Showing papers by "Neil Pearce published in 1998"

Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers

Abstract: The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted.

Chronic bronchitis, work related respiratory symptoms, and pulmonary function in welders in New Zealand.

Abstract: OBJECTIVES: A cross sectional study of respiratory symptoms and lung function in welders was performed at eight New Zealand welding sites: 62 current welders and 75 non-welders participated. METHODS: A questionnaire was administered to record demographic data, smoking habit, and current respiratory symptoms. Current and previous welding exposures were recorded to calculate a total lifetime welding fume exposure index. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) were measured before the start of the shift. RESULTS: There were no significant differences in ethnicity, smoking habits, or years of work experience between welders and non-welders. Symptoms of chronic bronchitis were more common in current welders (11.3%) than in non-welders (5.0%). Of those workers with a cumulative exposure index to welding fume > or = 10 years, 16.7% reported symptoms of chronic bronchitis compared with 4.7% of those with a cumulative exposure index 10 years (OR 9.5, 1.3 to 71.9) were independent risk factors for chronic bronchitis. The report of any work related respiratory symptom was more prevalent in welders (30.7%) than non-welders (15.0%) and workers with these symptoms had significantly lower FEV, (p = 0.004) and FVC (p = 0.04) values. Multivariate analysis identified a high proportion of time spent welding in confined spaces as the main risk factor for reporting these symptoms (OR 2.8, 1.0 to 8.3). CONCLUSION: This study has documented a high prevalence of symptoms of chronic bronchitis and other work related respiratory symptoms in current welders. Also, workers with chronic bronchitis had reduced PEF and FEV/FVC compared with those without chronic bronchitis. These symptoms related both to cigarette smoking and a measure of lifetime exposure to welding fume.

Asthma Epidemiology: Principles and Methods

Abstract: 1. Introduction I. BASIC PRINCIPLES OF ASTHMA EPIDEMIOLOGY 2. Study Design Options 3. Study Design Issues II. ASTHMA MORBIDITY 4. Measuring Asthma Prevalence 5. Measuring Asthma Morbidity 6. Measuring Asthma Risk Factors III. ASTHMA MORTALITY 7. Studying Time Trends in Asthma Deaths 8. Studying the Causes of Asthma Deaths

Prevalence of adult asthma symptoms in relation to climate in New Zealand.

Abstract: We conducted an ecological study linking prevalence of adult asthma symptoms with climate in the 93 New Zealand general electorates. For each electorate, the 12-month period prevalence of self-repo...

Case-control study of salmeterol and near-fatal attacks of asthma.

Abstract: BACKGROUND: A case-control study was undertaken to investigate the hypothesis that the use of the long acting beta agonist salmeterol increases the risk of a near-fatal attack of asthma. METHODS: The cases comprised admissions to the intensive care unit (ICU) for asthma in 14 major hospitals within the Wessex region in 1992. For each of the cases four age-matched controls were selected from asthma admissions to the same hospital during the same period. Information on prescribed drug therapy for the 48 cases and 185 controls was collected from the hospital admission records. RESULTS: The patients admitted to the ICU had greater chronic asthma severity and had generally been prescribed more asthma drugs than the control admissions to hospital. The relative risk of a near-fatal attack of asthma in patients prescribed inhaled salmeterol was 2.32 (95% CI 1.05 to 5.16), p = 0.04. However, the salmeterol relative risk decreased to 1.42 (95% CI 0.49 to 4.10), p = 0.52 when the analysis was restricted to the more chronically severe patients (those in the subgroup of patients with a hospital admission for asthma in the previous 12 months). These findings suggest that the increased unadjusted relative risk with salmeterol is predominantly due to confounding by severity--that is, the increased relative risk is due to patients with more severe asthma (at greatest risk of a near-fatal asthma attack) being preferentially prescribed salmeterol. This interpretation is supported by the finding in this study that, within the control group (selected from the population of asthmatics requiring hospital admission), salmeterol was preferentially prescribed to the most severe patients (a threefold greater prescription of salmeterol to control patients if they had been admitted to hospital in the 12 months prior to the index admission). There was no increased risk of a near-fatal attack of asthma in patients prescribed a beta agonist by metered dose inhaler (OR 0.75 (95% CI 0.31 to 1.78), p = 0.51). In contrast, the relative risks for beta agonists delivered by nebulisation (OR 3.86 (95% CI 1.99 to 7.50), p

Classification of asthma severity: should the international guidelines be changed?

