The clinical effect and the effect on the ciliary motility of oral N-acetylcysteine in patients with cystic fibrosis and primary ciliary dyskinesia

The effect of peroral N-acetylcysteine (NAC) in patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) was investigated. 41 CF patients and 13 PCD patients completed the study which was a double-blind, placebo-controlled, cross-over trial. The patients received either NAC or placebo for two periods of three months followed by a three month follow-up period. Active treatment consisted of NAC, either 200 mg x 3 daily (patients weighing less than 30 kg) or 400 mg x 2 daily (greater than 30 kg). The effect was evaluated in terms of a subjective clinical score, weight, sputum bacteriology, blood leucocyte count, sedimentation rate, titres of specific antimicrobial antibodies, lung function parameters and measurement of the ciliary function. No effect was seen in PCD patients, but in CF patients an improved lung function was seen in the period when the patients suffer most from lower airway infections.     

Importance of smoking index for assessing lung damage by lung function tests

A total of 89 smokers of age varying between 15-52 years were assessed for lung function forced vital capacity (FVC), forced expiratory volume in one second (FEV1) ratio of FEV1 and FVC as FEV1% and peak expiratory flow rate (PEFR), before smoking (BS) and 30 min after smoking (AS). All the above lung function tests were reduced in smokers in comparison to those of age-matched non-smokers. Further, when observed test values of lung function were tabulated according to smoking index (SI), it was noted that reduction of lung function increased with SI.     

Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study.

Pulmonary sarcoidosis is a disease in which the pathological processes are distributed along lymphatic pathways, particularly those around the bronchovascular bundles. Delivery of disease-modulating drugs by the inhaled route is therefore an attractive option. The aim of this study was to determine the efficacy of inhaled fluticasone propionate 2 mg x day(-1) in adults with stable pulmonary sarcoidosis. Forty-four adult patients (22 from each centre) were enrolled from outpatient clinics in two London teaching hospitals in a two centre, double-blind, randomized, placebo-controlled trial. Primary end points were home recordings of peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Secondary end points were symptom scores, use of rescue bronchodilator medication, and clinic values for PEFR, FEV1, FVC, forced mid-expiratory flow (FEF25-75%), diffusion capacity of the lung for carbon monoxide (DL,CO), and total lung capacity (TLC). Symptom scores of cough, breathlessness and wheeze were lower in the active treatment group, but this did not reach statistical significance, and a general health perception assessment (Short Form (SF)-36) showed a difference between active and placebo treatment. No significant differences were found between the two groups in any physiological outcome measure. No new adverse reactions were detected. The results of this pilot study do not show an objective benefit of inhaled fluticasone propionate in pulmonary sarcoidosis where the disease is stable and is controlled without the use of inhaled corticosteroids.     

舒利迭辅助治疗对慢性阻塞性肺疾病肺功能的影响

目的 探讨舒利迭辅助治疗COPD患者肺功能的影响.方法 将我院收治的60例COPD患者随机分为观察组和对照组,每组30例,两组都均采用基础治疗,对照组加用孟鲁司特,观察组在对照组的基础上采用舒利迭辅助治疗,比较两组患者的临床疗效、肺功能、治疗前后的血气指标变化.结果 观察组的总有效率为90.0%显著高于对照组的76.7%,P<0.05.观察组治疗后的1 s用力呼气量(FEV1)、用力呼气流量(PEFR)及肺活量最大呼气流速(FRF)、动脉二氧化碳分压(PaCO2)、动脉血氧分压(PaO2)显著优于对照组,P<0.05.结论 舒利迭辅助治疗COPD的疗效较好,能够显著改善患者的肺功能和血气指标.     

Evaluation of lung function indices for bronchodilator trials. Results of a cross-over study of fenoterol.

In 10 patients with airway obstruction, spirographic indices and maximal expiratory flow rates were measured before inhalation of fenoterol and at different time intervals, for 5 h, following the inhalation of 200 mug of this substance. 10 min after inhalation of fenoterol, there was a statistically significant increase in all lung function indices. A further increase was observed later. 3 h after inhalation of fenoterol, all indices were still significantly higher than control values. No side effects were observed. At all time intervals, the increase of the forced expiratory volume in 1 sec (FEV1.0), peak expiratory flow rate (PEFR) and maximal expiratory flow rate at 50 and 75% of the vital capacity reached a similar level of statistical significance. It is concluded that for the trial of the bronchodilator drugs, any of these indices may be used, and for practical purposes FEV1.0 and PEFR are best suited.     

