T.J.H. Clark

Compliance with inhaled therapy and morbidity from asthma

Patient compliance with a standardized incremental regimen of inhaled anti-asthma therapy has been assessed in a large, prospective study in general practice. Urine salbutamol estimations were made in 30 patients who had the largest improvement with therapy (mean increase in FEV1 0.45 l above baseline: Responsive) and in 30 patients whose airflow obstruction failed to improve (FEV1-0.14 l: Nonresponsive). The urine salbutamol concentrations rose over the 9 month period in the responsive patients as expected with the incremental doses prescribed, and were significantly higher than urine levels in nonresponsive patients at two dose levels. Poor compliance with prescribed inhaled therapy is an important cause of persistent morbidity from asthma.

Bronchial disease in ulcerative colitis.

Ten patients with ulcerative colitis, all of whom were non-smokers, presented with a productive cough. In six, the chest radiography was normal and cough was the only symptom; three of these patients had a minor obstructive ventilatory defect on testing. Four patients complained of exertional dyspnoea and had both an abnormal chest radiograph with bilateral pulmonary shadows and a mixed obstructive and restrictive ventilatory defect. Bronchial epithelial biopsies from four patients (two with and two without pulmonary shadows) revealed basal reserve cell hyperplasia, basement membrane thickening, and submucosal inflammation, changes more usually associated with cigarette smoking. Inhaled beclomethasone diproprionate relieved cough in seven patients. The occurrence of airway epithelial disease in association with ulcerative colitis raises the possibility of a systemic mechanism affecting both bronchial and colonic epithelium. It does not seem likely that sulphasalazine was the cause of the pulmonary syndrome in these subjects.

Sleep apnoea in diabetic patients with autonomic neuropathy

Breathing during sleep was monitored in 8 diabetic patients with objective evidence of autonomic neuropathy and in 8 diabetic patients without neuropathy. Thirty or more periods of apnoea lasting 10 seconds or longer during one nights sleep were demonstrated in 3 of the diabetic patients with autonomic neuropathy. Such apnoeic periods may be related to the high incidence of cardiorespiratory arrests reported in such patients, particularly in association with anaesthesia or pneumonia.

INHALED THERAPY REDUCES MORNING DIPS IN ASTHMA

14 asthmatic patients with nocturnal symptoms and morning dips in peak expiratory flow rate (PEFR) were treated with regular inhaled salbutamol for 1 or 2 weeks, followed by regular inhaled beclomethasone dipropionate, in addition to salbutamol, for a further 2 weeks. Mean PEFR rose to normal values in all but 1 patient. Morning dips in PEFR were substantially reduced in 8 patients. There was an equivalent rise in mean PEFR in the other 6 patients, but their morning dips did not improve. Inhaled salbutamol reduced the dips in the responsive patients, but addition of inhaled steroid produced further improvement. Inhaled beta agonist alone improved mean PEFR in these patients, but inhaled steroids produced most of the improvement in the other subgroup. No patient experienced side-effects. Thus mean PEFR can be improved and morning dips in PEFR reduced in a high proportion of asthmatic patients by the use of regular inhaled therapy without resorting to less-well-tolerated oral agents.

ALCOHOLIC DRINKS AND ASTHMA: A SURVEY

A questionnaire was designed to investigate how commonly alcoholic drinks affected asthmatic patients in a population of 168 patients with asthma. Fifty-four patients (32.1%) reported that one or more types of drink made their asthma worse, the main offenders being wines, beer and whisky. Thirty-nine patients (23.2%) reported that alcohol, usually brandy or whisky, made their asthma better, particularly when their symptoms were severe. Patients in this latter group tended to be older and were likely to have worse asthma than those who reported no improvement with alcohol (P less than 0.003). In all 47% of patients reported that alcoholic drinks affected their asthma, indicating a more frequent influence of alcohol than is usually appreciated.

