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1.  Lack of association of MYO9B genetic variants with coeliac disease in a British cohort 
Gut  2006;55(7):969-972.
Background and aims
Development of coeliac disease involves an interaction between environmental factors (especially dietary wheat, rye, and barley antigens) and genetic factors (there is strong inherited disease susceptibility). The known human leucocyte antigen (HLA)‐DQ2 and ‐DQ8 association explains only a minority of disease heritability. A recent study in the Dutch population suggested that genetic variation in the 3′ region of myosin IXB (MYO9B) predisposes to coeliac disease. MYO9B is a Rho family GTPase activating protein involved in epithelial cell cytoskeletal organisation. MYO9B is hypothesised to influence intestinal permeability and hence intestinal antigen presentation.
Four single nucleotide polymorphisms were chosen to tag all common haplotypes of the MYO9B 3′ haplotype block (exons 15–27). We genotyped 375 coeliac disease cases and 1366 controls (371 healthy and 995 population based). All individuals were of White UK Caucasian ethnicity.
UK healthy control and population control allele frequencies were similar for all MYO9B variants. Case control analysis showed no significant association of any variant or haplotype with coeliac disease.
Genetic variation in MYO9B does not have a major effect on coeliac disease susceptibility in the UK population. Differences between populations, a weaker effect size than originally described, or possibly a type I error in the Dutch study might explain these findings.
PMCID: PMC1856329  PMID: 16423886
coeliac disease; myosin IXB; MYO9B
2.  Time trends in allergic disorders in the UK 
Thorax  2007;62(1):91-96.
Allergic disorders are common in the UK. This study reviews recent UK time trends in the prevalence, morbidity and mortality for allergic disorders, excluding asthma.
A trend analysis was performed over recent decades of national, representative or repeat surveys, primary care consultations, prescriptions, hospital admissions, and mortality.
Serial surveys showed that the prevalence of diagnosed allergic rhinitis and eczema in children have both trebled over the last three decades. While these long term trends were paralleled by the prevalence of disease symptoms, more recent symptom prevalence data suggest a decline. Similarly, GP consultation rates rose by 260% for hay fever and by 150% for eczema overall during the period 1971–91, but rates have stabilised over the past decade. Hospital admissions for eczema have been stable since 1995, and hospital admissions for allergic rhinitis have fallen to about 40% of their 1990 levels. Since 1990, admissions for anaphylaxis have increased by 700%, for food allergy by 500%, for urticaria by 100%, and for angio‐oedema by 40%. Prescriptions issued for all types of allergy have increased since 1991.
The prevalence and healthcare usage for eczema and hay fever have increased substantially over recent decades, but may now be stabilising or even falling. In contrast, admissions for some systemic allergic diseases have risen sharply in the last decade which may indicate a rising incidence of these conditions. Although changes in treatment and other healthcare factors may have contributed to these trends, there may also be a change in the aetiology of allergic disease in the UK.
PMCID: PMC2111268  PMID: 16950836
trend; allergic disease; epidemiology
3.  Temporal associations between daily counts of fungal spores and asthma exacerbations 
Outdoor aeroallergens are one of a number of environmental factors thought to precipitate asthma exacerbations.
To investigate the short term associations between daily fungal spore concentrations and indicators of daily asthma exacerbations in a large urban population.
Daily counts of visits for asthma to family physicians and hospital accident and emergency (A&E) departments and emergency hospital admissions in London 1992–93 were compiled. Daily concentrations of fungal spores (30 species), daily average temperature, humidity, and concentrations of pollen and outdoor air pollution were also compiled. The analysis was restricted to the period when fungal spores were most prevalent (June to mid October). Non‐parametric regression time series methods were used to assess associations controlling for seasonality, day of week, and meteorological factors. The sensitivity of the findings to the inclusion of pollen and air pollution into the models was also assessed.
