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1.  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
2.  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
3.  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
4.  Diabetic retinopathy: morphometric analysis of basement membrane thickening of capillaries in different retinal layers within arterial and venous environments. 
The British Journal of Ophthalmology  1995;79(12):1120-1123.
AIMS--To assess quantitatively variations in the extent of capillary basement membrane (BM) thickening between different retinal layers and within arterial and venous environments during diabetes. METHODS--One year after induction of experimental (streptozotocin) diabetes in rats, six diabetic animals together with six age-matched control animals were sacrificed and the retinas fixed for transmission electron microscopy (TEM). Blocks of retina straddling the major arteries and veins in the central retinal were dissected out, embedded in resin, and sectioned. Capillaries in close proximity to arteries or veins were designated as residing in either an arterial (AE) or a venous (VE) environment respectively, and the retinal layer in which each capillary was located was also noted. The thickness of the BM was then measured on an image analyser based two dimensional morphometric analysis system. RESULTS--In both diabetics and controls the AE capillaries had consistently thicker BMs than the VE capillaries. The BMs of both AE and VE capillaries from diabetics were thicker than those of capillaries in the corresponding retinal layer from the normal rats (p < or = 0.005). Also, in normal AE and VE capillaries and diabetic AE capillaries the BM in the nerve fibre layer (NFL) was thicker than that in either the inner (IPL) or outer (OPL) plexiform layers (p < or = 0.001). However, in diabetic VE capillaries the BMs of capillaries in the NFL were thicker than those of capillaries in the IPL (p < or = 0.05) which, in turn, had thicker BMs than capillaries in the OPL (p < or = 0.005). CONCLUSIONS--The variation in the extent of capillary BM thickening between different retinal layers within AE and VE environments may be related to differences in levels of oxygen tension and oxidative stress in the retina around arteries compared with that around veins.
PMCID: PMC505353  PMID: 8562548
5.  Why are hospital admission and mortality rates for childhood asthma higher in New Zealand than in the United Kingdom? 
Thorax  1990;45(3):176-182.
New Zealand has higher mortality and hospital admission rates for asthma than England and Wales. To determine the reasons for this the available data on asthma mortality and hospital admissions from the Auckland region of New Zealand were compared with data from the South West Thames Region of England for 1979-86 and data from previous surveys on prevalence of wheeze (Auckland 1985, Croydon 1978). In addition, a survey of general practitioners was carried out to determine their approach to the management of asthma, patient simulations being used. Asthma mortality in children of European descent aged 5-14 years was 2.5 times higher in Auckland than in South West Thames. The reported lifetime, 12 month, and one month prevalences of wheeze were also higher in Auckland (by 18.5%, 32.1%, and 87.5%). Unexpectedly, the hospital admission rate for asthma in children of European descent aged 5-14 years was 5% less in Auckland than in South West Thames. Comparative studies of hospital case notes and of the replies from general practitioners showed that in Auckland the duration of illness before admission was greater and that general practitioners were less likely to admit patients with acute asthma. The overall standard of general practitioner care in Auckland was, if anything, higher than in South West Thames but in both areas there was considerable variation. On balance it was concluded that the higher mortality rate in New Zealand is explained by higher levels of morbidity rather than relative deficiencies in care. Nevertheless, the implications of the lesser use of hospital care for acute asthma observed in Auckland need further consideration.
PMCID: PMC462378  PMID: 2330549
6.  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
7.  Selective loss of vascular smooth muscle cells in the retinal microcirculation of diabetic dogs. 
This study was undertaken to further characterise the fine structural changes occurring in the retinal circulation in early diabetes. The eyes of eight alloxan/streptozotocin and three spontaneously diabetic dogs were examined by trypsin digest and electron microscopy after durations of diabetes of between 1 and 7 years. Basement membrane (BM) thickening in the retinal capillaries was the only obvious fine structural change identified during the first 3 years of diabetes and was established within 1 year of induction. Widespread pericyte loss was noted after 4 years of diabetes and was paralleled by loss of smooth muscle (SM) cells, in the retinal arterioles. SM cell loss was most obvious in the smaller arterioles of the central retina. No microaneurysms were noted in the experimental diabetic dogs with up to 5 years' duration of diabetes but were widespread in a spontaneously diabetic animal at 7 years. This study has shown that SM cell loss, a hitherto unrecognised feature of diabetic microangiopathy, accompanies pericyte loss in the retinal circulation of diabetic dogs.