Inhaled budesonide in chronic bronchitis. Effects on respiratory impedance.

In a placebo controlled study the effects of 6 weeks' treatment with inhaled budesonide (1.6 mg daily) on the impedance of the respiratory system, spirometry and symptom scores were evaluated in 35 patients with chronic bronchitis with forced expiratory volume in one second (FEV1) greater than or equal to 70% predicted. Thirty patients completed the study. No statistically significant differences in the changes in morning peak expiratory flow rate (PEFR), symptom scores, use of terbutaline rescue medication and FEV1 were found between the placebo and the active treatment group. Budesonide treatment was found to result in a small decrease in resonant frequency and a less negative frequency dependence of resistance compared with the placebo group.     

Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux

AIM: To study the effect of combined omeprazole (Ome) and domperidone (Dom) therapy on asthma symptoms and pulmonary function in asthmatics with gastroesoph- ageal reflux. METHODS: We selected 198 asthmatics with gastroesophageal reflux diagnosed by 24-h esophageal pH monitoring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk (1:1 double-blind randomization). Spirometry was done at baseline and af- ter 16 wk of treatment. The primary outcome measures were: mean daily daytime and nighttime asthma symp- tom scores. Mean daily reflux symptom scores, albuterol use as rescue medication (number of puffs), daytime and nighttime peak expiratory flow rate (PEFR), postbroncho- dilator forced expiratory volume in 1 second (FEV1) and postbronchodilator forced vital capacity (FVC) were secondary outcome measures. RESULTS: Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score (17.4% vs 8.9%), nighttime asthma symptom score (19.6% vs 5.4%), reflux symptom score (8.7% vs 1.6%) and rescue medication use (23.2% vs 3.1%) after antire- flux therapy compared to mean change in placebo group (P < 0.001). There was significant improvement in morn- ing PEFR (7.9% vs 0.2%), evening PEFR (9.8% vs 0.5%), FEV1 (11.1% vs 3.78%) and FVC (9.3% vs 1.52%) in the antireflux therapy group compared to placebo on compar-ing the mean change from baseline after 16 wk (P < 0.01).     

Effects of indoor air pollution on lung function of primary school children in Kuala Lumpur

In a cross-sectional study of 7-12 year-old primary school children in Kuala Lumpur city, lung function was assessed by spirometric and peak expiratory flow measurements. Spirometric and peak expiratory flow measurements were successfully performed in 1,214 and 1,414 children, respectively. As expected, the main predictors of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were standing height, weight, age, and sex. In addition, lung function values of Chinese and Malays were generally higher than those of Indians. In multiple regression models which included host and environmental factors, asthma was associated with significant decreases in FEV1, FEF25-75, and PEFR. However, family history of chest illness, history of allergies, low paternal education, and hospitalization during the neonatal period were not independent predictors of lung function. Children sharing rooms with adult smokers had significantly lower levels of FEF25-75. Exposures to wood or kerosene stoves were, but to mosquito repellents were not, associated with decreased lung function.     

A study with cumulative doses of formoterol and salbutamol in children with asthma.

In a double-blind, cross-over study, 9 children (7-13 yrs old) with stable, moderate asthma inhaled formoterol (6, 18 and 54 micrograms) and salbutamol (100, 300 and 900 micrograms) at hourly intervals, in order to compare the peak effect of cumulative doses of the two drugs. One hour after the last dose, 1 mg salbutamol was inhaled to ensure that maximum bronchodilatation was obtained. The forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), forced vital capacity (FVC), pulse rate, blood pressure and tremor were measured regularly after each dose and the PEFR 5, 7, 9 and 20 h after the last dose. The first dose of each drug improved the FEV1, PEFR and FVC substantially while the following doses only gave minor improvement. The final addition of 1 mg salbutamol produced no further improvement. No statistically significant difference in bronchodilating effect was seen between the two drugs at any point in time. Side-effects were minimal. Our data indicate that doses of 6-24 micrograms formoterol can be recommended for school children. For most patients with mild to moderate bronchial asthma higher doses will not add much to the bronchodilating effect.     

Assessing physiological benefit from domiciliary nebulized bronchodilators in severe airflow limitation.