In children aged 0–14 years the relative risks for increases in the number of A&E visits and hospital admissions associated with changes in fungal spore concentrations from the lower to upper quartiles were 1.06 (95% CI 0.94 to 1.18) and 1.07 (0.97 to 1.19) respectively. The addition of pollen or air pollutants had little impact on the observed associations. A number of individual spore taxa, in particular Alternaria, Epicoccum, Agrocybe, Mildews, and both coloured and colourless Basidiospores and Ascospores, were associated with increases in the number of emergency visits and hospital admissions for asthma, although the precision of these estimates were low. No evidence was found for associations in adults.
Fungal spore concentrations may provoke or exacerbate asthma attacks in children resulting in visits to A&E departments and emergency hospital admissions. These findings were unlikely to be due to confounding by other environmental factors. The associations were comparable to those observed for ambient air pollution from similarly designed studies.
PMCID: PMC2078167  PMID: 16551756
aeroallergens; asthma exacerbations; time series
4.  Childhood asthma in South London: trends in prevalence and use of medical services 1991–2002 
Thorax  2006;61(5):383-387.
Hospital admission rates for asthma in Britain rose during the 1980s and fell during the 1990s, but less is known about recent trends in the prevalence of asthma.
In 1991 and 2002 the same questionnaire was distributed to parents of all school pupils in year 3 (aged 7–8 years) in the London borough of Croydon. Parents of currently wheezy children were then invited for home interview (100% targeted in 1991, 66% in 2002).
The prevalence of wheeze during the previous year increased from 12.9% in 1991 to 17.8% in 2002 (prevalence ratio 1.39 (95% CI 1.23 to 1.56)). Increases were observed in frequent (1.54 (95% CI 1.16 to 2.03)) and infrequent attacks, severe speech limiting episodes (2.25 (95% CI 1.34 to 3.77)), and night waking (1.36 (95% CI 1.07 to 1.72)), and in the reported use of steroids (19.9% v 64.1% of currently wheezy children). Nevertheless, the proportions reporting a visit to the GP at his/her surgery for wheeze in the previous year (prevalence ratio 1.15 (95% CI 0.91 to 1.45)) or an outpatient visit (0.98 (95% CI 0.49 to 1.94)) changed little and an increase in reported casualty attendance (1.66 (95% CI 0.89 to 3.07)) was non‐significant.
There is evidence of an increase in the prevalence of asthma among British primary school children between 1991 and 2002. The absence of a corresponding increase in health service utilisation data may reflect more widespread prophylactic treatment and/or changes in the use and provision of medical services.
PMCID: PMC2111176  PMID: 16449274
asthma; prevalence; children; medical services
5.  Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood 
Thorax  2008;63(11):974-980.
Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals.
Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV1), mid forced expiratory flow (FEF25-75)) and bronchial responsiveness were made at 7–9 years of age.
Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV1 per μmol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV1 per μmol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes.
The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.
PMCID: PMC2582336  PMID: 18678704
6.  Regional variations in wheezing illness in British children: effect of migration during early childhood. 
STUDY OBJECTIVE--The aim was to examine the regional distribution of wheezing illness among British children, and the age at which geographical differences may be determined. DESIGN--Cross sectional analyses and study of interregional migrants were used. SUBJECTS--The subjects were national cohorts of British children born in 1958 and 1970. MEASUREMENTS AND MAIN RESULTS--The regional distribution of wheezing illness showed significant heterogeneity at age 5 (1970 cohort) and 7 (1958 cohort). In both cohorts, children in Scotland had a low prevalence of wheeze, which could not be attributed to underreporting of mild cases. There was a less consistent tendency for high prevalence in Wales, and in the South Western and Midlands regions of England. In the 1958 cohort, the regional differentials diminished progressively with age and were negligible at age 23. There was a poor correlation between the regional distribution of childhood asthma and the common geographical pattern shown by eczema in infancy and hay fever at age 23. Analysis of interregional migrants suggested that the regional variation in each cohort at age 5-7 was primarily related to the region of current residence, and not to the region of birth. CONCLUSIONS--Genetic constitution, perinatal exposures, or early childhood experiences are unlikely to account for the regional variation in wheezing illness. Although local patterns of symptom reporting or disease labelling may be acquired by parents who move to a new region, environmental factors operating at a regional level probably determine the prevalence of asthma in primary school children. These influences do not appear to have long lasting effects upon the tendency to wheeze in adolescence and early adulthood.
