The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin.

BACKGROUND: Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. OBJECTIVE: We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. METHODS: The Global Asthma and Allergy Network of Excellence (GA(2) LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. RESULTS: One thousand nine hundred and fifty-five subjects aged 16-77 years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P = 0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons. CONCLUSIONS AND CLINICAL RELEVANCE: Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.

Geographical variation in the prevalence of sensitization to common aeroallergens in adults: the GA(2) LEN survey.

BACKGROUND: Geographical variation in the prevalence of sensitization to aeroallergens may reflect differences in exposure to risk factors such as having older siblings, being raised on a farm or other unidentified exposures. OBJECTIVE: We wanted to measure geographical variation in skin prick test positivity and assess whether it was explained by differences in family size and/or farm exposure. We also compared prevalence in younger and older subjects. METHODS: Within the Global Allergy and Asthma European Network (GA(2) LEN) survey, we measured the prevalence of skin prick positivity to a panel of allergens, and geometric mean serum total immunoglobulin E (IgE), in 3451 participants aged 18-75 years in 13 areas of Europe. Estimated prevalence was standardized to account for study design. We compared prevalence estimates in younger and older subjects and further adjusted for age, gender, smoking history, farm exposure, number of older siblings and body mass index (BMI). RESULTS: Skin prick test positivity to any one of the measured allergens varied within Europe from 31.4% to 52.9%. Prevalence of sensitization to single allergens also varied. Variation in serum total IgE was less marked. Younger participants had higher skin prick sensitivity prevalence, but not total IgE, than older participants. Geographical variation remained even after adjustment for confounders. CONCLUSION: Geographical variation in the prevalence of skin prick test positivity in Europe is unlikely to be explained by geographical variation in gender, age, smoking history, farm exposure, family size and BMI. Higher prevalence in younger, compared to older, adults may reflect cohort-associated increases in sensitization or the influence of ageing on immune or tissue responses.

Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis--a GA² LEN study.

BACKGROUND: The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA(2) LEN European survey. METHODS: On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chance-corrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. RESULTS: There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers (-3.0%, 95% CI: -5.0 to -1.0%, I(2) = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. CONCLUSION: Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS.

Chronic rhinosinusitis in Europe--an underestimated disease. A GA²LEN study.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this study, conducted by the GA²LEN network of excellence, the European Position Paper on Rhinosinusitis and nasal Polyps (EP³OS) diagnostic criteria are applied to estimate variation in the prevalence of Chronic rhinosinusitis (CRS) for Europe. METHOD: A postal questionnaire was sent to a random sample of adults aged 15-75 years in 19 centres in Europe. Participants reported symptoms of CRS, and doctor diagnosed CRS, allergic rhinitis, age, gender and smoking history. Definition of CRS was based on the EP³OS diagnostic criteria: the presence of more than two of the symptoms: (i) nasal blockage, (ii) nasal discharge, (iii) facial pain/pressure or (iv) reduction in sense of smell, for >12 weeks in the past year--with at least one symptom being nasal blockage or discharge. RESULTS: Information was obtained from 57,128 responders living in 19 centres in 12 countries. The overall prevalence of CRS by EP³OS criteria was 10.9% (range 6.9-27.1). CRS was more common in smokers than in nonsmokers (OR 1.7: 95% CI 1.6-1.9). The prevalence of self-reported physician-diagnosed CRS within centres was highly correlated with the prevalence of EP³OS-diagnosed CRS. CONCLUSION: This is the first European international multicentre prevalence study of CRS. In this multicentre survey of adults in Europe, about one in ten participants had CRS with marked geographical variation. Smoking was associated with having CRS in all parts of Europe.

Maternal Nrf2 and gluthathione-S-transferase polymorphisms do not modify associations of prenatal tobacco smoke exposure with asthma and lung function in school-aged children.

