Bronchial reactivity to isocapnic hyperventilation: results in an unselected population of outpatients with known or suspected asthma.

Isocapnic hyperventilation with dry air is nearly as effective as with dry cold air, and appears to be a valuable screening test for bronchial hyperresponsiveness. However some incidental factors such as prechallenge bronchoconstriction, level of hyperventilation, age and smoking habits have barely been examined or were investigated in small samples of either normals or well-characterised asthmatics. In an inhomogeneous population of 186 outpatients with known asthma, 286 with suspected asthma and 32 normals, a single isocapnic hyperventilation challenge of 6-min duration was performed. There was a weak, but significant correlation between the degree of prechallenge airway function and the bronchial response, assessed by the change in forced expiratory volume in 1 s (r = 0.27, p = 0.000) in known asthmatics, but not in patients with suspected asthma and in normals. No significant relation was found between the level of hyperventilation and the bronchial response when comparing the bronchial response to the single-dose hyperventilation test between the subjects (NS). Increasing age appears to be associated with an attenuation of the response in known asthmatics (r = 0.21, p = 0.004), but not in patients with suspected asthma. Smoking habits did not affect the bronchial response in this study. In conclusion, the main finding is that there is a weak correlation between baseline airway obstruction and the subsequent response to isocapnic hyperventilation, a slow decline in response with age and no increase in responsiveness in smokers. Hence, isocapnic hyperventilation is a relatively robust test for assessing bronchial reactivity in an inhomogeneous population of outpatients like ours.

[Budesonide (Pulmicort) and exertion-induced asthma]. / Budesonid (Pulmicort) und anstrengungs-induziertes Asthma.

Twelve young adult asthmatic patients were selected in an asthma-free interval to be tested for exercise-induced bronchoconstriction. The degree of bronchoconstriction was estimated indirectly by spirometry, using FEV1 as parameter. Exercise was performed on a 10% steep treadmill for six minutes, leading to a pulse rate of more than 180 beats/min. Spirometry was done before, immediately after, and 10 and 20 min after the work. Only patients with more than a 10% fall in FEV1 during the 20 min period of recovery were selected. In the randomized crossover double blind trial the asthmatic patients received placebo inhalations for one week and budesonide inhalations for another week (2 X 800 micrograms daily). Spirometry was repeated at the end of each week. Under placebo we found a surprisingly high rate of protection against exercise-induced bronchoconstriction (50%, p less than 0.05). With budesonide 8% additional protection (compared to placebo) was achieved (mean of all 12 patients). The patient-drug-interaction was significant at the level of F = 30, p less than 0.05. There are some nonresponders to budesonide. Of the 12 asthmatics, 8 recognized the drug inhalation period. We conclude that one week of high dosage budesonide regimen recudes the tendency to exercise-induced asthma in adults. Budesonide seems to influence and mitigate bronchial hyperreactivity in the responder group.

[Exercise-induced asthma and arterial hypoxemia]. / Anstrengungs-induziertes Asthma und arterielle Hypoxämie.

40 young asthmatic patients performed submaximal work on a treadmill ergometer for 6 minutes. In 20 cases the PaO2 was found to be below 77.5 mm Hg (arterial hypoxemia) at the 10th or the 20th minute of post-exercise recovery time. A first subgroup A of 9 asthmatics presented hypoxemia together with a fall of FEV1 below 90% of control at the first to the 20th minute post-exercise recovery phase. A second subgroup B of 11 asthmatics showed hypoxemia with FEV1's higher than 90%, often higher than 100% of the control value. The following features of the recovery period were observed: 1. 10 minutes delay of onset of hypoxemia in relation to the FEV1 drop in group A. 2. Progressive hypoxemia despite a clear return of FEV1 versus the control value during the late recovery phase of group A. 3. Appearance of arterial hypoxemia despite unchanged normal FEV1's in group B. These three observations suggest that there are 2 kinds of post-exercise bronchoconstrictions. The first may be situated in the large bronchi (FEV1-drop), the second in the small peripheral airways (PaO2-drop), from the first to the 20th and from the 20th to the 40th minute respectively after the end of submaximal work load. It is concluded that there must be 2 sequential bronchoconstrictions due to cooling of the airways and these constrictions may guarantee alveolar homeostasis for body temperature and full saturation with water vapour. However, the first barrier in the large airways can be abolished by high blood levels of adrenaline. In such cases the second barrier in the small airways becomes important and may protect the alveoli from cooling and dry air.