PMCID: PMC1060648  PMID: 2273362
7.  Passive smoking, salivary cotinine concentrations, and middle ear effusion in 7 year old children. 
BMJ : British Medical Journal  1989;298(6687):1549-1552.
OBJECTIVE--To assess the contribution of passive exposure to tobacco smoke to the development of middle ear underpressure and effusion. DESIGN--Cross sectional observational study. SETTING--One third of the primary schools in Edinburgh. SUBJECTS--892 Children aged 6 1/2 to 7 1/2 were examined, and satisfactory tympanograms were obtained in 872. Results of assay of salivary cotinine concentrations were available for 770 children, and satisfactory tympanograms were available for 736 of these. END POINT--Correlation of the prevalence of middle ear underpressure and effusion with concentrations of the marker of nicotine, cotinine, in the saliva of the children. MEASUREMENTS AND MAIN RESULTS--Middle ear pressure and compliance were measured in both ears by impedance tympanometry. Salivary cotinine concentrations were assayed by gas-liquid chromatography. Cotinine concentrations increased with the number of smokers in the household. Girls had higher concentrations than boys, and children living in rented housing had higher concentrations than those living in housing owned by their parents. There was a trend towards more abnormal tympanometric findings with increasing cotinine concentration, the odds ratio for a doubling of the cotinine concentration being 1.14 (95% confidence interval 1.03 to 1.27). After adjustment for the sex of the child and housing tenure the odds ratio for a doubling of the cotinine concentration was 1.13 (1.00 to 1.28). CONCLUSIONS--The results of this study are consistent with those of case-control studies of children attending for an operation to relieve middle ear effusion. They indicate that the disease should be added to the list of recognised hazards associated with passive smoking. About one third of the cases of middle ear effusion in this study were statistically attributable to exposure to tobacco smoke.
PMCID: PMC1836817  PMID: 2503113
8.  Asthma as a link between chest illness in childhood and chronic cough and phlegm in young adults 
The link between chest illnesses in childhood to age 7 and the prevalence of cough and phlegm in the winter reported at age 23 was investigated in a cohort of 10 557 British children born in one week in 1958 (national child development study). Both pneumonia and asthma or wheezy bronchitis to age 7 were associated with a significant excess in the prevalence of chronic cough and phlegm at age 23 after controlling for current smoking. This excess was largely attributable to the association of cough and phlegm at age 23 with a history of asthma or wheezy bronchitis from age 16. When adjustment was made for recent wheezing, current cigarette consumption, previous smoking habit, and passive exposure to smoke the relative odds of cough or phlegm, or both, in subjects with a history of childhood chest illness was 1·11 (95% confidence interval 0·97 to 1·27). When analysed separately asthma, wheezy bronchitis, and pneumonia up to age 7 did not significantly increase the prevalence of either cough or phlegm.
The explanation for the observed continuity between chest illness in childhood and respiratory symptoms in later life may lie more in the time course of functional disturbances related to asthma than in the persistence of structural lung damage.
PMCID: PMC2546285  PMID: 3129062
9.  Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease. 
Heart  1997;78(3):273-277.
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.
PMCID: PMC484930  PMID: 9391290
10.  Acute effects of summer air pollution on respiratory function in primary school children in southern England. 
Thorax  1996;51(11):1109-1114.