In steroid resistant chronic obstructive pulmonary disease (COPD) we assessed the effect of q.i.d. domiciliary nebulized fenoterol (F) 1.25 mg and ipratropium (I) 0.5 mg for three weeks in a placebo-controlled, randomized, double-blind, crossover study. The twenty patients studied (mean forced expiratory volume in one second (FEV1) 0.8 l) all showed less than 20% increase in FEV1 to 200 micrograms inhaled salbutamol (S) and less than 20% increase in peak expiratory flow rate (PEFR) after 2 weeks prednisolone therapy. Respiratory function tests, 5 min walking distance (5 MWD), visual analogue scales (VAS) for breathlessness, oxygen cost diagrams and reversibilities were performed weekly for three weeks with patients on their usual therapy, after three weeks domiciliary F+I, after three weeks saline and, finally, after a further three weeks on usual therapy again. Primary end-points, selected prior to unblinding, were mean home twice daily PEFR, trapped gas volume, FEV1 and 5 MWD. Home PEFR rose from 164 l.min-1 on saline to 196 l.min-1 on F+I (p = 0.0001). Secondary end-point analysis revealed a fall in home inhaler usage and a rise in VAS. Using the criterion of +15% and greater than 20 l.min-1 increase in home PEFR, 11 out of 20 patients had a "positive" trial. We suggest that such patients, but not others, benefit from long-term, nebulized beta 2-agonist and ipratropium. Trials using home PEFR recordings should be used to identify them.     

Oral terbutaline alone and in combination with theophylline: dose, plasma concentration, and effect in long-term treatment of bronchial asthma

Oral terbutaline, in gradually increasing doses from 2.5 to 10 mg three times daily (t.i.d.) was administered to 12 patients with chronic bronchial asthma. There was a linear relationship between dose and steady-state plasma concentrations in individual patients, but the plasma levels varied fourfold between patients taking similar doses. The need for other medication tended to decrease, and the symptom score, peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV1) improved significantly during the treatment, with a roughly linear dose-effect relationship for the doses 2.5, 5 and 7.5 mg t.i.d. An increase in the dose from 7.5 to 10 mg did not improve PEFR and FEV1 any further. Side-effects were generally few and mild. Oral theophylline 200 mg t.i.d. added to terbutaline 10 mg t.i.d. brought about a further improvement in pulmonary function without adding any troublesome side-effects. Our data indicate that there is little to gain by prescribing terbutaline doses higher than 7.5 mg t.i.d. Instead, theophylline might be added, since this combination seems to have a favourable therapeutic index.     

Bronchodilatory and circulatory effects of inhaling increasing doses of an anti-cholinergic drug, ipratropium bromide (SCH 1000).

Dynamic spirometry with flow-volume curves and measurement of static lung volumes in a body plethysmograph were done in 11 patients with reversible airways obstruction before and up to 240 min after inhalation of 20 mug SCH 1000 and of another 40 mug 60 min later. Forced expiratory volume in 1 s (FEV1), vital capacity (VC) and maximal expiratory flow at 50% VC (V 50% VC) increased successively, reaching maximum after 120 min. In a second part of the study 13 patients inhaled 2+4+8 puffs of SCH 1000 (280 mug in all) at 30-min intervals. PEFR increased significantly up to 224 l/min (44% of predicted normal), with increasing number of SCH 1000 inhalations; no further general effect occurred after additional 3 puffs of terbutaline. Heart rate and blood pressure showed no clinically significant changes. No subjective or objective side-effects were noted.     

Sustained-release theophylline in chronic bronchitis

Twenty-one patients with chronic bronchitis entered a double-blind, cross-over study in which they received sustained-release theophylline ('Nuelin'SA) 350 mg daily for 4 days followed by 700 mg daily for 4 days and matching placebo tablets for 8 days with one week separation. Seventeen patients completed the study. Three patients receiving higher doses for weight than the mean for the group were withdrawn because of side-effects. Mild side-effects only were reported in six other patients. Theophylline given twice daily produced a steady-state mean serum concentration of 13.9 micrograms/ml, 13 patients having concentrations inthe range of 10-20 micrograms/ml. There was no demonstrable improvement of symptoms but pulmonary function measurements in the clinic at the end of active treatment showed a statistically significant improvement in PEFR, 1-second forced expiratory volume and forced vital capacity.     

