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Background Eczema is common in infancy; however, there is little evidence about its natural history to adulthood. Objectives To study the natural history of eczema from birth to young adult life with particular reference to its relation to atopy. Methods A birth cohort of children with atopic family histories was followed for 23 years. Clinical examinations were conducted until the age of 7 years, skin-prick tests and serum total IgE were recorded in infancy and at ages 7 and 23 years, and questionnaires about eczema symptoms were completed at 15 and 23 years. Results Information was obtained on 497 subjects at birth, 482 at 1 year, 440 at 7 years, 363 at 15 years and 304 at 23 years. Eczema usually remitted from age 1 to 7 years but became more persistent from the age of 15 years, especially in those who were atopic. The prevalence of eczema rose in women from age 15 to 23 years but declined in men. Adults with eczema had higher IgE than those without at 3 months (geometric mean 3·0 vs. 1·7 kU L-1; P = 0·01), 7 years (107·9 vs. 45·2 kU L-1; P = 0·01) and 23 years (123·4 vs. 42·3 kU L-1; P = 0·01), and were more likely to have had positive skin-prick tests at 1 year of age. Current eczema was associated with raised IgE in infancy and adulthood but not in childhood. Conclusions Predisposed infants and children with eczema usually grow out of the disease, but in adolescence it is more likely to persist. Adult eczema is related to atopy from the age of 3 months. What's already known about this topic? Eczema is associated with atopy, asthma and rhinoconjunctivitis. Eczema in infancy usually remits but is more likely to persist if the child is atopic. After puberty eczema often persists to adult life. What does this study add? Adult eczema is associated with atopy from the age of 3 months. Atopy increases the likelihood of persistence after adolescence.

Background: A study was undertaken to see whether the prevalence of asthma has changed since a survey was conducted in 1988, using the same methods that showed an increase during the previous 15 years. Methods: A survey of 12 year old children was conducted in schools in South Wales where surveys had taken place in 1973 and 1988. The survey comprised a parentally completed questionnaire and an exercise challenge test, performed when no bronchodilator had been recently used. Results: In 1973, 1988, and 2003, questionnaires were obtained for 817, 965 and 1148 children, respectively; the exercise test was performed by 812, 960 and 1019 children, respectively. The prevalence of reported wheeze in the last year rose during each 15 year period (9.8%, 15.2%, 19.7%), with an even steeper rise in reported asthma ever (5.5%, 12.0%, 27.3%). There was a continued increase in wheeze attributed to running, in terms of all children (5.8%, 10.5%, 16.0%) and also as the proportion of those with a history of wheeze (34.1%, 47.0%, 57.3%). The use of inhaled corticosteroids (not available in 1973) increased fourfold between 1988 and 2003. The prevalence of exercise induced bronchoconstriction rose between 1973 and 1988 but had declined by 2003. Conclusions: The rise in the prevalence of asthmatic symptoms has continued since 1988. This appears to conflict with a reported recent decline, unless asthma prevalence peaked in the 1990s. The decline in exercise induced bronchoconstriction is probably attributable to better control of the disease as more children are now using inhaled corticosteroids as preventive treatment.

Two successive randomized trials examined the effect of an increased intake of fatty fish, or the use of fish oil supplements, in reducing mortality in men with heart disease. The Diet and Reinfarction Trial (DART) was conducted in 2033 men who were recovering from acute myocardial infarction (MI). Those who were advised to eat fatty fish (or who opted to take fish oil capsules instead) had a 29% reduction in all-cause mortality over the following two years compared with those not so advised. The effect appeared in the first few months of the trial. The Diet and Angina Randomized Trial (DART 2) involved 3114 men with stable angina. Advice to eat fatty fish did not reduce mortality, and taking fish oil capsules was associated with a higher risk of cardiac and sudden death. The adverse effects of fish or fish oil were restricted to men not taking beta-blockers or dihydropyridine calcium-channel blockers, and were greater in those taking digoxin. Evidence from other sources strongly suggests an anti-arrhythmic action of fish oil, particularly after MI or in the presence of acute ischemia. The apparently conflicting results of the two trials may reflect different actions of n-3 fatty acids in acute and chronic conditions, together with different effects of eating fish and taking fish oil capsules. A mechanism is proposed that could account for these findings.

Objective To address the risk factors for coronary heart disease (CHD) and back pain in workplaces employing less than 50 people in the Merthyr/Cynon area of South Wales. Design A comparative study of small workplaces randomly allocated into either CHD or musculo-skeletal intervention groups. Setting Small workplaces, employing 50 staff or less. Method Following random allocation into CHD or musculo-skeletal groups, participating workplaces received a dual approach consisting of organisational health promotion policy advice and support with individual employee health screening, advice and limited intervention. Results Stress was the most commonly reported CHD risk factor amongst respondents and was more prevalent amongst women, although there was also an important differentiation identified between 'workplace' and 'domestic' stress. Advice about stress was twice as often reported in the private than in the public sector, although the prevalence of'current stress' was slightly higher among the public than the private workers. Most smokers wanted to stop. Over 50 per cent of respondents reported some form of musculo-skeletal problem and physical inactivity was generally high across all sectors. There appeared to be an increased awareness of health messages following the interventions but no statistically significant changes in behaviour were evident. Nearly all workplaces (97 per cent) had smoking policies. The commonest obstacle to health promotion was lack of obvious benefit as perceived by the employer. Conclusions Overall, there appeared to be a resistance to workplace health promotion, which was viewed as not benefiting the business, requiring too much time, and not the employer's responsibility. Most small businesses do not have the resources available to larger employers to address the health needs of their workforce and alternative ways of helping these workplaces needs to be explored. The major issue that needs to be addressed is stress, which may originate in the workplace or at home. Other important health related matters include exercise, diet, smoking and spinal pain.