BACKGROUND: There is growing concern about health effects of air pollution in the UK. Studies in the USA have reported adverse effects on lung function among children but no comparable studies have been published in the UK. This study investigates the relationship between daily changes in ambient air pollution and short term variations in lung function in a panel of school children. METHODS: One hundred and fifty four children aged 7-11 attending a primary school adjacent to a major motorway in Surrey, south-east England, were studied. Bellows spirometry was performed daily on 31 schooldays between 6 June and 21 July 1994. Levels of ozone, nitrogen dioxide, and particulates of less than 10 microns in diameter (PM10) were measured continuously at the school and the pollen count was measured six miles away. Relationships between daily changes in forced expiratory volume in 0.75 seconds (FEV0.75), forced vital capacity (FVC), the FEV0.75/FVC ratio and pollutants were analysed using separate autoregressive models for each child. A weighted average of the resulting slopes was then calculated. RESULTS: There was a significant inverse relationship between daily mean PM10 levels lagged one day and FVC, with a reduction in lung function of 1% (95% CI 0.3% to 2%) across the whole range of PM10 levels (20-150 micrograms/m3). The effect on FEV0.75 was similar (-0.5%) but was not significant when weighted by 1/SE2 (95% CI -1.2% to 0.2%). There was no effect of PM10 levels on the FEV0.75/FVC ratio. No significant association was seen between FEV0.75, FVC, or the FEV0.75/FVC ratio and either ozone or nitrogen dioxide levels. There was no evidence that wheezy children were more affected than healthy children. Pollen levels on the previous day had no effect on lung function and did not change the air pollution results. CONCLUSIONS: There is a very small, but statistically significant, adverse effect of airborne respirable particulate matter, measured as PM10, on lung function in this study group. There is no evidence for an inverse association of lung function with levels of ozone or NO2 measured on the previous day.
PMCID: PMC1090522  PMID: 8958894
11.  Seasonality of tuberculosis: the reverse of other respiratory diseases in the UK. 
Thorax  1996;51(9):944-946.
BACKGROUND: In Western societies there is a winter peak in mortality, largely accounted for by respiratory and cardiovascular deaths. In view of the known seasonal variation in vitamin D, and of the postulated link between tuberculosis and vitamin D deficiency, a study was undertaken to examine whether the presentation of tuberculosis had the same seasonal rhythm as other pulmonary infections. METHODS: Using cosinor analysis the presence or absence of seasonality was determined for 57,313 tuberculosis notifications for England and Wales. OPCS data in four weekly notifications over a 10 year period (1983-92) were examined as two quinquential sets (1983-7 and 1988-92). These were compared with two groups of acute respiratory illness: 138,992 notifications to OPCS of pneumonia deaths for 1988-92 and all admissions to Scottish hospitals with respiratory disease (252,163 cases) during 1980-4. RESULTS: Analysis of notifications of tuberculosis revealed a summer peak with an amplitude of 10%. This pattern differs markedly from other respiratory disorders in which a winter peak and summer trough is observed. CONCLUSIONS: The unusual seasonality of tuberculosis is currently unexplained. One possibility is that low post-winter trough levels of vitamin D (which are known to affect macrophage function and cell mediated immunity) might result in impaired cellular immunity leading, after a latent period, to reactivation of dormant mycobacterial infection.
PMCID: PMC472621  PMID: 8984709
Thorax  1995;50(8):916.
PMCID: PMC474925
Thorax  1995;50(8):915.
PMCID: PMC474923
14.  Vegetarian diet as a risk factor for tuberculosis in immigrant south London Asians. 
Thorax  1995;50(2):175-180.
BACKGROUND--In a previous retrospective study of tuberculosis in south London among Asian immigrants from the Indian subcontinent Hindu Asians were found to have a significantly increased risk for tuberculosis compared with Muslims. This finding has been further investigated by examining the role of socioeconomic and lifestyle variables, including diet, as risk factors for tuberculosis in Asian immigrants from the Indian subcontinent resident in south London. METHODS--Using a case-control study technique Asian immigrants from the Indian subcontinent diagnosed with tuberculosis during the past 10 years and two Asian control groups (community and outpatient clinic controls) from the Indian subcontinent were investigated. Cases and community controls were approached by letter. A structured questionnaire concerning a range of demographic, migration, socioeconomic, dietary, and health topics was administered by a single trained interviewer to subjects (56 cases and 100 controls) who agreed to participate. RESULTS--The results confirmed earlier findings that Hindu Asians had an increased risk of tuberculosis compared with Muslims. However, further analysis revealed that religion had no independent influence after adjustment for vegetarianism (common among Hindu Asians). Unadjusted odds ratios for tuberculosis among vegetarians were 2.7 (95% CI 1.1 to 6.4) using community controls, and 4.3 (95% CI 1.8 to 10.4) using clinic controls. There was a trend of increasing risk of tuberculosis with decreasing frequency of meat or fish consumption. Lactovegetarians had an 8.5 fold risk (95% CI 1.6 to 45.4) compared with daily meat/fish eaters. Adjustment for a range of other socioeconomic, migration, and lifestyle variables made little difference to the relative risks derived using either community or clinic controls. CONCLUSIONS--These results indicate that a vegetarian diet is an independent risk factor for tuberculosis in immigrant Asians. The mechanism is unexplained. However, vitamin D deficiency, common among vegetarian Asians in south London, is known to affect immunological competence. Decreased immunocompetence associated with a vegetarian diet might result in increased mycobacterial reactivation among Asians from the Indian subcontinent.
