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BACKGROUND: Parental allergic diseases and smoking influence respiratory disease in the offspring but it is not known whether they influence fractional exhaled nitric oxide (FeNO) in the offspring. We investigated whether parental allergic diseases, parental smoking and FeNO levels in parents were associated with FeNO levels in their offspring. METHODS: We studied 609 offspring aged 16-47 years from the Respiratory Health in Northern Europe, Spain and Australia generation (RHINESSA) study with parental information from the Respiratory Health in Northern Europe (RHINE) III study and the European Community Respiratory Health Survey (ECRHS) III. Linear regression models were used to assess the association between offspring FeNO and parental FeNO, allergic rhinitis, asthma and smoking, while adjusting for potential confounding factors. RESULTS: Parental allergic rhinitis was significantly associated with higher FeNO in the offspring, both on the paternal and maternal side (percent change: 20.3 % [95%CI 5.0-37.7], p = 0.008, and 13.8 % [0.4-28.9], p = 0.043, respectively). Parental allergic rhinitis with asthma in any parent was also significantly associated with higher offspring FeNO (16.2 % [0.9-33.9], p = 0.037). However, parental asthma alone and smoking were not associated with offspring FeNO. Parental FeNO was not associated with offspring FeNO after full adjustments for offspring and parental factors. CONCLUSIONS: Parental allergic rhinitis but not parental asthma was associated with higher levels of FeNO in offspring. These findings suggest that parental allergic rhinitis status should be considered when interpreting FeNO levels in offspring beyond childhood.

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.

Introduction. Whether systemic and airway inflammation persist in remitted asthma and whether such inflammation is associated with adverse long-term respiratory outcomes remains unclear. Objective. To determine the prevalence of systemic and airway inflammation in adults with remitted asthma, and to examine their associations with asthma relapse and lung function decline. Methods. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort first studied in 1968 (n = 8,583). In 2004 (age 44), biomarkers of systemic inflammation (serum IL-4, IL-5, IL-6, IL-8, IL10, TNF-) were measured in a subgroup (n = 1,389) and categorised into cytokine profiles using latent profile analysis (LPA). In 2010 (age 50), markers of airway inflammation, methacholine challenge tests (n = 836) and total nitric oxide products in exhaled breath condensate (EBC NOx), were measured. Asthma relapse and lung function decline were assessed at follow-up in 2014. Multivariable linear and Poisson regression were used to examine relevant associations. Results. Of adults with remitted asthma at age 50 years, 20.8% [95% CI 15.9, 26.7] had bronchial hyperresponsiveness (BHR) and 7.1% [95% CI 4.2 ,11.9] had an elevated EBC NOx (>5.05 mumol/L). Asthma relapse was associated with BHR (RR 2.25 [95%CI 1.52, 3.32]), but not with elevated EBC NOx. Three distinct cytokine profiles were identified via LPA: A reference anormala cytokine profile, a aTh2-higha profile associated with accelerated post-BD FEV1/FVC decline (MD-0.18% predicted/year [-0.33,-0.02]), and a aTh2-lowa profile associated with accelerated postBD FEV1 (MD-0.41% predicted/year [-0.75,-0.06]) and post-BD FVC decline (MD-0.31% predicted/year [-0.62, 0.01]). Conclusion. BHR and elevated biomarkers of asthma activity have prognostic value in adults with remitted asthma. At-risk individuals may benefit from closer follow-up, repeat spirometry and potentially antiinflammatory agents.

Introduction/Aim. Recent evidence suggest that effects of adverse exposures before conception can be transferred across generations to increase the risk of asthma in offspring. Our aim was to investigate the association between preconception Body Mass Index (BMI) trajectories of parents and risk of asthma in their offspring. Methods. We analysed data collected from the Tasmanian Longitudinal Health Study (TAHS). In 1961, TAHS recruited 8583, 7-year-old children attending schools in Tasmania. Age, height and weight of these participants were extracted from their school medical records from ages 4 a- 15 years. Calculated BMI was standardized according to UK reference growth charts. At the age of 53 years, TAHS original participants (hereafter referred to as parents) were asked about their offspringas asthma. Group-based trajectory modelling was used to identify parentsa distinct BMI trajectories. Multinomial regression models adjusted for potential confounders were employed to estimate the association between parentsa BMI trajectories and risk of asthma phenotypes in their offspring. Results. Information on BMI were available for 2011 parents, who had 4670 offspring. Four BMI trajectories were identified as the best fit model: 1) Low BMI (8.8%), 2) Normal BMI (44.1%), 3) In-between normal and high BMI (40.2%), and 4) High BMI (7.0%). Paternal "High BMI" trajectory was associated with increased risk of allergic asthma before the age of 10 years (OR 1.72 (95%CI 0.97, 3.05)) and after 10 years (OR 3.96 (95% CI 1.11, 14.1)) in offspring. Similarly, paternal "High BMI" trajectory was associated with increased risk of allergic ever asthma in offspring, OR 1.99 (95%CI 1.13, 3.50). No associations were observed for maternal BMI trajectories. Conclusion. This cohort study over six decades of life and across two generations provides evidence that a high BMI trajectory in fathers, well before conception, may increase the risk of diagnosed asthma in their offspring. Such a risk s

