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BACKGROUND: Despite chronic obstructive pulmonary disease (COPD) being a major global cause of mortality and hospitalisation, it is often undiagnosed or inaccurately diagnosed in clinical settings. OBJECTIVE: To systematically synthesise all peer-reviewed papers from primary healthcare settings that have reported data on: (1) undiagnosed COPD, that is, patients with respiratory symptoms and postbronchodilator airflow obstruction consistent with COPD, without a formal clinician's diagnosis of COPD either documented in health records or reported by patients and (2) 'overdiagnosed COPD', that is, clinician's diagnosis without postbronchodilator airflow obstruction. METHODS: Studies investigating these diagnostic metrics in patients from primary healthcare clinics (according to predefined inclusion/exclusion criteria) were sourced from Medline and Embase and assessed for bias (Johanna Briggs Institute tools for prevalence studies and case series). Meta-analyses of studies of adequate sample size used random effect modelling stratified by risk factor categories. RESULTS: Of 26 eligible articles, 21 cross-sectional studies investigated 3959 cases of spirometry-defined COPD (with or without symptoms), and 5 peer-reviewed COPD case series investigated 7381 patients. The prevalence of spirometry-confirmed COPD without a diagnosis documented in their health records was 14%-26% in studies of symptomatic smokers (N=3). 1 in 4 patients taking inhaled therapies (25% (95% CI 22% to 28%), N=2) and 1 in 6 smokers irrespective of symptoms (16% (95% CI 14% to 18%), N=6) fulfilled diagnostic spirometry criteria but did not report receiving a COPD-related diagnosis. In an adequately powered series of COPD cases documented in primary healthcare records (N=4), only between 50% and 75% of subjects had any airflow obstruction on postbronchodilator spirometry performed by study researchers, therefore, COPD was clinically 'overdiagnosed' in 25%-50% of subjects. DISCUSSION: Although data were

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 as

BACKGROUND: Temperature fluctuations can affect human health independent of the effect of mean temperature. However, no study has evaluated whether short-term temperature fluctuations could affect DNA methylation. METHODS: Peripheral blood DNA methylation for 479 female siblings of 130 families were analysed. Gridded daily temperatures data were obtained, linked to each participant's home address, and used to calculate nine different metrics of short-term temperature fluctuations: temperature variabilities (TVs) within the day of blood draw and preceding one to seven days (TV 0-1 to TV 0-7), diurnal temperature range (DTR), and temperature change between neighbouring days (TCN). Within-sibship design was used to perform epigenome-wide association analyses, adjusting for daily mean temperatures, and other important covariates (e.g., smoking, alcohol use, cell-type proportions). Differentially methylated regions (DMRs) were further identified. Multiple-testing comparisons with a significant threshold of 0.01 for cytosine-guanine dinucleotides (CpGs) and 0.05 for DMRs were applied. RESULTS: Among 479 participants (mean age ± SD, 56.4 ± 7.9 years), we identified significant changes in methylation levels in 14 CpGs and 70 DMRs associated with temperature fluctuations. Almost all identified CpGs were associated with exposure to temperature fluctuations within three days. Differentially methylated signals were mapped to 68 genes that were linked to human diseases such as cancer (e.g., colorectal carcinoma, breast carcinoma, and metastatic neoplasms) and mental disorder (e.g., schizophrenia, mental depression, and bipolar disorder). The top three most significantly enriched gene ontology terms were Response to bacterium (TV 0-3), followed by Hydrolase activity, acting on ester bonds (TCN), and Oxidoreductase activity (TV 0-3). CONCLUSIONS: Short-term temperature fluctuations were associated with differentially methylated signals across the human genome, which provides evide

Landscape fires are increasing in frequency and severity globally. In Australia, extreme bushfires cause a large and increasing health and socioeconomic burden for communities and governments. People with asthma are particularly vulnerable to the effects of landscape fire smoke (LFS) exposure. Here, we present a position statement from the Thoracic Society of Australia and New Zealand. Within this statement we provide a review of the impact of LFS on adults and children with asthma, highlighting the greater impact of LFS on vulnerable groups, particularly older people, pregnant women and Aboriginal and Torres Strait Islander peoples. We also highlight the development of asthma on the background of risk factors (smoking, occupation and atopy). Within this document we present advice for asthma management, smoke mitigation strategies and access to air quality information, that should be implemented during periods of LFS. We promote clinician awareness, and the implementation of public health messaging and preparation, especially for people with asthma.

