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Biomedical subjects

S C Stenton

Publications and source records attributed to S C Stenton.

At least 37 records · Page 2Linked to original sources
PubMed1995

Occupational asthma due to ceftazidime.

A worker employed in the manufacture of the new third generation cephalosporin antibiotic, ceftazidime, developed asthmatic symptoms, and a series of inhalation challenge tests was undertaken to investigate the problem. The inhalation of increasing daily doses of ceftazidime up to 3.2 mg, using a double-blind challenge protocol gave rise to symptoms, late asthmatic reactions, and increases in airway responsiveness to methacholine. A repeat challenge with the 3.2 mg dose additionally gave rise to a clear immediate reaction. Ceftazidime was, thus, shown to be capable of inducing occupational asthma.

Adult↗
PubMed1994

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↗
PubMed1994

Statistical approaches to the identification of late asthmatic reactions.

Late asthmatic reactions can be difficult to recognize because of their prolonged time course and the confounding effects of superimposed circadian rhythms of ventilatory function. Conventional methods of analysis are rather arbitrary. They depend for example on a 15 or 20% fall in forced expiratory volume in one second (FEV1) from baseline or from time-matched control measurements. We have, therefore, investigated whether statistical approaches applied to individual subjects can assist in the identification of late asthmatic reactions. In two separate series of aerosol inhalation tests, three symptomatic workers, three asthmatic controls and three nonasthmatic controls were challenged blindly with increasing doses of two chemical agents, and saline. One of the agents, sodium isononanoyl oxybenzene sulphonate (SINOS) was a suspected cause of occupational asthma. Prior to the challenges, FEV1 was measured hourly on three control days. Cumulative late changes on both control and active challenge days were quantified as the area between a line extrapolated from a 10.00 h baseline and the actual measurements from 12.00-22.00 h (the 2-12 h area decrement). The area decrement measurements on control and active challenge days were compared using Student's t-tests. The sensitivity of this method for detecting late asthmatic reactions among potentially positive tests (SINOS challenge tests in the workers) was examined, as was its specificity. The latter was determined from the false positive rate among the negative tests. A second statistical method based on the pooled standard deviation of serial (hourly) FEV1 measurements was investigated in the same way. In total, the data from 220 challenge and 30 control days were available for analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

The effect of GR32191 (a thromboxane receptor antagonist) on airway responsiveness in asthma.

Airway responsiveness to methacholine was measured in nine subjects (22-53 years, seven male) with chronic stable asthma. All subjects were taking inhaled beclomethasone (less than 1000 micrograms daily). The mean baseline FEV1 was 2.841 (77% of predicted) and the geometric mean PD20FEV1 was 31 micrograms. After a run-in period, the subjects were randomly allocated to two treatment periods with the specific thromboxane receptor antagonist GR32191, 40 mg four times daily for 3 weeks, and identical placebo capsules. A double-blind, placebo-controlled, cross-over design was employed with 4 weeks between the two treatment periods. Treatment with GR32191 did not result in any significant improvement in mean FEV1 (2.941 after placebo and 2.861 after GR3219; F7.71 = 1.02, P greater than 0.1) or PD20FEV1 (24.3 micrograms after placebo and 38.5 micrograms after GR32191; F7.71 = 0.59, P greater than 0.1). We conclude that thromboxane is not important in the maintenance of airway hyperresponsiveness in chronic asthma and that thromboxane receptor antagonists are unlikely to provide effective treatment for this group of patients.

Adult↗
PubMed1990

The relationship between atopy and non-specific bronchial responsiveness.

Atopy is often regarded as a risk factor for the development of asthma, particularly childhood asthma and occupational asthma. This could reflect an association with non-specific bronchial responsiveness (NSBR), though atopy could influence asthma independently. We have evaluated the possible relationship between atopy and NSBR (PD20FEV1 to methacholine) in the siblings of 59 probands with atopic asthma. Thirty-four (58%) were atopic (greater than or equal to 1 prick test with weal diameter greater than or equal to that of a 0.1% histamine control) and 28 (47%) showed NSBR. Atopy and NSBR occurred together more frequently than would be expected by chance (P less than 0.05); both variables being observed in 20 subjects, neither in 17, and only one in 22. A significant association was also noted when atopy was defined by a serum total IgE greater than 150 IU (or greater than 50 IU), but when atopy was defined by other commonly used criteria (greater than or equal to 2 prick tests with weal diameter greater than or equal to histamine control; or weal diameter 2 mm or more greater than a saline control), no significant association was demonstrated. Furthermore, linear logistic regression and multiple regression analyses showed that both the presence and the degree of NSBR were influenced much more by the baseline level of FEV1 than by atopic status. At best, atopy accounted for 10% of the variance of the PD20 measurements. We conclude that atopy is associated with NSBR but not strongly; that the relationship may be readily obscured according to the defining criteria used for atopy; and that atopy should not be used as a marker for NSBR.