PMCID: PMC473919  PMID: 7701458
15.  Systematic identification of twins by computerised searches of NHS patient registers in the UK. 
OBJECTIVES: This study aimed to assess the feasibility, sensitivity, and specificity of a systematic search of the NHS central register for twins of the same sex. DESIGN, SETTING, AND SUBJECTS: Computerised searches by alphanumeric NHS number, sex, and date of birth of 1.6 million patients registered with general practitioners in Kent, followed by validation by postal questionnaire sent to 66 pairs of children, 129 pairs of adult twins, and one set of triplets. MAIN OUTCOME MEASURES: These were as follows: confirmed twin status, previous involvement in research, and willingness to participate in future research based on a twin register. RESULTS: The procedure was most efficient at identifying twins among children, in males born from 1930 onwards, and females born before 1940. Altogether 2397 male sets and 1684 female sets were identified as probable twins, triplets, or quadruplets with identical surnames, same dates of birth, and consecutive NHS numbers. Among a further 4004 pairs of adult females with the same dates of birth (1940-79), consecutive NHS numbers, but different (married) surnames, an estimated third are twins. Response to the postal questionnaire was 60% (197/327), including only one singleton. Only 10% of responders had previously participated in medical research, but 63% (65/103) of complete sets who responded expressed a willingness to participate in a twin register. CONCLUSIONS: A systematic search of the NHS central register could identify large numbers of British twins. The procedure is efficient, reasonably sensitive, and highly specific, if supplemented by additional information from birth records for adult females born after 1939. The potential exists to create an important new resource for twin studies in Britain.
PMCID: PMC1060417  PMID: 9135796
18.  Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. 
BMJ : British Medical Journal  1995;311(7007):711-714.
OBJECTIVE--To investigate the relation between seropositivity to chronic infections with Helicobacter pylori and Chlamydia pneumoniae and both coronary heart disease and cardiovascular risk factors. DESIGN--Cross sectional study of a population based random sample of men. Coronary heart disease was assessed by electrocardiography, Rose angina questionnaire, and a history of myocardial infarction; serum antibody levels to H pylori and C pneumoniae were measured, risk factor levels determined, and a questionnaire administered. SETTING--General practices in Merton, Sutton, and Wandsworth, south London. SUBJECTS--388 white south London men aged 50-69. MAIN OUTCOME MEASURES--Evidence of coronary risk factors and infection with H pylori or C pneumoniae. RESULTS--47 men (12.1%) had electrocardiographic evidence of ischaemia or infarction. 36 (76.6%) and 18 (38.3%) were seropositive for H pylori and C pneumoniae, respectively, compared with 155 (45.5%) and 62 (18.2%) men with normal electrocardiograms. Odds ratios for abnormal electrocardiograms were 3.82 (95% confidence interval 1.60 to 9.10) and 3.06 (1.33 to 7.01) in men seropositive for H pylori and C pneumoniae, respectively, after adjustment for a range of socioeconomic indicators and risk factors for coronary heart disease. Cardiovascular risk factors that were independently associated with seropositivity to H pylori included fibrinogen concentration and total leucocyte count. Seropositivity to C pneumoniae was independently associated with raised fibrinogen and malondialdehyde concentrations. CONCLUSIONS--Both H pylori and C pneumoniae infectins are associated with coronary heart disease. These relations are not explained by a wide range of confounding factors. Possible mechanisms include an increase in risk factor levels due to a low grade chronic inflammatory response.