Introduction/Aim. Clinical guidelines on obstructive lung disease contain few recommendations on household air pollution (HAP), although it is known to cause oxidative stress, which is associated with pathogenesis of obstructive lung disease. Associations between HAP and obstructive lung disease may be modified by Glutathione S-Transferase (GST) gene polymorphisms and home ventilation. We aimed to identify longitudinal HAP profiles associated with asthma risk and lung function decline in middle-aged adults and whether these associations were modified by GST gene variants and home ventilation. Methods. We used measurements of HAP exposures (emission sources for heating/cooking, mould, smoking) asthma, and housing characteristics collected for the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n = 3314). Latent class analysis was used to characterize longitudinal exposure patterns. A sub group had data on lung function (n = 897) and GST polymorphisms (GSTM1, GSTT1 and GSTP1) (n = 928). Regression models assessed associations and interactions. Results. We identified seven longitudinal HAP profiles. Four of these ("wood heating", "all gas", "wood heating/smoking" and "wood heating/gas cooking") were associated with persistent asthma, greater lung function decline and greater bronchodilator reversibility (BDR) by age 53 years. Exposed participants with GSTP1 Ile/Ile and GSTM1 null genotypes were at higher risk of asthma or greater lung function decline compared to other genotypes. Home ventilation modified these adverse effects; participants not using cooking exhaust fans or living in newer, better sealed, buildings had increased risk of asthma. Conclusion. Longitudinal exposure to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risk of persistent asthma, lung function decline and increased BDR. There was evidence of effect modification by GST genotypes and home ventilation. These findings inform the developm

Rationale: It is unclear if childhood bronchitis is associated with adverse respiratory outcomes in middle-age Aim: To determine the relationships between childhood bronchitis frequency/duration and clinical outcomes in middle-aged Australians Methods: Data were from the Tasmanian Longitudinal Health Study (TAHS, 1968-2016). Four categories of parent-reported bronchitis by age 7 were none (reference), non-recurrent, recurrent (>5 episodes of 'loose, rattly' or chesty cough lasting <1 month), and recurrent-protracted (>5 episodes, >1 month average duration). Outcomes at age 53 included chronic bronchitis (CB), asthma and pre/post-bronchodilator (BD) spirometry. Trend tests, mediation analysis and multivariable regression were used Results: Increasing childhood bronchitis severity was associated with adult asthma/pneumonia-ever (p-trend<0.001) but not adult current CB. Associations with lung function were less clear. Asthma and FEV1 at age 7 were mediators View inline Conclusion(s): Dose-response relationships were seen between increasing childhood bronchitis and outcomes other than bronchitis in middle-age. Further delineation of longitudinal phenotypes is needed Grant Support: NHMRC; Clifford Craig & Asthma Foundations; GSK; RHH.

Introduction. Bronchodilator reversibility (BDR) is often used as a diagnostic test for adult asthma. However, there has been limited assessment of its diagnostic utility. Aim. To determine the discriminatory accuracy of currently used BDR cut-offs in the context of current asthma and asthma-COPD overlap (ACO) in middle-aged Australians. Methods. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort first studied in 1968 (n = 8,583). In 2012, participants completed respiratory questionnaires and spirometry (n = 3,609; mean age 53 years). Current asthma was defined as having a history of doctor-diagnosed asthma with asthma-related symptoms, healthcare or medication utilisation in the last one month. Receiver operating characteristic (ROC) curves were fitted for current asthma and ACO using continuous BDR measurements. Diagnostic parameters were calculated for different categorical cut-offs. Results. Area under the ROC curve (AUC) was highest when BDR was expressed as change in FEV1 as a percentage of initial FEV1, as compared with predicted FEV1. The corresponding AUC was 59% (95% CI 54-64%) for current asthma and 87% (95%CI 81-93%) for ACO. Of the cut-offs examined, the European Respiratory Society/American Thoracic Society (ERS/ATS) threshold (>=12% from baseline and >= 200 ml) was assessed as providing the best balance between positive and negative likelihood ratios, with corresponding sensitivities and specificities of 9% and 96% for current asthma, and 47% and 97% respectively for ACO. Conclusion. Current recommended cut-offs can assist with ruling in, but are poor at ruling out adult asthma, with an optimal threshold of >=12% and >= 200 ml from baseline. BDR was more useful as diagnostic test in those with co-existent post-bronchodilator airflow obstruction (ACO).