Background: Although there is growing knowledge about factors that may predispose to the onset of atopic dermatitis (AD), little is known about factors which may exacerbate existing disease. AD sufferers and those involved in the management of the disease are often aware of factors that influence its course and severity. However, there is little available evidence on the distribution and relative importance of such factors, and what information exists is derived from selected groups such as hospital patients and may not therefore be representative of the AD population as a whole. Objectives: To determine the distribution and relative importance of 19 potential exacerbating and relieving factors as perceived by a population-based sample of schoolchildren with AD. Methods: A questionnaire was used to identify all children with AD in years 8 and 9 (12–14-year-olds) from eight comprehensive schools across Wales. These individuals were then requested to complete a supplementary questionnaire which asked them to state for each of 19 factors whether (i) it makes their eczema better, (ii) it makes their eczema worse, (iii) it has no effect, or (iv) they do not know its effects. Results: Almost 10% (250 of 2501) of children surveyed were considered to have AD, and 90% (225 of 250) of these completed the supplementary questionnaire. Most AD sufferers found that none to two factors relieve their symptoms whilst none to five factors exacerbate them. Sweating from exercise, fabrics (especially wool) and hot weather were the three most common exacerbators, affecting 41·8%, 40% and 39·1%, respectively, of AD responders. The three key relievers were steroid creams (22·2% of AD responders), moisturizers/makeup (16·4%) and medicines/tablets (13·8%). Almost 60% of respondents believed foods have no effect on their symptoms. There was also evidence to suggest that 12·4% (28 of 225) of participants may use creams which they are not aware contain steroids. Conclusions: These findings shed light on the relative perceived importance of factors such as food, aeroallergens, sweat, climate, illness, stress and therapies for the course of AD in a representative population sample of AD sufferers. Such information might be explored during clinical consultations given the increasing participation of sufferers and their carers in the management of this chronic disease. These findings also form the basis of hypothesis generation for future analytical studies.

To determine whether residents of congested streets have a higher prevalence of respiratory symptoms than residents of nearby uncongested streets, and whether their respiratory health improves following a reduction in exposure to traffic related air pollutants.An area was identified where certain streets were subject to air pollution from heavy road traffic, which was likely to improve following the construction of a by-pass. A respiratory survey was conducted among the residents, together with the residents of nearby uncongested streets, at baseline and again a year after the by-pass opened. Measurements were made of air pollutant concentrations in both areas on both occasions.Initial concentrations of PM10 and PM2.5 were substantially higher in the congested than in the uncongested streets. When the by-pass opened, the volume of heavy goods traffic fell by nearly 50%. PM10 decreased by 23% (8.0 microg/m3) in the congested streets and by 29% (3.4 microg/m3) in the uncongested streets, with similar proportionate falls in PM2.5. There were no clear or consistent differences between the residents of the two areas initially in terms of symptoms or peak flow variability. Repeat questionnaires were obtained from 165 and 283 subjects in the congested and uncongested areas respectively, and showed a tendency for most symptoms to improve in both areas. For chest symptoms, the improvement tended to be greater in the uncongested area, although the difference between the areas was not statistically significant. Rhinitis and rhinoconjunctivitis tended to improve to a greater extent in the congested streets; the difference between the areas was significant for the degree to which rhinitis interfered with daily activities. Peak flow variability tended to improve in the uncongested area.The by-pass reduced pollutant levels to a degree that probably alleviates rhinitis and rhinoconjunctivitis but has little effect on lower respiratory symptoms.

Background Although pollens are major allergens associated with allergic rhinoconjunctivitis and asthma, there is little information about the relative prevalence of these conditions in populations with different pollen exposures. Objective The purpose of this study was to investigate the relationship between pollen exposure and allergic symptoms among children in different countries. Methods An ecological analysis was conducted to see whether pollen exposure (pollen counts, and duration and severity of pollen seasons) is associated with symptoms of allergic rhinoconjunctivitis, asthma and atopic eczema in 28 centres within 11 countries (nine being in Europe). Data on the prevalence of symptoms in 13–14-year olds were based on the responses to the written questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC). The analysis was adjusted for gross national product and mean annual relative humidity. Results There was little relationship between pollen exposure and symptom prevalence, except for a significant inverse association between grass pollen counts and lifetime prevalence of the symptoms of allergic rhinitis (P=0.03). Almost all the regression coefficients were negative. The associations were even weaker and all non-significant when the analyses were conducted within countries, using a random intercept fixed slope model, but there was still no evidence of a positive association between pollen exposure and symptoms. Conclusion There is a weak but consistent tendency for the prevalence of allergic symptoms to be inversely associated with pollen exposure. This finding accords with evidence from several countries, suggesting that the prevalence of hayfever and asthma tends to be lower in rural than in urban areas, and lowest among people living on farms. Exposure to allergenic pollen in early life does not appear to increase the risk of acquiring symptoms of respiratory allergy, and may even give some protection against them.

Objective: To assess and compare the effects of natural folate (100 microg) with those of folic acid from fortified sources (100 microg/day) on plasma folate and homocysteine. Design: Randomized controlled trial (parallel groups). Setting: Men and women living in South Wales, UK. Subjects: A total of 135 healthy individuals recruited from the local workforce and blood donor sessions. All subjects possessed the 'wild-type' CC genotype for C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). Interventions: Subjects underwent one of the following dietary interventions for 4 months: (1) fortified diet—usual diet plus 100 microg/day folic acid from fortified foods; (2) natural folate diet—usual diet plus 100 microg/day folate from natural sources; (3) control—usual diet. Results: The fortified group increased reported intake of folic acid from fortified foods compared to other groups (P

Objective: To assess the long-term effect of dietary advice on diet and mortality after a randomised trial of men with a recent history of myocardial infarction. Design: Questionnaire survey and mortality follow-up after a trial of dietary advice. Setting: Twenty-one hospitals in south Wales and south-west England. Subjects: Former participants in the Diet and Reinfarction Trial. Main outcome measures: Current fish intake and cereal fibre intake. All-cause mortality, stroke mortality and coronary mortality. Results: By February 2000, after 21147 person years of follow-up, 1083 (53%) of the men had died. Completed questionnaires were obtained from 879 (85%) of the 1030 men alive at the beginning of 1999. Relative increases in fish and fibre intake were still present at 10 y but were much smaller. The early reduction in all-cause mortality observed in those given fish advice (unadjusted hazard 0.70 (95% CI 0.54, 0.92)) was followed by an increased risk over the next 3 y (unadjusted hazard 1.31 (95% CI 1.01, 1.70). Fat and fibre advice had no clear effect on coronary or all-cause mortality. The risk of stroke death was increased in the fat advice group¾the overall unadjusted hazard was 2.03 (95% CI 1.14, 3.63). Conclusions: In this follow-up of a trial of intensive dietary advice following myocardial infarction we did not observe any substantial long-term survival benefit. Further trials of fish and fibre advice are feasible and necessary to clarify the role of these foods in coronary disease.