Comparison of Mometasone Furoate Dry Powder Inhaler and Fluticasone Propionate Dry Powder Inhaler in Patients with Moderate to Severe Persistent Asthma Requiring High-Dose Inhaled Corticosteroid Therapy: Findings from a Noninferiority Trial

Background. Inhaled corticosteroids (ICSs) are one of the suggested first-line therapies for patients with persistent asthma of moderate severity. Methods: The efficacy and safety of mometasone furoate (MF) 400 μg twice daily (BID) and fluticasone propionate (FP) 500 μ g BID administered for 12 weeks via dry powder inhaler (DPI) were compared in a noninferiority trial, in adults with moderate-to-severe persistent asthma. The primary variable was the change from baseline in am peak expiratory flow rate (PEFR). pm PEFR, forced expiratory volume in 1 second (FEV₁), asthma symptoms, rescue medication use, response to therapy, exacerbation rates, and adverse events were also assessed. Results. The lower bound of 95% CIs for treatment differences in the primary variable ranged from 2.6% to 5.6% throughout the 12-week study and were within the prespecified noninferiority range. No significant between-group differences were observed in lung function, rescue medication use, response to therapy, exacerbation rates, or adverse events. At most of the weeks assessed, there were no between-group differences in asthma symptoms. Most adverse events were mild-to-moderate. Conclusion. MF-DPI 400 μ g BID was therapeutically equivalent to FP-DPI 500 μ g BID in patients with moderate-to-severe persistent asthma.     

Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel (from the Platelet Inhibition and Patient Outcomes [PLATO] pulmonary function substudy)

The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor reduced the risk for cardiovascular events in patients with acute coronary syndromes compared to clopidogrel but was associated with increased incidence of dyspnea. This substudy assessed whether ticagrelor affects pulmonary function in patients with acute coronary syndromes: 199 patients enrolled in the PLATO trial and receiving randomized treatment with ticagrelor 90 mg twice daily (n = 101) or clopidogrel 75 mg/day (n = 98) took part in the pulmonary function substudy. Patients with advanced lung disease, congestive heart failure, or coronary artery bypass graft surgery after the index event were excluded. Pulse oximetry (blood oxygen saturation), spirometry (forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow between 25% and 75% of forced vital capacity before and 20 minutes after inhalation of a β(2) agonist), lung volumes (total lung capacity, functional residual capacity, residual volume), and diffusion capacity were performed after patients received study medication for 30 to 40 days. Tests were then repeated <10 days before and approximately 30 days after the discontinuation of study medication. After a mean treatment duration of 31 days, there were no differences between the groups for any of the pulmonary function parameters. At the end of treatment (mean 211 days) and after the discontinuation of study medication (mean 32 days after the last dose), there was also no evidence of a change in pulmonary function in either group. For example, forced expiratory volume in 1 second values before β(2) agonist inhalation in the ticagrelor and clopidogrel groups were 2.81 ± 0.73 and 2.70 ± 0.84 L, respectively, at the first visit and did not change significantly at subsequent visits. In conclusion, no effect of ticagrelor on pulmonary function was seen in this cohort of patients with acute coronary syndromes compared to clopidogrel.     

Bronchial challenge of tropical asthmatics with Ascaris lumbricoides.

Despite the fact that helminthic parasites can stimulate strong immediate hypersensitivity reactions, it is uncertain whether these are relevant to the development of allergic disease in infected patients. In order to examine this possibility, we tested 20 informed chronic asthmatic patients from an Ascaris-endemic area by bronchial challenge with a partially purified extract of this parasite. Sequential measurements were made of both the forced expiratory volume in the first second (FEV1) and the peak expiratory flow rate (PEFR) up to 6 h postchallenge, then of PEFR from 6 to 14 h and at 24 h. These were compared to the effect of control inhalations of saline. Extremely low doses of Ascaris antigen that did not exceed 10 PNU (6 x 10(-7) g of protein) induced significant reductions (> 20%) in FEV1 within 30 min in 3 (15%) patients, and in PEFR in 5 cases (25%). By 6 h postchallenge, 5 (25%) subjects showed significant alterations in FEV1, and 10 (50%) in PEFR. Significant changes in PEFR were recorded between 6 and 24 h in 12 (60%) patients. The challenge of nonasthmatic subjects from the same Ascaris-endemic area did not produce notable changes in pulmonary function, and although asthmatics with no evidence of prior contact with the parasite showed a certain degree of immediate bronchial reactivity to the parasite extract, the late responses were significantly less frequent than in the infected patients. No correlations were detected between the bronchial responses and skin test reactivities to the Ascaris extract, or serum levels of specific IgE or IgG antibody.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of Mometasone Furoate Dry Powder Inhaler and Fluticasone Propionate Dry Powder Inhaler in Patients with Moderate to Severe Persistent Asthma Requiring High-Dose Inhaled Corticosteroid Therapy: Findings from a Noninferiority Trial

