Seif O. Shaheen

Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease.

OBJECTIVE--To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease. DESIGN--Follow up study of men born during 1911-30 whose birth weights, weights at 1 year, and childhood illnesses were recorded at the time by health visitors. SETTING--Hertfordshire, England. SUBJECTS--5718 men born in the county during 1911-30 and a subgroup of 825 men born in the county during 1920-30 and still living there. MAIN OUTCOME MEASURES--Death from chronic obstructive airways disease, mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and respiratory symptoms. RESULTS--55 men died of chronic obstructive airways disease. Death rates fell with increasing birth weight and weight at 1 year. Mean FEV1 at age 59 to 70 years, adjusted for height and age, rose by 0.06 litre (95% confidence interval 0.02 to 0.09) with each pound (450 g) increase in birth weight, independently of smoking habit and social class. Bronchitis or pneumonia in infancy was associated with a 0.17 litre (0.02 to 0.32) reduction in adult FEV1 and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0.22 litre (0.02 to 0.42) reduction in adult FEV1. CONCLUSIONS--Lower birth weight was associated with worse adult lung function. Intrauterine influences which retard fetal weight gain may irrecoverably constrain the growth of the airways. Bronchitis, pneumonia, or whooping cough in infancy further reduced adult lung function. They also retarded infant weight gain. Consistent with this, death from chronic obstructive airways disease in adult life was associated with lower birth weight and weight at 1 year. Promoting lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of chronic obstructive airways disease in the next generation.

Measles and atopy in Guinea-Bissau

BACKGROUND Epidemiological studies have led to speculation that infections in early childhood may prevent allergic sensitisation but evidence to support this hypothesis is lacking. We investigated whether measles infection protects against the development of atopy in children of Guinea-Bissau, West Africa. METHODS We conducted a historical cohort study in Bandim, a semi-rural district of Bissau, the capital of Guinea-Bissau. 395 young adults, first surveyed in 1978-80 aged 0-6 years, were followed up in 1994. Our analyses were restricted to 262 individuals still living in Bandim for whom a measles history, documented in childhood, was judged to be reliable. We defined atopy as skin-prick test positivity (> or = 3 mm weal) to one or more of seven allergens. FINDINGS 17 (12.8 percent) of 133 participants who had had measles infection were atopic compared with 33 (25.6 percent) of 129 of those who had been vaccinated and not had measles (odds ratio, adjusted for potential confounding variables 0.36 [95 percent CI 0.17-0.78], p=O.O1). Participants who had been breastfed for more than a year were less likely to have a positive skin test to housedust mite. After adjustment for breastfeeding and other variables, measles infection was associated with a large reduction in the risk of skin-prick test positivity to housedust mite (odds ratio for Dermatophagoides pteronyssinus 0.20 [0.05-0.81], p=0.02; D farinae 0.20 [0.06-0.71], p=0.01). INTERPRETATION Measles infection may prevent the development of atopy in African children.

Birth weight, body mass index and asthma in young adults

BACKGROUND Impaired fetal growth may be a risk factor for asthma although evidence in children is conflicting and there are few data in adults. Little is known about risk factors which may influence asthma in late childhood or early adult life. Whilst there are clues that fatness may be important, this has been little studied in young adults. The relations between birth weight and childhood and adult anthropometry and asthma, wheeze, hayfever, and eczema were investigated in a nationally representative sample of young British adults. METHODS A total of 8960 individuals from the 1970 British Cohort Study (BCS70) were studied. They had recently responded to a questionnaire at 26 years of age in which they were asked whether they had suffered from asthma, wheeze, hayfever, and eczema in the previous 12 months. Adult body mass index (BMI) was calculated from reported height and weight. RESULTS The prevalence of asthma at 26 years fell with increasing birth weight. After controlling for potential confounding factors, the odds ratio comparing the lowest birth weight group (<2 kg) with the modal group (3–3.5 kg) was 1.99 (95% CI 0.96 to 4.12). The prevalence of asthma increased with increasing adult BMI. After controlling for birth weight and other confounders, the odds ratio comparing highest with lowest quintile was 1.72 (95% CI 1.29 to 2.29). The association between fatness and asthma was stronger in women; odds ratios comparing overweight women (BMI 25–29.99) and obese women (BMI ⩾30) with those of normal weight (BMI <25) were 1.51 (95% CI 1.11 to 2.06) and 1.84 (95% CI 1.19 to 2.84), respectively. The BMI at 10 years was not related to adult asthma. Similar associations with birth weight and adult BMI were present for wheeze but not for hayfever or eczema. CONCLUSIONS Impaired fetal growth and adult fatness are risk factors for adult asthma.

Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood

Background: Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals. Methods: Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV1), mid forced expiratory flow (FEF25-75)) and bronchial responsiveness were made at 7–9 years of age. Results: Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV1 per μmol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV1 per μmol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes. Conclusions: The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.

Early BCG vaccination and reduction in atopy in Guinea-Bissau.

It has been proposed that certain viral and bacterial infections in early childhood may prevent allergic sensitization, by inducing Th1‐type immune responses. This has led to speculation that mycobacterial vaccines might, through their Th1‐stimulating properties, also protect against atopy.

Frequent paracetamol use and asthma in adults

BACKGROUND The pulmonary antioxidant glutathione may limit airway inflammation in asthma. Since paracetamol (acetaminophen) depletes the lung of glutathione in animals, a study was undertaken to investigate whether frequent use in humans was associated with asthma. METHODS Information was collected on the use of analgesics as part of a population based case-control study of dietary antioxidants and asthma in adults aged 16–49 years registered with 40 general practices in Greenwich, South London. The frequency of use of paracetamol and aspirin was compared in 664 individuals with asthma and in 910 without asthma. Asthma was defined by positive responses to questions about asthma attacks, asthma medication, or waking at night with shortness of breath. The association between analgesic use and severity of disease amongst asthma cases, as measured by a quality of life score, was also examined. RESULTS Paracetamol use was positively associated with asthma. After controlling for potential confounding factors the odds ratio for asthma, compared with never users, was 1.06 (95% CI 0.77 to 1.45) in infrequent users (<monthly), 1.22 (0.87 to 1.72) in monthly users, 1.79 (1.21 to 2.65) in weekly users, and 2.38 (1.22 to 4.64) in daily users (p (trend) = 0.0002). This association was present in users and non-users of aspirin and was stronger when cases with more severe disease were compared with controls; amongst cases increasing paracetamol use was associated with more severe disease. Frequency of aspirin use was not associated with asthma when cases as a whole were compared with controls, nor with severity of asthma amongst cases. Frequent paracetamol use was positively associated with rhinitis, but aspirin use was not. CONCLUSIONS Frequent use of paracetamol may contribute to asthma morbidity and rhinitis in adults.

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.

Paracetamol use in pregnancy and wheezing in early childhood

Background: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18–20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30–42 months (n=9400) and eczema at 18–30 months (n=10 216) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at <6 months and at 30–42 months) were examined. Results: Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20–32 weeks), but not in early pregnancy (<18–20 weeks), was associated with an increased risk of wheezing in the offspring at 30–42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% CI 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% CI 1.24 to 4.40); p=0.008). Assuming a causal relation, only about 1% of wheezing at 30–42 months was attributable to this exposure. Frequent paracetamol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months. Conclusions: Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.

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.

Birth weight, childhood lower respiratory tract infection, and adult lung function

BACKGROUND Historical cohort studies in England have found that impaired fetal growth and lower respiratory tract infections in early childhood are associated with lower levels of lung function in late adult life. These relations are investigated in a similar study in Scotland. METHODS In 1985–86 a follow up study was carried out of 1070 children who had been born in St Andrew’s from 1921 to 1935 and followed from birth to 14 years of age by the Mackenzie Institute for Medical Research. Recorded information included birth weight and respiratory illnesses. The lung function of 239 of these individuals was measured. RESULTS There was no association between birth weight and lung function. Pneumonia before two years of age was associated with a difference in mean forced expiratory volume in one second (FEV1) of −0.39 litres (95% confidence interval (CI) −0.67, −0.11; p = 0.007) and in mean forced vital capacity (FVC) of −0.60 litres (95% CI −0.92, −0.28; p<0.001), after controlling for age, sex, height, smoking, type of spirometer, and other illnesses before two years. Similar reductions were seen in men and women. Bronchitis before two years was associated with smaller deficits in FEV1 and FVC. Asthma or wheeze at two years and older and cough after five years were also associated with a reduction in FEV1. CONCLUSIONS The relation between impaired fetal growth and lower lung function in late adult life seen in previous studies was not confirmed in this cohort. The deficits in FEV1 and FVC associated with pneumonia and bronchitis in the first two years of life are consistent with a causal relation.