1. Perception of asthma by patients can be assessed from the relationship between symptom scores and peak expiratory flows. This study was designed to investigate the possibility that medication can affect perception of the sensation of asthma independently of changes in lung function. 2. Twelve subjects whose asthma was inadequately controlled by inhaled bronchodilator alone were studied during four different drug treatments over 3 months. Subjective self-assessment of asthma was scored on a 10 cm visual analogue scale and followed by three consecutive measurements of peak expiratory flow, using a coded electronic peak flow meter. This was recorded not less than three times daily on diary cards. Observations were recorded during the second week of each of four treatments:(i) a run-in period using only inhaled salbutamol as required, (ii) inhaled beclomethasone, (iii) inhaled cromoglycate and (iv) oral theophylline at a dose adjusted to achieve blood levels of 10–20 mg/l. Inhaled salbutamol was permitted during the other treatments as required. Changes in the slope and position of the regression lines of asthma scores on PEF were used to measure changes in perception of asthma on each treatment. Dynamic lung volumes were measured in the clinic before the study and after each treatment period. 3. In the group as a whole, theophylline improved lung function (mean peak flow and dynamic lung volumes) without affecting mean visual analogue scores, beclomethasone improved mean visual analogue scores with much less effect on lung function, while cromoglycate had a small though consistent effect on both. 4. Perception of asthma, measured by the relationship between peak flow rate and visual analogue scores, was unaffected by cromoglycate. On theophylline, perception of asthma was heightened in five subjects despite a definite improvement in their peak flow. On beclomethasone, perception of asthma was reduced in most subjects, often with no discernible improvement in mean peak flow or dynamic spirometry. 5. Perception of bronchoconstriction in asthma can be affected by drugs independently of control of the condition. Theophylline may produce a paradoxical increase in awareness of asthma in some individuals. With beclomethasone therapy a reduction in symptoms of asthma may occur without any improvement in tests of air flow.

1. Resting pulmonary blood flow ( Q . ), using the uptake of the soluble inert gas Freon-22 and an indirect estimate of lung tissue volume, has been estimated during breath-holding ( Q . c ) and compared with direct Fick cardiac output ( Q . f ) in 16 patients with various cardiac disorders. 2. The effect of breath-hold time was investigated by comparing Q . c estimated using 6 and 10 s of breath-holding in 17 patients. Repeatability was assessed by duplicate measurements of Q . c in the patients and in six normal subjects. 3. Q . c tended to overestimate Q . f , the bias and error being 0.09 l/min and 0.59, respectively. The coefficient of repeatability for Q . c in the patients was 0.75 l/min and in the normal subjects was 0.66 1/min. For Q . f it was 0.72 l/min. There was no significant difference in Q . c measured at the two breath-hold times. 4. The technique is simple to perform, and provides a rapid estimate of Q . , monitoring acute and chronic changes in cardiac output in normal subjects and patients with cardiac disease.

1. Airway responses to inhaled salbutamol were measured in two groups of six normal non-atopic subjects. In each group there was a dose-dependent increase in specific airways conductance after salbutamol inhaled in cumulative doses from 25 to 600 μg. 2. In the first group these studies were repeated weekly during and after the subjects had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 500 μg four times daily by week 4. Then, while subjects were continuing to receive regular salbutamol, the studies were repeated after 48 h of inhaled sodium cromoglycate (20 mg four times daily) and again after 48 h of beclomethasone dipropionate (200 μg four times daily). 3. In the second group the studies were repeated after 10 days of regular inhaled salbutamol (500 μg four times daily). 4. There was no change in airway response to inhaled salbutamol after 4 weeks or 10 days regular salbutamol therapy, or after 48 h of sodium cromoglycate or beclomethasone dipropionate therapy. 5. This study did not show the development of resistance to β-agonists in the airways of normal subjects. These findings are discussed in the context of other studies which have shown the development of resistance, and we suggest that there may be a spectrum of susceptibility to the development of impaired airway responsiveness following regular treatment with β-adrenergic drugs.

1. A new CO 2 -rebreathing method for estimating cardiac output is described, and compared with a method employing N 2 O performed at the same time. 2. The subject inhales from a reservoir of 30% O 2 in N 2 and rebreathes into and out of an empty bag for 10s. 3. Oxygenated mixed venous P co 2 is then determined by rebreathing 7–15% CO 2 in O 2 , the mixture being selected to obtain a plateau of CO 2 concentration. 4. P co 2 rises exponentially towards the plateau value during the rebreathing of 30% O 2 . Cardiac output is calculated from the rate of change of the alveolar—mixed venous P co 2 difference by a differential version of the Fick equation employing published CO 2 dissociation curves for whole blood in vitro. 5. The slope of the regression of cardiac output on V̇o 2 is similar to that obtained in other studies employing direct Fick measurements. The slope is some 15% greater than obtained with N 2 O but the difference is significant only when O z consumption is greater than 2 litres/min. 6. The CO 2 dissociation slope of blood does not differ during pulmonary gas exchange in vivo from that determined at equilibrium in vitro. 7. The volume of pulmonary blood available for CO 2 exchange may rise to about 1 litre in heavy exercise, with a transit time of 1–2 s in the lungs. 8. The method can be employed for estimating pulmonary blood flow during physiological studies in subjects with normal lungs.

1. The left lower lobe of the lungs of six anaesthetized dogs were isolated by the introduction of a bronchial cannula at thoracotomy. Catheters were introduced into the main pulmonary artery and a vein draining the isolated lobe. 2. Blood-gas pressures and pH were measured across the isolated lobe and compared with gas pressures in alveolar samples from the lobe. 3. When the isolated lobe was allowed to reach gaseous equilibrium with pulmonary arterial blood for 30 min, there was no significant difference between alveolar and pulmonary venous P co 2 . Mean values of whole-blood base excess were similar in pulmonary arterial and pulmonary venous blood. 4. After injection of 20 ml of 8·4% sodium bicarbonate solution into a peripheral vein, P co 2 , pH and plasma bicarbonate concentrations rose in the mixed venous blood. There was no change of whole-blood base excess across the lung, indicating that HCO − 3 , as distinct from dissolved CO 2 , did not enter lung tissue in measurable amounts. 5. No systematic alveolar—pulmonary venous P co 2 differences were demonstrated in this preparation other than those explicable by maldistribution of lobar blood flow.