BACKGROUND: Maternal smoking during pregnancy has detrimental effects on the respiratory health of infants and children. Polymorphisms of antioxidant genes including glutathione-S-transferases (GSTs) have been proposed as candidates for asthma and reduced lung function in children. METHODS: Women enrolled in the Avon Longitudinal Study of Parents and Children reported smoking habits during pregnancy. Asthma status in their children was established at age 7.5 years from parental reports and lung function was measured by spirometry at age 8.5 years. Maternal and child DNA were genotyped for deletions of GSTM1 and GSTT1 and functional polymorphisms of GSTP1 and Nrf2 genes. Associations of prenatal tobacco smoke exposure with asthma and lung function in children were stratified by maternal genotype. RESULTS: In 6606 children, maternal smoking during pregnancy was negatively associated with maximal mid expiratory flow (FEF(25-75)) (-0.05 SD units, 95% CI -0.07 to -0.03, p<0.001). There was little evidence for interactions between maternal smoking and any maternal genotype considered on children's asthma or lung function. Maternal smoking was associated with reduced childhood FEF(25-75) only in mother-child pairs (n=1227) with both copies of GSTM1 deleted (-0.08 SD units, 95% CI -0.14 to -0.02, p=0.01) or (n=2313) at least one copy of GSTT1 present (-0.05 SD units, 95% CI -0.09 to 0, p=0.03). CONCLUSION: This study confirms a detrimental effect of intrauterine tobacco smoke exposure on childhood lung function but no strong evidence of modification by maternal genotype for important antioxidant genes. Adverse effects of fetal exposure to tobacco smoke on the respiratory health of children may be mediated by pathways other than oxidative stress.

Dietary patterns in pregnancy and respiratory and atopic outcomes in childhood.

BACKGROUND: Studies of the relation between maternal diet in pregnancy and respiratory and atopic outcomes in the offspring have focused on the effects of individual nutrients and foods rather than dietary patterns. A study was undertaken to determine whether dietary patterns in pregnancy are related to childhood asthma and related outcomes. METHODS: In a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), dietary patterns in pregnancy previously identified using principal components analysis ("health conscious", "traditional", "processed", "vegetarian" and "confectionery") were related to early wheezing phenotypes and eczema; wheezing, hay fever, eczema, doctor-diagnosed asthma, atopy and total IgE at 7 years; lung function and bronchial responsiveness at 8-9 years. In regression models, confounders were controlled for using propensity scores. RESULTS: Univariately, the "health conscious" pattern was positively associated with eczema, total IgE, forced expiratory volume in 1 s and forced expiratory flow and negatively associated with early wheezing and asthma (unadjusted odds ratios per standard deviation increase in pattern score for early persistent wheeze and asthma: 0.78 (95% CI 0.70 to 0.87), p = 7.3x10(-6), N = 8886 and 0.90 (95% CI 0.84 to 0.97), p = 0.007, N = 7625, respectively). The "processed" pattern was positively associated with early wheezing and negatively associated with atopy and forced vital capacity. On controlling for confounders, the effects were substantially attenuated and became non-significant (adjusted odds ratios for the associations of the "health conscious" pattern with early persistent wheeze and asthma: 1.00 (0.86 to 1.16), p = 0.99 and 0.95 (0.86 to 1.04), p = 0.27, respectively). CONCLUSIONS: In this cohort, dietary patterns in pregnancy did not predict asthma and related outcomes in the offspring after controlling for confounders.

The effects of allergens in outdoor air on both atopic and nonatopic subjects with airway disease.

BACKGROUND: Reports on air pollution and asthma exacerbations have been inconsistent, although effects of airborne allergen can be spectacular. With no generalized test for allergen in air, it is not known how far allergen is responsible for nonepidemic exacerbations of the disease. METHODS: Two hundred and ninety-seven patients using bronchodilators aged 18-64 years attending a London practice provided serum samples and were asked to report any acute respiratory events over the coming months. Small particles with a mean aerodynamic diameter <10 microm (PM(10)) were collected using a high volume sampler on the roof of the practice. The ability of airborne particles to bind IgE from the patients was compared for particles sampled on the weekend before their reported exacerbation with particles sampled on the weekend 2 weeks before or after. RESULTS: Exacerbations were associated with a 25% increase in IgE binding to particles collected on the previous weekend compared with the control weekends (95% confidence interval: 10-43%; P = 0.00089). This increase was not higher in patients with positive skin tests or in those sensitized to grass or tree pollens. CONCLUSIONS: Airborne allergen is an important cause of exacerbations even in those with 'intrinsic' asthma. It is important to identify the allergens responsible, as some of these may be controllable. Interpretation of associations of asthma exacerbations with other air pollutants is difficult in the light of these findings.

