SUMMARY1. The purpose of the study was to see whether the rate of rise of alveolar Pco, (PA, co2) in expiration was directly proportional to the rate of pulmonary elimination of C02 ( Vco2) in man in the steady state.2. Alveolar ventilation at rest and during exercise in man was calculated from the difference between total ventilation and dead space ventilation, and from the ratio of the rate of pulmonary C02 elimination to the mean expired alveolar C02 (total) fraction. The results were indistinguishable. In agreement with other workers' findings alveolar ventilation changed in direct proportion to the rate of carbon dioxide elimination, confirming the isocapnia of exercise ventilation in man.3. The rate of rise of expiratory alveolar PCO2 in individual breaths has been obtained by two methods. In the first, a pattern of respiration with constant expiratory flow in each breath brought expiratory alveolar profiles to the outermost end of the airway. In the second method, the early part of the alveolar PCO2 during normal expiration was calculated from airway PCO2 and expired volume.4. The data obtained with both methods show that, in the steady state, expiratory alveolar PCO2 rises at a rate which is directly proportional to the rate of C02 production.

Eight patients with chronic severe asthma, poorly controlled by conventional doses of inhaled bronchodilator, were treated with high-dose inhaled terbutaline (4 mg four times daily), via either wet nebulisation of terbutaline respirator solution, or by tube-spacer aerosol, using cannisters delivering 1 mg terbutaline per metered dose. All patients improved objectively and subjectively on these higher dosage regimens during both day and night. A trial of high-dose inhaled beta2 sympathomimetic therapy should be considered in any patient with chronic severe asthma who fails to obtain benefit from standard doses of inhaled bronchodilator.Patients with chronic severe asthma often respond poorly to inhaled bronchodilators in conventional dosage. Such patients are usually very disabled, require frequent hospital admissions, and are commonly prescribed long-term oral corticosteroids. Domiciliary high-dose inhaled bronchodilator therapy, delivered by wet nebulisation, may improve some patients with chronic asthma sufficiently for oral steroids to be discontinued.' However, the air compressors necessary for the domiciliary nebulisation of bronchodilator are expensive and inconvenient. We decided, therefore, to compare the efficacy of high-dose bronchodilator therapy delivered by wet nebulisation and by a new aerosol device, the tube-spacer.2 The tube-spacer was chosen because it achieves higher penetration of aerosol into the lung than does conventional aerosol,3 and also because it may be more effective than conventional aerosol in the management of some patients with asthma.4-6 The tube-spacer is cheaper and more convenient than the wet nebuliser. MethodsEight patients (four male and four female) with chronic severe asthma participated in the study. Mean first second forced expired volume (FEV1) was 0 83 I BTPS (range 0I5-1V61 BTPS).