Randomised trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: respiratory and neurological outcomes at 2 years.

BACKGROUND: The long term outcome of children entered into neonatal trials of high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) has been rarely studied. OBJECTIVE: To evaluate respiratory and neurodevelopmental outcomes for children entered into the United Kingdom Oscillation Study, which was designed to evaluate these outcomes. METHODS: Surviving infants were followed until 2 years of age corrected for prematurity. Study forms were completed by local paediatricians at routine assessments, and parents were asked to complete a validated neurodevelopmental questionnaire. RESULTS: Paediatricians' forms were returned for 73% of the 585 surviving infants. Respiratory symptoms were common in all infants, and 41% had received inhaled medication. Mode of ventilation had no effect on frequency of any symptoms. At 24 months of age, severe neurodevelopmental disability was present in 9% and other disabilities in 38% of children, but the prevalence of disability was similar in children who received HFOV or CV (relative risk 0.93; 95% confidence interval 0.74 to 1.16). The prevalence of disability did not vary by gestational age, but boys were more likely to have overall disability. Developmental scores were unaffected by mode of ventilation (relative risk 1.13; 95% confidence interval 0.78 to 1.63) and were lower in infants born before 26 weeks gestation compared with babies born at 26-28 weeks. CONCLUSIONS: Initial mode of ventilation in very preterm infants has no impact on respiratory or neurodevelopmental morbidity at 2 years. HFOV and CV appear equally effective for the early treatment of respiratory distress syndrome.

Risk factors for respiratory morbidity in infancy after very premature birth.

OBJECTIVES: To determine the occurrence of respiratory morbidity during infancy after very premature birth and to identify risk factors. DESIGN: Prospective follow up study. SETTING: The United Kingdom oscillation study. PATIENTS: 492 infants, all born before 29 weeks gestation. INTERVENTIONS: Structured questionnaires were completed by local paediatricians when the infants were seen in outpatients at 6 and 12 months of age corrected for prematurity. MAIN OUTCOME MEASURES: Cough, wheeze, and treatment requirements and the composite measure of respiratory morbidity (cough, frequent cough, cough without infection, wheeze, frequent wheeze, wheeze without infection, and use of chest medicine) and their relation to 13 possible explanatory variables. RESULTS: At 6 and 12 months of corrected age, 27% of the infants coughed and 6% had frequent (more than once a week) cough, and 20% and 3% respectively had wheeze or frequent wheeze. At 6 and 12 months, 14% of infants had taken bronchodilators and 8% inhaled steroids. After adjustment for multiple outcome testing, four factors were associated with increased respiratory morbidity: male sex, oxygen dependency at 36 weeks postmenstrual age, having older siblings aged less than 5 years, and living in rented accommodation. CONCLUSIONS: Male infants are particularly vulnerable to respiratory morbidity in infancy after very premature birth. It is important to identify a safe and effective strategy to prevent chronic oxygen dependency.

Frequent wheeze at follow up of very preterm infants: which factors are predictive?

OBJECTIVE: To determine if chest radiograph appearance at 28 days or 36 weeks postmenstrual age (PMA) can predict recurrent wheeze or cough at follow up in prematurely born infants more effectively than readily available clinical data. DESIGN: Chest radiographs of infants entered into the UKOS trial, who had had a chest radiograph at 28 days and 36 weeks PMA and completed six months of follow up, were assessed for the presence of fibrosis, interstitial shadows, cystic elements, and hyperinflation. At 6 months of corrected age, the occurrence and frequency of wheeze and cough since discharge were determined using a symptom questionnaire. PATIENTS: A total of 185 infants with a median gestational age of 26 (range 23-28) weeks. RESULTS: Thirty seven infants wheezed more than once a week, compared with the rest of the cohort. These infants had significantly higher chest radiograph scores at 28 days (p = 0.020) and 36 weeks PMA (p = 0.005), with significantly higher scores at 28 days for fibrosis (p = 0.017) and at 36 weeks PMA for fibrosis (p = 0.001) and cystic elements (p = 0.0007). They had also been ventilated for longer (p = 0.013). Forty four infants coughed more than once a week; they did not differ significantly from the rest of the cohort. An abnormal chest radiograph score at 36 weeks PMA had the largest area under the receiver operator characteristic curve with regard to prediction of frequent wheeze. CONCLUSION: An abnormal chest radiograph appearance at 36 weeks PMA predicts frequent wheeze at follow up and appears to be a better predictor than readily available clinical data.

