assay kits. The mean concentration of serum IL-5 was higher in patients with acute exacerbation (6.30 +/- 2.21 pg/mL) and in stable asthmatics (5.55 +/- 2.23 pg/mL) compared to control group subjects (4.81 +/- 0.54 pg/mL; p > 0.05). However, the difference was not statistically significant between the acute exacerbation and stable asthmatics groups (p > 0.05). Serum IL-5 is a poor indicator of disease activity in acute asthma; therefore, monitoring serum IL-5 concentration is of limited value. The clinical value of serum IL-5 as a marker of disease activity remains to be established.     

Randomized comparison of ciclesonide 160 and 640 microg/day in severe asthma

OBJECTIVE: Demonstrating clinical benefit of higher doses of inhaled corticosteroids in asthma is frequently problematic owing to their relatively flat dose-response curve in this condition. In this study we compared the efficacy and safety of a fourfold difference in the dose of ciclesonide-ciclesonide 320 microg twice daily (CIC640) versus ciclesonide 160 microg once daily (CIC160)-in patients with severe persistent asthma. METHODS: Patients with bronchial asthma (6 months) were included in this randomized, double-blind study. After receiving fluticasone propionate 250 microg twice daily during run-in, patients were randomized to CIC160 (n=339) or CIC640 (n=341) for 12 weeks. Primary endpoints were time to first asthma exacerbation and forced expiratory volume in 1s (FEV(1)). Secondary endpoints included other lung function variables, asthma symptom scores and rescue medication use (RMU). RESULTS: Asthma exacerbations occurred in 12.7% of patients receiving CIC160 and 6.7% receiving CIC640. CIC640 was superior for time to first exacerbation (p=0.0050, one-sided). FEV(1) increased significantly with CIC160 and CIC640 (least squares mean+/-SE of mean: 269+/-31 and 332+/-31 mL, respectively; p<0.0001), with no significant difference between groups. Change in % predicted FEV(1) and morning peak expiratory flow (PEF) were significantly higher with CIC640 (p<0.05). Asthma symptom score sums and RMU decreased in both groups; CIC640 was statistically superior (p=0.0108 and 0.0005, respectively). No unexpected adverse events were reported in either group and the majority of the events reported were mild or moderate in intensity. No significant changes in serum cortisol were observed from the baseline to the study end. Small decreases in creatinine-adjusted 24h urine cortisol levels from baseline were seen in both the treatment groups, which, due to the large patient numbers, were statistically significant (p<0.05); however, no dose-response effect was seen and the difference between groups was not significant (p=0.7892). CONCLUSION: CIC640 was superior to CIC160 for time to first exacerbation, % predicted FEV1, morning PEF, asthma symptom score sum and RMU in patients with severe asthma; both doses had similar tolerability profiles and no significant changes in serum cortisol were seen in either treatment group.     

噻托溴铵联合布地奈德治疗轻中度支气管哮喘的疗效观察

目的观察噻托溴铵联合布地奈德治疗轻中度支气管哮喘的临床疗效。方法选择我院2011年11月—2012年12月诊治的轻中度支气管哮喘患者60例,随机分为观察组和对照组,每组30例。对照组患者吸入布地奈德,观察组吸入布地奈德+噻托溴铵。检测两组患者治疗前及治疗后8周第一秒用力呼气容积(FEV1)、呼气峰流速(PEF);记录两组患者治疗后8周支气管哮喘急性发作次数及治疗期间不良反应情况。结果两组患者治疗前FEV1及PEF比较,差异均无统计学意义(P0.05);两组患者治疗后FEV1及PEF高于治疗前,且观察组患者治疗后FEV1及PEF高于对照组(P0.05)。治疗组患者治疗后8周支气管哮喘急性发作次数为(2.3±0.2)次,低于对照组的(9.2±0.3)次(P0.05)。观察组患者治疗期间出现口干2例,对照组患者治疗期间出现失眠1例,两组患者不良反应发生率比较,差异无统计学意义(P0.05)。结论噻托溴铵联合布地奈德治疗轻中度支气管哮喘疗效确切,可有效改善患者肺功能,减少支气管哮喘急性发作次数。     

Does an IV bolus of methylprednisolone relieve dyspnea in asthma exacerbations?

