Life course BMI trajectories from childhood to mid-adulthood are differentially associated with anxiety and depression outcomes in middle age.

BACKGROUND/OBJECTIVE: Obesity is a risk factor for multimorbidity, including depression and possibly anxiety. However, it is currently unclear how patterns of change in BMI over the life course differentially influence the magnitude in risk of depression and anxiety in mid-adulthood. We aimed to examine associations between BMI trajectories from childhood to adulthood and the risk of depression and anxiety in middle age. METHODS: In the Tasmanian Longitudinal Health Study (n = 2416), five distinct BMI trajectories were previously defined from age 5 to 45 years using group-based modelling. At age 53, current depression and anxiety were assessed using the Patient Health Questionnaire and the Generalized Anxiety Disorder scale, respectively. Logistic regression models adjusted for potential confounders estimated associations between BMI trajectories and these outcomes. RESULTS: Those belonging to the child average-increasing (OR = 2.24; 95%CI: 1.24, 4.06) and persistently high (OR = 2.64; 1.26, 5.52) trajectories were more likely to have depression in middle age, compared to the persistently average trajectory. However, the odds of experiencing greater severity of depressive symptoms was highest in the child average-increasing group (OR = 2.36; 1.59, 3.49). Despite finding no evidence of association between BMI trajectories and current anxiety, we observed less severe symptoms in the child high-decreasing trajectory (OR = 0.68; 0.51, 0.91). CONCLUSION: We found an increased risk of depression in middle age among individuals with a persistently high BMI from childhood to mid-adulthood and individuals with an average BMI in childhood which then increased consistently throughout adulthood. Encouragingly, resolving childhood adiposity by adulthood was associated with lesser anxiety symptoms. Taken together, these findings highlight the need to target mental health screening and treatment towards high-risk BMI trajectory groups and the importance of early interventions to prevent and resolve excess weight.

Childhood pneumonia, pleurisy and lung function: a cohort study from the first to sixth decade of life.

INTRODUCTION: Adult spirometry following community-acquired childhood pneumonia has variably been reported as showing obstructive or non-obstructive deficits. We analysed associations between doctor-diagnosed childhood pneumonia/pleurisy and more comprehensive lung function in a middle-aged general population cohort born in 1961. METHODS: Data were from the prospective population-based Tasmanian Longitudinal Health Study cohort. Analysed lung function was from ages 7 years (prebronchodilator spirometry only, n=7097), 45 years (postbronchodilator spirometry, carbon monoxide transfer factor and static lung volumes, n=1220) and 53 years (postbronchodilator spirometry and transfer factor, n=2485). Parent-recalled histories of doctor-diagnosed childhood pneumonia and/or pleurisy were recorded at age 7. Multivariable linear and logistic regression were used. RESULTS: At age 7, compared with no episodes, childhood pneumonia/pleurisy-ever was associated with reduced FEV1:FVC for only those with current asthma (beta-coefficient or change in z-score=-0.20 SD, 95% CI -0.38 to -0.02, p=0.028, p interaction=0.036). At age 45, for all participants, childhood pneumonia/pleurisy-ever was associated with a restrictive pattern: OR 3.02 (1.5 to 6.0), p=0.002 for spirometric restriction (FVC less than the lower limit of normal plus FEV1:FVC greater than the lower limit of normal); total lung capacity z-score -0.26 SD (95% CI -0.38 to -0.13), p<0.001; functional residual capacity -0.16 SD (-0.34 to -0.08), p=0.001; and residual volume -0.18 SD (-0.31 to -0.05), p=0.008. Reduced lung volumes were accompanied by increased carbon monoxide transfer coefficient at both time points (z-score +0.29 SD (0.11 to 0.49), p=0.001 and +0.17 SD (0.04 to 0.29), p=0.008, respectively). DISCUSSION: For this community-based population, doctor-diagnosed childhood pneumonia and/or pleurisy were associated with obstructed lung function at age 7 for children who had current asthma symptoms, but with evidence of 'smaller lungs' when in middle age.

Early menarche is associated with lower adult lung function: A longitudinal cohort study from the first to sixth decade of life.

