Association of pharmacogenomic, clinical and behavioural factors with oral levothyroxine (LT-4) dose of hypothyroid patients in Sri Lanka: a matched case control study.

BACKGROUND: Hypothyroidism is a common endocrine disorder that exerts a substantial influence on people all over the world. Levothyroxine (LT-4) is the drug of choice for the treatment of hypothyroidism and the starting oral dose is typically ranging from 1.5 to 1.7 µg/kg/day. The target is to achieve an optimum serum TSH level of 0.4-4.0 mIU/L; hence, the dose is titrated accordingly. Once the LT-4 dose is adjusted to obtain the target TSH level, it usually remains stable for a long period of time in most cases. However, some of the patients require frequent dose adjustments and some of them require unusually high doses. Therefore, the aim of this study is to determine the association of pharmacogenomic, clinical and behavioural factors with the oral levothyroxine (LT-4) dose requirement of hypothyroid patients in Sri Lanka. METHOD: This study will be conducted as a matched case-control study and will involve primary hypothyroid patients who visit the diabetes and endocrinology clinic at the National Hospital, Kandy, Sri Lanka. We will recruit a total of 292 cases and select 292 controls from the clinic who are matched in terms of age, sex and Body Mass Index (BMI). An interviewer-administered questionnaire will be used to collect data from the participants (n = 584). Of the 584 patients, blood samples will be collected from a sub-sample (n = 150) for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) will be performed for single nucleotide polymorphisms (SNP) analysis. DISCUSSION: Frequent dose adjustments of levothyroxine cause a serious economic burden to the healthcare system. By identifying the root causes of the variations in LT-4 dosage, a more comprehensive comprehension of hypothyroidism and its management can be attained in Sri Lanka. Furthermore, upon identification of a positive association/correlation between genetic polymorphisms and the LT-4 dose, SNP profiles can be used as a possible genetic marker for dose adjustment determination in future patients.

Can We Use Lung Function Thresholds and Respiratory Symptoms to Identify Pre-COPD? A Prospective, Population-based Cohort Study.

RATIONALE: The term 'pre-COPD' refers to individuals at high-risk of developing Chronic Obstructive Pulmonary Disease (COPD) who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. OBJECTIVE: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at-risk of developing COPD. METHODS: The Tasmanian Longitudinal Health Study is a population-based cohort first studied in 1968 (age 7). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity and static lung volumes were measured on a subgroup at age 45, and incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden Index. MEASUREMENTS AND MAIN RESULTS: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score < -1.264, corresponding to the lowest 10th percentile. Those below this threshold had 36-fold increased risk of developing COPD over an eight-year follow-up period (RR 35.8, 95%CI 8.88 to 144), corresponding to a risk difference of +16.4% (95%CI 3.7-67.4). The sensitivity was 88% and specificity 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. CONCLUSION: Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high-risk of developing COPD in community-based settings.

Exploration of associations between occupational exposures and current adult eczema.

OBJECTIVES: There is a scarcity of evidence on occupational exposures that may increase eczema in adults. We aimed to investigate potential associations between occupational exposures and eczema in middle-aged adults. METHODS: A lifetime work history calendar was collected from the Tasmanian Longitudinal Health Study participants when they were at age 53. Their work history was collated with the occupational asthma-specific job exposure matrix to define ever-exposure and cumulative exposure unit-years since no eczema job exposure matrix is available. Eczema was determined using the report of flexural rash that was coming and going for at least 6 months in the last 12 months. Skin prick tests were used to further subgroup eczema and atopic eczema (AE) or non-AE (NAE). Logistic and multinomial regression models were used to investigate the associations. RESULTS: Eczema prevalence was 9.1%. Current occupational exposure to animals (adjusted OR, aOR=3.06 (95% CI 1.43 to 6.58)), storage mites (aOR=2.96 (95% CI 1.38 to 6.34)) and endotoxin (aOR=1.95 (95% CI 1.04 to 3.64)) were associated with increased risk of current eczema. Furthermore, increased odds of NAE were associated with current exposure to animals (aOR=5.60 (95% CI 1.45 to 21.7)) and storage mites (aOR=5.63 (95% CI 1.45 to 21.9)). Current exposures to isocyanates (aOR=5.27 (95% CI 1.17 to 23.7)) and acrylates (aOR=8.41 (95% CI 1.60 to 44.3)) were associated with AE. There was no evidence of associations between cumulative exposures and eczema prevalence. Cumulative exposure to metalworking fluids (aOR=1.10 (95% CI 1.01 to 1.22)) was associated with NAE and acrylates (aOR=1.24 (95% CI 1.04 to 1.46)) with AE. CONCLUSIONS: In this exploratory assessment, multiple occupational exposures were associated with current eczema in middle-aged adults. Raising awareness and limiting these exposures during an individual's productive working life will likely have various health benefits, including reducing eczema prevalence.

