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Biomedical subjects

R Beasley

Publications and source records attributed to R Beasley.

At least 127 records · Page 7Linked to original sources
PubMed1992

Nebulized fenoterol causes greater cardiovascular and hypokalaemic effects than equivalent bronchodilator doses of salbutamol in asthmatics.

The pulmonary and extrapulmonary effects of two doses of nebulized fenoterol (5 mg) salbutamol (5 mg) and ipratropium bromide (0.5 mg) at 60 min intervals were compared in nine patients with asthma in a double-blind, randomized study. Measurements of heart rate, blood pressure, electromechanical systole (QS2I), QTc interval, FEV1 and plasma potassium were made at baseline and at 15, 30 and 60 min after each nebulization. Both beta-agonists caused significantly greater inotropic (QS2I), chronotropic (HR), electrocardiographic (QTc) and hypokalaemic effects than ipratropium bromide (IB), with fenoterol being more potent than salbutamol. Fenoterol had no greater effect on FEV1 than salbutamol although both were superior to IB. Only the first four subjects had two doses as originally intended, because the second administration of fenoterol resulted in marked cardiovascular effects and hypokalaemia. The observed differences in extrapulmonary effects between fenoterol and salbutamol provide a plausible group of mechanisms which may explain the increased risk of death associated with fenoterol in severe asthmatics.

Adult↗
PubMed1992

Albuterol and deaths from asthma in New Zealand from 1969 to 1976: a case-control study.

It has been suggested that the association between inhaled fenoterol and deaths from asthma in New Zealand occurred because patients with unstable asthma were switched to fenoterol after its introduction in 1976. If so, a similar pattern might also have occurred after the introduction of albuterol (salbumatol) in 1969. This hypothesis has been investigated in a case-control study of 17 deaths from asthma during the period from 1969 to 1976 in patients whose ages ranged from 5 to 45 years; as in a previous study in New Zealand, two control groups were used. The inhaled albuterol odds ratio was 0.88 (95% confidence interval, 0.29 to 2.62) using control group A and 1.40 (95% confidence interval, 0.48 to 4.09) using control group B. The major problem with this study is the very small number of cases, but the findings nevertheless indicate that albuterol was not associated with deaths from asthma after its introduction.

Adolescent↗
PubMed1992

Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma.

A case-control study has previously been reported of asthma deaths in people aged 5-45 years who had a hospital admission for asthma (the index admission) in New Zealand during 1981-1987. The study has been re-analysed to examine the association between markers of asthma severity and risk of asthma death or hospital admission; patients prescribed fenoterol were excluded from this re-analysis because of the previously reported interaction between fenoterol, asthma severity, and asthma deaths. The re-analysis included 39 patients who died of asthma during the 12 months after their index admission, 226 patients who had a readmission for asthma during the 12 months after their index admission, and 263 controls chosen from all index admissions. An admission in the previous 12 months was the strongest marker of subsequent risk of death (odds ratio (OR) = 3.5, 95% confidence interval (CI): 1.8-6.9, P less than 0.01), and was also a strong marker of subsequent risk of readmission (OR = 3.0, 95% CI: 2.1-4.2, P less than 0.01); the risk increased with the number of previous admissions. Three or more categories of prescribed asthma drugs was also associated with subsequent death (OR = 1.7, 95% CI: 0.9-3.3, P = 0.13) or readmission (OR = 1.9, 95% CI: 1.3-2.7, P less than 0.01); prescribed oral corticosteroids was only weakly associated with subsequent death (OR = 1.3, 95% CI: 0.6-2.8, P = 0.59), but was more strongly associated with subsequent readmission (OR = 1.9, 95% CI: 1.2-2.8, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Comparison of a video questionnaire with the IUATLD written questionnaire for measuring asthma prevalence.

