Haemoglobin concentrations in pregnancy and respiratory and allergic outcomes in childhood: Birth cohort study.

BACKGROUND: Limited epidemiological evidence suggests that low maternal iron status and anaemia in pregnancy may increase the risk of childhood respiratory and allergic outcomes. OBJECTIVES: To investigate the relation between maternal haemoglobin concentrations in pregnancy and childhood respiratory and allergic outcomes. METHODS: In the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined associations of maternal haemoglobin concentrations (g/dL) in pregnancy with hayfever, eczema, wheezing, doctor-diagnosed asthma, allergic sensitisation and total IgE at 7 years, and with lung function at 8-9 years in the offspring, after controlling for potential confounders (N = 3234-5335). RESULTS: Maternal haemoglobin was not associated with offspring hayfever, eczema, wheezing or asthma. However, the first haemoglobin measurement in pregnancy (<18 weeks' gestation) and the last measurement (>28 weeks' gestation) were negatively associated with allergic sensitisation (adjusted odds ratio [95% CI] per g/dL 0.91 [0.83 to 0.99] and 0.90 [0.83 to 0.98], respectively). The last haemoglobin measurement was also negatively associated with total IgE (adjusted geometric mean ratio 0.94 [0.88 to 0.99]). Anaemia (haemoglobin <11 g/dL) in late pregnancy was negatively associated with forced vital capacity (difference in standard deviation score -0.07 [-0.13 to -0.01]). CONCLUSIONS AND CLINICAL RELEVANCE: Lower maternal haemoglobin in pregnancy may be a risk factor for allergic sensitisation, elevated IgE and lower FVC in childhood, which may reflect effects of lower prenatal iron status. However, maternal haemoglobin was not associated with risk of childhood asthma or other allergic disorders.

Maternal 25-hydroxyvitamin D and its association with childhood atopic outcomes and lung function.

BACKGROUND: It has been suggested that maternal vitamin D status in pregnancy influences the risk of asthma and atopy in the offspring. The epidemiological evidence to support these claims is conflicting and may reflect chance findings and differences in how vitamin D was assessed. OBJECTIVE: To examine the association between blood total maternal 25-hydroxy vitamin D (25(OH)D) concentrations in pregnancy and offspring asthma, atopy and lung function in the largest birth cohort study to date. METHODS: Participants were largely of white European origin and resident in the South West of England. We examined the associations of maternal 25(OH)D concentrations in pregnancy with the following outcomes in the offspring: wheeze, asthma, atopy, eczema, hayfever, at mean age 7.5 years (n = 3652-4696 depending on outcome), IgE at 7 years (n = 2915) and lung function and bronchial responsiveness at mean age 8.7 years (n = 3728-3784). RESULTS: Sixty-eight per cent of mothers had sufficient (> 50 nmol/L) concentrations of 25(OH)D, 27% were insufficient (27.5-49.99 nmol/L) and 5% were deficient (< 27.5 nmol/L). There was no evidence to suggest that maternal 25(OH)D concentration in pregnancy was associated with any respiratory or atopic outcome in the offspring. These findings remained after adjustment for season of measurement and for potential confounders. There was also no evidence that these relationships followed a non-linear form and no evidence that either deficient or high concentrations of maternal 25(OH)D were associated with atopic or respiratory outcomes. CONCLUSIONS: We found no evidence that maternal blood 25(OH)D concentration in pregnancy is associated with childhood atopic or respiratory outcomes.

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.

The relationship of dietary patterns with adult lung function and COPD.

Previous studies of diet and lung function have focused on associations with individual nutrients and foods, and not dietary patterns. The relationships between dietary patterns and lung function and spirometrically defined chronic obstructive pulmonary disease (COPD) were investigated in 1,551 males and 1,391 females in Hertfordshire, UK. Dietary information was obtained by food frequency questionnaire and dietary patterns were identified using principal components analysis. Using regression analysis, after controlling for confounders, a "prudent" pattern (high consumption of fruit, vegetables, oily fish and wholemeal cereals) was positively associated with forced expiratory volume in 1 s (FEV(1)) (trend p-value <0.001 in males, 0.008 in females) (difference in FEV(1) between top and bottom quintiles of pattern score, 0.18 L (95% CI 0.08-0.28 L) in males, 0.08 L (95% CI 0.00-0.16 L) in females). This pattern was also positively associated with forced vital capacity (FVC) in both sexes. Males with a higher "prudent" pattern score had a higher FEV(1)/FVC (trend p-value 0.002) and a lower prevalence of COPD (odds ratio comparing top versus bottom quintile 0.46, 95% CI 0.26-0.81; trend p-value 0.012). Associations in males were stronger in smokers than nonsmokers (interaction p-value for FEV(1)/FVC 0.002). A "prudent" dietary pattern may protect against impaired lung function and COPD, especially in male smokers.

Dietary patterns and adult asthma: population-based case-control study.

