Search

Inhalation provocation tests were used to assess whether the volatile products of an activated resin had caused occupational asthma in a non-random sample of six asthmatic coal miners. The resin system uses the polymerization of polyester and styrene under the influence of the cross-linking agent dibenzoyl peroxide to secure roof, wall and floor bolts in mine tunnels. The tests were conducted sequentially in a double-blind fashion over a 'dose' range which extended just beyond the maximum likely to have been experienced occupationally during a single day's work. The tests were monitored by symptoms, changes in the forced expiratory volume in 1 s (FEV1) and changes in airway responsiveness. All subjects completed the series of tests without any significant decrements in FEV1 or significant increases in airway responsiveness. We conclude that the use of this resin system is not likely to have been the cause of the asthma in the test subjects, nor in the larger group of miners of which they were a sample, but neither possibility is fully excluded and the participants may not have been adequately representative of other asthmatic coal miners.

A 2-day conference on Advances in Inhalation Therapy drew together 16 speakers, experts in their respective fields, to summarize recent developments in delivery device design, drug formulation, in vitro and in vivo assessment, and to provide a clinical overview of the future of drug aerosol therapy. Concurrent advances are being made in the design of aerosol delivery devices in all areas. Reformulation of non-CFC pressurized metered dose inhalers (pMDIs) is overcoming technical, legal and engineering obstacles, although whether the new hydrofluorocarbon (HFA) products will already be limited and dated is a distinct possibility. New 'soft mist inhalers' offer a viable alternative for drug aerosol delivery that has potential advantages in efficiency in design and aerosol delivery compared to conventional pMDIs and DPIs. The reproducible generation and delivery of micronized macromolecules to the peripheral lung offers an efficient and novel means for the effective and safe delivery of peptides and proteins, with notable successes in delivery of analgesics and insulin. Novel means of designing 'smart drugs' through supercritical fluid engineering promises to further enhance the advantages of inhalation for routine drug administration.

The standardization of in vitro bench-top assessment of nebulizer performance could prove to be extremely beneficial in the advancement of aerosol delivered by nebulizers. At the present time, there is considerable confusion as to how different nebulizer systems perform. Clinical in vivo tests are often compromised, as high patient variability requires large study numbers before differences become significant. In vitro tests should offer less variability and much lower costs, but the test criteria must be standardized and be clinically representative. Standard methods to assess nebulizer performance should therefore be designed to reflect the clinical situation as far as practicable. This would incorporate test methods involving: 1. simulated breathing patterns to estimate the amount of aerosol released and inhaled 2. use of solute tracers to measure aerosol release of salts or drugs themselves 3. use of aerosol sizing instruments such as low-flow cascade impactors that would reflect in vivo deposition. Standards must be written to accommodate the variety of existing devices currently on the market. Because standards take a significant time (typically 1-3 years) to prepare and are intended to operate for a further 10 or more years, they should also aim to accommodate possible advancements in device technology. The potential for such developments should not be overlooked in preparing a standard for in vitro testing of nebulization devices.

By selective attachment of a DNA cleavage agent to specific residues in the yeast TATA box binding protein (yTBP), we demonstrate that, in solution, yTBP binds to the TATA boxes of both the adenovirus major late promoter and the yeast CYC1 promoter with only a modest preference in orientation and binds well to several overlapping binding sites. The general factors TFIIA and TFIIB each increase the rotational and translational selectivity of yTBP but are not sufficient, at least individually, to confer a unique polarity to the preinitiation complex. We conclude that TBP alone cannot define the productive orientation of general factor assembly on a promoter.

This paper describes the relationships between ultra-violet emission, ozone generation and CrVI production in MIG welding which were measured as a function of shield gas flow rate, welding voltage, electrode stick-out and shield gas composition using an automatic welding rig that permitted MIG welding under reproducible conditions. The experimental results are interpreted in terms of the physico-chemical processes occurring in the micro- and macro-environments of the arc as part of research into process modification to reduce occupational exposure to ozone and CrVI production rates in MIG welding. We believe the techniques described here, and in particular the use of what we have termed u.v.-ozone measurements, will prove useful in further study of ozone generation and CrVI formation and may be applied in the investigation of engineering control of occupational exposure in MIG and other welding process such as Manual Metal Arc (MMA) and Tungsten Inert Gas (TIG).

To clarify whether asthma may be caused by fume from welding mild steel and to evaluate the possible strength of such an effect, we quantified airway responsiveness among young shipyard workers with different levels of fume exposure. Clinical investigation comprised a cross-sectional survey of 19- to 27-yr-old workers who were completing 3 to 9 yr of employment in various trades, and a control group of 15- to 17-yr-old school leavers who were applying for apprenticeships within the same trades. Both groups were subdivided into negligible-, ambient-, or high-exposure subgroups according to expected levels of fume exposure. Actual exposures were assessed in a parallel environmental survey. Participants were investigated by questionnaire, skin prick tests, spirometry, and methacholine tests. Complete data sets were obtained from 1,024 of the 1,070 eligible subjects (96%). Among the workers but not the school leaver controls, there was an increasing prevalence of positive methacholine tests across the exposure subgroups-negligible 37%, ambient 44%, high 49% (p < 0.05). Regression analyses showed that in males after allowing for the effects of atopy, current smoking, and age, the estimated geometric mean level of airway responsiveness of regular welders was twice that of workers with negligible exposure after 5 yr of work. This implies that fume exposure may have been critical in causing asthma in about 1% of the welders. A lesser effect (though not significantly so) was noted among the workers with ambient exposure.

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.

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.

Drug nebulizers should be designed to produce an aerosol which efficiently targets drug to the respiratory tract. In this article we review the basic principles of aerosol generation from both jet and ultrasonic nebulizers, and the factors governing respiratory tract penetration and deposition. We review methods for accurate measurement of aerosol dose and size, with emphasis on evaporative effects and the implications to drug nebulizer design. We identify three forms of drug aerosol waste attributable to: generation of non-respirable aerosol, losses to the environment, and dead volume solution; and we consider how each may be minimized through good nebulizer design. Finally, we compare the relative merits of jet and ultrasonic nebulizers, and conclude by predicting a new trend in future drug nebulizer therapy.

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.

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.