Background. Inhaled corticosteroids (ICSs) are one of the suggested first-line therapies for patients with persistent asthma of moderate severity. Methods: The efficacy and safety of mometasone furoate (MF) 400 μg twice daily (BID) and fluticasone propionate (FP) 500 μ g BID administered for 12 weeks via dry powder inhaler (DPI) were compared in a noninferiority trial, in adults with moderate-to-severe persistent asthma. The primary variable was the change from baseline in am peak expiratory flow rate (PEFR). pm PEFR, forced expiratory volume in 1 second (FEV₁), asthma symptoms, rescue medication use, response to therapy, exacerbation rates, and adverse events were also assessed. Results. The lower bound of 95% CIs for treatment differences in the primary variable ranged from 2.6% to 5.6% throughout the 12-week study and were within the prespecified noninferiority range. No significant between-group differences were observed in lung function, rescue medication use, response to therapy, exacerbation rates, or adverse events. At most of the weeks assessed, there were no between-group differences in asthma symptoms. Most adverse events were mild-to-moderate. Conclusion. MF-DPI 400 μ g BID was therapeutically equivalent to FP-DPI 500 μ g BID in patients with moderate-to-severe persistent asthma.     

福莫特罗、孟鲁司特和溴醋茶碱治疗支气管哮喘的疗效比较

目的 比较福莫特罗、孟鲁司特和溴醋茶碱联合应用布地奈德治疗支气管哮喘(简称哮喘)的疗效.方法 利用观察、前瞻、对比研究方法,选取2014年5月至2015年2月于延安市人民医院诊断为哮喘患者78例,随机分成3组,分别接受福莫特罗(6 μg/喷)+布地奈德(100 μg/喷)联合吸入剂(2次/d,每次2喷)、口服孟鲁司特(10 mg,1次/d)+布地奈德(100μg/喷,2次/d,每次2喷)和口服溴醋茶碱(100mg,2次/d)+布地奈德(100 μg/喷,2次/d,每次2喷).患者在治疗后随访4周,记录治疗前后的肺量测定值包括FEV1和最大呼气流速(PEFR).利用哮喘生命质量问卷(AQLQ)方法评估患者治疗前后的生命质量情况.结果 与基线期相比,在接受4周药物治疗后3组患者的FEV1、PEFR和生命质量均表现出显著改善.3组每两组间比较结果显示,区域A、C和D无明显差异.但在区域B,福莫特罗组患者与其他2组相比能够更有效地控制哮喘症状(治疗4周后AQLQ评分为0.45±0.02 vs 0.61±0.03,0.83±0.15;t=2.18,2.25;P＜0.05).溴醋茶碱组中3例患者有胃刺激反应,而其他组患者无明显不良反应.结论 福莫特罗、孟鲁司特和溴醋茶碱联合应用布地奈德在治疗哮喘方面疗效类似.     

Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler.

A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.     

Airway response to inhaled fenoterol in hyperthyroid patients before and after treatment.

Bronchodilatory response to inhaled fenoterol was studied in 15 hyperthyroid patients before and after successful treatment with antithyroid drugs. Baseline forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were lower than the predicted values in 12 and 11 patients, respectively. Improved values were seen after treatment for hyperthyroidism although statistical significance was not reached. Even if some improvement occurred in PEFR (a rise by 0.24-0.48 L/s) and FVC (increase of 73-78 ml) in the hyperthyroid state in response to fenoterol inhalation after various time intervals, the increase in different parameters of lung function was significantly more after the patients achieved euthyroid state (increases in FVC by 290-165 ml; in FEV1 by 333-193 ml; in peak expiratory flow (PEFR) by 0.75-0.52 L/s and in forced expiratory flow (FEF50%) by 0.55-0.31 L/s). In the euthyroid state the mean absolute improvements from the baseline values were significantly higher (< 0.05-0.001). These observations indicate that bronchodilatory response is impaired in the presence of excess thyroid hormones and improves after euthyroid state is achieved.