BACKGROUND: The heterogeneity of development and progression of eczema suggests multiple underlying subclasses for which aetiology and prognosis may vary. A better understanding may provide a comprehensive overview of eczema development and progression in childhood. Thus, we aimed to determine longitudinal eczema subclasses based on assessments and identify their associations with risk factors and allergic outcomes. METHODS: A total of 619 participants with a family history of allergic disease were assessed at 24 time-points from birth to 12 years. At each time, eczema was defined as the report of current rash treated with topical steroid-based preparations. Longitudinal latent class analysis was used to determine eczema subclasses. Subsequent analyses using regression models assessed the associations between eczema subclasses and potential risk factors and allergic outcomes at 18- and 25-year follow-ups (eczema, allergic rhinitis, asthma and allergic sensitization). RESULTS: We identified five eczema subclasses 'early-onset persistent', 'early-onset resolving', 'mid-onset persistent', 'mid-onset resolving' and 'minimal eczema'. Filaggrin null mutations were associated with the early-onset persistent (OR = 2.58 [1.09-6.08]) and mid-onset persistent class (OR = 2.58 [1.32-5.06]). Compared with 'minimal eczema', participants from early-onset persistent class had higher odds of eczema (OR = 11.8 [5.20-26.6]) and allergic rhinitis (OR = 3.13 [1.43-6.85]) at 18 and at 25 years eczema (OR = 9.37 [3.17-27.65]), allergic rhinitis (OR = 3.26 [1.07-9.93]) and asthma (OR = 2.91 [1.14-7.43]). Likewise, mid-onset persistent class had higher odds of eczema (OR = 2.59 [1.31-5.14]), allergic rhinitis (OR = 1.70 [1.00-2.89]) and asthma (OR = 2.00 [1.10-3.63]) at 18 and at 25 years eczema (OR = 6.75 [3.11-14-65]), allergic rhinitis (OR = 2.74 [1.28-5.88]) and asthma (OR = 2.50 [1.25-5.00]). Allergic and food sensitization in early life was more common in those in the persistent eczem

BACKGROUND AND AIMS: Mega-wild fires are exposing large communities to weeks or months of high concentration smoke-related fine particulate air pollution (PM). However, little research has examined the long-term vascular responses from exposure to PM of this concentration and duration. We investigated whether level of exposure to 6 weeks of PM from the 2014 Hazelwood coal mine fire was associated with abnormal vascular responses approximately four years later. METHODS: A cross-sectional analysis was undertaken of 387 participants (225 exposed, 162 unexposed) aged 55-89 years, 3.5-4 years after the mine fire. The primary outcome was flow-mediated dilatation (FMD), with time to reach peak diameter as the secondary outcome. Other secondary markers included high-sensitivity C-reactive protein (hsCRP) and ischaemic Electrocardiogram (ECG) changes. RESULTS: There was no evidence of a difference in FMD between participants with high, medium, low or no mine-fire related PM2.5 exposure (4.09% vs 4.06% vs 4.02% vs 3.98%, respectively, p=0.99). Likewise, there was no difference in hsCRP or ischaemic ECG changes. In contrast, there was evidence of a difference in time to peak diameter (p=0.002) with more unexposed participants reaching peak diameter within 30 seconds (36%) compared to those who had high, medium, or low exposure (23%, 22%, 13%, respectively). Multivariate ordinal logistic regression analysis suggested that township, Morwell (exposed) vs Sale (unexposed), but not level of PM2.5 exposure, was associated with delayed time to peak diameter (OR 2.71; 95% CI 1.56, 4.69). Smokers also had delayed time to peak diameter. CONCLUSION: There was no association between level of exposure to PM2.5 from the 6-week Hazelwood coal mine fire smoke event and reduced FMD, elevated hsCRP or ischaemic ECG four years later. Evidence of delayed time to peak diameter observed in adults from the exposed town, compared to an unexposed town, requires further investigation.