Adolescent↗
PubMed1990

The actions of GR32191B, a thromboxane receptor antagonist, on the effects of inhaled PAF on human airways.

We investigated acute bronchoconstriction and changes in airway responsiveness to methacholine following the inhalation of platelet activating factor (PAF) in an open study of 12 non-asthmatic subjects. Ventilatory function was monitored using a flow rate at 30% of vital capacity (V30) and airway responsiveness was measured as PD40V30, i.e. the dose of metacholine causing a 40% fall in V30. PAF (3-422 micrograms) resulted in dose-related acute bronchoconstriction in 10 of the 12 subjects. There was no association between the airway responsiveness to PAF and to methacholine. Ten subjects showed some increase in airway responsiveness to methacholine 1 or 3 days following PAF. Overall, these changes were statistically significant (P less than 0.05) but were of small magnitude (geometric mean PD40V30pre-PAF = 457 micrograms; 24 hr after PAF = 259 micrograms; 72 hr after PAF = 258 micrograms) and variable: only seven subjects showing increased airway responsiveness on both day 1 and day 3 after PAF. Six subjects who appeared to show increases in airway responsiveness following PAF were re-studied with the inhaled PAF pre-medicated by either placebo or a specific thromboxane receptor antagonist (GR32191B) in a double-blind fashion. GR32191B did not reduce the acute bronchoconstriction due to PAF. In this part of the study, these six subjects did not show significant increases in airway responsiveness following the placebo pre-medicated PAF challenge and so no effect of the drug on airway responsiveness could be shown.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Asthmagenic properties of a newly developed detergent ingredient: sodium iso-nonanoyl oxybenzene sulphonate.

The suspicion that a newly developed detergent ingredient, sodium iso-nonanoyl oxybenzene sulphonate (SINOS), was inducing asthma among a workforce led to a series of inhalation challenge tests to determine the specificity and dose response characteristics of its asthma provoking properties. Three previously exposed workers, three non-exposed non-asthmatic controls, and three non-exposed asthmatic controls were challenged with SINOS 0.01-100 micrograms and another chemically similar surface active detergent ingredient, linear alkyl benzene sulphonate (LAS) 0.01-100 micrograms. Asthmatic symptoms, late falls in FEV1, and increases in non-specific bronchial responsiveness were seen after the inhalation of SINOS in all three workers, confirming SINOS as a cause of occupational asthma. No changes were seen after the inhalation of SINOS in either group of control subjects nor after LAS in any subject. These findings suggest that SINOS causes asthma through a specific hypersensitivity mechanism unrelated to its surface active properties.

Adult↗
PubMed1990

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↗
PubMed1990

The relative contribution of bronchoalveolar macrophages and neutrophils to lucigenin- and luminol-amplified chemiluminescence.

The relationship between differential cell counts and latex-stimulated luminol and lucigenin-amplified chemiluminescence (CL) was investigated by mixing alveolar macrophages (AM) obtained at bronchoalveolar lavage (BAL) with allogeneic peripheral blood neutrophils (PMN) in varying proportions. In 5 non-asthmatic subjects, the mean luminol-amplified CL increased linearly from 2.1 (0.9 SEM) x 10(5) counts per second (cps) with less than 2% PMN, greater than 96% AM to 47.3 (11.1 SEM) x 10(5) cps with greater than 94% PMN, 0% AM (r = 0.996, p less than 0.001). The regression had a y-intercept indistinguishable from 0 cps, suggesting that luminol-amplified CL exclusively reflected PMN activity. Using the same technique, the mean lucigenin-amplified CL showed a fall from 35 (2.3 SEM) x 10(5) cps with a cell population of greater than 96% AM, less than 2% PMN to 20 (2.3 SEM) x 10(5) cps with 0% AM, greater than 94% PMN. Both PMN and AM appeared to contribute to lucigenin-amplified CL, with AM contributing approximately 1.7 times as much activity per cell as PMN. Lucigenin-amplified CL appeared to be an appropriate technique for measuring AM activity when the proportion of PMN in mixed cell populations was small. A linear relationship was found between percent PMN count and luminol-amplified CL measured in a mixed BAL cell population from asthmatic subjects (p less than 0.01) and non-asthmatic controls (p less than 0.01). The slope of this regression line was significantly greater for subjects with asthma than for control subjects (p less than 0.01), suggesting a uniform increase in PMN activity in cells obtained from asthmatic airways.

