Effects of single-dose zileuton on bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids.

The aim of the study was to determine whether zileuton, an inhibitor of 5-lipoxygenase, attenuated bronchial hyperresponsiveness (BHR) in asthmatic subjects who had marked BHR during maintenance treatment with inhaled corticosteroids (ICS). In a randomized, double-blind, placebo-controlled, cross-over study, a challenge test with histamine (provocative concentration of histamine producing a 20% fall in forced expiratory volume in one second (FEV1) (PC20,Hist)) and with ultrasonically nebulized distilled water (UNDW) (provocative dose of UNDW producing a 20% fall in FEV1 (PD20,UNDW)) was performed in seven patients with asthma after intake of either 400 mg zileuton or placebo. All patients (mean age 33 yrs, mean FEV1 111% of predicted) had marked BHR, as indicated by a mean PD20,UNDW of 4.74 mL under treatment for at least 6 months with up to 800 microg ICS (mean 536 microg daily). On four different occasions, separated by at least 5 days, two UNDW and two histamine challenge tests were performed in random order 3 h after a morning dose of either zileuton or placebo. Neither zileuton nor placebo changed baseline airway calibre prior to provocation. Zileuton increased PC20,Hist from 0.99 to 5.64 mg x mL(-1) (2.1 doubling doses; p<0.03 compared to placebo), and increased PD20,UNDW from 3.10 to 9.31 mL (1.3 doubling doses; p<0.05 compared to placebo). In conclusion, a single dose of 400 mg zileuton attenuates bronchial hyperresponsiveness to histamine and ultrasonically nebulized distilled water in asthmatic patients with marked bronchial hyperresponsiveness during treatment with inhaled corticosteroids.

The protective effects of ipratropium bromide and terbutaline on distilled water-induced bronchoconstriction.

In a randomized, double-blind, placebo-controlled study, we investigated the protective effects of ipratropium bromide 160 micrograms and 320 micrograms and terbutaline 500 micrograms on ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction in nine stable asthmatic patients. Both drugs caused a significant increase (P < 0.001) in baseline FEV1 with no significant differences between the drugs or both doses of ipratropium bromide. Pre-inhalation of ipratropium bromide 320 micrograms and terbutaline 500 micrograms inhibited UNDW-induced bronchoconstriction (P < 0.01), whereas ipratropium bromide 160 micrograms had no protective effect. The protective effects of ipratropium bromide showed a large interindividual variation. There was no correlation between the increase in baseline FEV1 and PD20 UNDW, indicating that the protective effect on UNDW-induced bronchoconstriction is not dependent on the bronchodilation induced by terbutaline and ipratropium bromide. It also appears that the UNDW-induced bronchoconstriction is at least partly vagally mediated.

[Favorable effects of rehabilitation in patients with CARA]. / Gunstige effecten van revalidatie bij patiënten met CARA.

OBJECTIVE: To examine the effects of a rehabilitation programme in patients with asthma or COPD who have major complaints despite the fact that their pulmonary function is not severely disturbed. SETTING: Medical Centre Dekkerswald, Groesbeek. DESIGN: Prospective clinical trial. PATIENTS AND METHODS: The treated group consisted of 44 patients with an obstructive lung disease, FEV1 68.3% of predicted value. This group was compared with 43 patients in a control group. These were volunteers, who were comparable for pulmonary function, reversibility, age, sex, Quetelet index, pulmonary medication and educational level. These groups were examined for 2 years by means of tests and questionnaires. Changes from baseline values were analysed by covariance analysis. Patients followed a rehabilitation programme which consisted of an optimal medical treatment in combination with training of physical endurance, health education and psychological and social support. The duration of the programme was 3 months, 38 hours a week. RESULTS: Pulmonary rehabilitation had a long-term beneficial effect on endurance, several psychological valuables, consumption of medical care, attitude towards way of life, skills, coordination and smoking habits. Bronchial hyperresponsiveness, need of pulmonary drugs and complaints of cough and sputum production did not change after rehabilitation. Airway obstruction and subjective feelings of dyspnoea, allergy and hyperresponsiveness only decreased in the short term (less than I year). CONCLUSION: This study shows that pulmonary rehabilitation improves many variables in the short as well as in the long run. When COPD patients do not improve on conventional treatment, pulmonary rehabilitation should be considered.

Target-flow inspiratory muscle training during pulmonary rehabilitation in patients with COPD.

The effects of additional target-flow inspiratory muscle training (TF-IMT) on the performance of the inspiratory muscles, on general exercise capacity, and on psychologic parameters during a pulmonary rehabilitation program (PR) were studied in 40 patients with COPD selected for ventilatory limitation during exercise. The mean age of the patients was 59 years, and the mean FEV1 was approximately 50 percent of predicted. All patients participated in a ten-week PR program. They were randomized to receive either additional TF-IMT (PR + IMT) or not (PR). The TF-IMT was performed by means of a target-flow resistive device; the generated mouth pressure and the duration of inspiration and of the respiratory cycle were imposed. After the training period, maximal inspiratory mouth pressure and EMG-fatigability of the diaphragm were significantly better in the PR + IMT group than in the PR group. Maximal work load and psychologic symptoms increased to the same extent in both groups. The 12-minute walking distance also increased in both groups, but it increased significantly more in the PR + IMT group than in the PR group. We believe that additional TF-IMT during PR in a selected group of patients with COPD who have ventilatory limitation has an extra beneficial effect on the performance of the inspiratory muscles and on exercise performance.