The survival of treated hypertensive patients and their causes of death: a report from the DHSS hypertensive care computing project (DHCCP).

A prospective study has been carried out to determine the causes of death and risk factors for survival in 4994 patients referred with a diagnosis of hypertension to hospital specialist clinics and 457 patients treated by their general practitioners for this condition. At the time of entering the prospective study, 69% of the patients were already being treated for hypertension. Four hundred and eleven patients have died, and their causes of death and death rates have been compared with the rates for the population of England and Wales. Ischaemic heart disease accounted for over one-third of the deaths and stroke for one-fifth. The death rates for these conditions were two to five times those expected for men and women aged 50-59 years and up to twice the rate expected for the age group 60-69 years. Survival in these selected patients was impaired by the following independent risk indicators: cigarette smoking, previous history of myocardial infarction or stroke, diagnosis of angina, impaired renal function and raised blood sugar. The following factors were not independent positive risk factors: smoking a pipe or cigars, obesity, a low plasma potassium and an elevated serum uric acid.

Mortality from venous thromboembolism among young women in Europe: no evidence for any effect of third generation oral contraceptives.

STUDY OBJECTIVE: To investigate whether there has been an increase of venous thromboembolism (VTE) mortality in European countries, concurrent with the replacement of second generation by third generation combined oral contraceptives (COCs). Such an increase has been predicted, and reportedly detected, because published studies have detected an increased incidence of VTE associated with third generation rather than second generation COC use. DESIGN: Data were collected on population and annual VTE mortality in women 15-34 and 35-49 years old, and on second and third generation COC sales, from 1981 to 1994 in 13 European countries. Data from the seven most populous countries were analysed by linear regression of annual VTE mortality, in the 15-34 and 15-49 age groups, with respect to calculated total and third generation COC use rates, and the regression coefficients used to estimate mortality differences between second generation users and non-users and between third and second generation users, respectively. MAIN RESULTS: The estimated mortality differences in all seven countries had confidence intervals wide enough to contain both zero and the excess mortalities expected from the results of published studies. This was true both for the mortality difference between third and second generation COC users and for that between second generation users and COC non-users. CONCLUSIONS: Mortality differences of the size expected from the published studies cannot be measured using annual national VTE mortality and COC sales data alone, because of residual interannual variation in VTE mortality, and possibly confounding between rising third generation market share and total COC use.

Beta adrenoceptor blockade is associated with increased survival in male but not female hypertensive patients: a report from the DHSS Hypertension Care Computing Project (DHCCP).

The DHCCP is a multicentre observational study of patients being treated for hypertension in the United Kingdom. The influence of the type of anti-hypertensive therapy on survival was examined in 2,697 patients followed from 1971 with 206 deaths up to November 1981. Patients were classified by three types of treatment after one year in the project: betablockers (1,387), methyldopa (452) and others (667), (70% on diuretics only). The data were analysed both for all patients and for a subset excluding patients with previous ischaemic heart disease by all cause and IHD age-adjusted rates and life table analysis. Men on beta blockers had lower rates for total mortality, when compared with men on methyldopa (64% of the methyldopa rate, P less than 0.05) and when compared with men on other treatments (76% of the other treatment rate, P less than 0.1). The results for IHD mortality were similar. This improved survival of men in the beta blocker group was also found in the subset with no prior history of IHD. The benefit of beta blockers was not apparent in women: the lowest rates were observed for women on methyldopa, but the confidence limits for the ratios of relative rates were wide. Adjustment for blood pressure and cigarette smoking using the Cox proportional hazards model did not substantially modify the ratios of the mortality rates for the treatment groups. A sub-group analysis showed the reduction in all cause and IHD mortality associated with beta blockers was mainly due to the effect in non-smoking men.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of anti-hypertensive drugs on sexual function in men and women: a report from the DHSS Hypertension Care Computing Project (DHCCP).