BACKGROUND AND OBJECTIVE: Inhalational challenge with dry mannitol powder may potentially induce cough by two mechanisms: airway bronchoconstriction or laryngeal irritation. This prospective observational study investigated laryngeal and bronchial components of cough induced by mannitol challenge. METHODS: We recruited consecutive patients referred for clinical mannitol challenge. The Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) was administered. Throughout testing, coughs were audio-recorded to derive a cough frequency index per time and dose of mannitol. Relationships between cough indices, laryngeal hypersensitivity and bronchial hyperresponsiveness (BHR) were examined. Participants were classified by cough characteristics with k-means cluster analysis. RESULTS: Of 90 patients who underwent challenge, 83 completed both the questionnaire and challenge. Cough frequency was greater in patients with abnormal laryngeal hypersensitivity (p = 0.042), but not in those with BHR. There was a moderate negative correlation between coughs per minute and laryngeal hypersensitivity score (r = -0.315, p = 0.004), with lower LHQ scores being abnormal. Cluster analysis identified an older, female-predominant cluster with higher cough frequency and laryngeal hypersensitivity, and a younger, gender-balanced cluster with lower cough frequency and normal laryngeal sensitivity. CONCLUSION: Cough frequency during mannitol challenge in our cohort reflected laryngeal hypersensitivity rather than BHR. Laryngeal hypersensitivity was more often present among older female patients. With the incorporation of cough indices, mannitol challenge may be useful to test for laryngeal hypersensitivity as well as BHR.

In a recent study we found that fathers' but not mothers' onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring's adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents' overweight on adult offspring's lung function within the paternal and maternal lines. We included 929 offspring (aged 18-54, 54% daughters) of 308 fathers and 388 mothers (aged 40-66). Counterfactual-based multi-group mediation analyses by offspring's sex (potential moderator) were used, with offspring's prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers' overweight before puberty had a negative indirect effect, mediated through sons' height, on sons' forced expiratory volume in one second (FEV1) (beta (95% CI): -144 (-272, -23) mL) and forced vital capacity (FVC) (beta (95% CI): -210 (-380, -34) mL), and a negative direct effect on sons' FVC (beta (95% CI): -262 (-501, -9) mL); statistically significant effects on FEV1/FVC were not observed. Mothers' overweight before puberty had neither direct nor indirect effects on offspring's lung function. Fathers' overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons' adult height but not through sons' prepubertal overweight.

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 pret

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 rais

BACKGROUND: While the relationship between pollen and respiratory allergies is well-documented, the role of short-term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population-based sample of children. METHODS: We investigated 1- (n = 1108) and 6-year-old (n = 675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1-lag 3) and cumulatively (lag 0-3). Associations between grass pollen and food skin-prick test reactivity (SPT ≥ 2 mm at age 1 year and ≥ 3 mm at age 6 years), eczema flares, challenge-confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food-specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers. RESULTS: Grass pollen at lag 0-3 (every 20 grains/m3 increase) was associated with an up to 1.2-fold increased odds of food SPT reactivity and eczema flares in 6-year-olds. In 1-year-olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut-allergic 1-year-olds only. CONCLUSION: Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut-allergic infants may be related to immune activation and/or peanut and grass pollen cross-reactivity leading to a lower reaction threshold.

BACKGROUND: Early life body mass index (BMI) trajectories influence the risk of asthma at 18 years of age. However, it is unclear if these are also associated with other allergic diseases. OBJECTIVES: We investigated the associations between BMI trajectories and subsequent allergic rhinitis, eczema and food sensitisation/allergies. METHODS: Parent-reported anthropometric data were collected 18 times in the first two years of life from a cohort of 620 participants in a high-risk cohort. Group-based trajectory modelling was applied to develop BMI trajectories. Associations between trajectories and allergic rhinitis, eczema and food sensitisation at 6, 12 and 18 years of age were assessed using logistic regression models. Potential effect modifications by parental allergic disease, sex and allocated infant formula were assessed. RESULTS: We identified five BMI trajectories: average, below average, persistently low, early low and catch up, and persistently high. None showed an association with allergic rhinitis. In participants with maternal allergic rhinitis, 'early-low and catch-up' (OR = 2.83;95%CI 1.34-5.96, Pint = 0.05) and 'below average' trajectories (OR = 2.39; 1.18-7.23, Pint = 0.02) were associated with allergic rhinitis at 18 years of age compared with the average trajectory. No associations were observed with eczema or food sensitisation. CONCLUSION: Infants with early-low and catch-up, or below average BMI growth, were at increased risk of allergic rhinitis at 18 years if they had a mother with allergic rhinitis. These results require replication, but suggest that interactions between poor intrauterine growth, failure to thrive and maternal allergies may influence the risk of allergic rhinitis.

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.

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.

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.