BACKGROUND AND OBJECTIVE: Early menarche is increasing in prevalence worldwide, prompting clinical and public health interest on its links with pulmonary function. We aimed to investigate the relationship between early menarche and lung function in middle age. METHODS: The population-based Tasmanian Longitudinal Health Study (born 1961; n = 8583), was initiated in 1968. The 5th Decade follow-up data (mean age: 45 years) included age at menarche and complex lung function testing. The 6th Decade follow-up (age: 53 years) repeated spirometry and gas transfer factor. Multiple linear regression and mediation analyses were performed to determine the association between age at menarche and adult lung function and investigate biological pathways, including the proportion mediated by adult-attained height. RESULTS: Girls reporting an early menarche (<12 years) were measured to be taller with greater lung function at age 7 years compared with those reporting menarche ≥12 years. By 45 years of age, they were shorter and had lower post-bronchodilator (BD) forced expiratory volume in 1 s (adjusted mean difference: -133 mL; 95% CI: -233, -33), forced vital capacity (-183 mL; 95% CI: -300, -65) and functional residual capacity (-168 mL; 95% CI: -315, -21). Magnitudes of spirometric deficits were similar at age 53 years. Forty percent of these total effects were mediated through adult-attained height. CONCLUSION: Early menarche was associated with reduced adult lung function. This is the first study to investigate post-BD outcomes and quantify the partial role of adult height in this association.

NOx in exhaled breath condensate is related to allergic sensitization in young and middle-aged adults.

BACKGROUND: Asthma and allergic diseases are heterogeneous. Measurement of biomarkers in exhaled breath condensate (EBC) may help to discriminate between different phenotypes and may assist with clinical prognostication. OBJECTIVES: We aimed to assess associations between total nitric oxide products (NOx ) in EBC and different allergic phenotypes and lung function in young and middle-aged adults. METHODS: Cross-sectional analyses were nested within two Australian longitudinal studies, the Melbourne Atopy Cohort Study (MACS, mean age 17.8 years) and the Tasmanian Longitudinal Health Study (TAHS, mean age 49.4 years). Levels of EBC NOx were determined by Griess-reaction fluorescent method. Associations were assessed between EBC NOx and different allergic phenotypes, lung function and airway reactivity. RESULTS: Atopy, with or without asthma or rhinitis, was associated with increased EBC NOx levels particularly in individuals with poly-aero-sensitization. These findings were generally consistent across the two age groups. In the older cohort, use of ICS in the previous 12 months masked the association between sensitization and EBC NOx (OR = 0.64, 95% CI = 0.21-1.96, p for interaction = 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: In these population-based samples, EBC NOx was most strongly associated with atopic sensitization, rather than either current asthma or rhinitis, possibly indicating underlying increased airway inflammation associated with atopy. Therefore, EBC NOx could be a key predictor of atopy in both young and middle-aged adults, regardless of the presence of concomitant asthma or rhinitis.

Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization.

BACKGROUND: Markers of microbial exposure are thought to be associated with risk of allergic sensitization; however, the associations are inconsistent and may be related to gene-environment interactions. OBJECTIVE: To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship. METHODS: We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi-level mixed-effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random-effects meta-analysis. RESULTS: CD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta-analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455-SNP (P = 0.001) but not with the rs2569190-SNP (P = 0.60). The pooled meta-analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455-C-allele than the T-allele (OR = 0.83 vs 1.05, respectively). CONCLUSION AND CLINICAL RELEVANCE: Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals.

Maternal age at delivery, lung function and asthma in offspring: a population-based survey.