PMCID: PMC2550716  PMID: 7549683
19.  Asthma from birth to age 23: incidence and relation to prior and concurrent atopic disease. 
Thorax  1992;47(7):537-542.
BACKGROUND: Few studies present prospective data on the incidence of asthma. Its associations with sex and with prior and concurrent hay fever and eczema were examined in a nationally representative sample followed from birth to 23 years of age (British 1958 birth cohort). METHODS: Reports of asthma or wheezy bronchitis, hay fever and eczema were obtained by interview of parents of children at ages 7, 11, and 16 years, and of cohort members at age 23 years. Linked data from all four interviews were available on 7225 subjects (43% of the original birth cohort). RESULTS: The cumulative incidence of asthma or wheezy bronchitis was 18.2%, 21.8%, 24.5%, and 28.6% by the ages of 7, 11, 16, and 23 years respectively. Over the four incidence periods examined (0 to 7 years, 8 to 11 years, 12 to 16 years, 17 to 23 years) the average annual incidence of new cases was 2.6%, 1.1%, 0.71%, and 0.76% respectively. The male:female incidence ratio rose from 1.23 in the 0 to 7 year period to 1.48 at 12 to 16 years but had reversed to 0.59 at 17 to 23 years. A prior report of hay fever or eczema each increased the subsequent incidence of asthma or wheezy bronchitis by a factor of 1.7 to 2.0 independently of sex. This effect of prior atopic illness, however, was largely explained by the strong independent association of incidence of asthma and wheezy bronchitis with atopic disease at the end of each incidence period (odds ratios 2.0 to 2.5 per atopic condition, p < 0.01). CONCLUSIONS: Gender differences in the incidence of asthma or wheezy bronchitis vary with age and are not explained by atopy. The incidence of asthma or wheezy bronchitis can be predicted from a clinical history of hay fever or eczema but is more strongly associated with the presence of atopic disease at the time of onset.
PMCID: PMC463865  PMID: 1412098
20.  Mortality from cardiovascular disease among interregional migrants in England and Wales. 
BMJ : British Medical Journal  1995;310(6977):423-427.
OBJECTIVE--To investigate the extent to which geographical variations in mortality from ischaemic heart disease and stroke in Britain are influenced by factors in early life or in adulthood. DESIGN--Longitudinal study of migrants. SUBJECTS--1% sample of residents in England and Wales born before October 1939 and enumerated at the 1971 census (the Office of Population Censuses and Surveys' longitudinal study). MAIN OUTCOME MEASURE--18,221 deaths from ischaemic heart disease and 9899 deaths from stroke during 1971-88 were analysed by areas of residence in 1939 and 1971. These included 2928 deaths from ischaemic heart disease and 1608 deaths from stroke among individuals moving between 14 areas defined by the major conurbations and nine standard administrative regions of England and Wales. RESULTS--The southeast to northwest gradient in mortality from ischaemic heart disease was related significantly to both the 1939 area (chi 2 = 6.09, df = 1) and area in 1971 (chi 2 = 5.05, df = 1). Geographical variations in mortality from stroke were related significantly to the 1939 area (chi 2 = 4.09, df = 1) but the effect of area in 1971 was greater (chi 2 = 8.07, df = 1). The effect of 1971 area on mortality from stroke was largely due to a lower risk of death from stroke among individuals moving into Greater London compared with migrants to the rest of the South East region (chi 2 = 4.54, df = 1). CONCLUSIONS--Geographical variations in mortality from cardiovascular disease in Britain may be partly determined by genetic factors, environmental exposures, or lifestyle acquired early in life, but the risk of fatal ischaemic heart disease and stroke changes on migration between areas with differing mortality. The low risk of death from stroke associated with residence in Greater London is acquired by individuals who move there.
PMCID: PMC2548815  PMID: 7873946
21.  Helicobacter pylori infection in childhood: risk factors and effect on growth. 
BMJ : British Medical Journal  1994;309(6962):1119-1123.