One thousand, two hundred and eighty-five men and 1,080 women being followed in the DHSS Hypertension Care Computing Project answered the questions on sexual activity included in a self-administered questionnaire. In men, both impotence and sexual inactivity were increased in patients receiving hydralazine. No gross excess of these complaints could be determined in patients receiving either beta-adrenoceptor blocking drugs or methyldopa, nor was failure of ejaculation increased with these drugs. The survey could not exclude any deterioration in sexual function occurring uniformly across all treatment groups. However, the rates of complaint were similar in men taking a diuretic alone, a beta-adrenoceptor blocking drug alone and those taking the combination of these two drug groups. In women with hypertension, frequency of sexual intercourse and the achievement of orgasm was not associated with the giving of hydralazine, beta-adrenoceptor blocking drugs or methyldopa.

Injection related anxiety in insulin-treated diabetes.

The presence of injection related anxiety and phobia may influence compliance, glycaemic control and quality of life in patients with insulin-treated diabetes. Unselected consecutive, insulin-treated patients attending a diabetes clinic for follow-up, completed a standardised questionnaire providing an injection anxiety score (IAS) and general anxiety score (GAS). A total of 115 insulin-treated (80 Type 1 and 35 Type 2) diabetic patients completed the questionnaire. Injections had been avoided secondary to anxiety in 14% of cases and 42% expressed concern at having to inject more frequently. An IAS > or = 3 was seen in 28% of patients and of these, 66% injected insulin one to two times/day, 45% had avoided injections, and 70% would be bothered by more frequent injections. A significant correlation between IAS and GAS was seen (Kendall's tau-a 0.30, 95% CI 0.19-0.41, P < 0.001). GAS was significantly associated with both previous injection avoidance and expressed concern at increased injection frequency. No significant correlation was seen with HbA1c and injection or general anxiety scores. Symptoms relating to insulin injection anxiety and phobia have a high prevalence in an unselected group of diabetic patients requiring insulin injections and are associated with higher levels of general anxiety.

CMVR diagnoses and progression of CD4 cell counts and HIV viral load measurements in HIV patients on HAART.

AIM: To assess the impact of highly active antiretroviral therapy (HAART) on the prevalence and progression of CMV retinitis (CMVR) among AIDS patients with baseline CD4 cell counts <100 cells x 10(6)/l. METHODS: A longitudinal cohort study of 1292 patients. CD4 cell counts and HIV viral load measurements were obtained before commencing therapy, at 3 months, 1 year, 2 years, and at last follow up. The CMVR prevalence rate was measured for the subgroup with baseline CD4 cell counts <100 cells x 10(6)/l. CMVR adverse event (AE) rates per 100 person days at risk were calculated for the subgroup with CMVR and baseline CD4 cell counts <100 cells x 10(6)/l. RESULTS: 1292 patients were started on HAART. 8% of patients had CD4 counts <50 cells x 10(6)/l and 40% had detectable HIV viral load at last follow up. The prevalence of CMVR for the subgroup with baseline CD4 <100 cells x 10(6)/l was 10%. For those with baseline CD4 <100 cells x 10(6)/l, the mean CMVR AE rate was greatest during the first 6 months of follow up after HAART commencement (p <0.003). The mean AE rate per 100 person days at risk was 0.36 (95% CI 0.167 to 0.551) before starting HAART, and 0.14 (95% CI 0.085 to 0.199) after starting HAART (p = 0.03). CONCLUSIONS: HAART significantly prolongs the disease-free intervals in patients with pre-existing disease but recurrences persist within the first 6 months of starting therapy. AE were absent beyond 18 months of follow up in all patients including those with persistently low CD4 counts and detectable HIV viral load indicating clinical immunorestoration. New methods for monitoring the response to therapy are needed to identify those at risk.