Objective:To study the effect of advice to increase dietary soluble fibre, including fruit and vegetables, on plasma folate and homocysteine in men with angina.Design:Data were collected on a subset of subjects from the Diet and Angina Randomised Trial (DART II). In a randomised (2 × 2) factorial design, subjects received advice on either, neither or both interventions to: (1) increase soluble fibre intake to 8.0 g day−1(fruit, vegetables and oats); (2) increase oily fish intake to 2 portions week−1. Those who received soluble fibre advice were compared with those who did not. Subjects were genotyped for C677T variant 5,10-methylenetetrahydrofolate reductase (MTHFR).Setting/subjects:Seven hundred and fifty-three male angina patients were recruited from general practice.Results:Plasma homocysteine concentrations were at the upper end of the normal range (median 11.5, 25% 9.4, 75% 14.0 μmol l−1). Baseline intake of fruit and vegetables was positively correlated with plasma folate (rs= 0.29,P< 0.01). Smokers had lower intakes of fruit and vegetables, lower plasma folate and higher homocysteine (allP< 0.01). Homozygotes for variant MTHFR had higher homocysteine concentrations at low plasma folate (P< 0.01). Reported intakes of fruit and vegetables and estimated dietary folate increased in the intervention group (ca.+75 g day−1,P< 0.01 andca.+20 g day−1,P< 0.05, respectively). However, neither plasma folate (baseline/follow-up 4.5 vs. 4.4 μg l−1,P= 0.40) nor homocysteine (baseline/follow-up 11.7 vs. 11.7 μmol l−1,P= 0.31) changed.Conclusions:Plasma homocysteine, a cardiovascular risk factor, is influenced by MTHFR genotype, plasma folate and smoking status. Dietary advice successfully led to changes in fruit and vegetable intake, but not to changes in plasma folate or homocysteine, possibly because the fruits and vegetables that were chosen were not those richest in folate.

OBJECTIVESWe sought to study the effect of low-dose folic acid supplementation or optimization of dietary folate intake on plasma homocysteine and endothelial function in healthy adults.BACKGROUNDElevated homocysteine is associated with cardiovascular disease, but it is not known whether this relationship is causal. Individuals homozygous (TT) for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (∼12% of the population) have increased homocysteine levels, particularly in association with suboptimal folate intake.METHODSHealthy subjects (n = 126; 42 of each MTHFR genotype) were included in this cross-over study of three interventions of four months each: 1) placebo plus natural diet; 2) daily 400-μg folic acid supplement plus natural diet; and 3) increased dietary folate intake to 400 μg/day.RESULTSAt baseline, homocysteine was inversely related to plasma folate and was higher in TT homozygotes. For the whole group, plasma folate increased by 46% after dietary folate and by 79% after supplementation, with reductions of homocysteine of 14% and 16%, respectively. Within the genotype, TT homozygotes exhibited the most marked changes in these variables. Brachial artery endothelial function, as determined by a change in end-diastolic diameter in response to increased flow, was not changed by increased folate intake (98 ± 73 μm at baseline, 110 ± 69 μm after a high-folate diet, 114 ± 59 μm after supplementation and 118 ± 68 μm after placebo). Plasma von Willebrand factor antigen was unaltered.CONCLUSIONSOptimization of dietary folate or low-dose folic acid supplementation reduces plasma homocysteine but does not enhance endothelial function, irrespective of the MTHFR (C667T) genotype.

Several studies have suggested that the increasing prevalence of symptoms of asthma, rhinitis and eczema, could be associated with dietary factors. In the present paper, a global analysis of prevalence rates of wheeze, allergic rhinoconjunctivitis and atopic eczema was performed in relation to diet, as defined by national food intake data.Analyses were based on the International Study of Asthma and Allergies in Childhood (ISAAC) data for 6–7 and 13–14 yr old children. Symptoms of wheeze, allergic rhinoconjunctivitis and atopic eczema symptom prevalence were regressed against per capita food intake, and adjusted for gross national product to account for economic development. Dietary data were based on 1995 Food and Agriculture Organisation of the United Nations data for 53 of the 56 countries that took part in ISAAC phase I (1994/1995).The 13–14 year age group showed a consistent pattern of decreases in symptoms of wheeze (current and severe), allergic rhinoconjunctivitis and atopic eczema, associated with increased per capita consumption of calories from cereal and rice, protein from cereals and nuts, starch, as well as vegetables and vegetable nutrients. The video questionnaire data for 13–14 yr olds and the ISAAC data for 6–7 yr olds showed similar patterns for these foods.A consistent inverse relationship was seen between prevalence rates of the three conditions and the intake of starch, cereals, and vegetables. If these findings could be generalised, and if the average daily consumption of these foods increased, it is speculated that an important decrease in symptom prevalence may be achieved.

BACKGROUND: Death from asthma is regarded as preventable in principle, especially under the age of 65 years. METHODS: In 1994 a confidential inquiry was set up to investigate deaths attributable to asthma in residents of Wales under the age of 65 years. During the period of the inquiry 92 cases were notified as being ascribed to asthma, or (in 1996) having a mention of asthma on the death certificate. Of these, 80 were investigated further with the help of general practitioners, hospital notes, and relatives. The details were then considered by a small panel of doctors who endeavoured to identify factors that may have contributed to the deaths. RESULTS: Asthma was considered to be the underlying cause of 52 deaths. Although disease severity was usually a major factor, some aspect of the patient’s behaviour or circumstances seemed to have contributed to 31 deaths, while in 15 cases there was probably a deficiency in medical care. CONCLUSIONS: Some preventable asthma deaths still occur, particularly in relation to inadequate treatment. Factors associated with patients’ behaviour and circumstances are more difficult to tackle but, if doctors are aware of high risk patients, increased vigilance may prevent some deaths.