Access to up-to-date Australian disease prevalence estimates assists health services and consumer organisations to plan and allocate resources. The Burden of Obstructive Lung Disease study was conducted between 2006 and 2012 and provided chronic obstructive pulmonary disease (COPD) (post-bronchodilator airflow limitation) prevalence estimates weighted to the 2006 Australian census. Using the 2016 Australian census, an updated prevalence estimate of all COPD is 8.30% (95% confidence interval = 6.59%-10.01%) for adults aged 40 or more years in Australia and includes 2.52% with mild breathlessness, 0.99% with moderate breathlessness and 0.91% with severe breathlessness.

Inhaled corticosteroids (ICS) suppress eosinophilic airway inflammation in asthma, but patients may not adhere to prescribed use. Mean adherence-averaging total doses taken over prescribed-fails to capture many aspects of adherence. Patients with difficult-to-treat asthma underwent electronic monitoring of ICS, with data collected over 50 days. These were used to calculate entropy (H) a measure of irregular inhaler use over this period, defined in terms of transitional probabilities between different levels of adherence, further partitioned into increasing (Hinc) or decreasing (Hdec) adherence. Mean adherence, time between actuations (Gapmax), and cumulative time- and dose-based variability (area-under-the-curve) were measured. Associations between adherence metrics and 6-month asthma status and attacks were assessed. Only H and Hdec were associated with poor baseline status and 6-month outcomes: H and Hdec correlated negatively with baseline quality of life (H:Spearman rS = - 0·330, p = 0·019, Hdec:rS = - 0·385, p = 0·006) and symptom control (H:rS = - 0·288, p = 0·041, Hdec: rS = - 0·351, p = 0·012). H was associated with subsequent asthma attacks requiring hospitalisation (Wilcoxon Z-statistic = - 2.34, p = 0·019), and Hdec with subsequent asthma attacks of other severities. Significant associations were maintained in multivariable analyses, except when adjusted for blood eosinophils. Entropy analysis may provide insight into adherence behavior, and guide assessment and improvement of adherence in uncontrolled asthma.

BACKGROUND: GPs have limited capacity to routinely provide smoking cessation support. New strategies are needed to reach all smokers within this setting. AIM: To evaluate the effect of a pharmacist-coordinated interdisciplinary smoking cessation intervention delivered in Australian general practice. DESIGN AND SETTING: Secondary analysis of a cluster randomised controlled trial (RCT) conducted in 41 Australian general practices. METHOD: In all, 690 current smokers were included in this study: 373 from intervention clinics (n = 21) and 317 from control clinics (n = 18). A total of 166 current smokers had spirometry-confirmed chronic obstructive pulmonary disease (COPD). In the intervention clinics, trained pharmacists provided smoking cessation support plus Quitline referral. Control clinics provided usual care plus Quitline referral. Those with COPD in the intervention group (n = 84) were referred for home medicines review (HMR) and home-based pulmonary rehabilitation (HomeBase), which included further smoking cessation support. Outcomes included carbon monoxide (CO)-validated smoking abstinence, self-reported use of smoking cessation aids, and differences between groups in readiness-to-quit score at 6 months. RESULTS: Intention-to-treat analysis showed similar CO-validated abstinence rates at 6 months in the intervention (4.0%) and control clinics (3.5%). No differences were observed in readiness-to-quit scores between groups at 6 months. CO-validated abstinence rates were similar in those who completed HMR and at least six sessions of HomeBase to those with COPD in usual care. CONCLUSION: A pharmacist-coordinated interdisciplinary smoking cessation intervention when integrated in a general practice setting had no advantages over usual care. Further research is needed to evaluate the effect of HMR and home-based pulmonary rehabilitation on smoking abstinence in smokers with COPD.

Although there are many health benefits from being active, there was no benefit observed in this study from vigorous physical activity in reducing the risk of asthma onset in middle-aged adults https://bit.ly/3bEtHDn.

In many epidemiological studies mobile phone use has been used as an exposure proxy for radiofrequency electromagnetic field (RF-EMF) exposure. However, RF-EMF exposure assessment from mobile phone use is prone to measurement errors limiting epidemiological research. An often-overlooked aspect is received signal strength levels from base stations and its correlation with mobile phone transmit (Tx) power. The Qualipoc android phone is a tool that provides information on both signal strength and Tx power. The phone produces simultaneous measurements of Received Signal Strength Indicator (RSSI), Reference Signal Received Power (RSRP), Received Signal Code Power (RSCP), and Tx power on the 3G and 4G networks. Measurements taken in the greater Melbourne area found a wide range of signal strength levels. The correlations between multiple signal strength indicators and Tx power were assessed with strong negative correlations found for 3G and 4G data technologies (3G RSSI −0.93, RSCP −0.93; 4G RSSI −0.85, RSRP −0.87). Variations in Tx power over categorical levels of signal strength were quantified and showed large increases in Tx power as signal level decreased. Future epidemiological studies should control for signal strength or factors influencing signal strength to reduce RF-EMF exposure measurement error.

