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Biomedical subjects

D J Hendrick

Publications and source records attributed to D J Hendrick.

At least 37 records · Page 2Linked to original sources
PubMed1996

Occupational tuberculosis and a failed postgraduate medical examination.

A 40 year old pathologist presented with a tuberculous pleural effusion approximately one year after performing an autopsy as part of a postgraduate medical examination. She had made a diagnosis of disseminated tuberculosis but was told that this was incorrect and failed the examination. Bladder tissue from the cadaver was subsequently found to have grown M tuberculosis though none was cultured from lung tissue. No particular precautions against airborne infection were taken at the time of the autopsy and we speculate not only that the pathologist's original diagnosis was correct but that she became infected with M tuberculosis during the examination.

Adult↗
PubMed1996

Asthma, airways responsiveness and air pollution in two contrasting districts of northern England.

BACKGROUND: To assess the possible magnitude of differences between normal populations an epidemiological investigation of asthma was conducted in two strongly contrasting districts of northern England--rural West Cumbria on the west coast and urban Newcastle upon Tyne on the east coast. METHODS: A cross sectional survey of randomly identified men aged 20-44 years was conducted in two phases: phase 1, a postal survey of respiratory symptoms and asthma medication in 3000 men from each district; and phase 2, a clinical assessment of 300 men from each district comprising investigator administered questionnaires, skin prick tests, spirometry, and methacholine challenge tests. RESULTS: The phase 1 (but not phase 2) study showed a small excess of "ever wheezed" in Newcastle (44% versus 40%), but neither phase showed differences between the two districts for recent wheeze or for other symptoms characteristic of asthma. There were also no differences with regard to diagnosed asthma, current asthma medication, spirometric parameters, or airways responsiveness. The prevalence of quantifiable airways responsiveness (PD20 < or = 6400 micrograms) was 27.7% in West Cumbria and 28.2% in Newcastle. Regression analyses showed that PD20 was negatively associated with atopy and positively with forced expiratory volume in one second (FEV1); that an association between PD20 and current smoking could be explained by diminished FEV1; and that PD20 was not related to geographical site of residence. CONCLUSIONS: Neither airways responsiveness nor the other parameters of diagnostic relevance to asthma varied much between the two study populations, despite the apparent environmental differences. The most obvious of these were the levels of outdoor air pollution attributable to vehicle exhaust emissions, the ambient levels of which were 2-10 fold greater in Newcastle. Our findings consequently shed some doubt over the role of such pollution in perceived recent increases in asthma prevalence. It is possible, however, that an air pollution effect in Newcastle has been balanced by asthmagenic effects of other agents in West Cumbria.

Adult↗
PubMed1996

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.

Adult↗
PubMed1996

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.

Administration, Inhalation↗
PubMed1995

Asthmatic symptoms, airway responsiveness and recognition of bronchoconstriction.

During an epidemiological investigation of asthma in an occupational setting, 1126 subjects completed a modified Medical Research Council respiratory questionnaire, then underwent airway responsiveness measurements as PD20FEV1 to methacholine. Previous experience of bronchoconstriction was assessed in the 481 subjects with measurable airway responsiveness (PD20FEV1 < 6400 g) by asking 'have you ever felt like this before' at the end of their methacholine challenge tests, i.e. when the subjects were bronchoconstricted by FEV1 decrements of at least 20%. The responses to this question bore no relationship to the previously administered questionnaire responses about wheezing, chest tightness, coughing, or breathlessness. However, there was an inverse relationship with PD20FEV1 measurements (P < 0.001), the positive response rate to the question falling from 92% among those with PD20FEV1 < 50 micrograms to 27% among those with PD20FEV1 in the highest measurable range (3200-6400 micrograms). This suggests that airway responsiveness measurements are a more reliable guide to subjects' previous experience of substantial bronchoconstriction (i.e. asthma) than are the responses to respiratory questionnaires.

Adult↗
PubMed1995

Effects of diurnal variation and prolonged refractoriness on repeated measurements of airways responsiveness to methacholine.