PMCID: PMC504692  PMID: 8110701
9.  Social determinants of nutrient intake in smokers and non-smokers during pregnancy. 
STUDY OBJECTIVE--The aim was to investigate the effects of social factors (education, income, marital status, partners' employment status, housing tenure, social class), smoking, and maternal height on the dietary intake of pregnant women. DESIGN--The study was a prospective investigation on a two phase sample. SETTING--The study involved women attending the antenatal clinic at a district general hospital. PATIENTS--A group of pregnant Caucasian women, selected because they were heavy smokers (15+ cigarettes/day) (n = 94) and a randomly selected sample of never smokers (n = 112) were studied. MEASUREMENTS AND MAIN RESULTS--Data on social factors were collected by interviewer administered questionnaire. A 7 day weighed intake method was used to determine dietary intake at 28 weeks gestation. In univariate analyses, income, housing tenure and social class had significant effects on intakes of both macro- and micronutrients, and maternal education and smoking had significant effects on intakes of micronutrients. Using a stepwise multivariate analysis with income, smoking and maternal education, income was a significant factor in the intake of most nutrients but this effect disappeared when social class and housing tenure factors were entered into the model. Only social class and housing tenure had any significant effect on intakes of macronutrients--energy, protein and fat. Smoking and maternal education were the most important determinants of quality of diet (nutrient density); other factors had only negligible effects. Income was the only significant factor in alcohol intake. It is suggested that the effects of social class and income are overlapping. CONCLUSIONS--Smoking, being renters of accommodation, and being of minimum education and low social class are risk factors for poor dietary intake. It is recommended that such higher risk groups be specifically targeted for nutritional advice in pregnancy.
PMCID: PMC1060643  PMID: 2273357
10.  Short-term associations between outdoor air pollution and mortality in London 1992-4 
OBJECTIVES: A previous study of the short term effects of air pollution in London from April 1987 to March 1992 found associations between all cause mortality and black smoke and ozone, but no clear evidence of specificity for cardiorespiratory deaths. London data from 1992 to 1994 were analysed to examine the consistency of results over time and to include particles with a mean aerodynamic diameter of 10 microns (PM10) and carbon monoxide. METHODS: Poisson regression was used of daily mortality counts grouped by age and diagnosis, adjusting for trend, seasonality, calendar effects, deaths from influenza, meteorology, and serial correlation. The pollutants examined were particles (PM10 and black smoke), nitrogen dioxide, ozone, sulphur dioxide, and carbon monoxide with single and cumulative lags up to 3 days. RESULTS: No significant associations were found between any pollutant and all cause mortality, but, with the exception of ozone, all estimates were positive. Each pollutant apart from ozone was significantly associated with respiratory mortality; PM10 showed the largest effect (4% increase in deaths of all ages for a 10th-90th percentile increment). The pollutants significantly associated with cardiovascular deaths were nitrogen dioxide, ozone, and black smoke but there was no evidence of an association with PM10. In two pollutant models of respiratory deaths, the effect of black smoke, which in London indicates fine particles of diesel origin, was independent of that of PM10, but not vice versa. CONCLUSION: These results from a new data set confirm a previous report that there are associations between various air pollutants and daily mortality in London. This new study found greater specificity for associations with respiratory and cardiovascular deaths, and this increases the plausibility of a causal explanation. However, the effects of ozone found in the earlier study were not replicated. The fraction of PM10 which comprises black smoke accounted for much of the effect of PM10.
PMCID: PMC1757726  PMID: 10450240
11.  Investigating regional differences in short-term effects of air pollution on daily mortality in the APHEA project: a sensitivity analysis for controlling long-term trends and seasonality. 
Environmental Health Perspectives  2001;109(4):349-353.