Target-flow inspiratory muscle training at home and during pulmonary rehabilitation in COPD patients with a ventilatory limitation during exercise.

The effects of a 10-week inspiratory muscle training (IMT) program at home were compared to IMT during a 10-week pulmonary rehabilitation program (PR) in 40 COPD patients with a ventilatory limitation of the exercise capacity. IMT was performed with a target-flow resistive device; the generated mouth pressure as well as the duty cycle were imposed. The mean age of the patients was 59, the mean FEV1 was 48% of predicted. In the training period the inspiratory muscle strength improved in both groups to the same degree. EMG fatigability of the diaphragm improved in the PR+ IMT group, but not in the IMT group. In the IMT group, the 12-min walking distance increased after the training period, but maximal workload (Wmax), VO2,max, and ADL scores did not change. In the PR + IMT group, however, Wmax, VO2,max, walking distance, and ADL scores improved significantly after the training period. Walking distance and ADL scores showed a significantly greater improvement in the PR + IMT group than in the IMT group. It is concluded that both isolated IMT and PR + IMT in COPD patients with a ventilatory limitation have a beneficial effect on inspiratory muscle strength, but PR + IMT improves the physical exercise capacity significantly more than IMT alone.

Psychological changes during pulmonary rehabilitation and target-flow inspiratory muscle training in COPD patients with a ventilatory limitation during exercise.

The effects of pulmonary rehabilitation (PR), target-flow inspiratory muscle training (IMT) and a combination of both treatments (PR + IMT) on psychological parameters and the physical performance were studied in a group of sixty chronic obstructive pulmonary disease (COPD) patients with a ventilatory limitation during exercise (mean age +/- 59, mean FEV1 +/- 50% of predicted). After the ten week training period scores of anxiety and depression were decreased in the PR and the PR + IMT group, but not in the IMT group. In the PR group these scores were still decreased after a one year follow up period. Maximal workload and the activities in daily life (ADL) scores were improved significantly after the training period in the PR and the PR + IMT group. Most of these improvements had disappeared after one year. The 12 min walking distance was increased in all patient groups after the training period and was still increased after the follow up period. The exercise capacity was correlated significantly to lung function parameters. The psychological well-being, however, was not correlated with lung function parameters, but was closely related to ADL scores. The improvement of the psychological parameters was not correlated to the improvement of the exercise capacity after the training period or after one year. The results indicate that the psychological well-being and the physical condition are improved by different mechanisms during a pulmonary rehabilitation programme.

Sauna to transiently improve pulmonary function in patients with obstructive lung disease.

The influence of sauna on pulmonary functioning in patients with an obstructive pulmonary disease was studied in 12 male patients by measuring forced vital capacity (FVC) and forced expiratory volume in one second on seven measure points the day of the sauna program. Despite the fact that body cooling and changes in osmolality of bronchial liquid can induce bronchoconstriction, we measured a significant improvement of the lung function parameters: FVC values were 3.22 +/- 0.89 and 3.6 +/- 0.99 before and after the sauna program, respectively. It is concluded that patients with an obstructive pulmonary disease can take part in sauna programs without eliciting bronchoconstriction; sauna even causes transient improvement of the lung function.

Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintenance treatment with theophylline.

Some of the new quinolone derivatives may be of value in the treatment of respiratory tract infections. It has been demonstrated that enoxacin, pefloxacin and ciprofloxacin, but not ofloxacin, decreased the metabolic clearance of the bronchodilator theophylline. This resulted in elevated plasma theophylline concentrations and, in some of the patients, theophylline toxicity. When the pharmacokinetic parameters of enoxacin, pefloxacin, ciprofloxacin and ofloxacin obtained in the present study were compared with those obtained from other studies in healthy volunteers not given concomitant theophylline, there was no evidence of theophylline influencing the clearance of the investigated quinolones.

Enoxacin in lower respiratory tract infections.

In this open, non-comparative study 45 lower respiratory tract infections were treated with the new 4-quinolone, enoxacin. Special attention was paid to infections caused by Pseudomonas aeruginosa. Pseudomonas infections were treated with 600 mg bd. whereas infections caused by other bacteria were treated with 400 mg enoxacin bd. In 43 cases efficacy could be assessed. In six out of 23 cases Pseudomonas spp. were eradicated from the sputum. In 12 of the remaining 17 cases a clear reduction in bacterial numbers and a decrease of sputum volume and purulence were obtained. Clinical improvement or cure was obtained in 20 out of the 23 cases. Most of the causative microorganisms in the other infections were eradicated. In two patients Staphylococcus aureus persisted. Overgrowth with streptococci occurred in three patients. Adverse reactions were frequent and occurred in 29 out of 45 treatment periods. They were mainly related to the gastrointestinal tract and the central nervous system. In 25 out of 30 patients on concomitant treatment with theophylline an elevation of plasma theophylline concentrations occurred. Twelve of these patients developed signs and symptoms possibly related to theophylline toxicity. After treatment with enoxacin the MICs of most persisting Pseudomonas strains were two to four times higher than pre-treatment values.