Asthmagenicity of coal mine roof-bolting resins: an assessment using inhalation provocation tests.

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 confidential enquiry into certified asthma deaths in the North of England, 1994-96: influence of co-morbidity and diagnostic inaccuracy.

To understand more fully the nature of events leading to asthmatic death, we conducted a confidential enquiry prospectively throughout 1994-96 among the surviving relatives and respective general practitioners of subjects whose deaths could be attributed to asthma, whether wholly or partly. We also reviewed relevant hospital records and autopsy reports, and we submitted all the gathered information to an enquiry panel for evaluation. The subjects were identified from death certificates issued in five districts of the Northern Health Region of England (population 1 million) on which asthma was recorded as the primary cause of death. The enquiry panel agreed that asthma had been a critical factor in causing death in only 33 of the 79 certified cases for which there were sufficient data. The level of concordance was substantially greater for subjects aged < 65 years (76%) than for those who were older (17%). In 16 of the 33 cases asthma alone appeared to be responsible for death, but in 17 cases a wide variety of additional, co-morbid, disorders appeared to have contributed. They included, during the 24 h preceding death, gastric aspiration, septicaemia, a single dose of a beta-blocker, the abuse of organic solvents or illicit drugs and possibly, an inadvertent exposure to horse allergen. More chronic causes of co-morbidity included ischaemic heart disease, chronic obstructive pulmonary disease (COPD), thoracic cage deformity and alcohol abuse. There were possible errors of judgement in two cases by the supervising physician (6%) and in three cases by the patient (9%). Poor compliance and psychosocial disruption probably exerted an additional adverse influence in nine cases (27%). We conclude: (1) that asthma death certification in subjects aged 65 years or more is very unreliable, (2) that for approximately half of the deaths in which asthma exerted a critical role there were critical co-morbid disorders and (3) that errors of judgement, poor compliance, or psychosocial disruption are likely to have exerted an additional adverse influence in an important minority of cases.

The duration of action of inhaled formoterol dry powder.

The duration of action of formoterol inhaled as a dry powder formulation is compared with placebo and a reference treatment of salbutamol dry powder in patients with bronchial asthma. This single-centre, double-blind, cross-over study recruited 23 outpatients with clinically stable asthma. These patients were treated with 12 micrograms formoterol, 400 micrograms salbutamol or placebo in a randomly allocated sequence, with at least 2 days between treatments. Forced expiratory volume in 1s of expiration (FEV1) was measured at specified time points from 15 min to 15 hours post-treatment. Formoterol produced significantly higher values of FEV1 at the primary endpoint of 12 hours compared with placebo and salbutamol. No differences between FEV1 values were seen for the active treatments of formoterol and salbutamol for the first 5 hours post-inhalation. Formoterol was significantly superior to placebo at all time points, whereas salbutamol was significantly superior to placebo for the first 5 hours. This study demonstrates that formoterol, when given as a dry powder inhalation, has a significantly longer duration of acute bronchodilator action than 400micrograms salbutamol inhaled as a dry powder. The duration of action of formoterol of at least 12 hours seen in this study is at least as long as that reported following administration from a metered dose inhaler (MDI) at the same dose level. The study also demonstrates that 12micrograms formoterol dry powder is well tolerated by patients.

An epidemiologic investigation of asthma in welders.

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.

Speeds of action of single doses of formoterol and salbutamol compared with placebo in reversing methacholine-induced bronchoconstriction.

We compared the speeds of action of two doses of the long acting beta-agonist formoterol (12 micrograms and 24 micrograms) with those of salbutamol (400 micrograms) and placebo using a double-blind, randomized, cross-over study design in 16 asthmatic subjects. A methacholine test was used on four separate study days to produce a standardized degree of bronchoconstriction (a decrement in FEV1 > or = 20%) and one of the study medications as dry powder was administered immediately afterwards via an Aerolizer inhaler device. The speeds of recovery were estimated from measurements of FEV1 over the following 2-90 min. All active treatments produced significantly greater bronchodilation than placebo as early as 2 min after administration, and their peak effects within 10 min; and no significant differences were noted between them. Mean recovery times by 50% of the FEV1 decrement provoked by methacholine were significantly shorter for the active medications: 5.7 min (formoterol 24 micrograms), 6.4 min (salbutamol 400 micrograms), 10.2 min (formoterol 12 micrograms), and 53.1 min (placebo); the respective times for recovery by 80% being 18.0, 17.4, 22.1, and 83.3 min. We conclude that single doses of the dry powder formulations of all three active treatments produce rapid and effective bronchodilation. This conclusion should not, however, be extrapolated to the regular use of these medications, since differential down-regulation and tachyphylaxis may then exert an influence.