Background: The risk of allergic disease may be influenced by the degree of "westernization" survey was conducted to ascertain whether the prevalence of allergy was lower in Albania than elsewhere in Europe, as it has been the most isolated European country. Methods: The subjects were residents of Tirana aged 20-44 years. A screening questionnaire was completed by 2653 subjects. A more detailed questionnaire was administered to a random sample of 564 respondents, together with skin prick tests and serum IgE assay.Results: The prevalence of wheeze in the last year, and of wheeze without a cold, was lower in Albania than in any country that participated in the European Community Respiratory Health Survey. Nasal allergy and atopy (as indicated by serum specific IgE) were also uncommon in Albania, although serum total IgE concentrations were high.Conclusions: The findings confirmed the hypothesis of a low prevalence of allergy in Albania. Possible reasons include the recent economic isolation of Albania, the infrequency of smoking by women, the lack of domestic pets, and the high incidence of childhood infection and parasitic infestation. The prevalence of allergy and its potential determinants should be monitored in Albania as that country acquires the characteristics of other parts of Europe.

We combined data from 5 prospective studies to compare the death rates from common diseases of vegetarians with those of nonvegetarians with similar lifestyles. A summary of these results was reported previously; we report here more details of the findings. Data for 76172 men and women were available. Vegetarians were those who did not eat any meat or fish (n = 27808). Death rate ratios at ages 16-89 y were calculated by Poisson regression and all results were adjusted for age, sex, and smoking status. A random-effects model was used to calculate pooled estimates of effect for all studies combined. There were 8330 deaths after a mean of 10.6 y of follow-up. Mortality from ischemic heart disease was 24% lower in vegetarians than in nonvegetarians (death rate ratio: 0.76; 95% CI: 0.62, 0.94; P5 y. Further categorization of diets showed that, in comparison with regular meat eaters, mortality from ischemic heart disease was 20% lower in occasional meat eaters, 34% lower in people who ate fish but not meat, 34% lower in lactoovovegetarians, and 26% lower in vegans. There were no significant differences between vegetarians and nonvegetarians in mortality from cerebrovascular disease, stomach cancer, colorectal cancer, lung cancer, breast cancer, prostate cancer, or all other causes combined.

OBJECTIVES To describe the prevalence of atopic symptoms in children throughout the UK. METHOD A questionnaire survey of 12–14 year olds throughout England, Wales, Scotland, and the Scottish Islands using the international study of asthma and allergies in childhood (ISAAC) protocol. RESULTS A total of 27 507 (86%) children took part. Recent rhinoconjunctivitis was reported by 18.2%, with 6.2% reporting symptoms between March and September; 16.4% reported itchy flexural rash in the past 12 months. The prevalence of atopic symptoms was higher in girls and subjects born within the UK. The prevalence of severe wheeze was highest in subjects reporting perennial rhinoconjunctivitis, as opposed to summertime only symptoms. Winter rhinoconjunctivitis was associated with severe wheeze and severe flexural rash. One or more current symptoms were reported by 47.6% of all children and 4% reported all three symptoms. CONCLUSION In general, geographical variations were small but the prevalence of symptoms was significantly higher in Scotland and northern England. The study demonstrates the importance of atopic diseases both in their own right and in association with asthma.

BACKGROUND Respiratory diseases are common in childhood and may lead to chronic disease in adult life; environmental factors probably play an important part in their causation. METHODS A survey of respiratory symptoms in children aged 12–14 years was conducted throughout Great Britain as part of the International Study of Asthma and Allergies in Childhood (ISAAC). Information was obtained on certain aspects of the home environment in order to assess their importance as risk factors. RESULTS The response rate was 79.3%, and 25 393 children in 93 schools participated. In a multiple regression analysis, wheeze was reported more often in non-metropolitan areas and in association with active smoking, passive smoking, the presence of a furry pet, bottled gas, paraffin, and other unusual heating fuels; small regional differences persisted. Current smoking, previous smoking, and passive smoking accounted for 10.4%, 6.8%, and 6.5%, respectively, of wheezing in the past 12 months, and furry pets accounted for 5.0%. Cough and phlegm were associated with active and passive smoking and with the miscellaneous fuels; similar associations were found for rhinitis, but were less consistent for rhinitis occurring in spring and summer. Gas cooking showed little association with respiratory symptoms. CONCLUSIONS Passive as well as active smoking is an important cause of respiratory symptoms in adolescence. Pets seem to increase the risk of wheeze and rhinitis, and fumes from certain unusual heating fuels may have adverse effects. Home environment and geographical location have independent effects on the prevalence of respiratory symptoms.

Besides environmental triggers, a family history of asthma is a strong risk factor for the development of asthma in offspring. The pooled data from 13,963 interviews of randomly selected, 20 to 48 yr-old participants from the 30 centers of the European Community Respiratory Health Survey (ECRHS) were analyzed with conventional logistic regression and a Class A regressive model adapted for the segregation of various transmission modes in families. The asthma prevalence in the interviewed index generation was 6.9% (95% confidence interval [CI]: 6.5 to 7.3), and in the parent generation was 6.1% (5.8 to 6.4). As with asthma prevalence, the risk of a subject having asthma if a parent had asthma also had a large geographic variation across the survey centers. The mean risk if a father had asthma was 2.9 (2.4 to 3.5), and If the mother had asthma was 3.2 (2.6 to 3.9). The risk increased to 7.0 (3.9 to 12.7) if both parents were affected. For developing extrinsic asthma, extrinsic asthma in any parent was a greater risk factor (4.9 [3.9 to 6.0]) than intrinsic asthma of the parent (1.5 [0.8 to 2.6]), and the risk for women was slightly higher than that for men (4.3 [3.3 to 5.5] versus 3.6 [2.6 to 5.0]). Applying different segregation models, only a model for a two-allele gene with a codominant inheritance could not be rejected, assuming a major gene with a population frequency of 24.2%. Further results make a multilocus/threshold model likely. In conclusion, a history of asthma in parents is a strong risk factor for asthma in the offspring. Under the assumptions of the applied segregation analysis, at least one major gene exists which could be a gene involved also in allergy. However, asthma is not fully described by a single-gene model. The risk for asthma varies within the European countries, and should be seen in the context of a complex genetic and environmental pathophysiology.