Longitudinal risk factors for obstructive sleep apnea: A systematic review.

Despite substantial disease burden, existing evidence on the risk factors for obstructive sleep apnea (OSA) have been derived primarily from cross-sectional studies without determining temporality. Therefore, we aimed to systematically synthesize the literature on longitudinal risk factors for sleep study-assessed OSA and questionnaire-assessed probable OSA from cohort studies in the general adult population settings. We systematically searched Embase and Medline (on OVID) databases. Eleven studies met the inclusion criteria. Meta-analyses were not conducted due to methodological heterogeneity of exposure and outcome measurements. There was consistent evidence that weight gain was associated with incident (n = 2) and greater severity (n = 2) of OSA. One study each observed an association of higher baseline body-mass index, male sex, asthma, a specific genetic polymorphism in rs12415421, and insulin resistance/hyperglycemia, with incident OSA. Long-term exposure to ambient air pollution (NO2, n = 1) was associated with OSA, and menopausal transitions (n = 1) with higher apnea-hypopnea index. There were no eligible studies on long-term smoking or alcohol use. In conclusion, approximately 10% increase in weight, especially in males, might alert clinicians to consider potential or worsening OSA. Large, well-designed longitudinal studies are needed to consolidate knowledge on other associations with OSA development, especially on potentially modifiable risk factors.

Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study.

BACKGROUND: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected. OBJECTIVE: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey. METHODS: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990-1994), 44 (1999-2003), and 55 (2010-2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures. RESULTS: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (-1.25 mL/year [95% confidence interval: -2.18 to -0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent associations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. CONCLUSIONS: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detrimental association requires verification in future studies.

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.

Longitudinal Asthma Phenotypes from Childhood to Middle-Age: A Population-based Cohort Study.

Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. Current-asthma and ever-asthma status was determined at each time point, and group-based trajectory modeling was used to characterize distinct longitudinal phenotypes. Linear and logistic regression models were fitted to investigate associations of the longitudinal phenotypes with childhood factors and adult outcomes. Measurements and Main Results: Of 8,583 original participants, 1,506 had reported ever asthma. Five longitudinal asthma phenotypes were identified: early-onset adolescent-remitting (40%), early-onset adult-remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). All phenotypes were associated with chronic obstructive pulmonary disease at age 53 years, except for late-onset remitting asthma (odds ratios: early-onset adolescent-remitting, 2.00 [95% confidence interval (CI), 1.13-3.56]; early-onset adult-remitting, 3.61 [95% CI, 1.30-10.02]; early-onset persistent, 8.73 [95% CI, 4.10-18.55]; and late-onset persistent, 6.69 [95% CI, 3.81-11.73]). Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age.

Household use of biomass fuel, especially traditional stove is associated with childhood wheeze and eczema: a cross sectional study of rural communities in Kandy, Sri Lanka.

BACKGROUND: Most households in low- and middle-income countries (LMICs) rely on biomass fuel for daily cooking. Studies investigating the association between early life exposure to household air pollution and health outcomes in children in LMICs are limited. OBJECTIVE: To investigate the effects of biomass fuel for cooking and different types of stoves on wheeze and allergies in children of rural Sri Lankan communities. METHODS: A cross-sectional study was conducted on 452 children aged 5 years and younger in Kandy, Sri Lanka. Mothers completed a questionnaire on the use of biomass fuel and respiratory and allergic outcomes in children. The associations between biomass fuel and outcomes were analyzed using logistic regression models, adjusting for potential confounders. RESULTS: Use of biomass fuel for cooking was associated with increased risk of childhood wheeze (aOR 2.29; 95% CI 1.04-5.08) and eczema (aOR 4.57; 95% CI 1.24-16.89) compared with households that used clean fuel (liquid petroleum gas (LPG), electricity and/or biogas). Among households that used biomass fuel, use of traditional biomass stoves was associated with a higher risk of childhood wheeze (aOR 2.95; 95% CI 1.19-7.33), allergic rhinitis (aOR 3.01; 95% CI 1.42-6.39), and eczema (aOR 7.39; 95% CI 1.70-32.06) compared with households that used clean stoves. CONCLUSION: Children living in households that use biomass fuel, especially traditional biomass cookstoves, have a higher risk of wheeze and allergic diseases. Access to affordable clean energy sources that reduce air pollution may help improve the health of children in rural LMICs.Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Biomarkers of asthma relapse and lung function decline in adults with spontaneous asthma remission: A population-based cohort study.