STUDY OBJECTIVES: To assess whether IV methylprednisolone exerts a specific early effect on dyspnea in patients with an exacerbation of asthma. DESIGN: Randomized, placebo-controlled, double-blind crossover trial. SETTING: Medium-sized university general hospital. PATIENTS: Twenty-five asthma patients attending the chest clinic with spontaneous complaints of increases in dyspnea and with a Borg scale dyspnea rating >/= 1 at rest. INTERVENTIONS: At 0 min, IV methylprednisolone (125 mg) vs saline solution; at 60 min, 5 x 500 microg terbutaline inhaled from an inhaler device. Measurements and results: Change in dyspnea was assessed with bipolar visual analog scale (VAS) (much more short of breath, -100%; much less short of breath, + 100%), FEV(1), and visual memory (using the Benton visual retention test). Eighteen subjects (mean age, 61 years) completed the study. At 5 min and 60 min, shortness of breath improved with no statistically significant difference between saline solution and methylprednisolone. The mean (SD) VAS rating at 60 min was 29% (39%) on the day that saline solution was administered and 36% (25%) on the day the steroid was administered. FEV(1) and Benton score did not significantly change from baseline on either study day. Shortness of breath and FEV(1) improved following terbutaline administration, with no significant difference between the days on which saline solution and the steroid were administered. In the seven subjects who were randomized to receive methylprednisolone on the first day, baseline dyspnea rated on the Borg scale was significantly lower on the second day (first day: median, 3; range, 3 to 4; second day: median, 2; range, 0.5 to 3; p = 0.040). CONCLUSIONS: We conclude that in patients with an exacerbation of asthma, an IV bolus of methylprednisolone does not reduce dyspnea more than saline solution after 5 min and 60 min.     

Evaluation of serum interleukin-8 as a marker of disease activity in acute asthma in children.

Cytokine-mediated interactions among the inflammatory cells may play a role in the pathogenesis of bronchial asthma. Interleukin-8 (IL-8) is a major cytokine in the recruitment of neutrophils to the area of inflammation. Serum IL-8 is a marker of disease activity and treatment efficacy in bronchial asthma. To understand the role of IL-8 in disease activity in acute asthma, changes in serum concentrations of IL-8 elaborated by activated eosinophil before and after prednisolone therapy with clinical improvement were determined in the present study. Circulating levels of IL-8 in 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in stable condition were determined by using commercially available assay kits. The mean concentration of serum IL-8 was statistically significantly higher in asthmatic children with acute exacerbation (63.62 +/- 11.41 pg/mL) and in stable asthmatics (64.22 +/- 10.31 pg/mL) compared to the control group subjects (50.40 +/- 30.70 pg/mL; p < 0.01). However, the difference was not statistically significant between the acute exacerbation and stable asthmatics groups (p > 0.05). Serum IL-8 is a poor indicator of disease activity in acute asthma; therefore, monitoring by serum IL-8 concentration is of limited value. The clinical value of serum IL-8 as a marker of disease activity remains to be established.     

Effect of long-term treatment with inhaled budesonide or theophylline on lung function,airway reactivity and asthma symptoms