There is limited information about potential impact of maternal age on the respiratory health of offspring. We investigated the association of maternal age at delivery with adult offspring's lung function, respiratory symptoms and asthma, and potential differences according to offspring sex.10 692 adults from 13 countries participating in the European Community Respiratory Health Survey (ECRHS) II responded to standardised interviews and provided lung function measurements and serum for IgE measurements at age 25-55 years. In logistic and linear multilevel mixed models we adjusted for participants' characteristics (age, education, centre, number of older siblings) and maternal characteristics (smoking in pregnancy, education) while investigating for differential effects by sex. Maternal age was validated in a subsample using data from the Norwegian birth registry.Increasing maternal age was associated with increasing forced expiratory volume in 1 s (2.33 mL per year, 95% CI 0.34-4.32 mL per year), more consistent in females (ptrend 0.025) than in males (ptrend 0.14). Asthma (OR 0.85, 95% CI 0.79-0.92) and respiratory symptoms (OR 0.87, 95% CI 0.82-0.92) decreased with increasing maternal age (per 5 years) in females, but not in males (pinteraction 0.05 and 0.001, respectively). The results were consistent across centres and not explained by confounding factors.Maternal ageing was related to higher adult lung function and less asthma/symptoms in females. Biological characteristics in offspring related to maternal ageing are plausible and need further investigation.

Do Glutathione S-Transferase Genes Modify the Link between Indoor Air Pollution and Asthma, Allergies, and Lung Function? A Systematic Review.

PURPOSE OF REVIEW: Glutathione S-transferase (GST) genes are involved in oxidative stress management and may modify the impact of indoor air pollution. We aimed to assess the influence of GST genes on the relationship between indoor air pollution and allergy/lung function. RECENT FINDINGS: Our systematic review identified 22 eligible studies, with 15 supporting a gene-environment interaction. Carriers of GSTM1/T1 null and GSTP1 val genotypes were more susceptible to indoor air pollution exposures, having a higher risk of asthma and lung function deficits. However, findings differed in terms of risk alleles and specific exposures. High-exposure heterogeneity precluded meta-analysis. We found evidence that respiratory effects of indoor air pollution depend on the individual's GST profile. This may help explain the inconsistent associations found when gene-environment interactions are not considered. Future studies should aim to improve the accuracy of pollution assessment and investigate this finding in different populations.

Critical age windows in the impact of lifetime smoking exposure on respiratory symptoms and disease among ever smokers.

BACKGROUND: Despite extensive knowledge of smoking effects on respiratory disease, there is no study including all age windows of exposure among ever smokers. The objective of this study was to assess the effects from smoking exposure in utero, early childhood, adolescence and adulthood on respiratory health outcomes in adult male and female ever smokers. METHODS: Respiratory health outcomes were assessed in 10,610 participants of the European Community Respiratory Health Survey (ECRHS) I who reported a history of ever smoking by questionnaire. The associations of maternal smoking in utero, maternal smoking during childhood, age of smoking debut and pack-years of smoking with respiratory symptoms, obstructive diseases and bronchial hyperreactivity were analysed using generalized linear regression, non-linearity between age of smoking debut and outcomes were assessed by Generalized additive mixed models. RESULTS: Respiratory symptoms and asthma were more frequent in adults if their mother smoked during pregnancy, and, in men, also if mother smoked in childhood. Wheeze and ≥3 respiratory symptoms declined with later smoking debut among women [≤10 years: OR = 3.51, 95% CI 1.26, 9.73; 11-12 years: 1.57[1.01-2.44]; 13-15 years: 1.11[0.94-1.32] and ≤10 years: 3.74[1.56-8.83]; 11-12 years: 1.76[1.19-2.56]; 13-15 years: 1.12[0.94-1.35], respectively]. Effects of increasing number of packyears were pronounced in women (Chronic Obstructive Pulmonary Disease (COPD): OR/10 packyears women: 1.33 [1.18, 1.50], men: 1.14 [1.04, 1.26] pinteraction = 0.01). CONCLUSIONS: Among ever smokers, smoking exposure in each stage of the lifespan show persistent harmful effects for adult respiratory health, while women appeared to be more vulnerable to an early age of smoking debut and amount of smoking in adulthood.