Health effects of an air pollution episode in London, December 1991.

BACKGROUND: In December 1991 London experienced a unique air pollution episode during which concentrations of nitrogen dioxide rose to record levels, associated with moderate increases in black smoke. The aim of this study was to investigate whether this episode was associated with adverse health effects and whether any such effects could be attributed to air pollution. METHODS: The numbers of deaths and hospital admissions occurring in Greater London during the week of the episode were compared with those predicted using data from the week before the episode and from equivalent periods from the previous four years. Relative risks (RR) (episode week versus predicted) for adverse health events were estimated using log linear modelling and these were compared with estimates from control areas which had similar cold weather but without increased air pollution. RESULTS: In all age groups mortality was increased for all causes (excluding accidents) (relative risk = 1.10) and cardiovascular diseases (1.14); non-significant increases were observed for all respiratory diseases (1.22), obstructive lung diseases (1.23), and respiratory infections (1.23). In the elderly (65 + years) the relative risk of hospital admission was increased for all respiratory diseases (1.19) and for obstructive lung diseases (1.43), and a non-significant increase was observed for ischaemic heart disease (1.04). In children (0-14 years) there was no increase in admissions for all respiratory diseases and only a small non-significant increase for asthma. When compared with control areas the relative risks became non-significant but remained increased. CONCLUSIONS: The air pollution episode was associated with an increase in mortality and morbidity which was unlikely to be explained by the prevailing weather, a coincidental respiratory epidemic, or psychological factors due to publicity. Air pollution is a plausible explanation but the relative roles of nitrogen dioxide and particulates cannot be distinguished.

Attitudes and ischaemic heart disease in the Caerphilly Study: the Health Attitude Inventory.

BACKGROUND: The Health Attitude Inventory (HAI) is developed to assess attitudes, beliefs and values towards coronary-related behaviour in epidemiological studies. It comprises a 76-item self-administered questionnaire which can be completed in under 10 minutes by most adults. METHODS: The HAI was administered to 2100 men aged 50-64 years along with measures of ischaemic heart disease risk factors, including the following coronary-related behaviours: smoking, exercise, type A behaviour and the consumption of fried food, dairy produce, wholemeal bread and vegetables. RESULTS: Cross-sectional analyses using linear regression showed attitudes, beliefs and values to explain between 8% and 27% of the variance in the dietary coronary-related behaviour. For exercise 13% of the variance was explained, and for type A behaviour 18%. Similar analysis for smoking using logistic regression (non-smoker versus current smoker) showed a predictive concordance of 95%. CONCLUSIONS: The HAI has demonstrated the assessment of attitudes, beliefs and values in an epidemiological setting to show associations with a range of coronary risk behaviours. This finding has potential public health as well as aetiological application in that influential attitudes, values and beliefs can be identified to aid increasing healthy as well as reducing risky coronary-related behaviour.

Childhood asthma in four countries: a comparative survey.

