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Biomedical subjects

J R Beach

Publications and source records attributed to J R Beach.

30 records · Page 2Linked to original sources

Effect of dietary sodium on airways responsiveness and its importance in the epidemiology of asthma: an evaluation in three areas of northern England.

BACKGROUND: Although several investigations have shown a relationship between asthma (or its surrogate, airways responsiveness) and dietary or urinary sodium, others have not, and the matter remains controversial. This "salt effect" has been investigated during two recent epidemiological surveys of men in northern England. The first assessed the possible effect on airways responsiveness of occupational exposure to welding fumes, and the second characterised airways responsiveness in two geographically distinct residential areas. Thus, three separate study areas/populations were involved. METHODS: Investigation 1 involved 1059 shipyard workers aged 16-27 years who were exposed variously to welding fumes, and Investigation 2 involved 587 men aged 20-44 years who lived in rural West Cumbria or in urban Newcastle upon Tyne. In Investigation 1, a 24 hour urine specimen was requested from each subject with quantifiable airways responsiveness (PD20 < or = 6400 micrograms methacholine) and from an equal number of subjects without measurable airways responsiveness from the same occupational subgroup. In Investigation 2, every subject was asked to provide a 24 hour urine specimen. RESULTS: Of the men undergoing methacholine tests, satisfactory 24 hour urine specimens were obtained from 234 (22.1%) in Investigation 1 and 232 (39.5%) in Investigation 2. Analysis using multiple linear regression, multiple linear logistic regression, and multiple regression for censored data produced consistent results within each study population but conflicting results between them, such that there was no hint of a relationship between airways responsiveness and 24 hour urinary sodium excretion in the shipyard workers of Investigation 1 nor in the rural West Cumbrian population of Investigation 2, but an association was found in the urban Newcastle population of Investigation 2. All study populations were sufficiently large to demonstrate anticipated relationships between airways responsiveness and atopy, baseline FEV1, and (Newcastle only) age. CONCLUSIONS: If airways responsiveness is related to dietary sodium the relationship is not likely to be strong.

Adolescent↗

Glutaraldehyde, asthma and work--a cautionary tale.

A 46-year-old endoscopy nurse developed symptoms suggestive of occupational asthma after seven years of exposure to glutaraldehyde. An initial inhalation challenge test at the endoscopy suite caused a very dramatic immediate fall in FEV1 from 3.6 to 1.5 litres. To further evaluate the case and establish a threshold for the response, a technique was devised to allow a series of double-blind inhalation challenges with activated glutaraldehyde vapour at exposure levels of 0.01-0.32 ppm. The results suggested marked dual asthmatic reactions following challenges with 0.032 ppm glutaraldehyde; however, similar 'reactions' were observed on control days. These were associated with an increase in airway responsiveness to methacholine, with the PD20FEV1 falling from > 6400 micrograms to 135 micrograms. The interpretation of these results was potentially confounded by an intercurrent respiratory tract infection and by technically poor FEV1 recordings, so the challenge series was repeated three weeks later. The second series of double-blind inhalation challenges with carefully controlled exposures to glutaraldehyde (up to 0.32 ppm for 10 min) gave rise to no obvious asthmatic reactions, in marked contrast to the results of the unblinded workplace challenge. There was a slight increase in airway responsiveness, with the PD20FEV1 falling from > 6400 micrograms to 1850 micrograms. These results illustrate the potential for misdiagnosis of occupational asthma when unblinded challenge tests are used and show that, even with sophisticated investigatory techniques, a clear-cut diagnostic result may be elusive.

Asthma↗

Effect on airway responsiveness of six weeks treatment with salmeterol.