Childhood measles contributes to post-bronchodilator airflow obstruction in middle-aged adults: A cohort study.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) has potential origins in childhood but an association between childhood measles and post-bronchodilator (BD) airflow obstruction (AO) has not yet been shown. We investigated whether childhood measles contributed to post-BD AO through interactions with asthma and/or smoking in a non-immunized middle-aged population. METHODS: The population-based Tasmanian Longitudinal Health Study (TAHS) cohort born in 1961 (n = 8583) underwent spirometry in 1968 before immunization was introduced. A history of childhood measles infection was obtained from school medical records. During the fifth decade follow-up (n = 5729 responses), a subgroup underwent further lung function measurements (n = 1389). Relevant main associations and interactions by asthma and/or smoking on post-BD forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC; continuous variable) and AO (FEV1 /FVC < lower limit of normal) were estimated by multiple regression. RESULTS: Sixty-nine percent (n = 950) had a history of childhood measles. Childhood measles augmented the combined adverse effect of current clinical asthma and smoking at least 10 pack-years on post-BD FEV1 /FVC ratio in middle age (z-score: -0.70 (95% CI: -1.1 to -0.3) vs -1.36 (-1.6 to -1.1), three-way interaction: P = 0.009), especially for those with childhood-onset asthma. For never- and ever-smokers of <10 pack-years who had current asthma symptoms, compared with those without childhood measles, paradoxically, the odds for post-BD AO was not significant in the presence of childhood measles (OR: 12.0 (95% CI: 3.4-42) vs 2.17 (0.9-5.3)). CONCLUSION: Childhood measles infection appears to compound the associations between smoking, current asthma and post-BD AO. Differences between asthma subgroups provide further insight into the complex aetiology of obstructive lung diseases for middle-aged adults.

Childhood Lung Function Predicts Adult Chronic Obstructive Pulmonary Disease and Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome.

RATIONALE: The burden of chronic obstructive pulmonary disease (COPD) is increasing, yet there are limited data on early life risk factors. OBJECTIVES: To investigate the role of childhood lung function in adult COPD phenotypes. METHODS: Prebronchodilator spirometry was performed for a cohort of 7-year-old Tasmanian children (n = 8,583) in 1968 who were resurveyed at 45 years, and a selected subsample (n = 1,389) underwent prebronchodilator and post-bronchodilator spirometry. For this analysis, COPD was spirometrically defined as a post-bronchodilator FEV1/FVC less than the lower limit of normal. Asthma-COPD overlap syndrome (ACOS) was defined as the coexistence of both COPD and current asthma. Associations between childhood lung function and asthma/COPD/ACOS were examined using multinomial regression. MEASUREMENTS AND MAIN RESULTS: At 45 years, 959 participants had neither current asthma nor COPD (unaffected), 269 had current asthma alone, 59 had COPD alone, and 68 had ACOS. The reweighted prevalence of asthma alone was 13.5%, COPD alone 4.1%, and ACOS 2.9%. The lowest quartile of FEV1 at 7 years was associated with ACOS (odds ratio, 2.93; 95% confidence interval, 1.32-6.52), but not COPD or asthma alone. The lowest quartile of FEV1/FVC ratio at 7 years was associated with ACOS (odds ratio, 16.3; 95% confidence interval, 4.7-55.9) and COPD (odds ratio, 5.76; 95% confidence interval, 1.9-17.4), but not asthma alone. CONCLUSIONS: Being in the lowest quartile for lung function at age 7 may have long-term consequences for the development of COPD and ACOS by middle age. Screening of lung function in school age children may identify a high-risk group that could be targeted for intervention. Further research is needed to understand possible modifiers of these associations and develop interventions for children with impaired lung function.

Traffic-related air pollution exposure is associated with allergic sensitization, asthma, and poor lung function in middle age.