Short-term effects of air pollution on daily mortality in eight western and five central-eastern European countries have been reported previously, as part of the APHEA project. One intriguing finding was that the effects were lower in central-eastern European cities. The analysis used sinusoidal terms for seasonal control and polynomial terms for meteorologic variables, but this is a more rigid approach than the currently accepted method, which uses generalized additive models (GAM). We therefore reanalyzed the original data to examine the sensitivity of the results to the statistical model. The data were identical to those used in the earlier analyses. The outcome was the daily total number of deaths, and the pollutants analyzed were black smoke (BS) and sulfur dioxide (SO(2)). The analyses were restricted to days with pollutant concentration < 200 microg/m(3) and < 150 microg/m(3) alternately. We used Poisson regression in a GAM model, and combined individual city regression coefficients using fixed and random-effect models. An increase in BS by 50 microg/m(3) was associated with a 2.2% and 3.1% increase in mortality when analysis was restricted to days < 200 microg/m(3) and < 150 microg/m(3), respectively. The corresponding figures were 5.0% and 5.6% for a similar increase in SO(2). These estimates are larger than the ones published previously: by 69% for BS and 55% for SO(2). The increase occurred only in central-eastern European cities. The ratio of western to central-eastern cities for estimates was reduced to 1.3 for BS (previously 4.8) and 2.6 for SO(2) (previously 4.4). We conclude that part of the heterogeneity in the estimates of air pollution effects between western and central-eastern cities reported in previous publications was caused by the statistical approach used and the inclusion of days with pollutant levels above 150 microg/m(3). However, these results must be investigated further.
PMCID: PMC1240274  PMID: 11335182
12.  Passive smoking and sudden infant death syndrome: review of the epidemiological evidence 
Thorax  1997;52(11):1003-1009.
BACKGROUND: This paper provides a systematic, quantitative review of the epidemiological evidence relating parental smoking and sudden infant death. METHODS: Thirty two relevant publications were identified after consideration of 692 articles selected by electronic search of the Embase and Medline databases using keywords and Mesh headings relevant to passive smoking in children. Eleven further articles were identified from reviews and by talking to authors. The search was completed in April 1997 and identified 39 studies. RESULTS: The unadjusted pooled odds ratio for prenatal maternal smoking was 2.77 (95% CI 2.45 to 3.13). After adjustment for a variety of confounders the pooled odds ratio was reduced to 2.08 (95% CI 1.83 to 2.38) and was similar in cohort and case-control studies. Four studies reported on maternal postnatal smoking after controlling for prenatal maternal smoking (pooled odds ratio 1.94 (95% CI 1.55 to 2.43)). Of three studies reporting on the risk of paternal smoking where the mother was a non-smoker, two found significant effects while one found no effect. Dose-response relationships with both prenatal and postnatal maternal smoking were present in most studies which provided data. CONCLUSIONS: Maternal smoking doubles the risk of sudden infant death syndrome. The relationship is almost certainly causal. There is good evidence that postnatal exposure to environmental tobacco smoke from both mother and father are important. Because prenatal smoking is almost invariably associated with postnatal smoking, the role of prenatal smoking per se will be difficult to resolve using epidemiological studies. 

PMCID: PMC1758452  PMID: 9487351
13.  Emergency hospital admissions for respiratory disorders attributable to summer time ozone episodes in Great Britain 
Thorax  1997;52(11):958-963.
BACKGROUND: There is accumulating evidence from various countries, including the UK, that ground level ozone concentrations are associated with increased daily hospital admissions for respiratory diseases. This paper estimates the impact of ozone episodes on daily hospital admissions for respiratory disease in Great Britain by combining locally based exposure-response relationships with mapped estimates of ozone exposure for the population in the summers of 1993 and 1995. METHODS: For the given years the available ozone measurements were used to construct maps of ozone concentrations for each day. The population exposed to a given concentration of ozone on a particular day was calculated from census data using a geographical information system. The additional hospital admissions for respiratory disease were then estimated using a regression coefficient for London. RESULTS: It is estimated that 0.10% (a total of 184) and 0.35% (a total of 643) of hospital admissions for respiratory disorders during the summers of 1993 and 1995, respectively, can be attributed to levels of ozone above 50 ppb (the recommended air quality standard for the UK). A sensitivity analysis for 1995 found that, if no threshold is assumed, the estimate is increased by about twenty fold (6% of admissions attributable). CONCLUSIONS: The additional hospital admissions for respiratory disease attributable to ozone are very small in both absolute and relative terms if a threshold of 50 ppb is assumed, but this estimate is very sensitive to threshold assumptions. 

PMCID: PMC1758440  PMID: 9487343
14.  The home environment and asthma symptoms in childhood: two population based case-control studies 13 years apart 
Thorax  1997;52(7):618-624.