BACKGROUND: It is uncertain as to what extent the development of allergic disease in childhood is predictable during early infancy. A number of environmental factors have been suspected of increasing the risk of acquiring allergy, but the evidence is conflicting. OBJECTIVE: To observe the development of atopy and allergic disease in a cohort of high-risk children so as to determine the importance of certain environmental factors and to study the relationship between early and later manifestations. METHODS: A cohort of infants, all at high risk of allergy, was followed up from birth to the age of 7 years. In half, selected at random, cow's milk protein was avoided for 4 months. Skin-prick tests were performed and serum IgE measured in infancy and at 7 years, when an AlaTOP test was also performed. RESULTS: Skin sensitivity to egg in the first year of life was strongly associated with eczema, asthma, mite sensitivity and serum IgE at the age of 7 years, when mother's atopic history was associated with AlaTOP status, father's atopic history with skin sensitivity, and male sex with both. Maternal smoking during pregnancy was associated positively with IgE at 3 months and negatively with skin sensitivity at 7 years. The development of allergy was unrelated to infant feeding method or number of older siblings. CONCLUSION: Allergic disease in childhood is to a large degree determined before birth or during infancy.

This study was conducted to see whether children living in socially deprived areas were more likely than other children to be admitted to hospital for asthma, and, if so, whether their excess risk was attributable to a higher prevalence of asthma or poorer treatment. Hospital admission rates for asthma were obtained for Cardiff electoral wards and compared with the Townsend indices of deprivation. A survey of respiratory symptoms was conducted in schoolchildren; prevalence of symptoms was compared with Townsend index and asthma admission rate for the schools' catchment areas.Asthma admissions were strongly correlated with Townsend indices at all ages. The prevalence of reported asthma and various degrees of wheeze in the schools was not significantly correlated with Townsend index or hospital admission rate in the corresponding areas. The presence of a smoker in the house was strongly associated with Townsend index and admission rate; children whose houses contained a smoker were more likely than others to have wheezed in the past year and to have disturbed nights due to wheezing. There was a non-significant negative association between Townsend index and regular use of inhaled steroids.The relationship between hospital admission for asthma and social deprivation is not explained by variations in prevalence, but it may be attributable to the aggravation of symptoms by active or passive smoking, and perhaps also to differences in management.

Four hundred and fifty two male angina patients were randomised to receive stress management or no psychological intervention. Instruction in stress management was given in three group sessions each of about one hour. Patients were also asked to practice relaxation and read a course ‘manual’ at home. After six months the group instructed in stress management showed a reduction in the frequency of non-exertional chest pain (as measured by a 14 day diary) compared to the non-intervention group. Analysis of covariance showed a benefit of stress management irrespective of angina frequency at recruitment. Further analysis of covariance showed reduction in the frequency of non-exertional chest pain to be associated with increased ability to relax. This study has demonstrated that stress management can be effective in reducing the frequency on non-exertional chest pain, and that a possible mechanism for this lies in the practice of relaxation.

People with high intake of fish have lower reported rates of depression and a small trial in psychiatric patients suggested that fish oil supplements reduced episodes of depression and mania. As part of a factorial trial of interventions to reduce mortality in angina 452 men were randomised to advice to eat more fatty fish or no fish advice. Maxepa fish oil capsules were supplied to men who found the fish unpalatable. Fish intake and mood were assessed at baseline and six months. Most men (83%) had mood assessed using the Derogatis Stress Profile at baseline and follow-up. Self reported intake of fish was higher in the fish advice group at six months. There was, however, no difference in depression or anxiety in those allocated to receive fish advice. After controlling for baseline mood, the difference in depression score between those randomised to fish advice and those not was 1.29 (95% CI -0.29 to 2.88) and the difference in anxiety was 0.82 (95% CI -0.57 to 2.22) with positive differences indicating more depression or anxiety in those allocated to the fish arm. This trial provides no evidence that increased fatty fish intake in people without depressive symptoms has any substantial effect on mood.

This review considers the published evidence concerning the suggestion that the risk of acquiring cancer may be reduced by antioxidants found in fruit and vegetables. Evidence from studies of different designs is systematically reviewed: ecological studies; case controlled studies; cohort studies and randomized controlled trials. The mechanisms whereby antioxidant vitamins may inhibit neoplasia are indicated. Although evidence supports the view that eating plenty of fruit and vegetables reduces the risk of acquiring cancer, the role of antioxidants in this protective effect is still unproven.

Alterations of dietary fat that reduce serum cholesterol are beneficial to people who have the highest risk of death from coronary heart disease (CHD). For other people the benefits are less clear; there is a suggestion (hotly disputed) that cholesterol-lowering by drugs, and possibly by diet, increases the risk of non-CHD death, for reasons that are not understood. Furthermore, fat intake interacts with other dietary and non-dietary factors. The consequences of altering dietary fat seem to be more complex and uncertain than have hitherto been supposed.

The authors are indebted to the collaborators in the participating centres and all parents, children, teachers and other school staff who participated in the surveys. There are many field workers and funding agencies who supported data collection and national, regional and international meetings, including the meetings of the ISAAC Steering Committee. Unfortunately, these are too numerous to mention (they are acknowledged elsewhere) but the authors particularly wish to thank the funders who supported the ISAAC International Data Centre including the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the National Child Health Research Foundation, the Hawke’s Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand and Astra New Zealand, as well as Glaxo Wellcome International Medical Affairs for finding the regional coordinating centres. The International Data Centre is now supported by a grant from the BUPA Foundation., The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit., peer-reviewed

Road traffic noise exposure leads to annoyance and impairment of quality of life and may impair health. If this association is causal, a reduction in noise exposure should result in a reduction in noise annoyance and improvement in quality of life. This study examines whether the reduction in road traffic noise following the introduction of a bypass leads to reduction in noise annoyance and common mental disorder and an improvement in quality of life. Repeated measures field study with intervention in three small towns in North Wales, UK. Participants were residents 16 to 90 years living in areas of high or low exposure to road traffic noise. At baseline there was no difference in annoyance, quality of life or common mental disorder between traffic noise exposed and quiet areas. There was a small reduction in noise exposure (2-4 dBA) with the opening of the bypass. There was no reduction in noise annoyance and no change in levels of common mental disorder and quality of life following the introduction of the bypass. Traffic noise reduction associated with the introduction of the bypass was not associated with measurable changes in quality of life or common mental disorder. This study suggests that reduction in traffic noise level of 3dB or less is insufficient to influence annoyance or mental health. However, the methodological difficulties of the study limit the conclusions that can be drawn on whether there is a causal effect of noise on common mental disorder.

