Anticholinergic therapy in chronic asthma.

Although 'chronic asthma' is a loosely defined disease, it may be equated approximately with non-allergic or 'intrinsic' asthma arising in adult life. In patients with this condition anticholinergic agents, particularly ipratropium bromide, have been shown to have a useful and rather prolonged bronchodilator action. This bronchodilatation approaches that achieved by therapeutic doses of Beta-agonists and is not associated with undesirable effects such as difficulty in sputum clearance. In conclusion anticholinergic agents are a safe and useful adjunct to other bronchodilators in patients with chronic asthma.

The response of asthmatic patients and normal subjects to maximum respiratory manoeuvres. Spirometry--induced bronchoconstriction.

Fourteen atopic asthmatics, 12 non-atopic asthmatics, and 14 normal subjects performed a series of pairs of FEV1.0 measurements, with the first and second measurements separated by initially 10 seconds, then 30 seconds and finally 60 seconds. Two further pairs of FEV1.0 measurements were made at the interval that had produced the greatest fall in FEV1.0 to examine the consistency of this response. A correlation with bronchial lability on exercise testing was sought in 16 patients. In the asthmatics a further pair of FEV1.0 measurements was performed after bronchodilatation with 200 mcg salbutamol. Both atopic and non-atopic asthmatics showed a slight fall in FEV1.0 in successive measurements which was not seen in normal subjects. The small size of the fall is unlikely to interfere with spirometry results in clinical testing. Some subjects show a larger response and should be excluded from trials of drugs. Salbutamol diminished or abolished the response. The fall in FEV1.0 did not correlate with the results of exercise testing.

Hypercalcaemia and hypokalaemia in tuberculosis.

In two patients with extensive pulmonary tuberculosis who developed hypercalcaemia and hypokalaemia the hypercalcaemia appeared related to the use of small doses of vitamin D, which suggested patients with tuberculosis were hypersensitive to vitamin D. They were thus similar to patients with sarcoidosis, and it is interesting that the Kveim test result was positive in both cases. The hypercalcaemia was quickly suppressed with steroids. Hyperparathyroidism, thyrotoxicosis, Addison's disease, and multiple myeloma were excluded on clinical grounds and by the appropriate tests. The hypokalaemia was associated with increased renal excretion of potassium, and was probably due to distal tubular damage from hypercalcaemia.

The effect of alpha-adrenoreceptor stimulation on the airways of normal and asthmatic man.

1. The bronchial response to alpha-adrenoreceptor stimulation has been investigated in normal and asthmatic subjects with a specific alpha-receptor agonist, methoxamine hydrochloride, after atropine and beta-adrenergic blockade. 2. No significant changes in forced expiratory volume in 1 s (FEV1.0) were seen in normal subjects. 3. Methoxamine inhalation caused mild symptomatic wheezing and significant falls in FEV1.0 in asthmatic subjects. No change in FEV1.0 occurred after inhalation of distilled water as control. 4. It therefore appears that methoxamine causes bronchoconstriction in asthmatic subjects through its alpha-adrenergic-stimulating properties, since we were not able to detect any beta-receptor-blocking activity of methoxamine on the airways.

Beta-blockers and asthma.

In a single-blind, randomised, crossover study in 10 asthmatic patients, the effects of approximately equipotent oral doses of 3 cardioselective beta-blockers-atenolol (100 mg), metoprolol (100 mg), and acebutolol (300 mg)-and 4 non-cardioselective beta-blockers-proranolol (100 mg), oxprenolol (100 mg), pindolol (5 mg), and timolol (10 mg) upon FEV1 were compared. All drugs, except pindolol, produced a significant reduction in standing pulse rate and prevented an increase in heart rate after inhaled isoprenaline (1500 microgram). All drugs caused a fall in FEV1 but only atenolol did not differ significantly from placebo in this respect. The bronchodilator response to inhaled isoprenaline was blocked by the 4 non-cardioselective drugs; the 3 cardioselective agents permitted some bronchodilatation, but only atenolol did not differ from placebo.

Epipharyngeal receptors responding to mechanical stimulation.

1. Action potentials were recorded from twenty-one afferent nerve fibres from receptors in the epipharynx in anaesthetized, paralysed cats. Sixteen of the fibres had no spontaneous discharge.2. Gentle mechanical stimulation of the epithelium of the epipharynx with a nylon fibre caused all twenty-one receptors to discharge with rapidly adapting bursts of impulses at a mean peak frequency of 197 impulses/sec.3. Stimulation with a stream of air through the epipharynx sufficient to distend the whole pharynx caused seven out of twelve receptors to discharge in rapidly adapting bursts. Stimulation with a jet of air directly on to the epithelium of the epipharynx caused seven out of nine receptors to discharge.4. Chemical stimulation of the epipharynx with ammonia vapour caused an increased discharge in only three out of twenty receptors, and intravenous histamine had no effect on the four units tested.5. It is concluded that the receptors mediate the ;aspiration reflex' elicited by mechanical stimulation of the epipharyngeal mucosa.

Effects of beta-adrenergic receptor blockade on airway conductance and lung volume in normal and asthmatic subjects.

Ten normal and five asthmatic subjects were given intravenous injections of 10 ml. of 0.9% saline with and without 10 mg. of propranolol, and specific airway conductance was followed in a whole-body plethysmograph. Saline alone had no significant effect on conducatance in either group of subjects. Propranolol had no significant effect on conductance in normal subjects, but caused a mean fall of 34.9% in the asthmatics.