Abstract: Background International guidelines recommend that, in addition to symptoms and medication requirements, measurements of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) are necessary for the objective assessment of asthma severity. The guidelines suggest that parity exists between measurements of FEV1 and PEF when expressed as percentage of predicted normal values, and that asthma severity can be classified as mild, moderate or severe on the basis of FEV1 and PEF measurements of > 80%, 60–80% and < 60% of predicted values, respectively. Objective To determine the relationship between measurements of FEV1 and PEF when expressed as percentage predicted values. Methods A total of 1198 paired measurements of FEV1 and PEF were obtained from the medical records of a random sample of 25 adult asthmatic patients attending a hospital-based chest clinic. Measurements of lung function were expressed as a percentage of predicted normal values, using the European Respiratory Society prediction equations for PEF and FEV1. For the individual paired measurements, the mean differences between PEF and FEV1 percentage predicted were calculated. Measurements of lung function were used to determine asthma severity with 80% predicted FEV1 and PEF values representing severe, moderate and mild asthma, respectively. The proportion of paired measurements in which differences in classification resulted from the use of FEV1 or PEF percentage predicted values was then calculated. Results In asthma of differing severity, there was considerable variability between measurements of FEV1 and PEF when expressed as percentage predicted values; calculation of the FEV1% predicted resulted in lower values than those of the PEF percentage predicted, with a mean difference of −17.2% (95% CI −16.3%, −18.1%). There was agreement in classification of asthma severity in only 49.9% (598/1198) of paired measurements. Different prediction equations, while variably altering the degree of misclassification, did not correct the basic differences in the assessment of asthma severity dependent on the use of FEV1 or PEF. Conclusion FEV1 and PEF values, expressed as percentage predicted, are not equivalent. Pending further evaluation, the authors suggest that published asthma guidelines should avoid the assumption of parity between these two measurements.

Epidemiologic Studies of Beta Agonists and Asthma Deaths

Abstract: From their inception in the modern treatment of asthma, the history of beta agonists has been marked by reports of their undoubted efficacy as bronchodilator drugs, yet dogged by controversy concerning their possible adverse side effects. In particular, two relatively nonselective full agonists, isoprenaline forte and fenoterol, have been associated with epidemics of asthma deaths in six countries during the 1960s (isoprenaline forte) and again in New Zealand during the late 1970s and 1980s (fenoterol). In addition, there has been continuing concern about the possible hazards of beta agonists as a class. In this presentation we review the epidemiologic evidence linking isoprenaline forte with asthma mortality epidemics in six countries during the 1960s, and the evidence linking fenoterol with an epidemic of asthma deaths in New Zealand during the 1970s and 1980s. Finally, we consider the epidemiologic evidence on the possibility of a class effect of beta agonists on asthma mortality. Although we also consider evidence from studies of time trends in beta agonist sales and asthma mortality, we concentrate on analytic (cohort and case-control) studies of beta agonists and asthma deaths, and particularly on the methodological issues involved. In doing so, we have particularly drawn on our experience of involvement in the New Zealand studies of fenoterol and asthma deaths (NP) and on the Scientific Advisory Committee for the Saskatchewan (Canada) study of fenoterol, beta agonists, and asthma death (MJH). We emphasize that there are important pharmacologic differences between beta agonists, and it is therefore essential to distinguish between different beta agonists when considering the epidemiologic evidence.

Long-term reduction in asthma morbidity following an asthma self-management programme

Abstract: The adult "credit card" asthma self-management plan has been shown to be an effective and acceptable system for reducing asthma morbidity when introduced as part of a 6 month community-based asthma programme. The aim of the present study was to assess the effectiveness of the credit card plan 2 yrs after the end of the programme. Markers of asthma morbidity and use of medical services were compared during the 12 months before enrolment, and 2 yrs after completing the 6 month asthma programme. Of the 69 participants who originally enroled in the 6 month asthma programme, 58 were surveyed 2 yrs after completion of the programme. These participants showed a significant improvement in all but one of the asthma morbidity measures. The proportion waking most nights with asthma in the previous 12 months decreased from 29 to 9% (p=0.02), emergency visits to a general practitioner decreased from 43 to 16% (p=0.001), hospital emergency department visits with asthma decreased from 19 to 5% (p=0.02) and hospital admissions decreased from 17 to 5% (p=0.04). Only 24% of patients reported that they usually monitored their peak flow rate daily, but this increased to 73% during a "bad" attack of asthma. A long-term reduction in asthma morbidity and requirement for acute medical services can result following the introduction of the adult credit card asthma self-management plan. Adult patients with asthma are most likely to undertake peak flow monitoring preferentially during periods of unstable asthma, rather than routinely during periods of good control.

ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo

Abstract: A series of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids have been synthesized and evaluated as inhibitors of the recombinant human form of ATP-citrate lyase. The best of these have Ki's in the 200-1000 nM range. As the corresponding thermodynamically favored gamma-lactone prodrugs, a number of compounds are able to inhibit cholesterol and fatty acid synthesis in HepG2 cells and reduce plasma triglyceride levels in vivo. The best of these, compound 77, is able to induce clear hypocholesterolemic and hypotriglyceridaemic responses when administered orally to rat and dog. These results provide evidence to support the hypothesis that compounds which inhibit ATP-citrate lyase have the potential to be a novel class of hypolipidemic agent, which possess combined hypocholesterolemic and hypotriglyceridemic activities.

Work-related respiratory symptoms and lung function in New Zealand mussel openers.