Asthma is characterized by inflammation of the airways and long-term treatment with inhaled glucocorticosteroids improve clinical control in patients previously treated with inhaled rescue beta-2 agonist. We investigated whether the dose of inhaled glucocorticosteroid was related to outcome compared with oral theophylline. Budesonide 800 microg bd, budesonide 200 microg bd, or theophylline (Theo-Dur 300 mg bd was given double-blind, double-dummy and randomized, in a parallel group design for 9 months; when therapy was stopped patients were followed for an additional 3 months. Forced expiratory volume in 1 sec (FEV1), bronchial reactivity and asthma symptom scores were assessed before entering the study and after 1, 2, 3, 5, 7, and 9 months of treatment and monthly after treatment was stopped. Eighty-five patients (38 females and 47 males) were enrolled in the study during 1 1/2 year. Withdrawal from the study due to exacerbations during the treatment period was significantly increased (P <0.01) in the theophylline group. After treatment was stopped more patients withdrew in the budesonide group. In the budesonide 800 microg bd group, FEV1 improved significantly after 1 months treatment (P <0.01) and persisted throughout the study period. In the budesonide 200 microg bd group, FEV1 improved slightly and reached significance (P=0.05) after 5 months of treatment. In the theophylline group, FEV1 was unchanged during the 9 months of treatment. In both budesonide groups, FEV1 deteriorated significantly (P<0.01 and P<0.02, respectively) after termination of study medication and reached pretreatment values during the first month. In the budesonide 800 microg bd group, the concentration of histamine causing a 20% fall in FEV1 (PC20) increased significantly (P<0.01) after 1 months treatment and increased further after 9 months (P<0.0001), equivalent to two doubling dilutions. In the budesonide 200 microg bd, group PC20 histamine significantly increased (P <0.005) after 2 months of treatment and remained constant; theophylline was unchanged. After treatment with budesonide 800 microg bd and 200 microg bd were stopped, PC20 decreased significantly (P<0.002 and P=0.05, respectively) within the first month. PC20 remained unchanged after theophylline was stopped. After budesonide 800 microg bd and 200 microg bd treatment, symptom severity decreased in a dose-related and highly significant manner (P < 0.00001 and P < 0.0001, respectively). With theophylline, asthma symptoms decreased slightly after 1 and 2 months treatment (P < 0.01 and P < 0.02, respectively) and when treatment was stopped no increase in asthma symptoms was evident. Oral theophylline slightly reduced airways symptoms and had no influence on FEV1 and PC20 histamine. Maintenance treatment with inhaled budesonide gave a dose-related reduction in airways obstruction, bronchial reactivity and asthma symptom severity. The efficacy of inhaled corticosteroid was superior to oral theophylline.     

布地奈德雾化吸入佐治老年支气管哮喘的临床疗效研究

目的探讨老年支气管哮喘的治疗方法。方法选择90例老年支气管哮喘急性发作期患者随机分为布地奈德佐治组（试验组）和常规治疗组（对照组）,每组各45例。对照组患者接受常规治疗;试验组患者在常规治疗基础上加用布地奈德雾化吸人,共2W。分别检测两组患者的疗效、临床症状与体征消失时间、第一秒用力呼气容积／用力呼气量预计值的百分比（FEV1％）、第一秒用力呼气容积／用力肺活量百分比（FEV1／FVC％）、最大呼气峰值流速实测值占预计值的百分比（PEF％）,并进行比较与统计学分析。结果布地奈德佐治组的总有效率显著高于常规治疗组（84．44％VS．73．33％,P〈0．05）,咳嗽、喘息、胸闷、肺哮鸣音等症状、体征消失时间明显少于常规治疗组（均P〈0．01、P〈0．05）。各组治疗前后比较,治疗后FEV1％、FEV1／FVC％和PEF％均显著升高（P〈0．01）;与常规治疗组治疗后比较,布地奈德佐治组治疗后的FEV1％、FEV1／FVC％和PEF预计值均明显升高,差异有统计学意义（P〈0．01）。结论布地奈德对老年支气管哮喘有很好的辅助疗效。     

Peak expiratory flow variability and exercise responsiveness in methacholine-hyperresponsive adolescents with asthma remission.

The aim of this study was to investigate whether bronchial hyperresponsiveness in adolescents with long-term asthma remission is associated with increased peak expiratory flow (PEF) variability and/or increased bronchial response to exercise (BRE). Twenty-nine adolescents with asthma remission (neither symptoms nor any medication used during the previous two years), but with persistent methacholine hyperresponsiveness (PC20 < 18 mg/mL; remission group), 29 methacholine PC20-matched adolescents with symptomatic asthma (symptomatic group), and 20 healthy subjects (control group) were studied. Subjects recorded PEF twice daily for 14 days and PEF variability, expressed as amplitude % mean, was calculated. Subjects also underwent a standardized exercise challenge; BRE was defined as a maximal % fall in FEV1 within 30 min after exercise. The mean (+/- SD) PEF variations in the symptomatic group and in the remission group were 12.10 +/- 6.35% and 10.02 +/- 4.73%, respectively, which were significantly higher than that (5.94 +/- 2.44%) of the control group. On the other hand, the degree of BRE (7.36 +/- 3.85%) in the remission group was significantly lower than that (22.31 +/- 10.50%) of the symptomatic group, and similar to that (5.98 +/- 2.70%) of the control group. Methacholine hyperresponsiveness in asthma remission during adolescence is associated with increased PEF variability but not with increased BRE.     

