"Breathing" coal mines and surface asphyxiation from stythe (black damp).
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Adult↗
Biomedical subjects
D J Hendrick
Publications and source records attributed to D J Hendrick.
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↗
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↗
The origin of water and urea sampled at bronchoalveolar lavage in asthmatic and control subjects.
Bronchoalveolar lavage (BAL) urea has been advocated as a denominator that might allow for the dilution of the pulmonary epithelial lining fluid sampled at BAL, and so provide a meaningful method of expressing BAL data. We investigated the origin of water and urea sampled at BAL in five asthmatic and five control subjects using radiolabeled urea injected intravenously 5 min before BAL. Labeled BAL urea was found to be fully equilibrated with that in the bloodstream. A strong relationship was found between influx of radiolabeled water and radiolabeled urea from blood to BAL fluid, suggesting that urea sampled at BAL may be derived predominantly from an acute movement from the bloodstream into the BAL aspirate. We conclude that urea is an inappropriate denominator for the expression of BAL results, and that the fluid and solute dynamics that occur during BAL are both complex and variable.
Adult↗
Calibration of aerosol output from the Mefar dosimeter: implications for epidemiological studies.
Standardized methods for the measurement of airway responsiveness may use the Mefar MB3 inhalation dosimeter to generate standard doses of methacholine aerosol. The manufacturer provides calibrated output data for every nebulizer, so that a standard output may be achieved by varying nebulization time. This output is, however, measured by weight loss (WL), which may over-estimate true aerosol output (AO) because of concomitant evaporation. We have used a chemical (fluoride) tracer method to measure AO directly from two batches of Mefar nebulizers (batch 1 n = 5, batch 2 n = 10) and compared results with manufacturer's quoted WL. Mean AO from batch 1 was 10.56 mg.s-1 (range 9.50-11.63, SD = 0.92 mg.s-1), and mean AO from batch 2 was 5.66 mg.s-1 (range 4.92-6.58, SD = 0.57 mg.s-1), implying that AO varied little within, but substantially between, the two nebulizer batches. Manufacturer's quoted WL does not reflect this near two fold difference: mean WL batch 1 = 14.0 mg.s-1 (range 13-15 mg.s-1); mean WL batch 2 = 11.1 mg.s-1 (range 11-12 mg.s-1). The median aerosol fractions (AO/WL) for batches 1 and 2 were 76% (range 65-83%) and 50% (range 43-60%), respectively. Similar results were obtained with our own measurement of weight loss. This implies that if the median nebulizers of batches 1 and 2 were calibrated (as recommended) by the manufacture's WL to deliver a presumed 100 micrograms methacholine dose, the actual doses delivered would be 76 micrograms and 50 micrograms, the range for all 15 nebulizers being 43-83 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Inhalation↗
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↗
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↗
Late-onset asthma in a demented elderly patient. The value of methacholine challenge in diagnosis.
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Aged↗
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↗
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 reversible effect of lignocaine on the stimulated metabolic activity of bronchoalveolar lavage cells.
Lignocaine concentrations were measured in the aspirate from a low volume (100 ml) bronchoalveolar lavage (BAL) in twenty patients who had received topical 4% lignocaine as required, and compared to those found in the aspirate from a 180 ml BAL in ten patients who had received 1.5% isotonic lignocaine. The median BAL supernatant lignocaine concentration was significantly lower at 0.14 mM (range 0.07-0.44 mM) in the group who received 1.5% lignocaine, compared to 1.08 mM (range 0.03-7.05 mM) in those given 4% lignocaine (p less than 0.01). The effect of increasing concentrations of lignocaine on BAL neutrophil and pulmonary macrophage metabolic activity, as assessed by latex-stimulated luminol- and lucigenin-amplified chemiluminescence (CL), respectively, in mixed BAL cell populations, were measured following preincubation of "washed" harvested BAL cells with 0.4-8.0 mM lignocaine. There was no demonstrable decline in either cell activity with lignocaine concentrations of up to 2 mM, with dose-dependent inhibition of both above this threshold. Cell viability was unaffected. In a further experiment, the inhibition induced by 8 mM lignocaine on both pulmonary macrophage (lucigenin-amplified CL of harvested BAL cells) and isolated peripheral blood neutrophil metabolic activity was completely reversed by a single "wash", following both 30 and 60 min incubations at 4 degrees C, which was equivalent to resuspending harvested BAL cells in fresh medium after separation from BAL supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
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↗
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↗
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↗
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↗
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↗
Asthma: epidemics and epidemiology.
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Air Pollutants↗