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Biomedical subjects

D P Strachan

Publications and source records attributed to D P Strachan.

At least 37 records · Page 2Linked to original sources

Comparative epidemiology of atopic and non-atopic wheeze and diagnosed asthma in a national sample of English adults.

BACKGROUND: There is debate as to whether asthma has distinct atopic and non-atopic forms and whether in epidemiological studies asthma cases should be defined by a physician diagnosis or by self-reported asthma symptoms. METHODS: A total of 24,952 people aged 11 and over were surveyed as part of the 1995-6 health surveys for England. Participants were asked if they had experienced wheezing in the past year and if they had ever been given a diagnosis of asthma by a doctor. Serum total IgE and house dust mite (HDM) specific IgE were measured. RESULTS: Wheeze in the past year without an asthma diagnosis was more common in men and older age groups, whereas wheeze with an asthma diagnosis was more common in women and younger people. Both types of wheeze were more common in the lower social classes, among ex-smokers and current smokers, and in urban areas. Thirty two percent of people reporting wheezing and 22% of those with diagnosed asthma had neither raised total IgE nor HDM IgE. Among the non-atopic subjects the prevalence of wheeze rose with age and lower social class, largely due to an increase in wheeze without diagnosed asthma. In contrast, among atopic subjects there was no overall trend with age or social class, but wheeze with diagnosed asthma decreased with age. CONCLUSIONS: Clear epidemiological differences are evident between adult wheeze with and without an asthma diagnosis and between atopic and non-atopic wheeze. Subjects with diagnosed asthma are more likely to be atopic, but the results challenge the premise that adult asthma is almost always associated with some IgE mediated reaction.

Adolescent↗

Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins.

BACKGROUND: Previous twin studies of asthma and allergy implicate both genetic and environmental factors in disease risk, but few have related the occurrence of clinical disease to objective markers of allergic sensitization in twins. OBJECTIVE: We sought to investigate the concordance and interrelationships of self-reported allergic disease and total and aeroallergen-specific IgE levels within pairs of British adult female twins. METHODS: Three hundred forty monozygotic and 533 dizygotic pairs, aged 18 to 72 years, completed questionnaires about allergic disease. Of these, 282 monozygotic and 270 dizygotic pairs were tested for total IgE and specific IgE to Der p 1, mixed grass pollen, and cat dander by means of fluoroimmunoassay. RESULTS: Concordance rates for all variables were higher for monozygotic than for dizygotic twins, significantly (P < .05) so for hay fever, eczema, and specific IgE positivity but not (P > .05) for self-reported asthma or allergies. Within-pair correlations of log-transformed IgE were 0.59 for monozygotic twins and 0.29 for dizygotic twins, implying heritability of 60%. Within both monozygotic and dizygotic pairs discordant for hay fever or reported allergies, the affected twin had significantly higher total and specific IgE levels. Within pairs who were doubly discordant for 3 allergic diseases, associations between diseases were of similar strength for monozygotic and dizygotic pairs. CONCLUSIONS: These results confirm that genetic factors influence susceptibility to aeroallergen sensitization and clinical allergic disease. However, genetically identical twins are often discordant in their expression of atopy, suggesting a substantial modifying role for environmental factors.

Adolescent↗

The relationship of per capita gross national product to the prevalence of symptoms of asthma and other atopic diseases in children (ISAAC).

BACKGROUND: Increasing prevalence and worldwide variation in asthma and other atopic diseases suggest the influence of environmental factors, at least one possibly related to socioeconomic wellbeing. This paper examines the relationship of symptoms of asthma, rhinitis and eczema with gross national product per capita (GNP per capita). METHODS: The prevalences of atopic symptoms in 6-7- and 13-14-year-old children were assessed in 91 centres (from 38 countries) and 155 centres (from 56 countries), respectively, in the International Study of Asthma and Allergy in Childhood (ISAAC). These symptoms were related to 1993 GNP per capita for each country as reported by the World Bank. The relationships between symptoms of atopic diseases and infant mortality, the human development index and 1982 GNP per capita were also considered. RESULTS: The countries in the lowest quartile of GNP per capita have the lowest median positive responses to all the questions on symptoms of asthma, rhinitis and eczema. There was a statistically significant positive association between wheeze in the last 12 months and GNP per capita in the 13-14-year age group, but not in the 6-7-year age group. There was also a positive association between GNP per capita and eczema in both age groups. CONCLUSIONS: The positive associations between GNP per capita and atopic symptoms being of only moderate strength suggests that the environmental factors are not just related to the wealth of the country.