BACKGROUND: Traffic-related air pollution (TRAP) exposure is associated with allergic airway diseases and reduced lung function in children, but evidence concerning adults, especially in low-pollution settings, is scarce and inconsistent. OBJECTIVES: We sought to determine whether exposure to TRAP in middle age is associated with allergic sensitization, current asthma, and reduced lung function in adults, and whether these associations are modified by variants in Glutathione S-Transferase genes. METHODS: The study sample comprised the proband 2002 laboratory study of the Tasmanian Longitudinal Health Study. Mean annual residential nitrogen dioxide (NO2) exposure was estimated for current residential addresses using a validated land-use regression model. Associations between TRAP exposure and allergic sensitization, lung function, current wheeze, and asthma (n = 1405) were investigated using regression models. RESULTS: Increased mean annual NO2 exposure was associated with increased risk of atopy (adjusted odds ratio [aOR], 1.14; 95% CI, 1.02-1.28 per 1 interquartile range increase in NO2 [2.2 ppb]) and current wheeze (aOR, 1.14; 1.02-1.28). Similarly, living less than 200 m from a major road was associated with current wheeze (aOR, 1.38; 95% CI, 1.06-1.80) and atopy (aOR, 1.26; 95% CI, 0.99-1.62), and was also associated with having significantly lower prebronchodilator and postbronchodilator FEV1 and prebronchodilator forced expiratory flow at 25% to 75% of forced vital capacity. We found evidence of interactions between living less than 200 m from a major road and GSTT1 polymorphism for atopy, asthma, and atopic asthma. Overall, carriers of the GSTT1 null genotype had an increased risk of asthma and allergic outcomes if exposed to TRAP. CONCLUSIONS: Even relatively low TRAP exposures confer an increased risk of adverse respiratory and allergic outcomes in genetically susceptible individuals.

Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling.

BACKGROUND: Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) to identify risk-associated variants are needed. OBJECTIVE: We sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. METHODS: We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n = 46,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations. RESULTS: We tested the association between asthma and 17,190 genes that were found to have cis- and/or trans-eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1, TINF2, and SAFB). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3, USMG5, P2RY13, and P2RY14, which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14-purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively-were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs. CONCLUSION: We identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs.

Traffic-related air pollution exposure over a 5-year period is associated with increased risk of asthma and poor lung function in middle age.

Current evidence concerning the impact of exposure to traffic-related air pollution (TRAP) on adult respiratory morbidity mainly comes from cross-sectional studies. We sought to establish more robust measures of this association and potential gene-environment interactions using longitudinal data from an established cohort study.Associations between measures of TRAP (nitrogen dioxide (NO2) and distance to major roads) and wheeze, asthma prevalence and lung function were investigated in participants of the Tasmanian Longitudinal Health Study at 45- and 50-year follow-ups. Generalised estimating equations were used to quantify associations and the potential modifying effect of glutathione S-transferase gene variants.Living <200 m from a major road was associated with increased prevalence of current asthma and wheeze, and lower lung function. The association between living <200 m from a major road and current asthma and wheeze was more marked for carriers of the GSTT1 null and GSTP1 val/val or ile/val genotypes. Over the 5-year period, higher NO2 exposures were associated with increased current asthma prevalence. Higher NO2 exposure was associated with lower forced vital capacity for carriers of the GSTT1 null genotype.TRAP exposures were associated with increased risk of asthma, wheeze and lower lung function in middle-aged adults. The interaction with the GSTT1 genotype suggests that deficient antioxidant mechanisms may play a role in these adverse health effects.

Bronchial hyperresponsiveness and obesity in middle age: insights from an Australian cohort.

The association between obesity and bronchial hyperresponsiveness (BHR) is incompletely characterised. Using the 2006 follow-up of the Tasmanian Longitudinal Health Study, we measured the association between obesity and BHR and whether it was mediated by small airway closure or modified by asthma and sex of the patient.A methacholine challenge measured BHR. Multivariable logistic regression measured associations between body mass index (BMI) and BHR, adjusting for sex, asthma, smoking, corticosteroid use, family history and lung function. Mediation by airway closure was also measured.Each increase in BMI of 1 kg·m-2 was associated with a 5% increase in the odds of BHR (OR 1.05, 95% CI 1.01-1.09) and 43% of this association was mediated by airway closure. In a multivariable model, BMI (OR 1.06, 95% CI 1.00-1.16) was associated with BHR independent of female sex (OR 3.26, 95% CI 1.95-5.45), atopy (OR 2.30, 95% CI 1.34-3.94), current asthma (OR 5.74, 95% CI 2.79-11.82), remitted asthma (OR 2.35, 95% CI 1.27-4.35), low socioeconomic status (OR 2.11, 95% CI 1.03-4.31) and forced expiratory volume in 1 s/forced vital capacity (OR 0.86, 95% CI 0.82-0.91). Asthma modified the association with an increasing probability of BHR as BMI increased, only in those with no or remitted asthma.An important fraction of the BMI/BHR association was mediated via airway closure. Conflicting findings in previous studies could be explained by failure to consider this intermediate step.