BACKGROUND: Prevalence surveys of asthma and/or wheezing among all children aged between 7 1/2 and 8 1/2 attending state and private schools in the London Borough of Croydon were conducted in February 1978 and February 1991. Two population based case-control studies drawn from the survey responders were used to investigate the association between childhood wheeze and characteristics of the home environment and to assess whether changes in these characteristics between 1978 and 1991 may have contributed to an increase in the population prevalence of wheeze among school children. METHODS: Information on exposure to potential indoor environmental risk factors was obtained from parents by home interview and compared between cases-that is, children with frequent (> or = 5) or in-frequent (1-4) attacks of asthma or wheezing in the past 12 months- and controls, with adjustment for study. Changes in exposure over time were assessed by comparing control groups. RESULTS: Between 1978 and 1991 the population prevalence odds of wheeze increased by 20% (OR 1.20; 95% CI 1.04 to 1.39). Change in parental smoking, gas cooking, pet ownership, and central heating did not appear to explain the rise. Use of non-feather pillows was positively associated with childhood wheeze even after adjusting for other risk factors and after re-coding from non-feather to feather cases thought to have changed pillow in response to symptoms (OR 1.54; 95% CI 1.13 to 2.10). The proportion of control children reportedly using non-feather pillows was 44% in 1978 and 67% in 1991. CONCLUSIONS: Increased use of non-feather pillows was the only domestic indoor exposure studied which appeared to explain a modest rise in prevalence of wheeze from 1978 to 1991. Our analysis attempts to address behavioural change in response to the child's symptoms but an artifact arising from lifelong avoidance of feather bedding in atopic families cannot be entirely discounted. 

PMCID: PMC1758604  PMID: 9246133
15.  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
17.  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) 
BMJ : British Medical Journal  1998;316(7125):118-124.
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.
PMCID: PMC2665402  PMID: 9462318
18.  Daily time series for cardiovascular hospital admissions and previous day's air pollution in London, UK. 
OBJECTIVE: To test for a significant association between air pollution and emergency hospital admissions for circulatory diseases (international classification of diseases-9 390-459) in London, England, that would be consistent with a causal effect of pollution on the previous day. METHODS: Long term concurrent trends, temperature, humidity, day of the week, influenza epidemic of 1989, and cyclical covariations with periodicity > 20 days in daily measures of pollution and admissions for 1987-94 were allowed for. RESULTS: There were 373556 admissions. No association was found between O3 and circulatory diseases. Four other pollutants were associated with acute myocardial infarction and circulatory diseases combined. P values and attributable cases (95% confidence intervals) for acute myocardial infarction were: black smoke P = 0.003, 2.5% (0.8% to 4.3%); NO2 P = 0.002, 2.7% (0.8% to 4.6%); CO P = 0.001, 2.1% (0.7% to 3.5%); and SO2 P = 0.0006, 1.7% (0.7% to 2.6%). There were also associations between black smoke and angina (P = 0.02), NO2 and arrhythmia (P = 0.04), and CO and other circulatory diseases (P = 0.004), but none with heart failure. Acute myocardial infarction was the only diagnosis for which there were significant associations with and without adjustment for cyclical terms. The associations with acute myocardial infarction were significant only in the cool season. CONCLUSION: Population data were consistent with 1 in 50 heart attacks currently presenting at London hospitals being triggered by outdoor air pollution. Further research is now needed to investigate whether background concentrations of black smoke, NO2, CO, and SO2 are a preventable cause of myocardial infarction. These results, if applied to all myocardial infarctions in the United Kingdom, indicate a potential saving of 6000 heart attacks a year.
PMCID: PMC1128977  PMID: 9326156
19.  Short-term effects of ambient sulphur dioxide and particulate matter on mortality in 12 European cities: results from time series data from the APHEA project. Air Pollution and Health: a European Approach. 
BMJ : British Medical Journal  1997;314(7095):1658-1663.