BACKGROUND: Epidemiological studies of diet and asthma have focused on relations with intakes of individual nutrients and foods and evidence has been conflicting. Few studies have examined associations with dietary patterns. METHODS: We carried out a population-based case-control study of asthma in adults aged between 16 and 50 in South London, UK. Information about usual diet was obtained by food frequency questionnaire and we used principal components analysis to define five dietary patterns in controls. We used logistic and linear regression, controlling for confounders, to relate these patterns to asthma, asthma severity, rhinitis and chronic bronchitis in 599 cases and 854 controls. RESULTS: Overall, there was weak evidence that a 'vegetarian' dietary pattern was positively associated with asthma [adjusted odds ratio comparing top vs bottom quintile of pattern score 1.43 (95% CI: 0.93-2.20), P trend 0.075], and a 'traditional' pattern (meat and vegetables) was negatively associated [OR 0.68 (0.45-1.03), P trend 0.071]. These associations were stronger amongst nonsupplement users (P trend 0.030 and 0.001, respectively), and the association with the 'vegetarian' pattern was stronger amongst whites (P trend 0.008). No associations were observed with asthma severity. A 'prudent' dietary pattern (wholemeal bread, fish and vegetables) was positively associated with chronic bronchitis [OR 2.61 (1.13-6.05), P trend 0.025], especially amongst nonsupplement users (P trend 0.002). CONCLUSIONS: Overall there were no clear relations between dietary patterns and adult asthma; associations in nonsupplement users and whites require confirmation. The finding for chronic bronchitis was unexpected and also requires replication.

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.

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 (FEV(1)), mid forced expiratory flow (FEF(25-75))) 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 %FEV(1) per mumol, 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 %FEV(1) per mumol). 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.

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.

Cell mediated immunity after measles in Guinea-Bissau: historical cohort study.

OBJECTIVE: To investigate whether children who have had measles have reduced general cell mediated immunity three years later compared with vaccinated children who have not had measles. DESIGN: Historical cohort study. SETTING: Bissau, Guinea-Bissau. SUBJECTS: 391 children aged 3-13 years who were living in Bissau during a measles epidemic in 1991 and still lived there. These included 131 primary cases and 139 secondary cases from the epidemic and 121 vaccinated controls with no history of measles. MAIN OUTCOME MEASURES: General cell mediated immunity assessed by measurement of delayed type hypersensitivity skin responses to seven recall antigens. Anergy was defined as a lack of response to all antigens. RESULTS: 82 out of 268 cases of measles (31%) were anergic compared with 20 of the 121 vaccinated controls (17%) (odds ratio adjusted for potential confounding variables 2.2 (95% confidence interval 1.2 to 4.0); P 0.009). The prevalence of anergy was higher in secondary cases (33% (46/138)) than in primary cases (28% (36/130)), although this difference was not significant. Anergy was more common in the rainy season (unadjusted prevalence 31% (91/291) than in the dry season (11% (11/98)) (adjusted odds ratio 4.8 (2.2 to 10.3)). This seasonal increase occurred predominantly in the case of measles. CONCLUSION: Reduced general cell mediated immunity may contribute to the higher long term mortality in children who have had measles compared with recipients of standard measles vaccine and to the higher child mortality in the rainy season in west Africa.

Is lung function associated with bone mineral density? Results from the Hertfordshire Cohort Study.

UNLABELLED: Given limited information available regarding associations between lung function and bone mineral density among healthy subjects, we undertook these analyses in the Hertfordshire Cohort Study. Forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC were not associated with bone mineral density at any site; associations with bone mineral content were removed by adjustment for body size. PURPOSE: There is limited information available regarding the association between lung function and bone mineral density among healthy elderly subjects. We addressed this issue in the Hertfordshire Cohort Study. METHODS: From the above cohort, 985 subjects (496 men and 489 women) aged 60-72 years were recruited. All subjects underwent bone density measurements using dual energy X-ray absorptiometry and lung function tests using standardised spirometry. Chronic obstructive pulmonary disease (COPD) was defined as a FEV(1)/FVC ratio

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.

Dietary intake of flavonoids and asthma in adults.

Epidemiological studies have suggested that a high consumption of apples may protect against asthma and chronic obstructive pulmonary disease. This effect has been attributed to their high flavonoid content, but few studies have investigated the relationship between flavonoid intake and obstructive lung disease directly. In a population-based, case-control study of 1,471 adults aged 16-50 yrs in London (UK), the present study examined whether dietary intake of catechins, flavonols and flavones was negatively associated with asthma, asthma severity and chronic sputum production. Asthma was defined by positive responses to a standard screening questionnaire in 1996 and information about usual diet was obtained by a food frequency questionnaire in 1997. After controlling for potential confounders, dietary intake of these three flavonoid subclasses was not significantly associated with asthma, (odds ratio per quintile (95% confidence interval) = 0.94 (0.86-1.02); 1.00 (0.92-1.09); 0.98 (0.88 -1.08) for flavones, flavonols and total catechins, respectively) nor was it associated with asthma severity, or chronic sputum production. In conclusion, no evidence was found for a protective effect of three major subclasses of dietary flavonoids on asthma. It is possible that other flavonoids or polyphenols present in apples may explain the protective effect of apples on obstructive lung disease.

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.

Do lower respiratory tract infections in early childhood cause chronic obstructive pulmonary disease?

The hypothesis that lower respiratory tract infections (LRTI) in early childhood lead to chronic obstructive pulmonary disease (COPD) in late adult life has been difficult to test. However, a unique opportunity arose when records were discovered in the counties of Hertfordshire and Derbyshire, England, that contained information about childhood LRTI recorded 60 to 70 years ago. The lung function of some men still living in these counties was examined. In Hertfordshire men, bronchitis or pneumonia in infancy was associated with reduced mean FEV1, adjusted for age and height. In Derbyshire men, pneumonia before 2 yr of age was associated with a large and highly significant reduction in mean FEV1, adjusted for age and height. These findings were independent of smoking and social class. These data support a causal relationship between LRTI in early life and subsequent COPD.

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.

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 (

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.