A video questionnaire (VQ) for measuring asthma prevalence in adolescents was assessed for repeatability and validity in relation to bronchial hyperresponsiveness (BHR) (PD20 less than or equal to 7.8 mumol methacholine). Comparison was also made with a standard, self completed written questionnaire (SQ), based on the IUATLD Bronchial Symptoms Questionnaire, which included five questions seeking comparable data to those in the VQ. Both the VQ and SQ were administered to 707 schoolchildren (13-16 years), in whom English was the primary language. One hundred and six randomly selected children subsequently underwent bronchial challenge to methacholine. Both the sensitivity and specificity for BHR were higher for a combination of three or more positive responses to the VQ (0.73 and 0.88), than to the SQ (0.63 and 0.82), although these differences were not statistically significant (P = 0.24). When administered again after a two week interval, the VQ had a significantly higher (P = 0.03) coefficient of repeatability (0.79) than the SQ (0.50). We conclude that the VQ is a valid and reliable method of determining asthma prevalence, and propose that by providing data relatively free from biases due to language, culture, literacy or interviewing techniques it may be particularly useful when comparing asthma prevalence and severity in different populations.

Adolescent↗
PubMed1992

Cardiovascular effects of fenoterol under conditions of hypoxaemia.

BACKGROUND: The reason for the association of increased risk of death with fenoterol in patients with asthma in New Zealand is unknown but may relate to its cardiovascular effects. Most deaths from asthma occur outside hospital, where hypoxaemia is likely to be a complicating factor. The cardiovascular effects of fenoterol have been investigated therefore under conditions of normoxaemia and hypoxaemia. METHOD: Eight healthy men were studied on two occasions. Measurements of heart rate, blood pressure, total electromechanical systole (QS2I), electrocardiographic QTc interval, cardiac index, stroke volume, and ejection fraction were made under conditions of normoxaemia and hypoxaemia (arterial oxygen saturation 90%) before and after administration of 800 micrograms of fenoterol by a metered dose inhaler. The order in which treatments were applied was according to a Latin square design. RESULTS: Before inhalation of fenoterol hypoxaemia was associated with a significant increase in heart rate (8 beats/min) and QTc interval (15.6 ms). Under conditions of normoxaemia fenoterol caused a significant increase in heart rate (14.3 beats/min), systolic blood pressure (7.7 mm Hg), stroke volume (27.7 ml), cardiac index (1.6 1/min/m2), ejection fraction (11.48), and QTc interval (32.9 ms) and a fall in QS2I (-23.2 ms) and diastolic blood pressure (-8.4 mm Hg). Under conditions of hypoxaemia the changes after inhalation of fenoterol were similar to those recorded during normoxaemia; thus the effects of hypoxaemia and fenoterol were additive (heart rate 21.9 beats/min, QTc 43.5 ms with fenoterol and hypoxaemia). CONCLUSION: The chronotropic and electrophysiological effects of fenoterol were enhanced by conditions of hypoxaemia.

Adult↗
PubMed1992

The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects.

BACKGROUND: Attention has recently been focused on the basal cells of the tracheobronchial epithelium as the mechanism of anchorage of the tall columnar cells, which themselves do not appear to form hemidesmosomes with the basement membrane of the epithelium. Residual basal cells have been described as remaining attached to the basement membrane after epithelial denudation. This led this group to formulate the hypothesis that there may be a potential plane of cleavage between the basal cells and the overlying columnar cell layer within the bronchial epithelium, which becomes disrupted in asthma. METHODS: Bronchoalveolar lavage samples were obtained during bronchoscopy from eight patients with atopic asthma and four normal controls. Ultrathin sections of lavage cell pellets were examined by electron microscopy and the number of columnar and basal cells found in each epithelial cell cluster was counted. Cytocentrifuge preparations of the lavage samples from the same subjects were also examined for free epithelial cells and epithelial cell clusters. RESULTS: Electron microscopic examination of the cell pellets showed that basal cells were present in very small numbers in the epithelial clusters in all subjects (mean 0.03 (SE 0.02)/cluster) and the ratio of columnar cells to basal cells was far greater than was encountered in the intact bronchial epithelium (167 nu 4). The cytocentrifuge preparations showed an increased number of epithelial cell clusters and epithelial cells in the asthmatic patients. Although these clusters were similar in size in the two groups of subjects (6.3 nu 5.1 cells/cluster) the ratio of free epithelial cells to cells within the cluster was higher in the non-asthmatic subjects. CONCLUSIONS: It is proposed that shedding of epithelial cells occurs along a suprabasal plane and that there is a potential plane of cleavage between the suprabasal and the basal cell layers, which might be more vulnerable to the various insults.