BACKGROUND: The extent to which biomarkers of asthma activity persist in spontaneous asthma remission and whether such markers are associated with future respiratory outcomes remained unclear. We investigated the association between sub-clinical inflammation in adults with spontaneous asthma remission and future asthma relapse and lung function decline. METHODS: The Tasmanian Longitudinal Health Study is a population-based cohort (n = 8583). Biomarkers of systemic inflammation were measured on participants at age 45, and latent profile analysis was used to identify cytokine profiles. Bronchial hyperresponsiveness (BHR) and nitric oxide products in exhaled breath condensate (EBC NOx) were measured at age 50. Participants with spontaneous asthma remission at ages 45 (n = 466) and 50 (n = 318) were re-evaluated at age 53, and associations between baseline inflammatory biomarkers and subsequent asthma relapse and lung function decline were assessed. RESULTS: We identified three cytokine profiles in adults with spontaneous asthma remission: average (34%), Th2-high (42%) and Th2-low (24%). Compared to the average profile, a Th2-high profile was associated with accelerated decline in post-BD FEV1 /FVC (MD -0.18% predicted per-year; 95% CI -0.33, -0.02), while a Th2-low profile was associated with accelerated decline in both post-BD FEV1 (-0.41%; -0.75, -0.06) and post-BD FVC (-0.31%; -0.62, 0.01). BHR and high TNF-α during spontaneous remission were associated with an increased risk of asthma relapse. In contrast, we found no evidence of association between EBC NOx and either asthma relapse or lung function decline. CONCLUSION: BHR and serum inflammatory cytokines have prognostic value in adults with spontaneous asthma remission. At-risk individuals with BHR, Th2-high or Th2-low cytokine profiles may benefit from closer monitoring and on-going follow-up.

Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study.

BACKGROUND: Interest in lifetime lung function trajectories has increased in the context of emerging evidence that chronic obstructive pulmonary disease (COPD) can arise from multiple disadvantaged lung function pathways, including those that stem from poor lung function in childhood. To our knowledge, no previous study has investigated both obstructive and restrictive lifetime patterns concurrently, while accounting for potential overlaps between them. We aimed to investigate lifetime trajectories of the FEV1/forced vital capacity (FVC) ratio, FVC, and their combinations, relate these combined trajectory groups to static lung volume and gas transfer measurements, and investigate both risk factors for and consequences of these combined trajectory groups. METHODS: Using z scores from spirometry measured at ages 7, 13, 18, 45, 50, and 53 years in the Tasmanian Longitudinal Health Study (n=2422), we identified six FEV1/FVC ratio trajectories and five FVC trajectories via group-based trajectory modelling. Based on whether trajectories of the FEV1/FVC ratio and FVC were low (ie, low from childhood or adulthood) or normal, four patterns of lifetime spirometry obstruction or restriction were identified and compared against static lung volumes and gas transfer. Childhood and adulthood characteristics and morbidities of these patterns were investigated. FINDINGS: The prevalence of the four lifetime spirometry patterns was as follows: low FEV1/FVC ratio only, labelled as obstructive-only, 25·8%; low FVC only, labelled as restrictive-only, 10·5%; both low FEV1/FVC ratio and low FVC, labelled as mixed, 3·5%; and neither low FEV1/FVC ratio nor low FVC, labelled as reference, 60·2%. The prevalence of COPD at age 53 years was highest in the mixed pattern (31 [37%] of 84 individuals) followed by the obstructive-only pattern (135 [22%] of 626 individuals). Individuals with the mixed pattern also had the highest prevalence of parental asthma, childhood respiratory illnesses, adult asthma, and depression. Individuals with the restrictive-only pattern had lower total lung capacity and residual volume, and had the highest prevalence of childhood underweight, adult obesity, diabetes, cardiovascular conditions, hypertension, and obstructive sleep apnoea. INTERPRETATION: To our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV1/FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age. FUNDING: National Health and Medical Research Council of Australia, 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.

