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Biomedical subjects

D P Strachan

Publications and source records attributed to D P Strachan.

At least 19 recordsLinked to original sources

Relation of Helicobacter pylori infection to 13-year mortality and incident ischemic heart disease in the caerphilly prospective heart disease study.

BACKGROUND: Associations have been suggested between Helicobacter pylori seropositivity, cardiovascular risk factors, and ischemic heart disease (IHD). The effect of this common infection on mortality is uncertain. METHODS AND RESULTS: Plasma specimens collected during 1979 to 1983 from 1796 men in Caerphilly, South Wales, were analyzed for IgG antibodies to H pylori. Cause of death and occurrence of incident IHD events were ascertained over an average of 13.7 years from death certificates, hospital records, and ECG changes at 5-yearly follow-up examinations. Seventy percent of men were seropositive. The prevalence of IHD at entry was similar in men with and without H pylori antibodies (odds ratio [OR], 1.10; 95% CI, 0.87 to 1.40). Seropositivity was significantly (P<0.05) associated with poorer socioeconomic status currently and in childhood, shorter stature, and poorer ventilatory function at entry but not with age, smoking, body mass index, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, fibrinogen, plasma viscosity, or heat shock protein antibodies. Thirteen-year incidence of IHD was not significantly associated with H pylori (OR, 1.05; 95% CI, 0.80 to 1.39), but there was a stronger relationship with all-cause mortality (OR, 1.46; 95% CI, 1.12 to 1.92) and fatal IHD (OR, 1.54; 95% CI, 1.03 to 2.30). After adjustment for cardiovascular risk factors and both adult and childhood socioeconomic status, ORs were slightly reduced and lost statistical significance (OR=1.32 [95% CI, 0.99 to 1.78] for all-cause mortality and OR=1.52 [95% CI, 0.99 to 2.34] for fatal IHD). CONCLUSIONS: H pylori infection is unlikely to be as strong a risk factor for IHD as some previous studies have suggested, but its relationship to mortality, including fatal IHD, deserves further investigation. The mechanism underlying these associations is unlikely to involve hypertension, circulating lipid profile, fibrinogen, or cross-reacting antibodies to bacterial heat shock proteins.

Helicobacter Infections

Effect of pneumonia and whooping cough in childhood on adult lung function.

BACKGROUND: Previous studies have suggested that respiratory infection during childhood is associated with respiratory disease in adulthood, but the link is unclear because of retrospective ascertainment of childhood infection, selection bias, and confounding factors. METHODS: We studied the effects of childhood pneumonia and whooping cough in 1392 British adults followed from birth in 1958. Of these, 193 had a history of pneumonia and 215 a history of whooping cough by the age of seven years. When the subjects were 34 or 35 years old, their forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured before and after they inhaled albuterol. RESULTS: A history of pneumonia was associated with deficits (+/-95 percent confidence limits) in both FEV1 (102+/-73 ml, P=0.006) and FVC (173+/-70 ml, P=0.001) when the analysis was adjusted for sex, height, and smoking, with no change in the ratio of FEV1 to FVC. These deficits persisted after inhalation of albuterol. In subjects with no history of wheezing, the deficit in FEV1 was 155+/-122 ml (P=0.01), in those with past wheezing it was 41+/-128 ml (P=0.53), and in those with current wheezing it was 119+/-133 ml (P=0.08). The effect was no greater for the subjects who had pneumonia at less than two years of age than for those who had it between the ages of two and seven years and was not diminished after control for multiple confounding factors. The deficits associated with whooping cough were smaller (FEV1, 41+/-70 ml; P=0.25; FVC, 81+/-76 ml; P=0.04). CONCLUSIONS: Childhood pneumonia is associated with reduced ventilatory function in adults. This reduction is independent of a history of wheezing and is not explained by other confounding factors.