[Protection from exercise-induced asthma after salbutamol (Ventolin) in powder form, inhaled with the Rotahaler]. / Schutz vor Anstrengungsasthma (exercise-induced asthma) nach Salbutamol (Ventolin) in Pulverform mit dem Rotahaler inhaliert.

15 asthmatic patients with exercise-induced asthma proved by a first run of 6 minutes were selected for a second run some days later. Salbutamol powder (0.4 mg) was inhaled from a Rotahaler immediately before the second run. FEV1 decreased to 83 +/- 10%, 75 +/- 9% and 78 +/- 14% at the end, and 10 and 20 minutes after the first run. FEV1 increased to 110 +/- 16%, 110 +/- 15% and 113 +/- 14%, respectively, when salbutamol powder was inhaled from the Rotahaler before the second run (p less than 0.0005). Control values of FEV1 before the two runs were comparable (p less than 0.25). The heart rate increased to 186 +/- 3 per minute during the first run, to 182 +/- 3 after the second run (p less than 0.0025). Bronchodilation by salbutamol was evident in spite of the 6 minutes of exhausting exercise (p less than 0.0125). Furthermore, salbutamol powder partially or totally suppressed exercise-induced bronchoconstriction in 14 out of 15 cases. Powder inhalation of salbutamol from the Rotahaler is recommended as a valuable alternative medication to inhalation from a pocket pressurized metered aerosol device. The Rotahaler offers advantages, e.g. in patients with known exercise-induced asthma before exhausting athletic activity. The absence of fluorohydrocarbons in the airways may be important in such situations.

[Euphyllin retard and "exercise-induced" asthma]. / Euphyllin retard und "exercise-induced" Asthma.

In a double blind crossover experiment the protective effect of theophylline slow-releasing coated tablets (Euphyllin retard) on exercise-induced asthma has been compared with that of a placebo. Sixteen patients with bronchial asthma (mean age 23 years, range 16-49 years) who were selected in a preliminary test exhibited an FEV1 decrease greater than 15% 10 minutes after an exhausting 6 minute run on the treadmill. Euphyllin retard and placebo were given 6 hours before the exercise test. Venous blood was sampled 6 hours prior to and immediately before exercise in order to determine the plasma concentrations of theophylline by a tritium radioimmunoassay method. FEV1 was measured prior to and immediately after exercise, 10 and 20 minutes later and after a final orciprenaline inhalation. A group of 9 patients (group 1) has plasma concentrations of theophylline lower than 6.2 microgram/ml (4.8 +/- 0.9 microgram/ml), and a group of 7 patients (group 2) had concentrations higher than 10.0 microgram/ml (13.8 +/- 3.3 microgram/ml). Compared with placebo, a protective effect of Euphyllin retard could be observed in group 2 only (p < 0.025). In group 1 the asthma protection was indistinguishable form that of placebo. Hence, plasma concentrations higher than 10 microgram/ml appear to be required to protect asthmatics from exercise-induced asthma. Although in some patients an effective concentration can be achieved by the recommended dose of one tablet of Euphyllin retard (350 mg aminophylline) every 12 hours, the importance of measuring plasma concentrations must be emphasized in view of the variable absorption and elimination of theophylline. Side effects may occur at concentrations higher than 15 microgram/ml.

[The new anticholinergic bronchospasmolytic oxitropium bromide. Is long lasting protective effect through the night]. / Das neue anticholinergische Bronchospasmolytikum Oxitropiumbromid. Sein lang anhaltender Schutz über die Nacht hinweg.