Small for gestational age is associated with reduced lung function in middle age: A prospective study from first to fifth decade of life.

BACKGROUND AND OBJECTIVE: The association between birth weight, particularly relative to gestational age, and adult lung function is uncertain. We investigated the associations between birth weight relative to gestational age and measures of lung function in middle age, and mediation of these associations by adult height. METHODS: Participants in the Tasmanian Longitudinal Health Study who had both known birth weight and lung function assessment at age 45 years were included (n = 849). Linear regression models were fitted to investigate the association between small for gestational age and birth weight with post-bronchodilator lung function measures (forced expiratory volume in 1 second [FEV1 ], forced vital capacity [FVC], FEV1 /FVC, diffusing capacity for carbon monoxide [DL co], residual volume [RV] and total lung capacity [TLC]), adjusting for potential confounders. The contribution of adult height as a mediator of these associations was investigated. RESULTS: Compared with infants born with normal weight for gestational age, those born small for gestational age had reduced FEV1 (coefficient: -191 ml [95%CI: -296, -87]), FVC (-205 ml [-330, -81]), TLC (-292 ml [-492, -92]), RV (-126 ml [-253, 0]) and DL co (-0.42 mmol/min/kPa [-0.79, -0.041]) at age 45 years. However, they had comparable FEV1 /FVC. For every 1 kg increase in birth weight, lung function indices increased by an average of 117 ml (95%CI: 40, 196) for FEV1 , 124 ml (30, 218) for FVC, 215 ml (66, 365) for TLC and 0.36 mmol/min/kPa (0.11, 0.62) for DL co, independent of gestational age, but again not for FEV1 /FVC. These associations were significantly mediated by adult height (56%-90%). CONCLUSION: Small for gestational age was associated with reduced lung function that is likely due to smaller lungs with little evidence of any specific parenchymal impairment.

Childhood 'bronchitis' and respiratory outcomes in middle-age: a prospective cohort study from age 7 to 53 years.

BACKGROUND: Chronic bronchitis in childhood is associated with a diagnosis of asthma and/or bronchiectasis a few years later, however, consequences into middle-age are unknown. OBJECTIVE: To investigate the relationship between childhood bronchitis and respiratory-related health outcomes in middle-age. DESIGN: Cohort study from age 7 to 53 years. SETTING: General population of European descent from Tasmania, Australia. PARTICIPANTS: 3202 participants of the age 53-year follow-up (mean age 53, range 51-55) of the Tasmanian Longitudinal Health Study cohort who were born in 1961 and first investigated at age 7 were included in our analysis. STATISTICAL METHODS: Multivariable linear and logistic regression. The association between parent reported childhood bronchitis up to age 7 and age 53-year lung conditions (n=3202) and lung function (n=2379) were investigated. RESULTS: Among 3202 participants, 47.5% had one or more episodes of childhood bronchitis, classified according to severity based on the number of episodes and duration as: 'non-recurrent bronchitis' (28.1%); 'recurrent non-protracted bronchitis' (18.1%) and 'recurrent-protracted bronchitis' (1.3%). Age 53 prevalence of doctor-diagnosed asthma and pneumonia (p-trend <0.001) and chronic bronchitis (p-trend=0.07) increased in accordance with childhood bronchitis severities. At age 53, 'recurrent-protracted bronchitis' (the most severe subgroup in childhood) was associated with doctor-diagnosed current asthma (OR 4.54, 95% CI 2.31 to 8.91) doctor-diagnosed pneumonia (OR=2.18 (95% CI 1.00 to 4.74)) and, paradoxically, increased transfer factor for carbon monoxide (z-score +0.51 SD (0.15-0.88)), when compared with no childhood bronchitis. CONCLUSION: In this cohort born in 1961, one or more episodes of childhood bronchitis was a frequent occurrence. 'Recurrent-protracted bronchitis', while uncommon, was especially linked to multiple respiratory outcomes almost five decades later, including asthma, pneumonia and raised lung gas transfer. These findings provide insights into the natural history of childhood 'bronchitis' into middle-age.

Impact of lifetime body mass index trajectories on the incidence and persistence of adult asthma.