Adult

Prevalence of asthma symptoms, diagnosis, and treatment in 12-14 year old children across Great Britain (international study of asthma and allergies in childhood, ISAAC UK)

OBJECTIVE: To investigate variations in the prevalence of self reported symptoms, diagnosis, and treatment of asthma in 12-14 year old children. DESIGN: Self completion questionnaire. SETTING: Great Britain. SUBJECTS: All pupils aged 12-14 years in a stratified cluster sample of 93 large mixed secondary schools in 1995. MAIN OUTCOME MEASURES: Self reported prevalence of symptoms, diagnosis, and treatment of asthma at four geographical levels. RESULTS: 27,507 questionnaires were completed (85.9% response rate). The national 12 month prevalence of any wheezing, speech limiting wheeze, four or more attacks of wheeze, and frequent night waking with wheeze was 33.3% (n = 9155), 8.8% (2427), 9.6% (2634), and 3.7% (1023) respectively. The prevalence of ever having had a diagnosis of asthma was 20.9% (5736). In total, 19.8% (5438/27,507) of pupils reported treatment with anti-asthma drugs in the past year, but, of pupils reporting frequent nocturnal wheeze in the past year, 33.8% (342/1012) had no diagnosis of asthma and 38.6% (395/1023) denied receiving inhaler therapy. The 12 month prevalence of wheeze was highest in Scotland (36.7%, 1633/4444), but in England and Wales there was no discernible north-south or east-west gradient. Wheeze prevalence was slightly higher in non-metropolitan areas (35.0%, 6155/17,605) than in metropolitan areas (30.3%, 3000/9902). The prevalence of self reported asthma diagnosis and inhaler use showed no discernible national, regional, north-south, or east-west geographical pattern but was higher in non-metropolitan areas. CONCLUSION: Prevalence of self reported symptoms, diagnosis, and treatment of asthma was high among 12-14 year olds throughout Great Britain with little geographical or urban-rural variation. Underdiagnosis and undertreatment were substantial.

Adolescent

The natural history of childhood eczema: observations from the British 1958 birth cohort study.

The National Child Development Study (NCDS) is a birth cohort study whose longitudinal design makes it suitable for examining the natural history of common diseases in childhood such as atopic eczema. We have analysed the age of onset and clearance rates for examined and/or reported eczema in 6877 children born during the period 3-9 March 1958 for whom linked data were available at birth and at the ages of 7, 11, 16 and 23 years. Of the 870 cases with examined or reported eczema by the age of 16 years, 66% had age of onset by the age of 7 years. Of the 571 children with reported or examined eczema by the age of 7 years, the proportion of children who were clear in terms of examined eczema or reported eczema in the last year at ages 11 and 16 years was 65% and 74%, respectively. These 'apparent' or short-term clearance rates fell to 53% and 65%, respectively, after allowance for subsequent recurrences in adolescence and early adulthood. Age of onset of community-ascertained cases of atopic eczema may be later than that reported in hospital-based studies. The long-term prognosis of childhood eczema may be worse than some previous studies have suggested, especially when subsequent recurrences are taken into account.

Adolescent

Non-gastrointestinal consequences of Helicobacter pylori infection.

Evidence relating H. pylori to non-gastrointestinal disease is sparse and inconclusive. Suggested mechanisms whereby infection might increase cardiovascular risk include release of acute-phase reactants including fibrinogen, reduction of HDL cholesterol, elevation of homocysteine levels and immunological cross-reactivity between bacterial and human heat shock proteins. Six published studies relating H. pylori seropositivity to various measures of ischaemic heart disease (IHD)-angiography, acute myocardial infarction, angina symptoms, or electro-cardiographic abnormalities-are all consistent with a modest (up to 2-fold) elevation in risk of IHD among infected subjects after adjustment for age, socioeconomic status and conventional cardiovascular risk factors. The pooled odds ratio from 1 longitudinal, 3 case-control and 2 cross-sectional studies is 1.4 (95% confidence interval 1.1-1.8). Further large-scale longitudinal studies are required to quantify the predictive value of seropositivity, to clarify the causal interpretation and to assess the underlying mechanisms for any link between H. pylori infection and ischaemic heart disease.

Child

Epidemiology of Epstein-Barr virus infection in pre-adolescent children: application of a new salivary method in Edinburgh, Scotland.