Adolescent↗

Ischaemic heart disease and Cag A strains of Helicobacter pylori in the Caerphilly heart disease study.

OBJECTIVE: To look for the presence of the more virulent strains of Helicobacter pylori (H pylori) in men who developed ischaemic heart disease over a 10 year period and in controls. DESIGN: The Caerphilly prospective heart disease study recruited 2512 men aged 45-59 years during 1979-83. Western blot analysis or enzyme linked immunosorbent assay (ELISA) was performed on serum taken from those who subsequently died of ischaemic heart disease, or developed non-fatal myocardial infarction, to determine H pylori and Cag A status. Similar information was available on age matched controls. RESULTS: During the first decade of the study, 312 men died of ischaemic heart disease or developed non-fatal myocardial infarction. Serum was available from 172 of these (55%). There was no evidence of an association between Cag A seropositivity and incident ischaemic heart disease or ischaemic heart disease mortality, either before or after adjustment for potential confounders (adjusted odds ratios 1.18 (95% confidence interval (CI) 0.76 to 1.85) and 1.13 (95% CI 0.61 to 2.07), respectively). Further, the odds ratios for ischaemic heart disease incidence and ischaemic heart disease mortality by H pylori seropositivity did not appear to depend on the presence or absence of Cag A strains (p = 0.76 and 0.77, respectively). CONCLUSIONS: In this cohort of middle aged men, followed over a 10 year period, there is little evidence of an association between Cag A seropositivity and either incident ischaemic heart disease or ischaemic heart disease mortality.

Antigens, Bacterial↗

Immunization and symptoms of atopic disease in children: results from the International Study of Asthma and Allergies in Childhood.

OBJECTIVES: This study tested the hypothesis that immunization is related to the prevalence of atopic disease in childhood. METHODS: We used data from the International Study of Asthma and Allergies in Childhood to perform an ecologic analysis of national and local immunization rates for tuberculosis, diphtheria and tetanus toxoids and pertussis (DTP), and measles and prevalence of atopic disease symptoms (asthma, allergic rhinoconjunctivitis, and atopic eczema). RESULTS: In 13- to 14-year-old children, there were significant negative associations with local birth-year immunization rates for DTP and measles but none with rates for tuberculosis. No associations were found in 6- to 7-year-old children. No associations with national immunization rates were found. CONCLUSIONS: International variations in childhood atopic diseases are unlikely to be explained by variations in immunization.

Adolescent↗

C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors.

Whether or not C-reactive protein (CRP) predicts heart disease in adults because it is a marker of damage or atherosclerosis is difficult to assess. In children, there is no confounding with coronary disease or active smoking. We measured CRP in 699 children aged 10-11 years. CRP levels were 47% higher in girls than boys, and rose with age by 15%/year. CRP levels were 270% (95% CI, 155-439%) higher in the top fifth than the bottom fifth of Ponderal index (weight/height(3)). After adjustment, CRP levels remained 104% (95% CI, 23-236%) higher in the 56 children of South Asian origin. CRP was unrelated to: birth weight, height, social class, Helicobacter pylori infection or passive smoke exposure. CRP was correlated with several cardiovascular risk factors, but only fibrinogen (r = 0.33, P = 0.0001), HDL-cholesterol (r = -0.13, P = 0.0006), heart rate (r = 0.12, P = 0.002) and systolic blood pressure (r = 0.08, P = 0.02) remained statistically significant after adjustment. We conclude that adiposity is the major determinant of CRP levels in children while physical fitness has a small independent effect. The strong relationships with fibrinogen and HDL-cholesterol suggest a role for inflammation throughout life in the development of atherosclerosis and cardiovascular disease. Longitudinal studies are needed to determine whether these associations reflect long term elevations of these risk factors in some individuals, or short term fluctuations in different individuals.