OBJECTIVE--To investigate the current prevalence of Helicobacter pylori infection in childhood, the risk factors for infection, and the effect of infection on growth in preadolescent schoolchildren. DESIGN--Population based sample of 7 year old schoolchildren followed up at age 11; data on risk factors for infection collected at age 7; presence of infection at age 11 determined by measurement of salivary IgG against H pylori by a newly developed enzyme linked immunosorbent assay (ELISA). Height was measured at 7 and 11 years of age. SUBJECTS--554 schoolchildren from Edinburgh. RESULTS--62 (11%) children had H pylori infection. Independent risk factors for infection were single parent families (adjusted odds ratio = 2.5; 95% confidence interval 1.1 to 5.7), the 10% most crowded homes (3.1; 1.3 to 7.2), and schools serving predominantly rented housing estates (2.5; 1.0 to 6.5). School catchment area was more important than parental social class or housing tenure. Growth in height between 7 and 11 was diminished in infected children by a mean of 1.1 cm (0.3 to 2.0 cm) over four years. This growth reduction was largely confined to girls (1.6 cm over four years), among whom it correlated with salivary IgG (P = 0.015). CONCLUSION--Data from salivary assay to investigate the epidemiology of H pylori suggest that factors relating to the type of community in which the child lives may now be as important for acquisition of this infection as features of the family home. The greater reduction of growth among infected girls raises the possibility that H pylori infection may delay or diminish the pubertal growth spurt.
PMCID: PMC2541954  PMID: 7987103
22.  Ventilatory function and winter fresh fruit consumption in a random sample of British adults. 
Thorax  1991;46(9):624-629.
The relation between ventilatory function and the reported frequency of consumption of fresh fruit and fruit juice was studied among 1502 lifelong non-smokers and 1357 current smokers aged 18-69 with no history of chronic respiratory disease. Forced expiratory volume in one second (FEV1) was assessed by turbine spirometry. As winter fruit consumption was more widely dispersed than summer consumption and few subjects ate fruit more frequently in the winter, winter fruit consumption was taken as an indicator of habitual (year round) consumption. After adjustment for sex, age, height, cigarette consumption, region of residence, and household socioeconomic group, FEV1 was associated with winter fruit consumption. The mean adjusted FEV1 among those who never drank fresh fruit juice and ate fresh fruit less than once a week during the winter was 78 ml lower (95% confidence interval 24-132 ml) than the mean for the other subjects. A similar difference was found in all age-sex groups and among both current smokers and lifelong non-smokers. Antioxidant and other actions of vitamin C may protect against pulmonary emphysema, or reduce bronchoconstrictor responses to environmental pollutants.
PMCID: PMC463343  PMID: 1948789
23.  Trends in prevalence and severity of childhood asthma. 
BMJ : British Medical Journal  1994;308(6944):1600-1604.
OBJECTIVE--To test the null hypothesis that there has been no change in the prevalence or severity of childhood asthma over recent years. DESIGN--Repeated population prevalence survey with questionnaires completed by parents followed by home interviews with parents. SETTING--London borough of Croydon, 1978 and 1991. SUBJECTS--All children in one year of state and private primary schools aged 7 1/2 to 8 1/2 years at screening survey. MAIN OUTCOME MEASURES--Trends in symptoms, acute severe attacks, and chronic disability. RESULTS--For 1978 and 1991 respectively, the response rates were 4147/4763 and 3070/3786, and home interviews were obtained from 273/288 and 319/395 parents of currently wheezy children. Between 1978 and 1991 there were significant relative increases in prevalence ratios in the 12 month prevalence of attacks of wheezing or asthma (1.16; 95% confidence interval 1.02 to 1.31), the one month prevalence of wheezing episodes (1.78; 1.15 to 2.74), and the one month prevalence of night waking (1.81; 1.01 to 3.23) but not in frequent (> or = 5) attacks over the past year (1.05; 0.79 to 1.40). There were substantial and significant decreases in the 12 month prevalence of absence from school of more than 10 days due to wheezing (0.52; 0.30 to 0.90), any days in bed (0.67; 0.44 to 1.01), and restriction of activities at home (0.51; 0.31 to 0.83) and an equivalent but not significant fall in speech limiting attacks (0.51; 0.24 to 1.11). CONCLUSION--The small increase in the prevalence of wheezy children and relatively greater increase in persistent wheezing suggests a change in the environmental determinants of asthma. In contrast and paradoxically the frequency of wheezing attacks remains unchanged and there are indications that severe attacks and chronic disability have fallen by about half; this may be due to an improvement in treatment received by wheezy children.