STUDY OBJECTIVE: To describe the epidemiology of Epstein-Barr virus (EBV) among primary school children by testing saliva with a new EBV capsid antigen "G" antibody capture radioimmunoassay (GACRIA). DESIGN: A population based sample of 7 year old schoolchildren were followed up at age 11. SETTING: 30 randomly chosen primary schools in Edinburgh, Scotland. PARTICIPANTS: 552 schoolchildren. MEASUREMENTS: Data on risk factors for infection were collected by questionnaire at ages 7 and 11. Saliva samples collected at age 11 were examined by GACRIA for evidence of previous infection with EBV. For 102 subjects, a second salivary specimen collected approximately one month after the first sample was available for testing as a measure of the repeatability of the method. MAIN RESULTS: Unequivocal results were found in 91% of samples and the repeatability of the test was good (kappa = 0.71). Fifty six per cent of children had antibodies to EBV. In a logistic regression analysis, independent risk factors for infection were sharing a room (odds ratio 1.78, 1.14, 2.79), head of household's social class IV/V compared with I (odds ratio 2.87, 1.08, 7.34), and schools serving predominantly rented housing estates (odds ratio 2.3, 1.09, 4.84). CONCLUSION: This study is the first application of EBV viral capsid GACRIA to salivary samples. The method was successfully used to describe the epidemiology of EBV. In this study, characteristics of the home seemed to be more important than those of the school in determining the likelihood of infection with EBV.

Adult

Health effects of passive smoking. 4. Parental smoking, middle ear disease and adenotonsillectomy in children.

BACKGROUND: A systematic quantitative review was conducted of evidence relating parental smoking to acute otitis media, recurrent otitis media, middle ear effusion, and adenoidectomy and/or tonsillectomy. METHODS: Forty five relevant publications were identified after consideration of 692 articles selected by electronic search of the Embase and Medline databases using keywords relevant to passive smoking in children. The search was completed in April 1997 and identified 13 studies of acute otitis media, nine of recurrent otitis media, five of middle ear effusion, nine of glue ear surgery, and four of adenotonsillectomy. A quantitative meta-analysis was possible for all outcomes except acute otitis media, using random effects modelling where appropriate to pool odds ratios from each study. RESULTS: Evidence for middle ear disease is remarkably consistent, with pooled odds ratios if either parent smoked of 1.48 (95% CI 1.08 to 2.04) for recurrent otitis media, 1.38 (1.23 to 1.55) for middle ear effusion, and 1.21 (0.95 to 1.53) for outpatient or inpatient referral for glue ear. Odds ratios for acute otitis media are in the range 1.0 to 1.6. No single study simultaneously addresses selection bias, information bias and confounding, but where these have been investigated or excluded in the design or analysis, the associations with parental smoking persist virtually unchanged. Large French and British studies are inconsistent with regard to the association of parental smoking and tonsillectomy. CONCLUSIONS: There is likely to be a causal relationship between parental smoking and both acute and chronic middle ear disease in children.

Acute Disease

Health effects of passive smoking .5. Parental smoking and allergic sensitisation in children.

BACKGROUND: A systematic review was conducted of the effects of parental smoking on immunoglobulin (IgE) levels, skin prick positivity, and allergic rhinitis or eczema in children. Asthma was excluded in order to distinguish more clearly the effect of passive smoke exposure on allergic sensitisation. METHODS: Thirty six relevant publications were identified after consideration of 692 articles selected by electronic search of the Embase and Medline databases using keywords relevant to passive smoking in children. The search was completed in April 1997 and identified nine studies of IgE in neonates, eight of IgE in older children, 12 which included skin prick tests, and 10 describing symptoms of allergic disease other than asthma or wheezing. A quantitative meta-analysis was possible only for the studies reporting skin prick tests. RESULTS: Several large studies failed to confirm early reports of a substantial or statistically significant association of maternal smoking with concentrations of total serum IgE in neonates or in older children. No consistent association emerged between parental smoking and allergic rhinitis or eczema. Few of these studies adjusted for potential confounding variables. The quantity and quality of evidence was greatest for skin prick tests, and studies of parental smoking during pregnancy or infancy were broadly consistent in showing no adverse effect on prick positivity (pooled odds ratio 0.87, 95% confidence interval 0.62 to 1.24). There was much greater and statistically significant (p = 0.002) heterogeneity of odds ratios relating current parental smoking to skin prick positivity. CONCLUSIONS: Parental smoking, either before or immediately after birth, is unlikely to increase the risk of allergic sensitisation in children.

Adolescent

Health effects of passive smoking. 6. Parental smoking and childhood asthma: longitudinal and case-control studies.