Age Distribution↗

Is there a geographical variation in eczema prevalence in the UK? Evidence from the 1958 British Birth Cohort Study.

Some studies have suggested that the prevalence of atopic eczema may vary between geographical regions. This descriptive study investigates the regional and subregional geography of reported and examined eczema prevalence at the age of 7, 11 and 16 years in Britain using data from the 1958 birth cohort study (n = 828). Estimates of the relative risk of reported eczema associated with residence in each region of the country were calculated and the regional distribution of reported and examined eczema prevalence was compared. The reported prevalence of eczema was mapped at the smaller county level. Comparisons were made with the county-level distribution of asthma and hay fever prevalence. The study showed a marked and statistically significant variation in eczema prevalence across the regions in Britain which was present for examined as well as reported eczema. The highest risk was associated with four regions: North Midlands; Eastern; London and the South-East; and Southern. This regional pattern was not altered significantly after adjustment for social class and family size. The geographical distribution of eczema prevalence was largely maintained when analysed at the county level. Few similarities were found between the county-level distribution of eczema prevalence and that for asthma and hay fever. Explanations for this strong regional variation now need to be sought in terms of environmental and life-style associations.

Adolescent↗

C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men.

BACKGROUND: There is much interest in reported associations between serum C-reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Disease Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease. METHODS: Plasma specimens collected during 1979-83 from 1395 men with sufficient sample remaining were assayed for serum C-reactive protein by ELISA. Subsequent mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records and electrocardiographic changes at 5-yearly follow-up examinations. RESULTS: There was a positive association between C-reactive protein and incident ischaemic heart disease (P<0.005) mainly with fatal disease (P<0.002). There was also a positive association with all-cause mortality (P<0.0001). C-reactive protein was significantly associated with a number of non-circulating risk factors including body mass index (P<0.0001), smoking (P<0.0001), low forced expiratory volume in 1 s (P<0.0001), height (P=0.025), low childhood social class (P=0.014) and age (P=0.036). C-reactive protein was also associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0.0001) and insulin (P=0.0058). After adjustment for non-circulating risk factors the association with all-incident ischaemic heart disease and ischaemic heart disease death became non-significant, but the association with all-cause mortality remained (P=0.033). Further adjustment for fibrinogen however removed any hint of an increasing trend in odds for all three outcomes. CONCLUSION: C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.

Biomarkers↗

Western blotting is useful in the salivary diagnosis of Helicobacter pylori infection.

BACKGROUND: The salivary diagnosis of Helicobacter pylori infection offers attractive possibilities for the epidemiological study of infection in children. Salivary enzyme linked immunosorbent assay (ELISA) is less reliable then serum ELISA, owing to variable transudation of immunoglobulin. In addition, children are more difficult to study because of lower specific serum antibody concentrations to H pylori. The performance of salivary western blotting in comparison with serum western blotting and serum ELISA was investigated in school children. SUBJECTS AND METHODS: Paired serum and saliva specimens were obtained from 669 [corrected] school children aged 9-11 in 10 British towns. All saliva and serum specimens were first analysed by ELISA; subsequently, western blotting of both specimens was performed on 31 and 34 specimens, respectively, to establish the criteria for positivity for western blotting. The remaining 121 specimens were then tested blindly and saliva was compared with the serum. RESULTS: The sensitivity and specificity of salivary ELISA in the 669 [corrected] specimens was 32 of 50 (64%) and 530 of 619 (86%) [corrected], respectively, when compared with serum ELISA. The western blotting validation was performed on 28 subjects with positive serum and positive salivary ELISA, 28 saliva positives with negative serum, 16 saliva negatives with positive serum, and 50 doubly negative subjects. Compared with serum western blots, the sensitivity and specificity of salivary western blots was 38 of 47 (81%) and 68 of 75 (91%), respectively. Using serum ELISA as the gold standard, the sensitivity and specificity were 32 of 44 (73%) and 72 of 78 (92%), respectively, the specificity being significantly higher than salivary ELISA (p < 0.001). CONCLUSION: Salivary western blotting for IgG is useful in the diagnosis of H pylori infection and is superior to ELISA. It also permits the identification of pathogenic strains.