A comparison of the effects of different methods of administration of β-2-sympathomimetics in patients with asthma

Double-blind cross-over studies of oral and inhaled terbutaline and salbutamol have been performed in two groups of asthmatic patients. Both drugs at the doses recommended by the manufacturers produced similar maximal effects. The onset of response was faster with inhaled treatment and there was no difference in length of action between the drugs or the routes of administration. Side-effects were much more common with oral treatment. In a separate study oral and inhaled terbutaline were compared in 11 asthmatic patients and this also showed a similar maximal response in tests of forced expiration. A greater response was seen in sGaw following inhaled treatment (P less than 0.05). These results suggest that beta-2-sympathomimetic drugs should be administered by the inhaled in preference to the oral route.

Airways responses to oral ethanol in normal subjects and in patients with asthma.

The effect of oral ethanol on airflow was studied in 5 normal subjects and 5 patients with asthma. On 4 different study days, each subject was asked to drink 40 ml of either water or 20%, 40% or 60% ethanol, and measurements were made of specific airways conductance (sGaw), blood ethanol levels, pulse rate and blood pressure. In some subjects in both groups there was a significant immediate fall in sGaw after drinking ethanol (below 5% confidence limits). Once absorbed, ethanol had a slight bronchodilator effect in 2 normal subjects and in 3 patients with asthma (5% level). Sixty per cent ethanol, when drunk slowly, showed significant bronchodilatation in 4 out of 5 patients with asthma and in one normal subject (5% level) with no acute fall in sGaw. Pulse rate and blood pressure did not change after water, 20% and 40% ethanol in either group, but immediately after 60% ethanol normal subjects showed a significant rise in pulse rate (P less than 0.01) which was not seen in patients with asthma. The immediate changes in sGaw and pulse rate may be due to stimulation of irritant receptors in the upper airways. Ethanol may act directly on bronchial smooth muscle to produce bronchodilatation and may be useful as a bronchodilator when given intravenously.

Closing volume in healthy non-smokers

Abstract ‘Closing volume’, defined as that lung volume at which the dependent lung zones ceases expiration, was measured in 41 healthy non-smokers aged seventeen to sixty-nine years using xenon-133. Subjects were studied erect before and after inhalation of a β-adrenergic bronchodilator aerosol and in 31 subjects the studies were repeated in the supine position. Results in individual subjects showed good reproducibility. The regression with age and standard deviation of the measurements were similar to previous reports and no change was observed after inhalation of bronchodilator. The relationship of Phase 4 to vital capacity was unaltered by change in posture. It is suggested that the use of standard deviation (i.e. ± 2 SD) to define the limits of a normal range may be unduly optimistic. Tolerance limits to include 95% of healthy subjects calculated from studies of this size would provide unacceptably wide ranges for epidemiological purposes if the technique were introduced as a screening test for early disease of small airways. It is suggested that further developmental studies are required.

Is there a circadian variation in respiratory morbidity

In a retrospective study of the time of presentation to an accident and emergency department patients with acute respiratory symptoms presented more commonly at night compared to a control group with abdominal pain. In a subsequent prospective study doctors from a GP deputizing service were called much more frequently at night by patients with asthma than by those with other symptoms. These findings refute the suggestion that the observed increased mortality from respiratory diseases at night results from reduced medical care as a consequence of a reluctance of patients to present during the night.

Assessment of antitussive effects by citric acid threshold.

The cough threshold to citric acid inhalation was measured in eight subjects by single inhalations of increasing concentrations of citric acid until a cough was consistently produced. The cough threshold was measured before and after 60 mg glaucine, 60 mg codeine and matched placebo on three separate days a week apart. Base-line cough threshold in each subject was consistent from week to week. Codeine increased the threshold by more than one citric acid concentration in three subjects. Placebo and glaucine did not produce a threshold change of more than one citric acid concentration. We conclude that the citric acid threshold is a simple measure of antitussive activity. No such activity was found with glaucine.