BACKGROUND: High body mass index (BMI) trajectories from childhood to adulthood are associated with the development of some chronic diseases, but whether such trajectories influence adult asthma has not been investigated to date. Therefore, we investigated associations between BMI trajectories from childhood to middle age (5-43 years) and incidence, persistence and relapse of asthma from ages 43 to 53 years. METHODS: In the Tasmanian Longitudinal Health Study (n=4194), weight and height were recorded at eight time-points between 5 and 43 years of age. BMI trajectories were developed using group-based trajectory modelling. Associations between BMI trajectories and asthma incidence, persistence and relapse from age 43 to 53 years, bronchial hyperresponsiveness (BHR) at age 50 years, and bronchodilator responsiveness at age 53 years were modelled using multiple logistic and linear regression. RESULTS: Five distinct BMI trajectories were identified: average, low, child high-decreasing, child average-increasing and high. Compared with the average trajectory, child average-increasing and high trajectories were associated with increased risk of incident asthma (OR 2.6, 95% CI 1.1-6.6 and OR 4.4, 95% CI 1.7-11.4, respectively) and BHR in middle age (OR 2.9, 95% CI 1.1-7.5 and OR 3.5, 95% CI 1.1-11.4, respectively). No associations were observed for asthma persistence or relapse. CONCLUSIONS: Participants with child average-increasing and high BMI trajectories from childhood to middle age were at higher risk of incident adult asthma. Thus, encouraging individuals to maintain a normal BMI over the life course may help reduce the burden of adult asthma.

Association between very to moderate preterm births, lung function deficits, and COPD at age 53 years: analysis of a prospective cohort study.

BACKGROUND: Prematurity has been linked to reduced lung function up to age 33 years, but its long-term effects on lung function and chronic obstructive pulmonary disease (COPD) are unknown. To address this question, we investigated associations between prematurity, lung function, and COPD in the sixth decade of life using data from the Tasmanian Longitudinal Health Study (TAHS). METHODS: Data were analysed from 1445 participants in the TAHS. Lung function was measured at 53 years of age. Gestational ages were very preterm (28 weeks to <32 weeks), moderate preterm (32 weeks to <34 weeks), late preterm (34 weeks to <37 weeks) and term (≥37 weeks). Linear and logistic regression models were fitted to investigate associations of prematurity with lung function measures (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, forced expiratory flow at 25-75% of FVC [FEF25-75%], diffusing capacity for carbon monoxide [DLCO]) and COPD (post-bronchodilator FEV1/FVC less than the lower limit of normal), adjusting for sex, age, height, parental smoking during pregnancy, number of older siblings, maternal age at birth, and childhood socioeconomic status. Interactions with smoking and asthma were also investigated. RESULTS: Of 3565 individuals with available data on gestational age from the TAHS cohort, 1445 (41%) participants were included in this study, 740 (51%) of whom were female. Compared with term birth, very to moderate preterm birth was significantly associated with an increased risk of COPD at age 53 years (odds ratio 2·9 [95% CI 1·1-7·7]). Very-to-moderate preterm birth was also associated with lower post-bronchodilator FEV1/FVC ratio (beta-coefficient -2·9% [95% CI -4·9 to -0·81]), FEV1 (-190 mL [-339 to -40]), DLCO (-0·55 mmol/min/kPa [-0·97 to -0·13]), and FEF25-75% (-339 mL/s [-664 to -14]). The association between very-to-moderate preterm birth and FEV1/FVC ratio was only significant among smokers (pinteraction=0·0082). Similar findings were observed for moderate preterm birth when analysed as a separate group. Compared with term birth, late preterm birth was not associated with lower FEV1/FVC ratio or COPD. INTERPRETATION: This is the first study to investigate the effect of prematurity on lung function into middle-age. Data show that very-to-moderate prematurity is associated with obstructive lung function deficits including COPD well into the sixth decade of life and that this effect is compounded by personal smoking. FUNDING: National Health and Medical Research Council (NHMRC) 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.

Parental preconception BMI trajectories from childhood to adolescence and asthma in the future offspring.