吸入呋塞米对急性发作期支气管哮喘患者肺通气功能的影响

目的 探讨吸入呋塞米对急性发作期支气管哮喘（哮喘）患者肺通气功能的影响。方法 将６例经、中度发作期哮喘患者随机分为Ａ、Ｂ、Ｃ三组,每组各２０例。Ａ组吸入生理盐水５ｍｌ,Ｂ组吸入呋塞米５０ｍｇ（５ｍｌ,１０ｍｇ／ｍｌ）,Ｃ组吸入０．１％沙丁胺醇溶液５ｍｌ。观察三组患者吸药后１５ｍｉｎ肺通气功能的变化。结果 吸药后１５ｍｉｎＢ、Ｃ组用力肺活量（ＦＶＣ）、第１ｓ用力呼气容积（ＦＥＶ１）、最在呼气流量（Ｐ     

Analysis of sputum cell counts during spontaneous moderate exacerbations of asthma in comparison to the stable phase.

BACKGROUND: Acute airway inflammation is considered to characterize asthma exacerbations, but its specific cellular pattern has not yet been completely evaluated. AIM: To evaluate the prevalence of sputum eosinophilia during acute asthma exacerbations of moderate severity, compared with a stable phase of the disease, and to assess the concordance between changes in pulmonary function and sputum eosinophilia in the period between exacerbation and post exacerbation. METHODS: We compared sputum and blood inflammatory cell counts in 29 asthmatic subjects during a spontaneous moderate exacerbation of asthma (visit 1) with sputum and blood cell counts measured 4 weeks after the resolution of asthma exacerbation (visit 2). At visit 1, all subjects required an appropriate 1 week treatment with oral corticosteroids. RESULTS: At visit 1, all subjects were able to collect spontaneous sputum, whereas at visit 2 sputum was induced by inhalation of hypertonic saline (NaCl 3, 4, and 5%, 10 minutes each) with beta2-agonist pretreatment. Asthma exacerbation was accompanied by a significant increase in sputum eosinophil percentages compared with levels after exacerbation [25% (1-78) versus 4% (0-23), p<0.05). Only four subjects showed low sputum eosinophil percentages during exacerbation, and these showed no differences in main clinical findings with respect to subjects with sputum eosinophilia. At visit 2, the stability of asthma was assessed on the basis of PEF, FEV1, symptoms, and use of rescue beta2-agonist. Asthma was defined as stable in 21 out of 29 subjects. Sputum eosinophil percentages fell significantly between visit 1 and visit 2 in both stable and unstable patients, but at visit 2 sputum eosinophil percentages were still high in subjects with unstable asthma. In patients who proved to be stable at visit 2, there was a significant correlation between the changes recorded in sputum eosinophil percentages and in FEV1 between the two visits (rho: 0.723, p<0.001). CONCLUSION: Sputum cosinophil but not neutrophil percentages increase in most asthmatic subjects during moderate exacerbation of asthma. Changes in the degree of airway eosinophilic inflammation are related to changes in the severity of airway obstruction during asthma exacerbation.     

Serum levels and bronchodilatation after intravenous administration of theophylline in asthmatic patients

Forced expiratory volume in the first second (FEV1) and serum theophylline levels were measured comparatively in 26 patients with stable bronchial asthma after a 240 mg theophylline infusion. The mean (+/- s.e.m.) elimination half-life and clearance of theophylline were 6.37 +/- 2.03 hours and 0.78 +/- 0.31 ml/min/kg respectively. A bronchodilator response (more than 20% increase in FEV1) was obtained in 17 patients whose pretreatment FEV1 was less than 30% of predicted normal values. No significant bronchodilator response was obtained in the other patients. There was no relationship in responders between changes in FEV1 and simultaneous serum theophylline levels. Maximal ventilatory response was apparent 1 to 2 hours only after the theophylline peak concentration.     

Effects of ipratropium bromide nebulizer solution with and without preservatives in the treatment of acute and stable asthma.