Oxitropium bromide (Ba 253, Boehringer, Ingelheim) is a scopolamine-like atropine derivate with a mode of action approximating to that of ipratropium bromide (Atrovent, Sch 1000). The peak effect and duration of bronchodilatation with oxitropium bromide appears to be better than that of ipratropium bromide. Fifteen patients with a stable chronic bronchial obstruction were investigated in a double blind cross-over study. The obstruction was partially reversible by beta-stimulation. The patients inhaled 0.2 mg oxitropium bromide or placebo at 9.30 p.m. after two controls of FEV1 at 9 p.m. and 9.15 p.m. We re-examined the patients at 7 a.m. and 7.15 a.m. the following day and observed a significant parasympathetic additional obstruction under placebo, whereas, under the medication with oxitropium bromide overnight, significant bronchodilation was observable. When 0.2 mg oxitropium bromide was given at 7.30 a.m. to all patients, those pretreated with placebo showed significantly better bronchodilation than those pretreated with oxitropium bromide. It is concluded that oxitropium bromide is a long-acting (10 hours) overnight bronchodilator. The bronchodilation is probably due to prolonged parasympathicolysis in the airways.

[The bronchospasmolytics salbutamol, fenoterol, terbutaline and reproterol. Their effects and side effects in asthmatics after inhalation with an electric nebulizer]. / Die Bronchospasmolytika Salbutamol, Fenoterol, Terbutalin und Reproterol. Ihre Wirkung und ihre Nebenwirkungen bei Asthmatikern nach Inhalation mit dem elektrischen Vernebler.

A double-blind crossover trial was conducted in 10 asthmatic patients for comparison of fenoterol with salbutamol, in 12 other asthmatic patients for comparison of reproterol with salbutamol, and in 15 other asthmatic patients for comparison of terbutaline with salbutamol. The following doses were given: 1.25 mg fenoterol, 2.5 mg reproterol, 2.5 mg terbutaline and 1.25 mg salbutamol. 5 drops of each of the inhalation solutions (in 2 ml of saline) were aerosolized by a powered machine and inhaled for 15 min. FEV1 was measured before, and 15 and 45 min after inhalation. Immediately before FEV1 the following parameters for side effects were also determined: 1. heartbeats per min, systolic and diastolic blood pressure; 2. minute ventilation, arterial PCO2 and oxygen consumption; 3. arterial SO2, PO2 and the alveolar-arterial O2-gradient (AaDO2). To estimate the selectivity of each of the 3 betastimulators the ratio (formula: see text) was established for each parameter and compared to that obtained with salbutamol. In further steps the ratio of all parameters for side effects was shown, then only that of the 3 most important side effects tachycardia, hypocapnia (PaCO2) and hypoxemia (PaO2). The following order of selectivity was found: 1. salbutamol, 2. fenoterol, 3. terbutaline, 4. reproterol.

[Exercise-induced asthma and placebos]. / Anstrengungsinduziertes Asthma unter Placebo.

The effectiveness of a placebo in 15 patients with exercise-induced asthma (E.I.A., decrease of FEV1 by more than 10% after a standard run uphill on a treadmill) has been measured. 7 patients repeated the test without placebo protection, to separate the psychological effect of placebo from the emotional influences of the unusual environment of a technically highly developed hospital and adaptation to test procedures. On selection day FEV1 in % of preexercise value 10 min after exercise was 68.2 +/- 7.9% and on control day 67.1 +/- 9.5% (no statistical difference). The second stage comprised 14 patients who took the placebo or Cromolyn (Lomudal) before exercise; on selection day FEV1 in % of preexercise value 10 min after exercise was 70.1 +/- 4.8%; on placebo day it was 76.0 +/- 3.4% and on Cromolyn day 90.7 +/- 3.3%. There was statistically significant (p less than 0.025) protection by placebo. However, the protective effect of Cromolyn was much better than that of placebo (p less than 0.005). Placebo has a significantly greater protective effectiveness in E.I.A. than expected, and one much greater than previously suggested in preexisting asthma. As environmental influences were ruled out, the only explanation for the high degree of protection by placebo is the patients' trust in the placebo.