Preterm birth and low birth weight continue to increase the risk of asthma from age 7 to 43.

BACKGROUND: Perinatal events can influence the development of asthma in childhood but current evidence is contradictory concerning the effects on life-time asthma risk. OBJECTIVE: To assess the relationship between birth characteristics and asthma from childhood to adulthood. METHODOLOGY: All available birth records for the Tasmanian Longitudinal Health Study (TAHS) cohort, born in 1961 were obtained from the Tasmanian State Archives and Tasmanian hospitals. Low birth weight (LBW) was defined as less than 2500 grams. Preterm birth was defined as delivery before 37 weeks' gestation. Small for gestational age (SGA) was defined as a birth weight below the 10th percentile for a given gestational age. Multivariate logistic and cox regression were used to examine associations between birth characteristics and lifetime risk of current and incident asthma, adjusting for confounders. RESULTS: The prevalence of LBW was 5.2%, SGA was 13.8% and preterm was 3.3%. LBW (OR = 1.65, 95%CI 1.12,2.44) and preterm birth (OR = 1.81, 95%CI 0.99, 3.31) were both associated with an increased risk of current asthma between the ages of 7 to 43 years. There was no association between SGA and current asthma risk. However, SGA was associated with incident asthma (HR = 1.32, 95%CI 1.00, 1.74), and there was an interaction with sex (p value = 0.08), with males having a greater risk of incident asthma (HR = 1.70, 95%CI 1.16-2.49) than females (HR = 1.04, 95%CI 0.70-1.54). CONCLUSIONS: Preterm birth and LBW were associated with an increased risk of current asthma into middle-age. These findings are the first to demonstrate the continuing impact of these characteristics on asthma risk into middle-age.

Early smoke exposure is associated with asthma and lung function deficits in adolescents.

OBJECTIVE: Early life tobacco smoke exposure may influence asthma, lung function and lung function growth into adolescence. We aimed to determine the associations between perinatal smoke exposure and asthma and lung function up to 18 years of age. METHODS: We prospectively recorded perinatal parental smoking and measured respiratory outcomes at 12 and 18 years in the Melbourne Atopy Cohort Study (MACS), a longitudinal birth cohort. Multiple logistic regression was used to analyse the associations between perinatal smoke exposure and asthma at 12 (n = 370) and 18 years (n = 411). Multiple linear regression was used to investigate the relationship between perinatal smoking and: lung function (12 and 18 years) and lung function growth (between 12 and 18 years). RESULTS: At 18 years, girls exposed to parental smoking during the perinatal period had increased odds of asthma (OR: 3.45, 95%CI: 1.36, 8.77), reduced pre-bronchodilator Forced expiratory volume in one-second (FEV1) (-272 ml/s; -438, -107); FEV1/ forced vital capacity (FVC) (-0.038; -0.065, -0.010); mid expiratory flow (MEF25-75) (-430 ml/s; -798, -61), and reduced post-bronchodilator FEV1/FVC (-0.028, -0.053, -0.004). No associations were found for boys (pre-bronchodilator FEV1 26ml/s; -202, 255; FEV1/FVC 0.018; -0.013, 0.049). CONCLUSIONS: Perinatal smoke may affect risk of asthma, reduce lung function and lung function growth in adolescence. Girls appear to be more susceptible than boys.

Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy.

BACKGROUND: There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. OBJECTIVE: We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. METHODS: From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype; high, the GG genotype). RESULTS: Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0; 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7; 95% CI, 0.2-2.0; P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10; 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6; 95% CI, 1.5-106.6), particularly in those with the GG genotype. CONCLUSIONS: Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy.

The Dose-Response Association between Nitrogen Dioxide Exposure and Serum Interleukin-6 Concentrations.