It has been suggested that the new long-acting beta 2-agonist, salmeterol, has anti-inflammatory properties--properties which should improve airway responsiveness (AR). Conversely, several recent studies have suggested that regular beta 2-agonist treatment may worsen asthma and AR. Furthermore, a short-lived rebound increase in AR has been described following cessation of regular treatment with these agents. We have consequently assessed the effects on AR of regular treatment with either salmeterol or salbutamol at conventional doses over 6 weeks. FEV1 and AR were measured five times in 20 asthmatic subjects randomly allocated to one or other treatment regimen; twice during a 2-week run-in period; and 24 h, 72 h, and 2 weeks after the last dose of the study medication. Peak expiratory flow rate (PEFR) was also recorded throughout the study period. There were no statistically significant changes in FEV1 or AR between the run-in period and any of the post treatment measurements for either of the treatments used. Mean PEFR was significantly higher during the treatment period than the run-in period for the salmeterol group, but not the salbutamol group, confirming that therapeutically adequate doses of salmeterol had been given. We conclude that if the regular use of salmeterol is associated with beneficial or adverse effects on AR, this is not apparent after a treatment period of 6 weeks.

Adrenergic beta-Agonists↗

The value of questionnaires and spirometry in asthma surveillance programmes in the workplace.

Shipyard workers and job applicants (n = 1126) completed an asthma questionnaire, and underwent measurements of ventilatory lung function (FEV1, FEV1/FVC and PEFR) and airway responsiveness. Airway responsiveness (to inhaled methacholine) was expressed as the dose calculated to provoke a 20 per cent fall in FEV1, ie the PD20. Results were categorized into four levels: high (PD20 < 200 micrograms), medium (200-1000 micrograms), low (1001-6400 micrograms) and unquantifiable (> 6400 micrograms), which correspond with definite, possible, doubtful and no asthmatic activity. These categories agreed closely with diagnoses of asthma by general practitioners and the use of bronchodilator medication. The sensitivity and specificity of the questionnaire and the measurements of ventilatory function for detecting asthmatic activity were then determined. The questionnaire symptoms (wheeze, chest tightness, undue coughing or abnormal breathlessness) had a low (28 per cent) sensitivity for detecting definite or possible asthmatic activity and a specificity of only 73 per cent. The sensitivity of the ventilatory function tests (any one abnormal) was also low at 21 per cent with a specificity of 92 per cent. When the FEV1 < 80 per cent predicted criterion was considered separately, its sensitivity was 11 per cent and its specificity was 98 per cent. These results illustrate that caution is needed when interpreting the results of questionnaires and measurements of ventilatory lung function in the diagnosis of asthma among working populations.

Asthma↗

Measurement of airway responsiveness to methacholine: relative importance of the precision of drug delivery and the method of assessing response.

BACKGROUND: The value of measuring airway responsiveness in asthma research is currently limited by the number of different methods used by different investigators, by the lack of a standardised method of expressing precision, and by an inability to equate the results of one method with those of another. METHODS: Two pairs of measurements of airway responsiveness to methacholine were performed in 20 asthmatic subjects, one pair using a dosimeter method (AR-D) and one pair using the conventional Wright nebuliser tidal breathing method (AR-W). The two methods normally use different techniques for quantifying changing levels in forced expiratory volume in one second (FEV1) after each dose of methacholine (the mean of the highest three of six measurements for AR-D, the lower of two measurements for AR-W), and different techniques for expressing measurements of airway responsiveness (the provoking dose (PD20) and the provoking concentration (PC20) respectively responsible for a 20% decrement in FEV1). RESULTS: The coefficient of repeatability (and hence precision) for the measurement of airway responsiveness was significantly better for AR-D (3.0) than for AR-W (10.9), but the technique for quantifying FEV1 contributed more to this than the technique for delivering methacholine. A PC20 of 1 mg/ml with AR-W was equivalent to a PD20 of 103 micrograms with AR-D. CONCLUSIONS: It is practical as well as desirable to compare the precision of different techniques for the measurement of airway responsiveness and to derive conversion factors so that results may be equated.

Adolescent↗

A comparison of the speeds of action of salmeterol and salbutamol in reversing methacholine-induced bronchoconstriction.

We compared the speed of action of the long acting beta-agonist salmeterol with that of salbutamol in order to assess whether reported in vitro differences are likely to have clinical significance. We used methacholine tests to produce a standardized level of bronchoconstriction and then observed the rate of recovery of FEV1 towards baseline after the administration by metered dose inhaler of salmeterol 50 micrograms or salbutamol 200 micrograms--doses which are considered to have similar bronchodilator potency. Twenty asthmatic subjects participated, and a double-blind, randomized, cross-over study design was followed. Salmeterol showed a significantly slower speed of action with median recovery to 90% and 95% of the baseline FEV1 (pre-methacholine) occurring after 9.6 and 19.4 min, respectively, compared with 4.8 and 8.3 min, respectively, for salbutamol (P less than 0.01). These observations are consistent with in vitro findings and suggest that salmeterol is likely to be less satisfactory than salbutamol as a 'rescue medication' for the treatment of acute episodes of bronchoconstriction.