PMCID: PMC2540454  PMID: 8025426
24.  Time trends in respiratory symptoms in childhood over a 24 year period. 
Archives of Disease in Childhood  1993;68(6):729-734.
Two cross sectional surveys, 24 years apart, using the same respiratory questionnaire, were carried out to examine changes in prevalence rates of cough, phlegm, and wheeze and to relate changes in wheeze to objective peak expiratory flow rates (PEFRs). The surveys were done in towns in southern and northern England and South Wales in schoolchildren aged 6.0-7.5 years; n = 1655 in 1966 and n = 2323 in 1990. Parents reported on winter cough and winter phlegm (early morning or day/night) and wheeze; PEFRs were also measured. The proportion of children reported as wheezing on most days or nights increased from 3.9% to 6.1% (95% confidence interval (CI) for increase -0.2 to 4.6), with a smaller increase in the prevalence of those who had ever wheezed. The proportion of children with day or night time cough increased from 21.1% to 33.3% (95% CI for increase 3.8 to 20.6) and the proportion with day or night time phlegm increased from 5.8% to 10.0% (95% CI for increase 0.4 to 8.0). Smaller increases in the prevalence of persistent cough (from 9.0% to 12.4%) and persistent phlegm (from 2.4% to 3.5%) were also observed, while morning cough and morning phlegm showed little change. The increases in cough and phlegm were apparent in subjects with and without a history of wheeze. Both absolute and proportional changes in symptom prevalence were generally greater in the north than in the south. Similar social class trends were seen in each survey. The mean difference in PEFR between subjects with and without wheeze was smaller in 1990 than in 1966, but this result could be influenced by a greater proportion of subjects receiving antiasthmatic treatment in the 1990 survey. These apparent increases in the prevalence of persistent wheeze, day and night time cough and phlegm, occurring over a period during which outdoor air pollution levels have decreased substantially, deserve further investigation.
PMCID: PMC1029362  PMID: 8333760
25.  Quantification of airborne moulds in the homes of children with and without wheeze. 
Thorax  1990;45(5):382-387.
A population survey of 1000 7 year old children found a significant excess of wheeze among children whose homes were reported to be mouldy (odds ratio 3.70, 95% confidence limits 2.22, 6.15). The airborne mould flora was quantified by repeated volumetric sampling during the winter in three rooms of the homes of 88 children. All of these had previously completed spirometric tests before and after a six minute free running exercise challenge. Total airborne mould counts varied from 0 to 41,000 colony forming units (CFU)/m3, but were generally in the range 50-1500 CFU/m3, much lower than the concentrations found outdoors in summer. The principal types of fungi identified are all known to be common out of doors, and most were found on at least one occasion in most of the homes. Median and geometric mean total mould counts were not related to reports of visible mould in the home, or to a history of wheeze in the index child. The heterogeneous group of non-sporing fungi (mycelia sterilia) were the only airborne fungi present at significantly higher concentrations in the homes of wheezy children (geometric mean 2.1 v 0.7 CFU/m3. A non-significant increase in total mould counts was observed in the homes of children with a 10% or greater decline in FEV1 after exercise (geometric mean 354 v 253 CFU/m3). Questionnaire reports of mould in the home may be a poor indicator of exposure to airborne spores. The total burden of inhaled mould spores from indoor sources is probably not an important determinant of wheeze among children in the general population. Although the association with mycelia sterilia could be a chance finding, these non-sporing isolates may include a potent source of allergen.
PMCID: PMC462482  PMID: 2382244

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