Blotting, Western↗

Which spirometric indices best predict subsequent death from chronic obstructive pulmonary disease?

BACKGROUND: Previous epidemiological studies have related mortality from chronic obstructive pulmonary disease (COPD) to forced expiratory volumes (FEV(1) or FEV(0.75)) and it is unknown whether other spirometric indices might have greater predictive power. METHODS: A case-control study of fatal COPD was conducted within a cohort of London civil servants who performed forced expiratory spirograms in 1967-9 and were followed up for mortality over 20 years. The spirograms of 143 men who died of COPD (ICD8 491, 492 or 519.8) were compared with those of 143 controls individually matched for age, height, and smoking habit who survived longer than their matched case. Flow rates in different parts of the spirogram were compared within case-control pairs and analysed as predictors of fatal COPD by conditional logistic regression. RESULTS: Within pair case:control ratios of FEV(1), mid expiratory flow rates (e.g. FEF(50-75)) and FEF(75-85) were highly intercorrelated (r>0.7) but correlations with FEF(85-95) were weaker (r<0.5). All indices except the FEV(1)/FVC ratio were stronger predictors of death from COPD within the first 10 years than of later deaths (15-19 years). After adjustment for FEV(1), mid expiratory flow rates independently predicted fatal COPD but end expiratory flow rates did not. The FEV(1) adjusted mortality ratios associated with a 10% decrement in each index were 2.24 (95% CI 1.54 to 3.76) for FEF(50-75), 1.20 (95% CI 1.00 to 1.42) for FEF(75-85), and 1.10 (95% CI 0.96 to 1.26) for FEF(85-95). CONCLUSION: This study confirms FEV(1) and mid expiratory flow rates as powerful predictors of mortality from COPD, and suggests that measurement of end expiratory flow rates would add little extra predictive information.

Adult↗

Chlamydia pneumoniae serology, lung function decline, and treatment for respiratory disease.

Associations have been reported between Chlamydia pneumoniae seropositivity and both acute and chronic obstructive airway diseases. Plasma specimens collected between 1979 and 1983 from 1, 773 men 45 to 59 yr of age in Caerphilly, South Wales, were tested for IgG and IgA antibodies to C. pneumoniae (TW183) by microimmunofluorescence. Subsequent mortality and medication for obstructive airway disease were ascertained at 5-yr follow-up examinations. Spirometry was performed at the first and second examinations and analyzed both cross-sectionally and longitudinally; 642 men (36%) had IgG antibodies at a titer of 1:16 or above, of whom 362 also had detectable IgA antibodies. No statistically significant associations were found between either IgG titer or IgA titer and any of the outcome measures: inhaler therapy at entry; commencement of inhalers during follow-up; death from respiratory causes; baseline FEV(1), FVC, and FEV(1)/FVC ratio; and decline in FEV(1) (p > 0.1 throughout). Men with high IgG titers (>/= 1:64) had a slower rate of decline of FEV(1) than did seronegative subjects (adjusted mean difference in 5-yr change in FEV(1): +22 ml, 95% confidence interval: -31 ml to +76 ml). Men with high IgA titers (>/= 1:16) had a slightly faster rate of decline (-12 ml, - 96 ml to +71 ml). This first prospective assessment suggests that chronic C. pneumoniae infection is not a major risk factor for progressive airflow obstruction.

Antibodies, Bacterial↗

The role of environmental factors in asthma.