Abstract: Our objectives were to measure the prevalence of work-related and nonwork-related respiratory symptoms in a group of New Zealand mussel openers who open green-lipped mussels, and to relate these to demographic factors, work history, smoking history, and pulmonary function measurements. A cross-section study of respiratory symptoms and lung function was performed on 224 New Zealand mussel openers (99.6% of the study population) at nine work sites. In addition, peak expiratory flow (PEF) change across-shift was measured at one work site in 19 workers. The mean age of all mussel openers was 33.4 years and the mean duration of mussel opening was 5.0 years; 25% were male, 54.7% were current smokers, and 13.9% were ex-smokers. The reported symptom prevalences were: any wheeze, 35%; work-related wheeze, 23%; any chest tightness, 30.5%; work-related chest tightness, 20.2% (work-related symptoms were defined as symptoms improving on rest days or worse at work). Seventy-two mussel openers (32.3%) answered positively to at least 1 of 4 questions concerning work-related symptoms. The mean predicted FEV1 (SD) for this group was 74.3% (14.5), and the mean predicted FVC (SD) was 79.2 (16.0). Nineteen workers completed serial PEF, and the mean percentage change was +1.5% at 7 hr, but 8 workers had falls ranging between 1.1-14% after either 1 or 7 hr of work. Duration of mussel opening of greater than 2 years, but less than 7 years (OR = 2.29; 95% CI, 1.07-4.91), and duration of mussel opening greater than 7 years (OR = 3.72; 95% CI, 1.52-9.11), were significant predictors of work-related respiratory symptoms. Female sex (OR = 1.73; 95% CI, 0.83-3.60) was also associated with the presence of work-related symptoms. No relationship was found with measured hygiene parameters of cleaning agents used. In conclusions, duration of work as a mussel opener was associated with the present of work-related respiratory symptoms, after adjustment of age, sex, and smoking habit. There were marked abnormalities in mean FEV1 and FVC, although no consistent changes across working shift were noted.

The video questionnaire: one approach to the identification of the asthmatic phenotype

Abstract: Since clinicians, physiologists and pathologists cannot agree on how to define asthma, it is not surprising that genetic epidemiologists also have difficulty. Furthermore, the definition of asthma has become more complex as our understanding of its pathophysiology has increased. However, despite this increased complexity, the characteristic features of symptomatic reversible airflow obstruction and bronchial hyperresponsiveness (BHR) by which one recognizes or diagnoses the disease, remains the basis of the current WHO definition of asthma [1]: ‘Asthma is a chronic inflammatory disorder of the airways in which many cells play a role, in particular mast cells, eosinophils, and T lymphocytes. In susceptible individuals this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough particularly at night and/or in the early morning. These symptoms are usually associated with widespread but variable airflow limitation that is at least partly reversible either spontaneously or with treatment. The inflammation also causes an associated increase in airway responsiveness to a variety of stimuli.’ A fundamental problem is that, even when a single definition such as that proposed by the WHO is accepted, the diagnosis of asthma involves an overall assessment of the patient’s medical history, physical examination, and lung function results, and there are no universally accepted rules for combining the information from these various sources. A related problem is that the term ‘asthma’ unifies what may be a disparate group of disorders which produce similar clinical features. Furthermore, the phenotypic expression of asthma may vary by age [2]. By necessity most genetic epidemiological studies have defined the asthmatic phenotype on clinical information which can either be collected or measured at a single point in time. The main options in this regard are the administration of questionnaires based on self-reporting of symptoms or a previous diagnosis of asthma, tests of lung function including the response to bronchodilator therapy, bronchial responsiveness testing, physician assessment, or markers of related conditions such as atopy. In this manuscript issues relevant to each of these approaches are briefly discussed, with the exception of atopy which is the topic of other reviews in this series. Findings from preliminary studies of the use of a video questionnaire, a novel approach to the identification of the asthma phenotype, are also presented.

Health effects of occupational pentachlorophenol exposure in timber sawmill employees: a preliminary study.

Abstract: AIMS To study the health effects of pentachlorophenol (PCP) exposure in the timber sawmill industry. METHOD A questionnaire-based, non-random survey was undertaken amongst a group of current and ex-workers who had identified their health concerns as being related to PCP exposure. RESULTS Low, medium and high exposure groups were identified. A significant dose-response was found between past exposure to Pentachlorophenol and reported symptoms of fever/sweating (47% in the high exposure group), weight loss (33% in the high exposure group), persisting fatigue (74% in the high exposure group), nausea (40% in the medium and high exposure groups) and responses to a screening test for neuropsychological dysfunction (Questionnaire 16) (81% in the high exposure group). No associations were observed with other chronic diseases, apart from emphysema and chronic bronchitis. CONCLUSIONS This study is based on a self selected sample of PCP-exposed workers whose precise exposure levels are unclear. Thus the findings presented should be regarded as preliminary. Nevertheless, they support clinical experiences and point to the need for further investigation.