OBJECTIVES: To carry out a prospective combined quantitative analysis of the associations between all cause mortality and ambient particulate matter and sulphur dioxide. DESIGN: Analysis of time series data on daily number of deaths from all causes and concentrations of sulphur dioxide and particulate matter (measured as black smoke or particles smaller than 10 microns in diameter (PM10)) and potential confounders. SETTING: 12 European cities in the APHEA project (Air Pollution and Health: a European Approach). MAIN OUTCOME MEASURE: Relative risk of death. RESULTS: In western European cities it was found that an increase of 50 micrograms/m3 in sulphur dioxide or black smoke was associated with a 3% (95% confidence interval 2% to 4%) increase in daily mortality and the corresponding figure for PM10 was 2% (1% to 3%). In central eastern European cities the increase in mortality associated with a 50 micrograms/m3 change in sulphur dioxide was 0.8% (-0.1% to 2.4%) and in black smoke 0.6% (0.1% to 1.1%). Cumulative effects of prolonged (two to four days) exposure to air pollutants resulted in estimates comparable with the one day effects. The effects of both pollutants were stronger during the summer and were mutually independent. CONCLUSIONS: The internal consistency of the results in western European cities with wide differences in climate and environmental conditions suggest that these associations may be causal. The long term health impact of these effects is uncertain, but today's relatively low levels of sulphur dioxide and particles still have detectable short term effects on health and further reductions in air pollution are advisable.
PMCID: PMC2126873  PMID: 9180068
20.  Short term effects of air pollution on health: a European approach using epidemiologic time series data: the APHEA protocol. 
BACKGROUND AND OBJECTIVES: Results from several studies over the past five years have shown that the current levels of pollutants in Europe and North America have adverse short term effects on health. The APHEA project aims to quantifying these in Europe, using standardised methodology. The project protocol and analytical methodology are presented here. DESIGN: Daily time series data were gathered for several air pollutants (sulphur dioxide; particulate matter, measured as total particles or as the particle fraction with an aerodynamic diameter smaller than a certain cut off, or as black smoke; nitrogen dioxide; and ozone) and health outcomes (the total and cause specific number of deaths and emergency hospital admissions). The data included fulfilled the quality criteria set by the APHEA protocol. SETTING: Fifteen European cities from 10 different countries with a total population over 25 million. METHODOLOGY: The APHEA collaborative group decided on a specific methodological procedure to control for confounding effects and evaluate the hypothesis. At the same time there was sufficient flexibility to allow local characteristics to be taken into account. The procedure included modelling of all potential confounding factors (that is, seasonal and long term patterns, meteorological factors, day of the week, holidays, and other unusual events), choosing the "best" air pollution models, and applying diagnostic tools to check the adequacy of the models. The final analysis used autoregressive Poisson models allowing for overdispersion. Effects were reported as relative risks contrasting defined increases in the corresponding pollutant levels. Each participating group applied the analyses to their own data. CONCLUSIONS: This methodology enabled results from many different European settings to be considered collectively. It represented the best available compromise between feasibility, comparability, and local adaptibility when using aggregated time series data not originally collected for the purpose of epidemiological studies.
PMCID: PMC1060882  PMID: 8758218
21.  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
22.  Diabetic retinopathy: quantitative variation in capillary basement membrane thickening in arterial or venous environments. 
Diabetes mellitus was induced in male beagles by a single injection of an alloxan and streptozotocin cocktail and fasting blood sugar levels maintained between 15 and 20 mmol/l. Five years after induction of diabetes, three diabetic animals were sacrificed, together with sex and age-matched controls, and the retinas fixed for either transmission electron microscopy (TEM) or trypsin digestion. In TEM specimens, capillaries in close proximity to the major vessels were designated as either AE (arterial environment) or VE (venous environment) and the thickness of their basement membranes (BMs) measured using an image analyser based two dimensional morphometric analysis system. Results show that the BMs of retinal capillaries from the diabetic dogs were significantly thicker than those from control dogs. Furthermore, within the diabetic group the AE capillaries had thicker BMs than VE capillaries (p < or = 0.05). The controls, however, showed no significant difference in BM thickness between AE and VE capillaries. Although many of the capillaries designated as AE or VE would actually have been derived from the opposite side of the circulation, with respect to BM thickness, they conformed to values of their specific group. The conclusion is that diabetic capillaries are more vulnerable to BM thickening in an arterial environment than in a venous environment.
PMCID: PMC504717  PMID: 8123622
23.  Trends and district variations in the hospital care of childhood asthma: results of a regional study 1970-85. 
Thorax  1990;45(6):431-437.