Adult↗
PubMed1991

Neopterin quantification in acute severe asthma.

To investigate the pathogenic role of cell-mediated immunity (CMI) in acute severe asthma, 10 patients with acute asthma requiring admission to hospital had measurements of serum and urine absolute neopterin and neopterin/creatinine ratios. Serum was collected upon entry to hospital, 24 hr later and at 2 weeks; and urine at 24 hr and at 2 weeks after admission. Comparisons were made with 12 stable asthmatic patients, healthy control subjects, and six renal transplant patients undergoing transplant rejection. In contrast to the renal transplant patients who demonstrated T-lymphocyte-macrophage activation, neopterin concentrations and neopterin/creatinine ratios in both acute and stable asthmatic patients were not elevated. We have not found functional evidence that CMI participates in the pathogenesis of acute severe asthma.

Acute Disease↗
PubMed1991

Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study.

The association between inhaled fenoterol and death from asthma has been investigated further by studying 112 asthma deaths (cases) during 1981-7 in patients aged 5-45 years who had been admitted to a major hospital for asthma during the 12 months before death. Two age matched control groups were chosen. Control group A comprised 427 patients who had been admitted to hospital for asthma during the calendar year that the corresponding death occurred and who had also had a previous admission for asthma in the previous 12 months. Control group B comprised 448 patients admitted to hospital for asthma during the calendar year in which the admission of the corresponding case occurred. The inhaled fenoterol odds ratio was 2.11 (95% confidence interval (CI) 1.37-3.23, p less than 0.01) when group A was used as the control (the approach used in previous studies), and 2.66 (95% CI 1.74-4.06, p less than 0.01) with group B as the control (the approach recommended by critics of previous studies). Markers of chronic asthma severity were associated with asthma death when control group B was used, but not when control group A was used (which indicates that these markers were indirectly matched for when control group A was used). Information was also collected on various markers of acute asthma severity and prescription of psychotropic drugs, but it was found that these were not important confounders. These findings address the major criticisms of previous case-control studies of this issue, and add support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.

Administration, Inhalation↗
PubMed1991

Lack of evidence for beta-2 receptor selectivity: a study of metaproterenol, fenoterol, isoproterenol, and epinephrine in patients with asthma.

In order to investigate the pharmacodynamic selectivity of a number of beta-receptor agonists currently used in asthma, we compared the pulmonary and extrapulmonary effects of repeated inhalations of epinephrine, fenoterol, isoproterenol, and metaproterenol in 12 patients with asthma in a randomized double-blind crossover study. The drugs were administered from metered-dose inhalers at 15-min intervals for five doses (total dose, 10 puffs of each compound). Measurements of heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval, plasma potassium, and FEV1 were made 5 min after each dose and 30 min after the final dose. Fenoterol and metaproterenol had significantly greater inotropic, electrocardiographic, chronotropic, and hypokalemic effects than did both isoproterenol and epinephrine. There was no difference in the bronchodilating effect of metaproterenol, fenoterol, or isoproterenol although these agents caused a significantly greater increase in FEV1 than did epinephrine. The concept of increasing beta-2 selectivity for metaproterenol and fenoterol compared with isoproterenol are not supported in the clinical setting.

Adrenergic beta-Agonists↗