A postal survey of dietary fibre intake was conducted in two British towns in 1983, and repeated five years later. Consumption of dietary fibre had risen, the rise being greater in the town where the initial intake was higher. Changes in intake appeared to be related to health-consciousness as reflected by changes in body mass index (BMI) and smoking habit. Although dietary fibre consumption in Britain is rising overall, local differences may be widening rather than narrowing.

Factors influencing compliance with dietary advice were investigated in the Diet and Reinfarcation Trial (DART). In terms of achieved intakes, smokers had a lower mean P/S ratio and fibre intake than non-smokers; manual workers had a lower mean fibre intake than non-manual workers; and obese men had a higher percentage of energy from fat and lower P/S ratio than non-obese men. However the effect of the advice (difference in intakes of those advised and thosen not advised) was similar in smokers and non-smokers and was similar in all social classes. The effect of fat advice was less among obese men than among non-obese men, probably as a result of weight-reducing advice given to all overweight men. Fat advice tended to have a greater effect among those who gave up smoking after their heart attack than among non-smokers and those who continued to smoke but the difference was not statistically significant. This suggests that advice on diet and smoking can be given simultaneously and still be effective.

The seroprevalence of IgG antibodies to Helicobacter pylori was determined using a standard enzyme linked immunosorbent assay in a population of 749 randomly selected men, aged 30-75 years, from Caerphilly, South Wales. The overall prevalence of H pylori was 56.9%, increasing sharply in middle age from 29.8% in those aged 30-34 to over 59% in those aged 45 or older (p less than 0.0001). Age standardised seroprevalence rates were lowest in combined social class categories I and II (49.2%), intermediate in categories IIIN and M (57.5%), and highest in categories IV and V (62.2%) (p = 0.01). In those aged 30-34 years, the prevalence rate for those in combined social class categories IV and V was 57.9% - double the rate for social class categories IIIM and N (28.3%) and five times the prevalence rate in those in social class categories I and II (11.1%). These differences in the infection patterns of H pylori by social class are consistent with patterns of peptic ulcer disease and gastric cancer.

Children spend much of their time indoors, yet relatively little attention is paid to the effects of indoor air pollution owing to the difficulties of obtaining information about it. The most important single element is probably environmental tobacco smoke (passive smoking), which causes respiratory illness and impairment of lung function. Oxides of nitrogen, mostly derived from gas cookers, may cause symptoms in some children. House dust mites affect children with allergic asthma, but are very difficult to remove from the indoor environment. Indoor mould growth seems to be associated with ill-health, but it is not entirely clear whether this is attributable to exposure to the spores. Formaldehyde is emitted by some materials in buildings and furniture; it may affect children's respiratory health, but the information is rather sparse. VOCs are produced by a range of human activities; their significance for health is not known. More work is needed to ascertain the short-term and long-term effects of exposure to indoor air pollutants.

Background: A recent Cochrane meta-analysis did not confirm the benefits of fish and fish oil in the secondary prevention of cardiac death and myocardial infarction. We performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation on ventricular fibrillation and ventricular tachycardia to determine the overall effect and to assess whether heterogeneity exists between trials. Methods: We searched electronic databases (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL) from inception to May 2007. We included randomized controlled trials of fish-oil supplementation on ventricular fibrillation or ventricular tachycardia in patients with implantable cardioverter defibrillators. The primary outcome was implantable cardioverter defibrillator discharge. We calculated relative risk [RR] for outcomes at 1-year follow-up for each study. We used the DerSimonian and Laird random-effects methods when there was significant heterogeneity between trials and the Mantel-Hanzel fixed-effects method when heterogeneity was negligible. Results: We identified 3 trials of 1–2 years' duration. These trials included a total of 573 patients who received fish oil and 575 patients who received a control. Meta-analysis of data collected at 1 year showed no overall effect of fish oil on the relative risk of implantable cardioverter defibrillator discharge. There was significant heterogeneity between trials. The second largest study showed a significant benefit of fish oil (relative risk [RR] 0.74, 95% confidence interval [CI] 0.56–0.98). The smallest showed an adverse tendency at 1 year (RR 1.23, 95% CI 0.92–1.65) and significantly worse outcome at 2 years among patients with ventricular tachycardia at study entry (log rank p = 0.007). Conclusion: These data indicate that there is heterogeneity in the response of patients to fish-oil supplementation. Caution should be used when prescribing fish-oil supplementation for patients with ventricular tachycardia.

ObjectiveTo examine the effectiveness of two methods of increasing fruit and fruit juice intake in pregnancy: midwives' advice and vouchers exchangeable for juice.DesignPregnant women were randomly allocated to three groups: a control group, who received usual care; an advice group, given advice and leaflets promoting fruit and fruit juice consumption; and a voucher group, given vouchers exchangeable for fruit juice from a milk delivery firm. Dietary questionnaires were administered at ~16, 20 and 32 weeks of pregnancy. Serum β-carotene was measured at 16 and 32 weeks.SettingAn antenatal clinic in a deprived area.SubjectsPregnant women aged 17 years and over.ResultsThe study comprised 190 women. Frequency of fruit consumption declined during pregnancy in all groups, but that of fruit juice increased substantially in the voucher group. Serum β-carotene concentration increased in the voucher group, from 106.2 to 141.8 μmol l− 1in women with measurements on both occasions (P = 0.003), decreased from 120.0 to 99.8 μmol l− 1in the control group (P = 0.005), and was unchanged in the advice group.ConclusionsPregnant women drink more fruit juice if they receive vouchers exchangeable for juice supplied by the milk delivery service. Midwives' advice to eat more fruit has no great effect. Providing vouchers for fruit juice is a simple method of increasing its intake in a deprived population and may be useful for other sections of the community.