BACKGROUND: Asthma mortality among young people varies widely between different countries. Geographical differences in asthma prevalence are also believed to exist, but evidence is sparse owing to the lack of multicentre surveys using common protocols. A survey was conducted of 12-year-old children living in defined areas of New Zealand, Wales, South Africa and Sweden, in order to see whether asthma prevalence and mortality rates in children show parallel differences. METHODS: Questionnaires enquiring about a history of asthma and respiratory symptoms were issued to the parent. The children performed a simple exercise challenge test. RESULTS: Information was obtained for 4353 children. A history of asthma at any time was reported for 16.8% of children in New Zealand, 12.0% in Wales, 11.5% in South Africa and 4.0% of Sweden, and a similar pattern was shown by several other indices of asthma (various relevant symptoms, inhaler use, response to exercise challenge, and asthma mortality at ages 5-19 years). In Sweden wheezing was negatively associated with pet ownership; elsewhere there was a positive (though non-significant) association. Cat ownership was highest in New Zealand and lowest in Sweden. CONCLUSIONS: The prevalence of asthma in children shows geographical variation which is parallel to that of asthma mortality, being high in New Zealand and low in Sweden. Differential exposure to animal allergens is a possible factor in this variation.

A national survey of asthma prevalence, severity, and treatment in Great Britain.

Parents of 5472 children aged 5-17 years from 3209 families were interviewed in a nationwide household survey. In the past year, 15.0% of children had wheezed, 2.2% had more than 12 attacks, and 2.3% had experienced a speech limiting attack. Altogether 4.3% were woken more than once a week by wheezing, 13.1% had doctor diagnosed asthma, and 13.6% had been prescribed antiasthmatic drugs in the past year. With increasing age, morbidity related to wheezing declined to a greater extent than annual period prevalence. The prevalence of wheeze varied little by socioeconomic group, but there were marked trends in all three indices of severity towards increased morbidity in poorer families. Diagnostic labelling and drug treatment of wheezy children did not differ substantially with socioeconomic status. Thus, a degree of socioeconomic equality exists in the process of medical care for childhood asthma in Britain. This does not appear to have resulted in equality of outcome.

Shear-induced Filter Blockage. A Population Based Appraisal of a Method for the Assessment of Platelet, White Cell and von Willebrand Factor Interactions.

Blood behaviour under shear-stress is assessed by a filter method in the Caerphilly Prospective Heart Study. Associations with haemostatic and lifestyle factors in 941 men aged 55 to 69 years are reported. The importance of platelets in filter blockage is confirmed, and roles for white cells and plasma viscosity in determining flow prior to blockage are identified. The aspect of platelet activity involved in blockage appears to be independent of mechanisms mediated by cyclo-oxygenase and adenosine diphosphate. von Willebrand factor however is associated with filter blockage, probably as an inter-platelet ligand. Fibrinogen is not required for blockage. Men regularly consuming alcohol or garlic supplements show reduced blockage, and biochemical mechanisms are suggested which might explain these associations. No effects of aspirin, smoking or consumption of fish oil supplements were noted. Shear-induced filter blockage is a simple method for measuring complex flow-dependent interactions of haemostatic factors. Its application in a wide range of investigations, including epidemiological studies, would appear to be appropriate.

Temperature and risk factors for ischaemic heart disease in the Caerphilly prospective study.

OBJECTIVE: To examine the associations between air temperature and risk factors for ischaemic heart disease. METHOD: Data on risk factors are available from up to 2036 men in the Caerphilly Prospective Heart Disease Study. Daily temperatures were obtained from the Meteorological Office. Relations between these were examined by regression. RESULTS: The coldest month of the year has a mean temperature that is 16 degrees C lower than that in the warmest month. A fall in temperature of this magnitude is associated with higher blood pressures (by 3-5 mm Hg) and a lower concentration of high density lipoprotein cholesterol (by 0.08 mmol/l). The most important effects however, seem to be on the haemostatic system. Fibrinogen is 0.34 g/l higher in the coldest month than in the warmest (p < 0.001) and alpha 2 macroglobulin, a protein that inhibits fibrinolysis, is also raised. Platelet count is increased by 30% of a standard deviation and the sensitivity of platelets in whole blood to adenosine diphosphate is increased by cold. CONCLUSIONS: These effects on haemostasis, together with the effect on blood pressure, could explain a large part of the increase in ischaemic heart disease in the winter but are unlikely to explain much of the difference in mortality within different areas of England and Wales.