BACKGROUND: The relation of parental smoking to wheezing and asthma occurring after the first year of life was assessed by a systematic quantitative review of case-control and longitudinal studies, complementing earlier reviews of cross sectional surveys and wheezing in early childhood. METHODS: Fifty one relevant publications were identified after consideration of 1593 abstracts selected by electronic search of the Embase and Medline databases using keywords relevant to passive smoking in children. The search was completed in April 1997 and identified six studies of asthma incidence, seven of prognosis, 22 case-control studies, and 10 case series addressing disease severity. RESULTS: Maternal smoking was associated with an increased incidence of wheezing illness up to age 6 (pooled odds ratio 1.31, 95% CI 1.22 to 1.41), but less strongly thereafter (1.13, 95% CI 1.04 to 1.22). The long term prognosis of early wheezing illness was better if the mother smoked. The pooled odds ratio for asthma prevalence from 14 case-control studies was 1.37 (95% CI 1.15 to 1.64) if either parent smoked. Four studies suggest that parental smoking is more strongly associated with wheezing among non-atopic children. Indicators of disease severity including symptom scores, attack frequency, medication use, hospital attendance, and life threatening bronchospasm were in general positively related to household smoke exposure. CONCLUSIONS: The excess incidence of wheezing in smoking households appears to be largely non-atopic "wheezy bronchitis" with a relatively benign prognosis, but among children with established asthma, parental smoking is associated with more severe disease. This apparent paradox may be reconciled if environmental tobacco smoke is considered a co-factor provoking wheezing attacks, rather than a cause of the underlying asthmatic tendency.

Asthma

Parental smoking, bronchial reactivity and peak flow variability in children.

BACKGROUND: A systematic quantitative review was conducted of the evidence relating environmental tobacco smoke to bronchial hyperresponsiveness (BHR) during childhood. METHODS: Twenty-nine relevant studies were identified after consideration of 1593 articles selected by electronic search of the Embase and Medline databases using keywords relevant to passive smoking in children. The search was completed in April 1997. RESULTS: Of 19 studies using challenge tests in children of school age, 10 (5759 children) could be summarised as the odds ratio of being bronchial hyperreactive in children exposed to environmental tobacco smoke compared with those not exposed. The pooled odds ratio for maternal smoking was 1.29 (95% confidence limits 1.10 to 1.50) with no evidence of heterogeneity between studies. However, in five further studies of 3531 children providing some evidence, but not odds ratios, none were statistically significant. A further four studies on 5233 children have collected data but are not published. In contrast, all four studies of circadian variation in peak expiratory flow found increased variation in children exposed to environmental tobacco smoke. CONCLUSIONS: A clear effect of exposure to environmental tobacco smoke on BHR in the general population has not been established. While the meta-analysis suggests a small but real increase in BHR in school aged children, it seems likely that this estimate is biased upwards due to publication bias. In contrast, limited evidence suggests greater variation in peak expiratory flow in children of smoking parents.

Adolescent

Effects of changes in fresh fruit consumption on ventilatory function in healthy British adults.

Cross-sectional studies have shown frequent fresh fruit consumption to be associated with higher lung function in both children and adults. This relationship is investigated longitudinally in a national sample of 2,171 British adults age 18 to 73 initially examined in 1984, who were reexamined 7 yr later, and had no reported history of chronic respiratory disease throughout. Outcome was assessed by change in forced expiratory volume in one second (FEV1) between the two examinations, standardized for age, height, and sex and related to fresh fruit consumption estimated by food frequency questionnaires at both examinations. After adjustment for region, social class, and smoking, changes in fresh fruit consumption levels were positively associated with changes in FEV1 (p = 0.002), highlighted by a more marked fall in FEV1 (107 ml; 95% confidence interval, 36 to 178 ml) in subjects who reduced their fresh fruit consumption the greatest compared with those with no change. In contrast, average levels of fruit intake were not associated with change in FEV1 (p = 0.695). The implication is that the cross-sectional effects of fresh fruit consumption on ventilatory function appear to be reversible and not progressive, such that consistently low levels of fresh fruit intake do not appear to increase lung function decline.

Adolescent

Investigation into the increase in hay fever and eczema at age 16 observed between the 1958 and 1970 British birth cohorts.