The Diet and Reinfarction Trial (DART) involved 2033 men (mean age 56·5 years) recovering from myocardial infarction. They were randomly allocated to receive advice or to receive no advice on each of three dietary factors: an increase in fatty fish intake; a reduction in fat intake with an increase in polyunsaturated fat:saturated fat; an increased intake of cereal fibre. Compliance was satisfactory with the fish and fibre advice, but less so with the fat advice. The men given fish advice had 29% lower 2-year all-cause mortality; the other forms of advice did not have any significant effects. The Diet and Angina Randomized Trial (DART-2) involved 3114 men (mean age 61·1 years) with stable angina, who were followed up for 3–9 years. Advice to eat oily fish or take fish oil did not affect all-cause mortality, but it was associated with a significant increase in sudden cardiac death (P=0·018), and this effect was largely confined to the subgroup given fish oil capsules. Advice to eat more fruit and vegetables had no effect, probably because of poor compliance. The outcome of DART-2 appears to conflict with that of DART and some other studies; various possible explanations are considered. Nutritional interventions are not equally acceptable and should be tailored to the individuals for whom they are intended. Various distinct groups have a raised risk of CHD, and it cannot be assumed that the same nutritional interventions are appropriate to them all. Nutritional supplements do not necessarily have the same effects as the foods from which they are derived.

Background: heart failure and stroke are major causes of morbidity and mortality in older people. Angiotensin converting enzyme inhibitors improve symptoms and survival in left ventricular systolic dysfunction. Anticoagulants are effective in stroke prevention in atrial fibrillation with aspirin being a less effective alternative. Objectives: to determine the prevalence of left ventricular systolic dysfunction, health services utilisation and prescribing of diuretics and angiotensin converting enzyme inhibitors in left ventricular systolic dysfunction, and the prevalence of atrial fibrillation and anti-platelet/thrombotic therapy in atrial fibrillation in older people in the community. Methods: 500 subjects were drawn by two-stage random sampling from 5,002 subjects aged 70 years and over living at home. Subjects were screened for atrial fibrillation and left ventricular systolic dysfunction using electrocardiography and echocardiography. Results: the population prevalence amongst older people of left ventricular systolic dysfunction was 9.8% and of atrial fibrillation 7.8%. More than two-thirds of those with left ventricular systolic dysfunction were not on angiotensin converting enzyme inhibitors. Of those in atrial fibrillation, 35% were taking aspirin, 24% were taking warfarin and 41% were on neither aspirin nor warfarin. Nearly 90% of older people in the community have had contact with their general practitioner over the past year, and over half of those with left ventricular systolic dysfunction have had contact with hospital-based services over the past 2 years. Conclusions: left ventricular systolic dysfunction is under-treated in older people in the community. Despite the high level of contact with hospital and community-based services, the majority of those with systolic left ventricular dysfunction are not on angiotensin converting enzyme inhibitors and a significant proportion of those in atrial fibrillation are not on any treatment for stroke prevention.

The prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in children in the United Kingdom ranks among the highest in the world.The evidence from most repeat surveys is that prevalence has increased over the past three decades,2 but the most recent of these studies observed that from 1991 to 1998 the increase was confined to milder symptoms of asthma.3 Since the early 1990s the incidence of asthma episodes presenting to general practitioners, and of hospital admissions, has fallen substantially

Introduction: The long-term effects on diet of dietary advice to eat fruit and vegetables or fatty fish are not well described. Materials and methods: From 1990 to 1996 3114 men aged 37-70 with treated angina were recruited from general practices in South Wales. A dietitian randomly allocated the eligible men to receive advice to eat more fruit and vegetables, or advice to eat more fatty fish, or both these types of advice or neither. In 2000, a brief self-completion questionnaire was sent to a sample of 1191 of the men known to be alive at the end of March 1999.Results: The questionnaire was returned by 944 of the 1036 men alive at the time the questionnaire was sent. Those given fish advice were consuming more fatty fish but the difference was modest 21.9 g day(-1) vs. 14.0 g day(-1) (P < 0.01). The differences in fruit and vegetables intake between those given fruit advice and those not given fruit advice were small 373.2 g day(-1) vs. 351.7 g day(-1) (P = 0.05).Discussion: Men of this age group may be particularly resistant to fruit and vegetables advice; population-based interventions or interventions targeted at women might be more effective.

The 'French paradox' refers to the very low incidence of and mortality rates from ischaemic heart disease in France despite the fact that saturated fat intakes, serum choles terol, blood pressure and prevalence of smoking are no lower there than elsewhere. To some extent it is due to under-reporting, but this is not the whole explanation. The relative im munity of the French to ischaemic heart disease has been attributed to their high alcohol consumption and to their intake of antioxidant vitamins, both being supplied by wine. The custom of drinking wine with the meal may confer protection against some of the adverse effects of the food.

Objectives: to determine the prevalence of diastolic heart failure in older people in the community, identify associated risk factors and measure its impact on function and quality of life. Design: cross-sectional population-based study. Methods: a two-stage random sample of 500 subjects was drawn from 5,002 subjects aged 70 years and over living at home. Diastolic heart failure was diagnosed by a panel of three physicians, based on clinical assessment and echocardiographic indicators of diastolic dysfunction. Main outcome measures: prevalence of diastolic heart failure and its effect on function and quality of life as measured by Nottingham Extended Activities of Daily Living, Hospital Anxiety and Depression and SF-36 questionnaires. Results: the prevalence of diastolic heart failure was 5.54% (95% CI = 3.71, 7.87) and was higher in women (8.32%) than in men (1.25%), P = 0.008. On multivariate analysis of variance, diastolic heart failure was associated with female gender and history of ischaemic heart disease. Subjects with diastolic heart failure had signiWcantly poorer functional status and physical health than those without heart failure. Conclusions: Diastolic heart failure is relatively common in older people and is associated with adverse affects in older people’ s lives.

