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Biomedical subjects

N B Pride

Publications and source records attributed to N B Pride.

At least 19 recordsLinked to original sources

Asthma. Definition and clinical spectrum.

When variability and periodicity of symptoms and of airway function are accompanied by evidence of an allergic pathogenesis (identified inhalant precipitants, atopy, raised IgE, eosinophilia) the diagnosis of asthma is obvious to patient and physician. But many patients with asthma do not conform to this classic stereotype, so that considerable problems of distinction from other types of airway obstruction exist. These difficulties have practical significance because conferring the label of asthma is associated with physicians prescribing more intensive and effective treatment.

Asthma

Failure of inhaled corticosteroids to modify bronchoconstrictor or bronchodilator responsiveness in middle-aged smokers with mild airflow obstruction.

We have compared the effects of three-month periods of treatment with an inhaled corticosteroid, budesonide 600 micrograms twice daily and with placebo on bronchial responses to inhaled histamine and to bronchodilators in a double-blind crossover trial in 14 middle-aged male smokers (mean age, 59.6 years) with mild airways obstruction (mean FEV1 2.42 L, 80 percent predicted [range, 48 to 110 percent]). Responsiveness to inhaled histamine was assessed monthly by the provocative concentration (mg/ml) reducing FEV1 by 20 percent (PC20). Bronchodilator response to a combination of inhaled salbutamol (5 mg) and ipratropium (0.5 mg) was assessed before and after three months' treatment. Compliance with treatment was checked by weighing aerosol canisters, and by measuring plasma budesonide and metabolites. There was no significant change in FEV1 (budesonide mean 2.38 L [SEM 0.17] vs placebo 2.40 L [0.17]), vital capacity (budesonide mean 3.69 L [0.17] vs placebo 3.81 L [0.17]) or in bronchodilator responsiveness (mean increase over baseline FEV1, budesonide 11.6 [2.7] percent vs placebo 10.5 [3.2] percent). There was a small overall reduction in bronchoconstrictor responsiveness over the period of the trial, but there was no effect of 12 weeks of budesonide treatment compared with 12 weeks of placebo treatment (mean log PC20 during budesonide 0.595 [SEM 0.063], placebo 0.591 [SEM 0.055]). Following the three-month crossover trial, six men continued for nine more months to receive budesonide in a single-blind trial and the results were compared with those in six men who took no active treatment for the subsequent nine months. No improvements in baseline spirometry, home peak flow measurements, bronchoconstrictor or bronchodilator responsiveness were observed after 12 months of budesonide treatment. Thus, a regimen of budesonide treatment that consistently attenuates bronchial responsiveness in asthmatic subjects had no effect in these men; larger and longer trials will be required to establish whether a subgroup of smokers shows a favorable response.

Administration, Inhalation

European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): hypothesis and design.

Chronic obstructive pulmonary disease (COPD) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality. Cigarette smoking is the most important aetiological factor. The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers. In cigarette smokers with poorly reversible airflow obstruction, the effect over 3 yrs of an inhaled glucocorticosteroid, budesonide 400 micrograms b.i.d., on the decline of lung function, measured as postbronchodilator forced expiratory volume in one second (FEV1), will be compared with that of placebo. The trial has been designed to detect a difference in yearly decline of at least 30 ml.year-1. The study is a parallel group, randomised, double-blind, multicentre study. Patients will be recruited from 47 centres in 12 countries in Europe. It will start with a run-in consisting of two 3 month periods. During the first 3 months, the patients will be offered a smoking cessation programme. All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested. After these two periods, patients will be randomised to receive either inhaled budesonide, 400 micrograms b.i.d., or placebo for a period of 3 yrs.

Administration, Inhalation

Asthma in Asian immigrants.

Adult Asian immigrants to the United Kingdom attending an asthma clinic have been compared with a control group of non-immigrant Caucasian asthmatic patients of similar age distribution. The Asian immigrants had a later age of onset of asthma than their non-immigrant controls. Comparison with studies of asthmatic patients in India suggests that this may be an intrinsic ethnic difference but an effect of migration in early adult life is not excluded. Despite a later age of onset, the frequency of positive skin prick tests to common allergens was similar in the immigrant and control groups and 71% of the Asians had positive reactions to the house dust mite. Most other clinical features, the variability of airways obstruction and the requirements for treatment showed no significant differences between the two groups.

Adolescent

Lung distensibility and airway function in intermediate alpha 1-antitrypsin deficiency (Pi MZ).