OBJECTIVE: To investigate whether changes in certain perinatal and social factors explain the increased prevalence of hay fever and eczema among British adolescents between 1974 and 1986. DESIGN: Two prospective birth cohort studies. SETTING: England, Wales, and Scotland. SUBJECTS: 11,195 children born 3-9 March 1958 and 9387 born 5-11 April 1970. MAIN OUTCOME MEASURES: Parental reports of eczematous rashes and of hay fever or allergic rhinitis in the previous 12 months at age 16. RESULTS: The prevalence of the conditions over the 12 month period increased between 1974 and 1986 from 3.1% to 6.4% (prevalence ratio 2.04 (95% confidence interval 1.79 to 2.32)) for eczema and from 12.0% to 23.3% (prevalence ratio 1.93 (1.82 to 2.06)) for hay fever. Both conditions were more commonly reported among children of higher birth order and those who were breast fed for longer than 1 month. Eczema was more commonly reported among girls and hay fever among boys. The prevalence of hay fever decreased sharply between social classes I and V, increased with maternal age up to the early 30s, and was lower in children whose mothers smoked during pregnancy. Neither condition varied significantly with birth weight. When adjusted for these factors, the relative odds of hay fever (1986 v 1974) increased from 2.23 (2.05 to 2.43) to 2.40 (2.19 to 2.63). Similarly, the relative odds of eczema rose from 2.02 (1.73 to 2.36) to 2.14 (1.81 to 2.52). CONCLUSIONS: Taken together, changes between cohorts in sex, birth weight, birth order, maternal age, breast feeding, maternal smoking during pregnancy, and father's social class at birth did not seem to explain any of the observed rise in the prevalence of hay fever and eczema. However, correlates of these factors which have changed over time may still underlie recent increases in allergic disease.

Adolescent

The social origins of infantile colic: questionnaire study covering 76,747 infants.

OBJECTIVE: To describe risk factors for infantile colic. DESIGN: Questionnaire administered by health visitors. SETTING: Sheffield. SUBJECTS: Mothers of 76,747 infants born between 1 August 1975 and 31 May 1988, interviewed when the infant was 1 month old. MAIN OUTCOME MEASURES: Reporting of infantile colic and its duration; weight of infant leeding, state of the home, socioeconomic characteristics of the parents, parents' age, and mother's parity. RESULTS: The odds of reporting infantile colic were increased with breast feeding (odds ratio of breast v bottle feeding 1.35 (95% confidence interval 1.28 to 1.43)), increasing parental age, lower parity, increasing parental age at leaving full time education, and more affluent homes and districts of residence. In a logistic regression analysis, mother's age and parity and socioeconomic factors remained the most important risk factors for the reporting of infantile colic (each P < 0.005), and the effect of breast feeding was attenuated (odds ratio of breast v bottle feeding 1.09 (1.02 to 1.15)). CONCLUSION: At a population level, dietary factors contribute little to mothers' reporting of infantile colic, and dietary change should not be the primary intervention.

Age Factors

Childhood antecedents of allergic sensitization in young British adults.

OBJECTIVE: This study was designed to investigate whether associations of self-reported hay fever with sibship size, birth order, infant feeding, and childhood socioeconomic status reflect variations in sensitization to common aeroallergens. METHODS: One thousand three hundred sixty-nine persons born throughout Britain in 1958 were followed up to age 34 to 35 years. The cohort included 1050 subjects with a history of asthma, wheezy bronchitis, wheezing, or pneumonia and 319 with no history of wheezing illness at ages 7, 11, 16, 23, or 33 years. Skin prick tests with extracts of mixed grass pollen, house dust mite (Der p 1), and cat fur were performed; and wheal diameters were measured. RESULTS: The prevalence of positive skin test results (> or = 3 mm wheal) was independently related (p < 0.01) to male sex, reduced numbers of older siblings (but not younger siblings), and higher socioeconomic status in childhood. Current cigarette smoking and maternal smoking during pregnancy were independently associated (p < 0.01) with a reduced prevalence of skin prick test positivity. No significant independent effects (p > 0.10) were found for adult social class, maternal age, birth weight, gestation, breast feeding, preschool nursery attendance, urban birthplace, or gas stove exposure. CONCLUSION: Factors related to small families and relative affluence in childhood promote atopic sensitization to a variety of aeroallergens in later life. These observations are consistent with the suggestion that early infection may protect against subsequent allergic disease.

Adult

Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.

OBJECTIVE: To determine whether serum concentrations of the cytokines tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. DESIGN: A population based cross sectional study. SUBJECTS AND METHODS: 198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. RESULTS: Serum TNF alpha concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNF alpha was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNF alpha, each by approximately 50% (P < 0.05 for TNF alpha, P < 0.1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNF alpha and 36% for IL-6 (P = 0.14 for TNF alpha and P < 0.05 for IL-6). CONCLUSIONS: This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism.

Aged