Background Inhaled corticosteroids form the main therapy for asthma, but there is increasing concern about the potential systematic effects of long-term inhaled corticosteroids including their effect on bone metabolism and bone loss. Objectives To determine the effect of inhaled corticosteroids use on biochemical markers of bone turnover, bone mineral density and the development of fractures. Search methods We searched the Cochrane Airways Group trials register, electronic reference databases, UK National Research Register, bibliographies of included studies, and contacted pharmaceutical companies. Selection criteria Randomised trials of the effect of inhaled steroid versus placebo on markers of bone function and metabolism, in adults with asthma or mild COPD. Data collection and analysis Trial quality was assessed and data extracted from the papers included (2 reviewers per paper) and from additional data supplied by the authors. Main results Of 438 references found, seven met the inclusion criteria. Three studies were in healthy subjects asthma or COPD. The patients were generally less than 60 years old and the male:female ratio was 2:1. There was no evidence of increased risk of loss of bone mineral density (BMD) or fractures. There was no significant change in osteocalcin at conventional doses of inhaled corticosteroids (Standardised Mean Difference [SMD] -0.34 (95% Confidence Interval [CI] -0.72, 0.04), although a statistically significant change was seen in those studies using experimental doses of inhaled steroid in excess of the doses recommended by the British Thoracic Society SMD 0.97 (95% CI -1.61, -0.34). A statistically significant change in parathyroid hormone seen in one small short trial (n=10, 6 weeks) may have been due to the trial design and outcome measurements used. Authors' conclusions In patients with asthma or mild COPD, there is no evidence of an effect of inhaled corticosteroid at conventional doses given for two or three years on BMD or vertebral fracture. Higher doses were associated with biochemical markers of increased bone turnover, but data on BMD and fractures at these doses are not available. There is a need for further, even longer term prospective studies of conventional and high doses of inhaled corticosteroids.

The European Study Group on diastolic heart failure requires objective evidence of abnormal left ventricular diastolic function to establish the diagnosis of diastolic heart failure, which is common in older people. Reference values for Doppler indices of transmitral flow, used to assess left ventricular diastolic function, have not been reported for people 70 years and over in Europe. The aim of this study was to establish reference values for these Doppler indices of transmitral flow in older people. A random sample of 355 subjects aged 70 and over, living in the community underwent clinical assessment and echocardiography. Asymptomatic subjects with no cardiovascular disease and cardiovascular risk factors were identified. Measurements of five commonly used Doppler indices of transmitral flow from these subjects were obtained and reference range expressed as mean+/-2 standard deviations and as percentiles. We have therefore generated reference Doppler values of transmitral flow for people aged over 70 in a British population.

Objective:To compare the mortality of British vegetarians and non-vegetarians.Design:Analysis of original data from two prospective studies each including a large proportion of vegetarians – the Oxford Vegetarian Study and the Health Food Shoppers Study. Standardised mortality ratios (SMRs) compared with the population of England and Wales were calculated from deaths before age 90 for vegetarians and non-vegetarians in each study. Death rate ratios (DRRs) for vegetarians compared with non-vegetarians within each study were calculated for each of 14 major causes of death.Setting:UK.Subjects:Twenty-one thousand men and women aged 16–89 years at recruitment, including more than 8000 vegetarians.Results:SMRs for all causes of death were significantly below the reference level of 100 in both studies: 52 (95% confidence interval (CI) 49–56) based on 1131 deaths in the Oxford Vegetarian Study and 59 (57–61) based on 2346 deaths in the Health Food Shoppers Study. For all causes of death, the DRR for vegetarians compared with non-vegetarians was close to one in both studies: 1.01 (95% CI 0.89–1.14) in the Oxford Vegetarian Study, 1.03 (0.95–1.13) in the Health Food Shoppers Study.Conclusions:British vegetarians have low mortality compared with the general population. Their death rates are similar to those of comparable non-vegetarians, suggesting that much of this benefit may be attributed to non-dietary lifestyle factors such as a low prevalence of smoking and a generally high socio-economic status, or to aspects of the diet other than the avoidance of meat and fish.

BACKGROUND—Pulmonary rehabilitation programmes improve the health of patients disabled by lung disease but their cost effectiveness is unproved. We undertook a cost/utility analysis in conjunction with a randomised controlled clinical trial of pulmonary rehabilitation versus standard care. METHODS—Two hundred patients, mainly with chronic obstructive pulmonary disease, were randomly assigned to either an 18 visit, 6 week rehabilitation programme or standard medical management. The difference between the mean cost of 12 months of care for patients in the rehabilitation and control groups (incremental cost) and the difference between the two groups in quality adjusted life years (QALYs) gained (incremental utility) were determined. The ratio between incremental cost and utility (incremental cost/utility ratio) was calculated. RESULTS—Each rehabilitation programme for up to 20 patients cost £12 120. The mean incremental cost of adding rehabilitation to standard care was £ -152 (95% CI -881 to 577) per patient, p=NS. The incremental utility of adding rehabilitation was 0.030 (95% CI 0.002 to 0.058) QALYs per patient, p=0.03. The point estimate of the incremental cost/utility ratio was therefore negative. The bootstrapping technique was used to model the distribution of cost/utility estimates possible from the data. A high likelihood of generating QALYs at negative or relatively low cost was indicated. The probability of the cost per QALY generated being below £0 was 0.64. CONCLUSIONS—This outpatient pulmonary rehabilitation programme produces cost per QALY ratios within bounds considered to be cost effective and is likely to result in financial benefits to the health service.

Molds grow readily indoors in the presence of dampness. Their visibility enables their effects to be investigated by means of questionnaire surveys, although these are subject to imprecision and potential bias. Exposure to airborne mold particles can be measured in various ways that also have disadvantages and limitations. Many surveys have been conducted on the health effects of molds; most have examined the association between molds and symptoms, although some studies have used lung function tests and other objective health indices. Most surveys suggest that indoor mold growth is associated with ill health, particularly of the respiratory tract. Knowing how important mold exposure really is in health terms is difficult, owing to the tendency for mold growth to be associated with other factors that are prejudicial to health.