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.

Despite the challenges of diagnosing and managing adult patients with chronic cough, a systematic synthesis of evidence on aetiological risk factor is lacking. We systematically searched PubMed and EMBASE to synthesize the current evidence for longitudinal associations between a wide range of risk factors and chronic cough in the general adult population, following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Fixed-effect meta-analysis was conducted where appropriate. Of 26 eligible articles, 16 domains of risk factors were assessed. There was consistent evidence that asthma (pooled adjusted OR [aOR] = 3.01; 95% CI: 2.33-3.70; I2 = 0%; number of articles [N] = 3) and low education levels/socioeconomic status (SES) (pooled aOR = 1.46; 95% CI: 1.20-1.72; I2 = 0%; N = 3) were associated with an increased risk of chronic cough after adjusting for smoking and other confounders. While continuous smoking was associated with chronic cough (aOR = 1.81; 95% CI: 1.36-2.26; I2 = 57%; N = 3), there was too little evidence to draw conclusions for occupational exposures, outdoor air pollution, early-life exposures, diet, snoring and other chronic conditions, including obesity, chronic obstructive pulmonary disease, gastro-oesophageal reflux disease and chronic pain. Asthma, persistent smoking and lower education/SES were associated with an increased risk of chronic cough. Longitudinal associations between other factors frequently mentioned empirically (i.e., occupational exposures, air pollution and chronic respiratory conditions) need further investigation, ideally with objective and standardized measurement.

BACKGROUND: Classifying individuals at high chronic obstructive pulmonary disease (COPD)-risk creates opportunities for early COPD detection and active intervention. OBJECTIVE: To develop and validate a statistical model to predict 10-year probabilities of COPD defined by post-bronchodilator airflow obstruction (post-BD-AO; forced expiratory volume in 1 s/forced vital capacity<5th percentile). SETTING: General Caucasian populations from Australia and Europe, 10 and 27 centres, respectively. PARTICIPANTS: For the development cohort, questionnaire data on respiratory symptoms, smoking, asthma, occupation and participant sex were from the Tasmanian Longitudinal Health Study (TAHS) participants at age 41-45 years (n=5729) who did not have self-reported COPD/emphysema at baseline but had post-BD spirometry and smoking status at age 51-55 years (n=2407). The validation cohort comprised participants from the European Community Respiratory Health Survey (ECRHS) II and III (n=5970), restricted to those of age 40-49 and 50-59 with complete questionnaire and spirometry/smoking data, respectively (n=1407). STATISTICAL METHOD: Risk-prediction models were developed using randomForest then externally validated. RESULTS: Area under the receiver operating characteristic curve (AUCROC) of the final model was 80.8% (95% CI 80.0% to 81.6%), sensitivity 80.3% (77.7% to 82.9%), specificity 69.1% (68.7% to 69.5%), positive predictive value (PPV) 11.1% (10.3% to 11.9%) and negative predictive value (NPV) 98.7% (98.5% to 98.9%). The external validation was fair (AUCROC 75.6%), with the PPV increasing to 17.9% and NPV still 97.5% for adults aged 40-49 years with ≥1 respiratory symptom. To illustrate the model output using hypothetical case scenarios, a 43-year-old female unskilled worker who smoked 20 cigarettes/day for 30 years had a 27% predicted probability for post-BD-AO at age 53 if she continued to smoke. The predicted risk was 42% if she had coexistent active asthma, but only 4.5% if