In a recent study, it was suggested that the preservatives in ipratropium bromide nebulizer solution may cause a paradoxic bronchoconstrictor response in 20 percent or more of patients with stable asthma. The frequency of this response in patients with acute asthma is unknown. The aim of this study was to examine the acute effects of the usual dose of nebulized ipratropium bromide (0.25 mg) in patients with either stable or acute asthma using formulations with and without added preservatives. Twenty-five patients with stable asthma and 25 patients with acute asthma were studied. Each subject was given preservative-containing ipratropium bromide, preservative-free ipratropium bromide, pH 7 preservative-free ipratropium bromide, and saline solution in random order using a double-blind crossover technique with at least 4 h between drug administrations. Very frequent measurements of FEV1 were made for 30 min after each drug administration and then 5 mg of albuterol was nebulized and the FEV1 was measured again after another 30 min. Changes in FEV1 were expressed as a percentage of the predicted FEV1. Paradoxic bronchoconstriction to ipratropium was detected in only one patient with acute asthma (12 percent fall in FEV1) but in none of the patients with stable asthma. A 6 percent fall in FEV1 change occurred with the saline solution in this subject suggesting that the response may have been a nonspecific one due to increased bronchial responsiveness. The mean response (+/- 1 SD) to albuterol plus either preservative-containing ipratropium, preservative-free ipratropium, or pH7 preservative-free ipratropium was significantly greater (p less than 0.05) than the response to albuterol alone both in the patients with acute asthma (25 +/- 12 percent, 27 +/- 15 percent, 26 +/- 15 percent, and 20 +/- 15 percent, respectively) and stable asthma (26 +/- 7 percent, 25 +/- 8 percent, 24 +/- 6 percent, and 22 +/- 9 percent) supporting the use of ipratropium bromide as an additional bronchodilator in patients with asthma who do not show a satisfactory response to nebulized beta-adrenergic agonist.     

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 microg/day or equivalent at a stable dose for 4 weeks and have a forced expiratory volume in 1s (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 Delta FEV 1 12% after 200-400 microg salbutamol; and 1 day without asthma symptoms during the last 7 days. Patients were randomized to twice-daily ciclesonide 320 microg (ex-actuator) or twice-daily FP 330 microg (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: p0.0001) 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 microg and FP 330 microg 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.     

Perception of bronchoconstriction in elderly asthmatics.

The impaired perception of bronchoconstriction in asthmatic patients may increase the risk of severe exacerbation. To characterize the perception of bronchoconstriction in elderly asthma patients, we compared the perception in older patients with that of younger patients. To determine the influence of perception of long-standing diseases, we further evaluated the perception in early-onset elderly asthma patients and in late-onset elderly asthma patients. The study group consisted of 80 stable asthmatic patients. The patients were grouped according to their age (group 1, < 60 years, n = 37, group 2, > or = 60 years, n = 43). Each group was separated into two subgroups according to the duration of symptoms (late-onset asthma 1A and 2A, < 5 years, early-onset asthma 1B and 2B, > or = 5 years). A histamine inhalation test was performed for each patient. Dyspnea was assessed by modified Borg scale. The Borg score in forced expiratory volume in 1 sec (FEV1) reduction by 20% was determined as perception score 20 (PS20). The mean perception scores of the elderly asthmatic patients were significantly lower than those of the younger asthmatic patients (group 1, PS20 = 2.35 +/- 0.17; group 2, PS20 = 1.37 +/- 0.12, p < 0.0001). The differences of mean perception score (PS20) between early- and late-onset subgroups were insignificant (IA, 2.63 +/- 0.30 and IB, 2.07 +/- 0.16, p = 0.101; 2A, 1.36 +/- 0.19 and 2B, 1.59 +/- 0.120, p = 0.91). The mean perception scores of male asthmatic patients were significantly lower than those of female patients (p = 0.03). There was a correlation between PS20 and % FEV1 in the younger group (r = 0.392, p = 0.02), but not in the elderly group (r = 139, p = 0.375). The correlation between PS20 and PD20 in both younger and elderly group was insignificant (p > 0.05). Elderly asthmatics perceive less intense respiratory distress for a decrease of 20% in FEV1 than do younger asthmatics. This underperception of bronchoconstriction may result in a delay in medical care during an acute asthmatic episode. Thus, we strongly recommend that elderly asthmatic patients should be followed up more frequently and closely.