Total pulmonary resistance was measured from continuous records of flow and oesophageal pressure in five normal subjects on three separate days before and after inhalation of methacholine. The dose of methacholine produced, on average, a fivefold increase in airway resistance. Immediately after methacholine inhalation the subjects underwent a progressive exercise test on a cycle ergometer (day 1) or voluntary hyperventilation (day 2) or remained resting (day 3). On the first day during exercise pulmonary resistance fell rapidly to baseline levels within two to three minutes and remained there for the 10 minute duration of the exercise. On day 2 voluntary reproduction of the same level and pattern of ventilation as during exercise resulted in a similar fall of resistance. On the third day, when the subjects remained at rest, pulmonary resistance remained raised for 10 minutes. It is concluded that the bronchodilator effects of exercise can be explained by the increased ventilation rather than the exercise itself, but with much smaller tidal volumes than have previously been thought necessary to reduce drug induced bronchoconstriction.

We have examined the influence of total intrapulmonary deposition and its pattern on the bronchial response to aerosolized methacholine and atropine in 10 normal and 12 asthmatic subjects. On Day 1 we performed a dose-response challenge to methacholine and defined responsiveness as the provocative dose (PD35) needed to cause a 35% decrease in specific airway conductance (SGaw). On Day 2 we repeated methacholine challenge after premedication with aerosolized atropine, and we defined the response to atropine as dose ratio-1 (DR-1) where DR = PD35 after atropine/PD35 without atropine. On Day 3 we imaged intrapulmonary aerosol deposition by mixing 99mtechnetium with methacholine aerosol and scanning the thorax with a gamma camera during the development of bronchoconstriction. Total pulmonary aerosol deposition varied considerably between individuals (1.2 to 23.6% of nebulized dose) but there was no difference between normal and asthmatic subjects, and no correlation between deposition and baseline SGaw or PD35; there was a significant positive correlation between deposition and DR-1. Deposition of aerosol in central lung zones was inversely related to SGaw and correlated positively with DR-1; there was no significant relationship with PD35. Total intrapulmonary aerosol deposition and its pattern partially determine bronchial responsiveness to atropine, but we have not demonstrated any significant effect on responsiveness to methacholine.

Effect of aerosol and oral fenoterol on histamine and methacholine challenge in asthmatic subjects. Thorax, 36,

In eight normal and eight asthmatic subjects airway responsiveness to methacholine was measured by means of partial flow-volume loops at 0800 and 1800 hours on the same day. Airway responsiveness was lower in the evening in both normal and asthmatic subjects.methacholine producing a 20% fall in FEV, (PC,) ResultsDiurnal variation in airway calibre in asthmatic and nonasthmatic subjects is well documented.' De Vries et al2 found a diurnal variation of histamine responsiveness in asthmatic subjects challenged repeatedly over 24 hours. We have measured airway responsiveness to methacholine in normal subjects at 0800 and 1800 hours, and compared the results with those obtained in asthmatic subjects.There was no significant difference in baseline values of FEV, or V4, between 0800 and 1800 h in either group of subjects (asthmatic subjects: mean (SD) FEV, (007) v 248 200-, 100 - MethodsWe studied eight non-smoking subjects with no history of respiratory disease (seven male; mean age 30 5 years) and eight asthmatic subjects (five male; mean age 44 years). The asthmatic subjects had documented reversible airflow obstruction, but few symptoms. Subjects were asked to withhold all medication from 2200 h on the day before the study. All subjects gave their informed consent. Airway responses were determined by measurement of maximal and partial flow-volume loops according to the method of Zamel.3 FEV, was derived from the maximal loop and flow at 40% ofvital capacity above residual volume from the partial expiratory loop (04p). Methacholine was administered according to the method of Juniper et al,4 doubling concentrations from 0 05 to 200 mg/ml being used.Subjects attended the laboratory at 0800 and 1800 h on the same day. Repeated flow-volume manoeuvres were performed until stable values for FEV,, forced vital capacity (FVC), and Vp were obtained. Maximum values were taken as baseline readings. Doubling concentrations of methacholine were inhaled at five minute intervals until FEV, had fallen by at least 20% or the maximum concentration of methacholine had been given. Ninety seconds after each inhalation subjects performed a partial flow-volume loop manoeuvre followed immediately by a maximal flow-volume loop manoeuvre. FEV, and V40p were plotted against log concentration of methacholine, and the concentrations of

1. We have developed a method for non-invasive measurement of lung tissue mass, thoracic blood and interstitial volumes by a combination of transmission and emission scanning with technetium isotope (99mTc). 2. In a lung model we demonstrated that emission counts could be successfully corrected for attenuation with data obtained by transmission scanning, despite an uneven distribution of radioactivity and attenuation in the model. 3. In dogs we compared regional transthoracic tissue thickness, measured by transmission scanning, and regional 'thickness' of blood measured by transmission/emission scanning with direct gravimetric measurements made post mortem. Scanning and direct measurements correlated significantly. 4. In man we used a [99mTc]pertechnetate (99mTcO4) flood source to obtain antero-posterior transmission scans with a gamma-camera. The thickness of attenuating tissue was estimated in each pixel. Scans were obtained of thoracic blood (by labelling erythrocytes with 99mTcO4) and of interstitium (with 99mTc-labelled diethylenetriaminepenta-acetic acid and subtraction of the blood image). We used a computer program to correct the emission scans for attenuation using the transmission scan derived tissue thickness, pixel by pixel. Finally we took a lateral chest radiograph to estimate chest wall thickness. 5. In normal man lung tissue thickness at hilar level was 3.1 +/- 0.5 cm (n = 8). Thoracic blood thickness increased from the apex downwards in the upright lung, being 1.2 +/- 0.1 cm at the hilar level and 2.0 +/- 0.3 cm at the lung base. Interstitial thickness was 0.8 +/- 0.3 cm at the hilum and 0.85 +/- 0.2 at the base. These values compare well with data in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)