Inter-relationships between haemostatic tests and the effects of some dietary determinants in the Caerphilly cohort of older men.

Inter-relationships between fibrinogen, platelets and other haemostatic factors were examined in 1030 men aged 55-99 years. Fasting blood was taken and used for cell counts, platelet counts and platelet parameters, aggregation of platelets to ADP by a whole blood method and a filter test of platelet activation. Plasma fibrinogen, von Willebrand factor, factor VII and plasma viscosity were measured by standard methods. A stressed bleeding time was conducted on the forearm of the arm not used for venepuncture. Variability within the laboratory and short-term intra-subject variation were examined and found to be acceptably small. The effect of age on the tests was modest, except for von Willebrand factor which increased by about 50% of a SD for every 10 years of age. Cholesterol and triglyceride levels had small effects on the platelet tests and a large effect on factor VII. A number of dietary and life-style determinants were examined: smokers had increased levels of fibrinogen, viscosity and white cell count and reduced bleeding times. Alcohol drinkers showed reduced platelet activity and have lower levels of fibrinogen, von Willebrand factor and white cell count. Men who took fish oil capsules had substantially increased bleeding times and lower levels of von Willebrand factor and men who took capsules containing an extract of garlic showed reduced platelet retention in the filter test.

Infant feeding, wheezing, and allergy: a prospective study.

The determinants of wheezing and allergy were investigated in 453 children with a family history of allergic disease. A randomised controlled trial examined the effects of withholding cows' milk protein during the first three months of life and replacing cows' milk with soya milk. The children were followed up to the age of 7 years. Withholding cows' milk did not reduce the incidence of allergy or wheezing. Children who had ever been breast fed had a lower incidence of wheeze than those who had not (59% and 74% respectively). The effect persisted to age 7 years in the non-atopics only, the risk of wheeze being halved in the breast fed children after allowing for employment status, sex passive smoking, and overcrowding. Allergic disease was not associated with exposure to tobacco smoke, house dust mite antigen, or cats. Breast feeding may confer long term protection against respiratory infection.

Height: a risk marker for ischaemic heart disease: prospective results from the Caerphilly and Speedwell Heart Disease Studies.

The predictive power of height for future ischaemic heart disease (IHD) was examined in 4860 men from two communities in South Wales and the West of England. At follow-up, men in the shortest fifth of the height distribution had experienced twice as many incident IHD events (fatal and non-fatal myocardial infarction) as was the case for men from the tallest fifth. Adjustment for age, social class and smoking habit failed to alter these relationships significantly. In the data from South Wales, determinants of height were examined; birth rank and number of siblings showed a trend with height. This trend was found only in men whose fathers were manual workers and may be related to inadequate nutrition in the higher birth ranks and larger families. These results support the suggestion that early childhood factors may be relevant to IHD in middle age and possible mechanisms are discussed.

Prevalence of asthma among 12 year old children in New Zealand and South Wales: a comparative survey.

A survey of 12 year old schoolchildren was carried out in New Zealand and South Wales, the same questionnaire and exercise provocation test being used. The prevalence of a history of asthma at any time was higher in New Zealand (147/873, 17%) than in South Wales (116/965, 12%). The New Zealand children were also more likely than the Welsh children to have a history of "wheeze ever" (27% versus 22%), and wheeze brought on by running (15% versus 10.5%). The sex ratio of asthmatic and wheezy children was very similar in the two countries. A history of hospital admission for chest trouble was twice as common in New Zealand as in South Wales. An exercise test produced a fall in peak expiratory flow rate of 15% or more in more New Zealand children (12.2%) than Welsh children (7.7%). These results suggest that the prevalence of childhood asthma is higher in New Zealand than in South Wales.