Systemic inflammation is an integral part of chronic obstructive pulmonary disease (COPD), and air pollution is associated with cardiorespiratory mortality, yet the interrelationships are not fully defined. We examined associations between nitrogen dioxide (NO2) exposure (as a marker of traffic-related air pollution) and pro-inflammatory cytokines, and investigated effect modification and mediation by post-bronchodilator airflow obstruction (post-BD-AO) and cardiovascular risk. Data from middle-aged participants in the Tasmanian Longitudinal Health Study (TAHS, n = 1389) were analyzed by multivariable logistic regression, using serum interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) as the outcome. Mean annual NO2 exposure was estimated at residential addresses using a validated satellite-based land-use regression model. Post-BD-AO was defined by post-BD forced expiratory ratio (FEV1/FVC) < lower limit of normal, and cardiovascular risk by a history of either cerebrovascular or ischaemic heart disease. We found a positive association with increasing serum IL-6 concentration (geometric mean 1.20 (95% CI: 1.1 to 1.3, p = 0.001) per quartile increase in NO2). This was predominantly a direct relationship, with little evidence for either effect modification or mediation via post-BD-AO, or for the small subgroup who reported cardiovascular events. However, there was some evidence consistent with serum IL-6 being on the causal pathway between NO2 and cardiovascular risk. These findings raise the possibility that the interplay between air pollution and systemic inflammation may differ between post-BD airflow obstruction and cardiovascular diseases.

Clinical and functional differences between early-onset and late-onset adult asthma: a population-based Tasmanian Longitudinal Health Study.

BACKGROUND: Differences between early-onset and late-onset adult asthma have not been comprehensively described using prospective data. AIMS: To characterise the differences between early-onset and late-onset asthma in a longitudinal cohort study. METHODS: The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort. Respiratory histories and spirometry were first performed in 1968 when participants were aged 7 (n=8583). The cohort was traced and resurveyed from 2002 to 2005 (n=5729 responses) and a sample, enriched for asthma and bronchitis participated in a clinical study when aged 44 (n=1389). RESULTS: Of the entire TAHS cohort, 7.7% (95% CI 6.6% to 9.0%) had early-onset and 7.8% (95% CI 6.4% to 9.4%) late-onset asthma. Atopy and family history were more common in early-onset asthma while female gender, current smoking and low socioeconomic status were more common in late-onset asthma. The impact on lung function of early-onset asthma was significantly greater than for late-onset asthma (mean difference prebronchodilator (BD) FEV1/FVC -2.8% predicted (-5.3 to -0.3); post-BD FEV1FVC -2.6% predicted (-5.0 to -0.1)). However, asthma severity and asthma score did not significantly differ between groups. An interaction between asthma and smoking was identified and found to be associated with greater fixed airflow obstruction in adults with late-onset asthma. This interaction was not evident in adults with early-onset disease. CONCLUSIONS: Early-onset and late-onset adult asthma are equally prevalent in the middle-aged population. Major phenotypic differences occur with asthma age-of-onset; while both share similar clinical manifestations, the impact on adult lung function of early-onset asthma is greater than for late-onset asthma.

Childhood body mass index and adult mammographic density measures that predict breast cancer risk.

The aim of the present study is to determine if body mass index (BMI) during childhood is associated with the breast cancer risk factor 'adult mammographic density adjusted for age and BMI'. In 1968, the Tasmanian Longitudinal Health Study studied every Tasmanian school child born in 1961. We obtained measured heights and weights from annual school medical records across ages 7-15 years and imputed missing values. Between 2009 and 2012, we administered to 490 women a questionnaire that asked current height and weight and digitised at least one mammogram per woman. Absolute and percent mammographic densities were measured using the computer-assisted method CUMULUS. We used linear regression and adjusted for age at interview and log current BMI. The mammographic density measures were negatively associated: with log BMI at each age from 7 to 15 years (all p < 0.05); with the average of standardised log BMIs across ages 7-15 years (p < 0.0005); and more strongly with standardised log BMI measures closer to age 15 years (p < 0.03). Childhood BMI measures explained 7 and 10 % of the variance in absolute and percent mammographic densities, respectively, and 25 and 20 % of the association between current BMI and absolute and percent mammographic densities, respectively. Associations were not altered by adjustment for age at menarche. There is a negative association between BMI in late childhood and the adult mammographic density measures that predict breast cancer risk. This could explain, at least in part, why BMI in adolescence is negatively associated with breast cancer risk.