Association between intraocular pressure and loss of visual field in chronic simple glaucoma.

This paper reports the analyses on data from 747 patients with chronic simple glaucoma (CSG) recorded in the King's College Hospital glaucoma data base between January 1970 and February 1985, having a mean follow-up time of 5.1 years (mode 8 years) with the object of determining the relationship of intraocular pressure (IOP) and visual field loss in CSG. A highly significant negative relationship was found between the presenting visual field coefficient (FC) and the untreated IOP (r = -0.26, p = 0.0001) - that is, the higher the IOP on detection, the worse is the visual field. A weak negative correlation was present between the change of FC per year and the treated IOP (r = -0.06), p = less than 0.05). At treated IOPs less than or equal to 18 mmHg visual field loss averaged 0.6 unit per year and for IOPs greater than 18 mmHg the average loss was 1.2 units per year. The data confirm both the importance of a raised IOP in the causation of chronic glaucomatous visual field loss and the importance of reducing the IOP in patients with chronic simple glaucoma.

The treatment of depression in UK general practice: selective serotonin reuptake inhibitors and tricyclic antidepressants compared.

BACKGROUND: Antidepressants are commonly prescribed by general practitioners as treatment for depression. Controversy exists as to the effectiveness in everyday use of the older tricyclic antidepressants (TCAs) when compared to the newer selective serotonin reuptake inhibitors (SSRIs). AIM: To investigate the patterns of current prescribing of antidepressants for the treatment of depression and compare TCAs with the newer SSRIs. METHOD: The study population was patients attending 151 computerised general practices from throughout the United Kingdom between 1991 and 1996. Patients with new prescriptions for antidepressants and a diagnosis of depression were identified. Age and gender distributions, prescribed doses and drop-out rates were investigated. RESULTS: During the study period 9.8% of patients received a prescription for an antidepressant, there was a 40% increase in the prescribing rate of TCAs and a 460% increase in SSRI prescribing. TCAs were initially prescribed in sub-therapeutic doses. More than 50% of patients ceased taking their antidepressants within 6 weeks of starting treatment. Fluoxetine and paroxetine were more likely to be prescribed for a therapeutic period than were other antidepressants. CONCLUSIONS: General practitioners should prescribe a therapeutic dose of antidepressant for a recognised therapeutic period to ensure that patients with depression receive the most effective treatment.

Childhood asthma and fruit consumption.

The present authors investigated whether wheezing is less common in children who consume more apples and other fruits. A population-based survey of 2,640 primary school children aged 5-10 yrs was carried out in Greenwich (South London, UK). Information about asthma symptoms and fruit consumption was obtained by means of a questionnaire. After controlling for potential confounding variables, eating bananas at least once a day (compared with less than once a month) was negatively associated with current wheeze (odds ratio 0.66; 95% confidence interval 0.44-1.00) and ever wheeze (0.69 (0.50-0.95)), but not with ever asthma (0.80 (0.56-1.14)). Drinking apple juice from concentrate at least once a day (compared with less than once a month) was also negatively associated with current wheeze (0.53 (0.34-0.83)), weakly associated with ever wheeze (0.74 (-0.54-1.02)), but not associated with ever asthma. Consumption of apples, other fruits and orange juice was not significantly associated with asthma symptoms. No association was found between eating fresh apples and asthma symptoms in the study population, but some evidence was found to suggest that a higher consumption of apple juice from concentrate and bananas may protect against wheezing in children.

Maternal testosterone in pregnancy and atopic outcomes in childhood.