BACKGROUND: Physical activity levels are low in people with chronic obstructive pulmonary disease, and there is limited knowledge about how pulmonary rehabilitation transforms movement behaviors. This study analyzed data from a pulmonary rehabilitation trial and identified determinants of movement behaviors. METHODS: Objectively assessed time in daily movement behaviors (sleep, sedentary, light-intensity physical activity, and moderate- to vigorous-intensity physical activity) from a randomized controlled trial (n = 73 participants) comparing home- and center-based pulmonary rehabilitation was analyzed using conventional and compositional analytical approaches. Regression analysis was used to assess relationships between movement behaviors, participant features, and response to the interventions. RESULTS: Compositional analysis revealed no significant differences in movement profiles between the home- and center-based groups. At end rehabilitation, conventional analyses identified positive relationships between exercise capacity (6-min walk distance), light-intensity physical activity, and moderate- to vigorous-intensity physical activity time. Compositional analyses identified positive relationships between a 6-minute walk distance and moderate- to vigorous-intensity physical activity time, accompanied by negative relationships with sleep and sedentary time (relative to other time components) and novel relationships between body mass index and light-intensity physical activity/sedentary time. CONCLUSION: Compositional analyses following pulmonary rehabilitation identified unique associations between movement behaviors that were not evident in conventional analyses.

We investigated the association between respiratory symptoms and psychological distress in the context of a prolonged smoke event, and evaluated whether smoke exposure, or pre-existing respiratory and mental health conditions, influenced the association. Three thousand ninety-six residents of a rural town heavily exposed to smoke from the 6-week Hazelwood coal mine fire, and 960 residents of a nearby unexposed town, completed Kessler's psychological distress questionnaire (K10) and a modified European Community Respiratory Health Survey. Logistic regression models evaluated associations between distress and respiratory symptoms, with interactions fitted to evaluate effect modification. Smoke exposed participants reported higher levels of distress than those unexposed, and participants reporting respiratory symptoms recorded higher levels of distress than participants without respiratory symptoms, irrespective of exposure. 5-unit increments in K10 scores were associated with 21%-48% increases in the odds of reporting respiratory symptoms. There were significant interactions with pre-existing asthma, chronic obstructive pulmonary disease and mental health conditions, but not with smoke exposure. Although participants with pre-existing conditions were more likely to report respiratory symptoms, increasing distress was most strongly associated with respiratory symptoms among those without pre-existing conditions. Communities exposed to landscape fire smoke could benefit from interventions to reduce both psychological and respiratory distress.

BACKGROUND: Breathlessness is a major cause of suffering and disability globally. The symptom relates to multiple factors including asthma and lung function, which are influenced by hereditary factors. No study has evaluated potential inheritance of breathlessness itself across generations. METHODS: We analysed the association between breathlessness in parents and their offspring in the Respiratory Health in Northern Europe, Spain and Australia generation study. Data on parents and offspring aged ≥18 years across 10 study centres in seven countries included demographics, self-reported breathlessness, asthma, depression, smoking, physical activity level, measured Body Mass Index and spirometry. Data were analysed using multivariable logistic regression accounting for clustering within centres and between siblings. RESULTS: A total of 1720 parents (mean age at assessment 36 years, 55% mothers) and 2476 offspring (mean 30 years, 55% daughters) were included. Breathlessness was reported by 809 (32.7%) parents and 363 (14.7%) offspring. Factors independently associated with breathlessness in parents and offspring included obesity, current smoking, asthma, depression, lower lung function and female sex. After adjusting for potential confounders, parents with breathlessness were more likely to have offspring with breathlessness, adjusted OR 1.8 (95% CI 1.1 to 2.9). The association was not modified by sex of the parent or offspring. CONCLUSION: Parents with breathlessness were more likely to have children who developed breathlessness, after adjusting for asthma, lung function, obesity, smoking, depression and female sex in both generations. The hereditary components of breathlessness need to be further explored.

Despite the growing body of evidence on lung function trajectories over the life course and their risk factors, the literature has not been systematically synthesized. Publications related to lung function trajectories were identified from PubMed, EMBASE and CINAHL databases. Two authors independently identified publications for inclusion according to predefined selection criteria. Studies that modelled lung function trajectories and reported associated exposures were included. Meta-analyses could not be conducted due to heterogeneity in the exposures and methods used to model lung function trajectories. Nine publications were eligible for inclusion of which four used group-based trajectory modelling to model lung function trajectories, while five used latent profile analysis. Studies with repeated lung function measurements over the life course identified more trajectories than others. Only one study spanning from childhood to middle age reported catch-up trajectory. The following childhood risk factors for subnormal lung function trajectories were observed in at least across two studies: low birth weight, early wheezing, asthma, allergic sensitization, eczema, allergic rhinitis, lower respiratory tract infections, family history of asthma and second-hand smoke exposure. Adult active asthma and personal cigarette smoking were observed to be associated with accelerated decline lung trajectories. Our review identified 10 risk factors associated with the growth, catch-up, reduced plateau and decline trajectories of lung function. Intervention directed at childhood asthma and infections, and tobacco smoke exposure at all ages would help promote lung health and prevent subnormal lung function trajectories.

