1. Pulmonary function tests, including alveolar mixing efficiency by the single-breath and multi-breath methods, and ventilation scans were performed on 16 volunteer subjects. The tests were repeated after the inhalation of a methacholine aerosol in sufficient dosage to increase airways resistance. 2. After inhalation of methacholine there was a significant fall in mean series dead space of 31 ml ( P < 0.05), and mean multi-breath alveolar mixing efficiency fell from 68% to 36% ( P < 0.001), a fall occurring in all subjects. Mean single-breath alveolar mixing efficiency measured on the first breath of the nitrogen washout fell from 76% to 70%, but this change did not reach statistical significance (0.1 > P > 0.05). 3. In eight of the subjects, technically adequate lung scans and pulmonary function tests were obtained both before and not more than 30 min after methacholine inhalation. In seven there were obvious visible defects on the ventilation scans, and in five of these the computer-calculated underventilation score became abnormal. 4. Thus inhalation of methacholine causes maldistribution of ventilation, a fall in alveolar mixing efficiency and a fall in series dead space, presumably brought about by bronchoconstriction. The parallel component of this maldistribution of ventilation, as judged by 81m Kr ventilation scanning, does not of itself seem to be sufficient to explain the fall in alveolar mixing efficiency, and therefore a degree of diffusion limitation is probably involved as well.

1. Existing methods of assessing nocturnal episodic hypoxaemia are either insensitive or ignore the majority of the available data. 2. We describe a method of analysis using offline digital processing. A distribution of oxygen saturation ( S a o 2 ) with time is produced from all the available data, and subjected to moment analysis to produce a simple index which describes an entire night's S a o 2 . 3. Our results suggest that the mean and the coefficient of skew fully described a night's S a o 2 . However, in subjects with chronic air-flow obstruction, the third moment about 100% oxygen saturation (M 3 100), a single figure, has the same descriptive power as mean and skew. 4. In 17 subjects with chronic air-flow obstruction a significant correlation was found between both daytime S a o 2 and P a co 2 when plotted against either the M 3 100 or the skew. 5. Measurements made on two occasions in seven subjects showed good reproducibility for the skew and M 3 100 indices.

1. Atropine is known to diminish broncho-motor tone. In order to investigate the acute effect of atropine on respiration and alveolar gas mixing, a dose of 2.4 mg was given intravenously. 2. Ten normal male volunteers were each studied three times with a nitrogen washout method, once before administration of atropine and then 20 min and 60 min thereafter. 3. After the administration of atropine there was a reduction in tidal volume, a slight increase in frequency of respiration and an increase in series dead space. The tidal mixing volume showed a fall of 25%. In spite of the reduced alveolar dead space the effective mixing volume fell by 29%. Multi-breath alveolar mixing efficiency fell by 3.5%. 4. Multi-breath alveolar mixing efficiency was found to be less with smaller tidal mixing volumes, a fall of 518 ml in the latter causing a reduction of 17.2% in mixing efficiency. 5. A reduction of 100 ml in tidal volume in normal subjects was associated with a decrease of 6.9% in alveolar mixing efficiency. In the subjects receiving atropine tidal volume reduced by 96 ml, but the observed fall in alveolar mixing efficiency was only 3.5%, This suggests an improvement in alveolar mixing of 3.4% due to the administration of atropine. Despite this small improvement, the mixing efficiency is still only 66%. The residual inefficiency of 34% cannot therefore be explained on the basis of broncho-motor tone.

1. The lung nitrogen from ten normal nonsmoking subjects and ten patients with chronic respiratory disease was washed out by inspiration of 21% oxygen and 79% argon, whilst expired nitrogen concentration was measured with a mass spectrometer and flow with a box-bag system, and the quantity of nitrogen in each expirate calculated with a Varian 73 digital computer and plotted against expired volume. 2. The resulting curve from each breath was handled either as a linear or a polynomial regression, the intercept on the abscissa being designated the series dead space volume ( V D S ). This dead space has also been measured by the Fowler method and by the mathematical differentiation of phase II. 3. The nitrogen recovered from the first breath varied between 190 ml and 584 ml and this has been expressed as a percentage of that volume predicted assuming perfect alveolar mixing; this has been called the alveolar gas mixing efficiency for nitrogen. The mean values for alveolar mixing efficiency computed from the four different series dead space volumes were 89.8%, 90.8%, 89.0% and 85.7%. This suggests that the value of series dead space used in computing mixing efficiency is not of great importance, and any of the four methods gives satisfactory results. 4. The data from multi-breath washout were also similarly expressed as a percentage efficiency, making the results from the two methods directly comparable. The median value for alveolar gas mixing efficiency by the single breath test was 89%, and for the multi-breath test about 76%. The latter was apparently more discriminating for ventilatory defect. In patients the values were respectively 73% and 40%.

1. Nineteen patients (three normal subjects, and 16 patients with chronic airway disease) were investigated with radionuclide lung-imaging and pulmonary function tests. 2. There was a statistically significant correlation between the ratio of residual volume to total lung capacity and alveolar dead-space ventilation for nitrogen as a percentage of alveolar ventilation (an index of gas mixing inefficiency); r S = 0.54, P < 0.05. 3. There were statistically significant associations between an abnormal ventilation or perfusion radionuclide lung image and (a) the ratio of residual volume to total lung capacity and (b) the alveolar dead-space ventilation for nitrogen as a percentage of alveolar ventilation. 4. The radionuclide counts from the posterior images were normalized for lung size and injected dose; perfusion counts were then subtracted from ventilation counts at locations from the top to the bottom of the lungs. 5. There was a statistically significant association between low ventilation minus perfusion areas and arterial hypoxia. 6. There was a statistically significant association between high ventilation minus perfusion areas and an increased alveolar dead-space ventilation for carbon dioxide as a percentage of alveolar ventilation.

1. A comparison has been made between alkaline mannitol diuresis and alkaline glucose diuresis in the treatment of salicylate poisoning during an 8 hr period. 2. Mannitol gave a higher rate of urine flow, but there was no significant difference in the rate of salicylate excretion. 3. Serum levels of sodium, potassium and calcium fell in both groups, mainly during the first 2 hr. The mean fall in serum sodium was greater (21·4 mEq/l compared with 10·0 mEq/l) and that in serum potassium less (0·6 mEq/l compared with 1·5 mEq/l) in patients who received mannitol than in those who did not. 4. All serum electrolyte values had returned to normal within 24 hr of the end of the treatment period. 5. Acid—base changes occurring during treatment are described. 6. No adverse clinical features were seen in either treatment group. 7. Syrup of ipecacuanha was used to induce emesis. The mean recovery of salicylate in the vomitus was 38% of the apparent total ingested. The variability in recovery (0–81%) was not related to the delay between ingestion and vomiting. 8. It is concluded that mannitol does not increase the excretion of salicylate. It maintains good urinary excretion, thereby increasing the safety of the procedure. It is associated with a smaller fall in serum potassium and permits rapid removal of salicylate for a smaller rise in serum pH than does forced alkaline diuresis alone.