We examined the role of intermediate alpha 1-antitrypsin deficiency in predisposing to abnormalities of lung distensibility and airway function in 20 heterozygotes (Pi MZ) who were individually matched with a control Pi M subject of similar age, height, and smoking habits drawn from the same male, working population. There were no significant differences between the heterozygotes and their controls in the results of spirometry, maximum expiratory flow-volume curves (breathing air), single breath nitrogen test, arterialised capillary blood oxygen pressure, or single breath carbon monoxide transfer. Additional studies were made in 12 of the pairs of Pi MZ and Pi M subjects. Comparison of maximum expiratory flow-volume curves breathing air and 80% helium-20% oxygen showed no differences between the Pi MZ and Pi M subjects. Although airway function was similar in the two groups, four of 12 Pi MZ subjects showed abnormalities of the pressure-volume curve of the lung (reduction in lung recoil pressure, abnormal shape factor, increase in functional residual capacity). Abnormalities of washout of a helium-sulphur hexafluoride gas mixture, of a type previously described as characteristic of emphysema, were found in two of the men with abnormal pressure-volume curves. The results suggest that Pi MZ subjects have an increased susceptibility to alveolar abnormalities without increased abnormalities of airway function; this may explain the increased frequency of emphysema at necropsy despite many studies showing no predisposition to abnormal airway function in life. The functional changes we observed would be unlikely to cause symptoms. The risk of disablement from chronic lung disease appears to be only slightly enhanced by intermediate alpha 1-antitrypsin deficiency.

Adult

A double-blind trial of oral aminophylline (Phyllocontin Continus tablets) in airflow obstruction: preliminary communication.

Twenty-two patients with reversible airflow obstruction were entered into a double-blind crossover trial of Phyllocontin Continus tablets and placebo to assess the additional benefit of the controlled-release aminophylline preparation when added to the patients' medication. Most patients were taking inhaled or oral steroids in addition to inhaled beta-sympathomimetics throughout the trial. The dosage of Phyllocontin tablets was adjusted in a pre-trial study to provide serum theophylline levels in the accepted therapeutic range of 10--20 mg/l. In the seventeen patients who completed the 8-week study a small, but significant, increase in both the patients' own recordings of PEFR and weekly clinic measurements of FEV1 was seen whilst on the active drug. Ten patients had improvement in FEV1 greater than 200 ml. Eleven patients recorded subjective improvement on the active drug and five out of ten patients who used inhaled beta-sympathomimetics p.r.n. showed a reduction in their usage of greater than 10%. Side-effects were reported by twelve patients.

Adult

Use of exercise challenge to investigate possible tolerance to beta-adrenoceptor stimulation in asthma.

The effect of prolonged salbutamol administration on beta-adrenoceptor function in asthma has been examined. Six adult patients received salbutamol tablets (16 mg daily) for between 4 and 20 weeks and six adolescents received salbutamol aerosol (800 microgram daily) for 2--5 weeks. Before and after the treatment period the acute bronchodilator response to inhaled salbutamol and the ability of inhaled salbutamol to protect against exercise-induced asthma were examined. Lymphocyte beta-adrenoceptor function was also measured in the patients on tablet therapy. Inhaled salbutamol was less effective in protecting against exercise-induced asthma at the end of the treatment period in the patients who had received tablet therapy, but otherwise there was no significant change in beta-receptor function of either airways or lymphocytes. This apparent loss of efficacy of inhaled salbutamol in the prevention of exercise-induced asthma in some subjects, even when its acute bronchodilator effect is preserved, might reflect differences in the susceptibility of different beta-adrenoceptors to desensitization after prolonged stimulation: its clinical importance remains uncertain.

Adolescent

Ventilation and perfusion scans in the preoperative assessment of bronchial carcinoma.

Ventilation (krypton -81m) and perfusion (technetium -99m) lung scans were obtained in a consecutive series of 21 patients shortly before thoracotomy for proven or suspected carcinoma of the bronchus. In most patients ventilation and perfusion were impaired equally and the scan abnormality corresponded to the bronchoscopic and radiological findings. Unexpectedly large defects in the perfusion scan were seen in three patients, all of whom had extensive neoplastic involvement of the mediastinum at thoracotomy, but 11 other patients had mediastinal involvement which was not suspected from the scan. Ventilation scanning was useful in the prediction of postoperative ventilatory capacity in two patients who underwent pneumonectomy. We conclude that ventilation and perfusion scans are not sensitive indicators of neoplastic involvement of the mediastinum but they are valuable for the prediction of postoperative lung function.

Adult