Trends and district variations in the pre-hospital and hospital care of children aged 0-14 years admitted with acute asthma were surveyed in all 13 districts of a health region by examining case notes for 1970, 1978, and 1985. From 1970 to 1985 there was a substantial increase in admissions and some reduction of hospital stay. Over this time adrenergic drugs remained the most frequently used treatment with a large shift towards selective beta2 agonists administered by nebulisation. Use of corticosteroids fell in the under 5s with a decrease in the parenteral route of administration but rose in the 5-14 age group with an increase in the oral route of administration. There was an increase the use of oral xanthines but this was outweighed by falls in the use of suppositories and in parenteral administration. The use of antibiotics became less frequent and that of sedatives and antihistamines fell to almost nil. There were also important changes in other aspects of management, notably an increase in the use of lung function tests (from 3% to 70%) and falls in the use of chest radiographs, blood tests, bacteriology, and physiotherapy. In nearly all aspects of management there were significant and often very extreme variations in practice between districts, which were unlikely to be explained by differences in morbidity. These variations would be a suitable focus for medical audit, with the aim of establishing which treatment regimens have the best outcome and avoiding unnecessary cost and discomfort. Because early hospital drug treatment is closely related to the type of treatment given before admission such audit activities would need to include general practitioners.
PMCID: PMC462524  PMID: 1975463
24.  Randomised controlled trial of effects of coordinating care for terminally ill cancer patients. 
BMJ : British Medical Journal  1992;305(6865):1317-1322.
OBJECTIVES--To measure effects on terminally ill cancer patients and their families of coordinating the services available within the NHS and from local authorities and the voluntary sector. DESIGN--Randomised controlled trial. SETTING--Inner London health district. PATIENTS--Cancer patients were routinely notified from 1987 to 1990. 554 patients expected to survive less than one year entered the trial and were randomly allocated to a coordination or a control group. INTERVENTION--All patients received routinely available services. Coordination group patients received the assistance of two nurse coordinators, whose role was to ensure that patients received appropriate and well coordinated services, tailored to their individual needs and circumstances. MAIN OUTCOME MEASURES--Patients and carers were interviewed at home on entry to the trial and at intervals until death. Interviews after bereavement were also conducted. Outcome measures included the presence and severity of physical symptoms, psychiatric morbidity, use of and satisfaction with services, and carers' problems. Results from the baseline interview, the interview closest to death, and the interview after bereavement were analysed. RESULTS--Few differences between groups were significant. Coordination group patients were less likely to suffer from vomiting, were more likely to report effective treatment for it, and less likely to be concerned about having an itchy skin. Their carers were more likely to report that in the last week of life the patient had had a cough and had had effective treatment for constipation, and they were less likely to rate the patient's difficulty swallowing as severe or to report effective treatment for anxiety. Coordination group patients were more likely to have seen a chiropodist and their carers were more likely to contact a specialist nurse in a night time emergency. These carers were less likely to feel angry about the death of the patient. CONCLUSIONS--This coordinating service made little difference to patient or family outcomes, perhaps because the service did not have a budget with which it could obtain services or because the professional skills of the nurse-coordinators may have conflicted with the requirements of the coordinating role.
PMCID: PMC1883850  PMID: 1483075
25.  Increase in hospital admissions for childhood asthma: trends in referral, severity, and readmissions from 1970 to 1985 in a health region of the United Kingdom. 
Thorax  1989;44(8):614-619.
Admissions to hospital for childhood asthma have continued to increase, but the reasons are unknown. Because the incidence of acute asthmatic attacks in the community greatly exceeds the admission rate, this increase could be a result of changes in medical practice shifting the balance of care towards the hospital without there being any underlying change in morbidity. In the South West Thames Region (population 2.9 million) over the eight years 1978-85 the number of hospital admissions among those aged 0-4 and 5-14 rose by 186% and 56%. A random sample of case notes from all hospitals in the region was examined for evidence of changes in mode of referral, severity on admission (duration of episode, vital signs on admission), and readmission ratio. The findings indicate that there has been no reduction in severity on admission or increase in readmission rate since 1978. The findings for the 5-14 age group contrast with those from an earlier study (1970-8) in the same region, in which a substantial increase in self referral was observed together with an increase in readmissions and a reduction in the duration of the attack; pulse and respiration rates on admission have, however, remained unchanged over the 16 year period. Overall, these findings indicate that the increase in admissions cannot be satisfactorily explained by changes in medical practice alone and may be due to an increase in the number of asthmatic children experiencing severe attacks. This points to a change in the epidemiology of childhood asthma.
PMCID: PMC461986  PMID: 2799740

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