Adult↗

Jet and ultrasonic nebuliser output: use of a new method for direct measurement of aerosol output.

Output from jet nebulisers is calibrated traditionally by weighing them before and after nebulisation, but the assumption that the weight difference is a close measure of aerosol generation could be invalidated by the concomitant process of evaporation. A method has been developed for measuring aerosol output directly by using a solute (fluoride) tracer and aerosol impaction, and this has been compared with the traditional weight loss method for two Wright, six Turbo, and four Micro-Cirrus jet nebulisers and two Microinhaler ultrasonic nebulisers. The weight loss method overestimated true aerosol output for all jet nebulisers. The mean aerosol content, expressed as a percentage of the total weight loss, varied from as little as 15% for the Wright jet nebulisers to 54% (range 45-61%) for the Turbo and Micro-Cirrus jet nebulisers under the operating conditions used. In contrast, there was no discrepancy between weight loss and aerosol output for the ultrasonic nebulisers. These findings, along with evidence of both concentrating and cooling effects from jet nebulisation, confirm that total output from jet nebulisers contains two distinct fractions, vapour and aerosol. The vapour fraction, but not the aerosol fraction, was greatly influenced by reservoir temperature within the nebuliser; so the ratio of aerosol output to total weight loss varied considerably with temperature. It is concluded that weight loss is an inappropriate method of calibrating jet nebuliser aerosol output, and that this should be measured directly.

Aerosols↗

The distribution of lead in milk and the fate of milk lead in the gastrointestinal tract of suckling rats.

Milk can be a significant source of lead (Pb) for young mammals, including humans. Certain essential trace elements have previously been shown to be specifically associated with particular milk components and such associations often increase bioavailability. Thus, the first goal of this study was to determine the distribution of Pb in cream, casein, and whey fractions of various milks under various conditions using 203Pb as a tracer. In rat milk almost 90% of the Pb was found to be associated with the casein micelles, regardless of: 1) whether the milk was labeled in vivo or in vitro; b) whether the milk was fresh or frozen; and c) the added concentration of Pb (over the range 0.01-75 micrograms/ml). The remainder of the Pb was approximately equally distributed between cream and whey. A virtually identical pattern of Pb distribution was observed with bovine milk. Pb added to infant formula also associated predominantly with casein micelles, although the Pb content of this fraction was significantly less than with rat and bovine milks. The second goal of the study was to determine if Pb remained associated with casein as it traversed the gastrointestinal tract of infant rats. For this purpose, rat pups aged 15-16 days were gavaged with 203Pb-labeled rat milk, and lumenal contents from the stomach and small intestine were collected 2 h later. Differential centrifugation of the homogenized lumenal contents showed that in the stomach the Pb was associated primarily with the casein curd. By the time chyme reached the distal small intestine, Pb was found predominantly in a fraction that was not precipitable by high-speed centrifugation (thus, not intact casein micelles), but was nondialyzable. We conclude that Pb in milk is protein bound and remains this way as it traverses the stomach and proximal small intestine of the infant rat.

Animals↗

Immunologic versus toxicologic mechanisms in airway responses.

There is now considerable evidence that T lymphocytes play an important role in generating the IgE-mediated immune response of classical allergic asthma. An immune response can be generated by other routes, including IgG- and cell-mediated mechanisms, as well. Regardless of the mechanism, it is clear that allergic asthma is an inflammatory disease, with activated T lymphocytes, eosinophils, mast cells, and other leucocytes all playing a role. Recently, an irritant asthma called reactive airway dysfunction syndrome also has emerged. It appears to be due to direct irritant or toxic effects, but shares many features of allergic asthma. Thus, several different pathways lead to the inflammatory changes and nonspecific airway responsiveness underlying asthma.

Asthma↗