BACKGROUND: In mice, androgens downregulate Th2 cytokine responses, but whether androgen levels during pregnancy might influence the development of allergy in the offspring has not been studied. METHODS: In the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort of 14 541 pregnancies, we related maternal blood total testosterone during pregnancy, measured in a subset of the cohort, to allergic outcomes in the offspring, including asthma, hayfever, eczema (n=543) and wheezing (n=532) at 69-81 months, and atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n=386) and blood total immunoglobulin E (IgE; n=314) at 7 years. We used logistic and linear regression to analyse binary outcomes and log-transformed IgE, respectively, controlling for potential confounders. RESULTS: Maternal testosterone was negatively associated with total IgE in boys [adjusted geometric mean ratio (GMR), per doubling of testosterone, 0.33 (0.20-0.55), P=0.000038 (n=168)], but not in girls [GMR 1.04 (0.53-2.06), P=0.91 (n=146)], P-value interaction 0.0086. The effect in boys was even stronger in the absence of maternal atopic disease. Testosterone was not associated with skin test positivity or atopic disease in either sex. CONCLUSIONS: Higher testosterone levels in pregnancy are associated with lower IgE production in boys.

Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood.

BACKGROUND: We recently found that paracetamol (acetaminophen) use in late pregnancy was associated with an increased risk of early wheezing in the offspring. OBJECTIVE: To see whether use of paracetamol in late pregnancy is associated with an increased risk of asthma, wheezing and other atopic outcomes in the child at school age. METHODS: In the population-based Avon Longitudinal Study of Parents and Children, we measured associations of paracetamol and aspirin use in late pregnancy (20-32 weeks) with asthma, hayfever, eczema (n = 8511) and wheezing (8381) in the offspring at 69-81 months, and with atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n = 6527) and blood total IgE (n = 5148) at 7 years. We used logistic and linear regression to analyse binary outcomes and log-transformed IgE, respectively, controlling for potential confounders. RESULTS: Use of paracetamol, but not aspirin, in late pregnancy was positively associated with asthma (odds ratios (ORs), comparing children whose mothers took paracetamol 'sometimes' and 'most days/daily' with those whose mothers never took it, 1.22 (95% confidence interval (CI): 1.06-1.41) and 1.62 (95% CI: 0.86-3.04), respectively; P trend = 0.0037), wheezing (ORs 1.20 (95% CI: 1.02-1.40) and 1.86 (95% CI: 0.98-3.55), respectively; P trend = 0.011), and total IgE (geometric mean ratios 1.14 (95% CI: 1.03-1.26) and 1.52 (95% CI: 0.98-2.38), respectively; P trend = 0.0034), but not hayfever, eczema or skin test positivity. The proportion of asthma attributable to paracetamol use in late pregnancy, assuming a causal relation, was 7%. CONCLUSION: Paracetamol exposure in late gestation may cause asthma, wheezing and elevated IgE in children of school age.

Paracetamol sales and atopic disease in children and adults: an ecological analysis.

The authors recently observed that frequent paracetamol use was positively associated with asthma and rhinitis in young adults. Therefore, an ecological analysis was performed to measure international associations between paracetamol sales and atopic disease prevalences in children and adults. Published data from the International Study of Asthma and Allergies in Childhood (ISAAC) on the prevalence of four atopic symptoms in 13-14-yr-olds (112 centres) and 67-yr-olds (66 centres) in 1994/1995, and European Community Respiratory Health Survey (ECRHS) data on the prevalence of asthma symptoms, diagnosed asthma and rhinitis (44 centres), prevalence of atopy, mean bronchial responsiveness and mean total immunoglobulin E levels (34 centres) in young adults in 1991/1992, were used. Their associations with national 1994/1995 per capita paracetamol sales were measured using linear regression. Paracetamol sales were high in English-speaking countries, and were positively associated with asthma symptoms, eczema and allergic rhinoconjunctivitis in 13-14-yr-olds, and with wheeze, diagnosed asthma, rhinitis and bronchial responsiveness in adults. The prevalence of wheeze increased by 0.52% in 13-14-yr-olds and by 0.26% in adults (p<0.0005) for each gram increase in per capita paracetamol sales. These ecological findings require cautious interpretation, but raise the possibility that variation in paracetamol usage may explain some of the variation in atopic disease prevalence between countries.