BACKGROUND: A number of studies have suggested that diurnal variation in airways responsiveness underlies the circadian rhythm of ventilatory function in asthma. Measurements of airways responsiveness are therefore often performed at standardised times in order to avoid this possible effect, but this is not practical for epidemiological studies. Refractoriness to methacholine has also been reported and this, too, could confound the results of methacholine tests repeated over short intervals. This investigation was carried out to evaluate the possible magnitude of diurnal variation and refractoriness in repeated measures of airways responsiveness to methacholine. METHODS: To investigate diurnal variation in airways responsiveness, 24 asthmatic subjects aged 18-45 underwent five methacholine tests over three days which were not necessarily consecutive: day 1 at 08:00 hours; day 2 at 08:00 hours, 14:00 hours, 20:00 hours; day 3 at 20:00 hours. To investigate refractoriness a retrospective analysis was undertaken of all paired methacholine tests performed in individuals within our unit between 1984 and 1990 where there had been no intervention likely to affect the results. RESULTS: The first investigation revealed no diurnal change in airways responsiveness although there was a change in FEV1. Mean PD20 did, however, increase 1.57 fold from 08:00 hours on day 1 to 08:00 hours on day 2 for subjects studied on consecutive days. The second investigation confirmed that a test interval of up to 24 hours (but not of 48 or more hours) was associated with a refractory index (PD20 test 2/PD20 test 1) of > 1. CONCLUSIONS: No diurnal variation in airways responsiveness was detected for measurements made between 08:00 hours and 20:00 hours, but an interval between successive tests of up to 24 hours was associated with refractoriness. Diurnal variation is not likely to exert an important confounding effect on methacholine tests carried out between 08:00 hours and 20:00 hours, but confounding could result from refractoriness if tests are repeated at intervals up to 24 hours.

Adult↗
PubMed1995

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↗
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

Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics.

Using BAL, we studied the effects of 8 wk of treatment with salmeterol on airway inflammation in nine asthmatic subjects in a double-blind crossover placebo-controlled protocol. The study patients were all receiving regular inhaled corticosteroid therapy (400 to 1,000 micrograms beclomethasone dipropionate per day) and inhaled albuterol for symptomatic relief, i.e., subjects who might be considered suitable for treatment with salmeterol. The asthmatic group had significant differences in numbers of epithelial cells and eosinophils in BAL compared with a group of 15 normal control subjects (p < 0.01). During salmeterol treatment mean morning and evening peak flow rates were increased (p < 0.05). There was no significant change in BAL cell profile and no change in percentages of CD4 and CD8 lymphocytes or proportion of lymphocytes expressing HLA-DR after salmeterol. In conclusion, we were unable to demonstrate any significant anti-inflammatory effect of regular salmeterol therapy on airway inflammation using BAL in these asthmatic patients. At the same time, there was equally no evidence of a deterioration in the underlying inflammatory disease process.

Adrenergic beta-Agonists↗
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↗
PubMed1994

Management of occupational asthma.

The importance of occupational asthma and its management is usefully set in perspective by considering recent trends of increasing asthma incidence, morbidity and mortality in the population at large. The contribution to incidence made by asthma of occupational origin is of the order 20-100 cases per million workers per year; the individual worker's lifetime risk approaching 5% in some industrial environments. Management of the affected industry inevitably follows different pathways from that of the affected individual, though both need to start from a definitive diagnosis. For the affected industry, managers must identify the causative agent and assess the extent of the problem. Affected workers can then be removed from hazardous settings, and meaningful strategies of prevention can be introduced. The most promising preventive measures involve improvements in industrial hygiene or the substitution of alternative agents in the manufacturing process. The role of worker selection (i.e. the exclusion of applicant workers who may be unduly susceptible because they smoke, or have existing airway hyperresponsiveness or atopy) is small and controversial. More valuable is a strict surveillance programme of workers perceived to be at risk, so that emerging disease is recognized promptly, before it poses any major threat of permanent ill-health. Management choices beyond conventional medication and the avoidance of irritant environmental triggers are greatly limited for the affected individual worker. A change of job environment with complete cessation of exposure to the relevant asthma-inducing agent is to be favoured and offers the best chance of full recovery, but may not be practical if the worker is to avoid permanent unemployment.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