Acridines↗
PubMed1990

Platelet-activating factor in bronchoalveolar lavage fluid from asthmatic subjects.

Bronchoalveolar lavage (BAL) was performed on 28 asthma patients, 7 patients with emphysema and 11 control subjects. Total and differential cell counts were performed and cellular metabolic activity was assessed using luminol and lucigenin amplified chemiluminescence. BAL supernatants were assayed for platelet-activating factor (PAF) and lyso-PAF using a sensitive guinea-pig bioassay. Eight of the asthma patients but none of the emphysema patients or control subjects had PAF in their BAL fluid. Lyso-PAF was measurable in BAL fluid in most subjects and no differences were detected between groups. Among the asthma patients, the presence of PAF in BAL supernatant was significantly associated with a combination of low neutrophil and high lymphocyte counts (p less than 0.05) and with macrophage metabolic activity as assessed by lucigenin chemiluminescence (p less than 0.05).

Adolescent↗
PubMed1989

Occupational asthma due to a repair process for polyethylene-coated electrical cables.

We report the case of an electrical cable repairer who presented with symptoms suggestive of occupational asthma. A supervised workplace challenge test confirmed this diagnosis and laboratory challenge studies implicated heated polyethylene repair tape containing the chemical cross-linking agent dicumyl peroxide as the cause. Similar cross-linking processes are widely used in the cable manufacturing industry and the possibility of occupational asthma occurring in other settings may need to be considered.

Adult↗
PubMed1989

Lymphocyte subsets in bronchoalveolar lavage fluid obtained from stable asthmatics, and their correlations with bronchial responsiveness.

Bronchial responsiveness to methacholine (PD20 FEV1) was assessed in 22 asthmatic subjects approximately 5 days prior to bronchoalveolar lavage (BAL). A PD20 FEV1 could not be attained in 20 matched controls with normal pulmonary function. BAL was performed in all subjects, 3 x 60 ml aliquots of buffered saline being introduced into a segment of the middle lobe and immediately aspirated into siliconized glassware at 4 degrees C. After filtration, cells were counted, and the cell pellet resuspended in medium 199. Cytospin slides were prepared and a differential cell count performed. Lymphocyte subsets were identified by labelling further cytospin preparations with specific monoclonal antibodies (Leu series) against T3, T4, T8 and B cell markers, followed by a fluorescent antibody marker. The slides were coded, and 100 lymphocytes were then randomly scanned for fluorescence on each cytospin preparation. The median total lymphocyte counts were significantly greater in the asthmatic subjects, but this increase was confined to the T cell subgroups. The mean T4/T8 ratio was similar in asthmatic (1.51) and control (1.45) subjects. Log PD20 FEV1 correlated positively with total lymphocyte counts (r = 0.42, P less than 0.05), and with total T8 counts (r = 0.60, P less than 0.05). Correlations between bronchial responsiveness and T3, T4 and B lymphocyte numbers all failed to reach significance, and there was no correlation with T4/T8 ratios. The increase in BAL lymphocyte counts in asthma appears to be due to an absolute increase in T cell subsets, especially the T8 lymphocyte subgroup, and is most marked in mild asthmatics.

Adolescent↗
PubMed1989

Refractory period following bronchoconstriction provoked by histamine in asthmatic subjects.

To determine whether refractoriness to histamine induced bronchoconstriction occurs, 20 asthmatic subjects aged 19-50 years were tested. Subjects underwent two histamine challenge tests (1 and 2) on the same day, the second one being given 45-60 minutes after the first, once the FEV1 after test 1 had returned spontaneously to within 90% of baseline. A further "control" histamine challenge test was carried out on a different day at the same time (+/- 2 hours) as test 1. Bronchial responsiveness was recorded as the cumulative dose (microgram) of histamine provoking a 20% fall in FEV1 (PD20), and the ratio PD20 test 2:PD20 test 1 was used to assess refractoriness. The median value of this ratio (2.20) was significantly greater than 1 (p = 0.003), indicating refractoriness at the time of test 2. By contrast the median ratio PD20 control:PD20 test 1 of 1.03 was not significantly different from 1. Refractoriness could not be accounted for by failure to regain the initial baseline FEV1, though such failure may have exaggerated the effect. An increase in PD20 with the second test was observed uniformly in subjects with moderate or high initial PD20 values but not in those with low values. This suggests that there may be a PD20 threshold of the order 25-100 micrograms for refractoriness to occur. Refractoriness could exert an important confounding effect in investigations in which repeated histamine tests are carried out at short intervals.

Adult↗