Although the everyday experience of asthmatic patients provides ample anecdotal evidence that environmental exposures provoke bronchospasm, it has proved more difficult to assess the impact of air quality on the timing of asthma attacks and the prevalence of asthma in populations. Spectacular 'asthma epidemic days' are sometimes attributable to exceptional outdoor aero-allergen exposures. By comparison, effects of inorganic particles and gaseous pollutants in outdoor air on the incidence of asthma attacks are subtle and poorly quantified. Environmental tobacco smoke and mould growth are the indoor factors most consistently associated with respiratory morbidity, but their roles in initiating allergic asthma remain uncertain. Evidence relating asthma risk to fumes from gas cooking, and to allergens from dust mites and household pets remains confused and controversial. It is unlikely that trends in either outdoor or indoor air pollution have contributed substantially to the rise in prevalence of asthma and allergic disease in recent decades.

Adolescent↗

Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the caerphilly prospective heart disease study.

OBJECTIVES: To investigate the effect of Chlamydia pneumoniae infection on future development of ischaemic heart disease and mortality. DESIGN: Prospective longitudinal study. SETTING: Caerphilly, South Wales. SUBJECTS: Plasma specimens were collected during 1979-83 from 1773 men aged 45-59 years. These were tested for IgG and IgA antibodies to C pneumoniae (TW183) by microimmunofluorescence. OUTCOME MEASURES: 13 year mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records, and electrocardiographic changes at follow up every 4 to 5 years. RESULTS: 642 men (36.2%) had IgG antibodies at a titre of >/=1 in 16, of whom 362 (20.4% of all men) also had detectable IgA antibodies. The prevalence of ischaemic heart disease (a history of past or current disease) at entry was similar at all IgG antibody titres but was positively related to IgA antibody titre. IgA antibody titre was positively correlated with plasma viscosity but not with other cardiovascular risk factors. Incidence of ischaemic heart disease was not associated with either IgG antibody titre or IgA antibody titre, but there were stronger and significant relations of IgA antibodies with all cause mortality and fatal ischaemic heart disease, which persisted after adjustment for conventional cardiovascular risk factors. The odds ratios associated with detectable IgA antibodies were 1.07 (95% confidence interval 0.75 to 1.53) for all incident ischaemic heart disease, 1. 83 (1.17 to 2.85) for fatal ischaemic heart disease, and 1.50 (1.10 to 2.04) for all cause mortality. CONCLUSION: This is the first prospective demonstration of an association between IgA antibodies to C pneumoniae, a putative marker of chronic infection, and subsequent risk of death from ischaemic heart disease. In contrast to earlier case-control studies, IgG antibodies were not associated with either prevalent or incident ischaemic heart disease.

Antibodies, Bacterial↗

Fresh fruit intake and asthma symptoms in young British adults: confounding or effect modification by smoking?

Antioxidant vitamins have been postulated as a protective factor in asthma. The associations between the frequency of fresh fruit consumption in summer, and the prevalence of self-reported asthma symptoms were investigated. The analysis was based on 5,582 males and 5,770 females, born in England, Wales and Scotland between March 3-9, 1958 and aged 33 yrs at the time of survey. The 12-month period prevalence of wheeze and frequent wheeze were inversely associated with frequent intakes of fresh fruit and salad/raw vegetables and positively associated with smoking and lower social class. After adjustment for mutual confounding and sex, associations with smoking persisted, but those with social class and salad/raw vegetable consumption lost significance. The frequency of fresh fruit intake was no longer associated with wheeze after adjustment, but was inversely associated with frequent wheeze and speech-limiting attacks. The association with frequent wheeze differed significantly between smoking groups (never, former, current) and appeared to be confined to exsmokers and current smokers. These findings support postulated associations between infrequent fresh fruit consumption and the prevalence of frequent or severe asthma symptoms in adults. Associations appeared to be restricted to smokers, with effect modification as a more likely explanation of this pattern than residual confounding by smoking.

Adult↗