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.

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.

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.

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.

Trends in smoking initiation in Europe over 40 years: A retrospective cohort study.

BACKGROUND: Tobacco consumption is the largest avoidable health risk. Understanding changes of smoking over time and across populations is crucial to implementing health policies. We evaluated trends in smoking initiation between 1970 and 2009 in random samples of European populations. METHODS: We pooled data from six multicentre studies involved in the Ageing Lungs in European Cohorts consortium, including overall 119,104 subjects from 17 countries (range of median ages across studies: 33-52 years). We estimated retrospectively trends in the rates of smoking initiation (uptake of regular smoking) by age group, and tested birth cohort effects using Age-Period-Cohort (APC) modelling. We stratified all analyses by sex and region (North, East, South, West Europe). RESULTS: Smoking initiation during late adolescence (16-20 years) declined for both sexes and in all regions (except for South Europe, where decline levelled off after 1990). By the late 2000s, rates of initiation during late adolescence were still high (40-80 per 1000/year) in East, South, and West Europe compared to North Europe (20 per 1000/year). Smoking initiation rates during early adolescence (11-15 years) showed a marked increase after 1990 in all regions (except for North European males) but especially in West Europe, where they reached 40 per 1000/year around 2005. APC models supported birth cohort effects in the youngest cohorts. CONCLUSION: Smoking initiation is still unacceptably high among European adolescents, and increasing rates among those aged 15 or less deserve attention. Reducing initiation in adolescents is fundamental, since youngsters are particularly vulnerable to nicotine addiction and tobacco adverse effects.

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.

Prediction models for the development of COPD: a systematic review.

Early identification of people at risk of developing COPD is crucial for implementing preventive strategies. We aimed to systematically review and assess the performance of all published models that predicted development of COPD. A search was conducted to identify studies that developed a prediction model for COPD development. The Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies was followed when extracting data and appraising the selected studies. Of the 4,481 records identified, 30 articles were selected for full-text review, and only four of these were eligible to be included in the review. The only consistent predictor across all four models was a measure of smoking. Sex and age were used in most models; however, other factors varied widely. Two of the models had good ability to discriminate between people who were correctly or incorrectly classified as at risk of developing COPD. Overall none of the models were particularly useful in accurately predicting future risk of COPD, nor were they good at ruling out future risk of COPD. Further studies are needed to develop new prediction models and robustly validate them in external cohorts.

Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life.

BACKGROUND: Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade. METHODS: We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD. FINDINGS: Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, accelerated decline trajectory. INTERPRETATION: We identified six potential FEV1 trajectories, two of which were novel. Three trajectories contributed 75% of COPD burden and were associated with modifiable early-life exposures whose impact was aggravated by adult factors. We postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk. Clinicians and patients with asthma should be made aware of the potential long-term implications of non-optimal asthma control for lung function trajectory throughout life, and the role and benefit of optimal asthma control on improving lung function should be investigated in future intervention trials. FUNDING: National Health and Medical Research Council of Australia; European Union's Horizon 2020; The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; The Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline.

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.

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.

Traffic related air pollution and development and persistence of asthma and low lung function.

BACKGROUND AND AIMS: Traffic Related Air Pollution (TRAP) exposure is known to exacerbate existing respiratory diseases. We investigated longer term effects of TRAP exposure for individuals with or without existing asthma, and with or without lower lung function. METHODS: Associations between TRAP exposure and asthma (n = 689) and lung function (n = 599) were investigated in the prospective Tasmanian Longitudinal Health Study (TAHS). TRAP exposure at age 45 years was measured using two methods based on residential address: mean annual NO2 exposure; and distance to nearest major road. Adjusted multinomial logistic regression was used to model the association between exposure to TRAP at 45 years and changes in asthma and lung function, using three follow ups of TAHS (45, 50 and 53 years). RESULTS: For those who never had asthma by 45, living <200 m from a major road was associated with increased odds of new asthma that persisted from 50 to 53 years (adjusted Odds Ratio [aOR] 5.20; 95% CI 1.07, 25.4). Asthmatic participants at 45 had an increased risk of persistent asthma up to 53 years if they were living <200 m from a major road, compared with asthmatic participants living >200 m from a major road (aOR = 5.21; 95% CI 1.54, 17.6). CONCLUSION: For middle aged adults, living <200 m for a major road (a marker of TRAP exposure) influences both the development and persistence of asthma. These findings have public health implications for asthma prevention strategies in primary and secondary settings.

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

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.

Occupational exposures to solvents and metals are associated with fixed airflow obstruction.

Objectives This study investigated the associations between occupational exposures to solvents and metals and fixed airflow obstruction (AO) using post-bronchodilator spirometry. Methods We included 1335 participants from the 2002-2008 follow-up of the Tasmanian Longitudinal Health Study. Ever-exposure and cumulative exposure-unit (EU) years were calculated using the ALOHA plus job exposure matrix (JEM). Fixed AO was defined as post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7 and FEV 1/FVC

Validity of the Berlin questionnaire in detecting obstructive sleep apnea: A systematic review and meta-analysis.

We aimed to systematically review the Berlin questionnaire as a screening tool for obstructive sleep apnea. We systematically searched PubMed, Embase, and Scopus databases, reviewed articles reporting the Berlin questionnaire's diagnostic utility as measured against type-1 polysomnography, and performed meta-analyses where possible. Thirty five eligible articles showed that the Berlin questionnaire's diagnostic utility varied by study population, definition of hypopnea used, and apnea-hypopnea index threshold used. It had good sensitivity and specificity for detecting clinically relevant obstructive sleep apnea as well as any obstructive sleep apnea in the sleep clinic population. Despite limited evidence, it showed modest to high sensitivity for detecting clinically relevant obstructive sleep apnea or any obstructive sleep apnea in other clinical and general population subgroups. Its specificity was relatively low. Possible reasons for variability in reported diagnostic utility of the Berlin questionnaire are multifaceted. We conclude that the Berlin questionnaire is useful as a clinical screening test and epidemiological tool in the sleep clinic population. Despite limited evidence, it likely has potential clinical and research utility in other populations. Adopting more consistent methodological definitions and focussing more on the general population and specific clinical populations to determine its usefulness as a clinical or epidemiological screening tool are recommended.

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.