BACKGROUND: Recent evidence suggests that parental exposures before conception can increase the risk of asthma in offspring. OBJECTIVE: We investigated the association between parents' preconception body mass index (BMI) trajectories from childhood to adolescence and subsequent risk of asthma in their offspring. METHODS: Using group-based trajectory modeling from the Tasmanian Longitudinal Health Study, we identified BMI trajectories for index participants (parents) when aged 4 years to 15 years. Multinomial regression models adjusted for potential confounders were utilized to estimate the association between these early-life parents' BMI trajectories and asthma phenotypes in their subsequent offspring. RESULTS: The main analysis included 1822 parents and 4208 offspring. Four BMI trajectories from age 4 years to 15 years were identified as the best-fitting model: low (8.8%), normal (44.1%), above normal (40.2%), and high (7.0%). Associations were observed between father's high BMI trajectory and risk of asthma in offspring before the age of 10 years (relative risk ratio [RRR] =1.70 [95% CI = 0.98-2.93]) and also asthma ever (RRR = 1.72 [95% CI = 1.00-2.97]), especially allergic asthma ever (RRR = 2.05 [95% CI = 1.12-3.72]). These associations were not mediated by offspring birth weight. No associations were observed for maternal BMI trajectories and offspring asthma phenotypes. CONCLUSION: This cohort study over 6 decades of life and across 2 generations suggests that the high BMI trajectory in fathers, well before conception, increased the risk of asthma in their offspring.

The Asthma Family Tree: Evaluating Associations Between Childhood, Parental, and Grandparental Asthma in Seven Chinese Cities.

Objective: To evaluate the associations between childhood, parental, and grandparental asthma. Methods: We studied 59,484 children randomly selected from 94 kindergartens, elementary, and middle schools in seven Chinese cities from 2012 to 2013, using a cross-sectional survey-based study design. Information on their and their family members' (parents, paternal grandparents, and maternal grandparents) asthma status were reported by children's parents or guardians. Mixed effects logistic regressions were used to assess hereditary patterns of asthma and mediation analysis was performed to estimate the potential mediation effect of parents on the association between grandparental asthma and childhood asthma. Results: The magnitude of ORs for childhood asthma increased as the number of family members affected by asthma increased. Among children who had one family member with asthma, childhood asthma was associated with asthma in maternal grandmothers (OR: 2.08, 95% CI: 1.67-2.59), maternal grandfathers (OR: 2.08, 95% CI: 1.71-2.53), paternal grandmothers (OR: 2.40, 95% CI: 1.93-2.99), and paternal grandfathers (OR: 2.59, 95% CI: 2.14-3.13). Among children who had two family members with asthma, the highest asthma risk was found when both parents had asthma (OR: 15.92, 95% CI: 4.66-54.45). Parents had a small proportion of mediation effect (9-12%) on the association between grandparental asthma and childhood asthma. Conclusions: Grandparents with asthma were associated with childhood asthma and parents with asthma partially mediated the association.

Protein levels, air pollution and vitamin D deficiency: links with allergy.

This study provides novel insights into mechanisms of traffic-related air pollution-induced allergy by down-regulation via complement regulators (CFI, PROS1 and PLG) and its interaction with vitamin D deficiency via the complement inhibitor PLG https://bit.ly/3x0jYOw.

Childhood lung function as a determinant of menopause-dependent lung function decline.

RATIONALE: The naturally occurring age-dependent decline in lung function accelerates after menopause, likely due to the change of the endocrine balance. Although increasing evidence shows suboptimal lung health in early life can increase adult  susceptibility to insults, the potential effect of poor childhood lung function on menopause-dependent lung function decline has not yet been investigated. OBJECTIVES: To study whether menopause-dependent lung function decline, assessed as forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), is determined by childhood lung function. METHODS: The Tasmanian Longitudinal Health Study, a cohort born in 1961, underwent spirometry at age seven.  At ages 45 and 50 serum samples, spirometry and questionnaire data were collected (N = 506). We measured follicle stimulating and luteinizing hormones to determine menopausal status using latent profile analysis. The menopause-dependent lung function decline was investigated using linear mixed models, adjusted for anthropometrics, occupational level, smoking, asthma, asthma medication and study year, for the whole study population and stratified by tertiles of childhood lung function. MEASUREMENTS AND MAIN RESULTS: The overall menopause-dependent lung function decline was 19.3 mL/y (95%CI 2.2 to 36.3) for FVC and 9.1 mL/y (-2.8 to 21.0) for FEV1. This was most pronounced (pinteraction=0.03) among women within the lowest tertile of childhood lung function [FVC 22.2 mL/y (1.1 to 43.4); FEV1 13.9 mL/y (-1.5 to 29.4)]. CONCLUSIONS: Lung function declines especially rapidly in postmenopausal women who had poor low lung function in childhood. This provides novel insights into respiratory health during reproductive aging and emphasizes the need for holistic public health strategies covering the whole lifespan.