BACKGROUND: There is limited information on risk factors for eczema in adults. Recent evidence suggests that air pollution may be associated with increased incidence of eczema in adults. We aimed to assess this possible association. METHODS: Ambient air pollution exposures (distance from a major road, nitrogen dioxide [NO2 ], fine particulate matter with an aerodynamic diameter ≤2.5 µm [PM2.5 ]) were assessed for the residential address of Tasmanian Longitudinal Health Study participants at ages 43 and 53 years. Eczema incidence (onset after age 43 years), prevalence (at 53 years), and persistence were assessed from surveys, while IgE sensitization was assessed using skin prick tests. The presence or absence of eczema and sensitization was classified into four groups: no atopy or eczema, atopy alone, non-atopic eczema, and atopic eczema. Adjusted logistic and multinomial regression models were fitted to estimate associations between ambient air pollution and eczema, and interaction by sex was assessed. RESULTS: Of 3153 participants in both follow-ups, 2369 had valid skin prick tests. For males, a 2.3 ppb increase in baselineNO2 was associated with increased odds of prevalent eczema (OR = 1.15 [95% CI 0.98-1.36]) and prevalent atopic eczema (OR = 1.26 [1.00-1.59]). These associations were not seen in females (p for interaction = 0.08, <0.01). For both sexes, a 1.6 µg/m3 increase in PM2.5 exposure at follow-up was associated with increased odds of aeroallergen sensitization (OR = 1.15 [1.03-1.30]). CONCLUSION: Increased exposure to residential ambient air pollutants was associated with an increased odds of eczema, only in males, and aeroallergen sensitization in both genders.

PURPOSE: Spirometry is necessary to confirm COPD, but many patients are diagnosed based on clinical presentation and/or chest x-ray. There are also those who do not present to primary care for case finding and remain undiagnosed. We aimed to identify: (a) factors that are associated with undiagnosed COPD; and (b) factors that are associated with a potential misdiagnosis of COPD. PATIENTS AND METHODS: This analysis used data from the Burden of Obstructive Lung Disease (BOLD), a cross-sectional study of community dwelling adults randomly selected from six study sites, chosen to provide a representative sample of the Australian population (n= 3357). Participants were grouped by COPD diagnostic criteria based on spirometry and self-reported diagnosis. Odds ratios for predictors of undiagnosed and misdiagnosed were estimated using logistic regression. RESULTS: Of the BOLD Australia sample, 1.8% had confirmed COPD, of whom only half self-reported a diagnosis of COPD. A further 6.9% probably had COPD, but were undiagnosed. The priority target population for case finding of undiagnosed COPD was aged ≥60 years (particularly those ≥75 years), with wheezing, shortness of breath and a body mass index (BMI) <25kg/m2. The priority target population for identifying and reviewing misdiagnosed COPD was aged <60 years, female, with no wheezing and a BMI ≥25kg/m2. CONCLUSION: Challenges continue in accurately diagnosing COPD and greater efforts are needed to identify undiagnosed and misdiagnosed individuals to ensure an accurate diagnosis and the initiation of appropriate management in order to reduce the burden of COPD.

While asthma is known to be associated with an increased risk of progressive lung function impairments and fixed airflow obstruction, there is ongoing debate on whether inhaled corticosteroids (ICS) modify these long-term risks. Searches were performed of the PubMed, Embase and CENTRAL databases up to 22 July 2019 for studies with follow-up ≥1 year that investigated the effects of maintenance ICS on changes in lung function in asthma.Inclusion criteria were met by 13 randomised controlled trials (RCTs) (n=11 678) and 11 observational studies (n=3720). Median (interquartile range) follow-up was 1.0 (1-4) and 8.4 (3-28) years, respectively. In the RCTs, predominantly in individuals with mild asthma, ICS use was associated with improved pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) across all age groups (2.22% predicted (95% CI 1.32-3.12), n=8332), with similar estimates of strength in association for children and adults. Improvements in post-BD FEV1 were observed in adults (1.54% (0.87-2.21), n=3970), but not in children (0.20% (-0.49-0.90), n=3924) (subgroup difference, p=0.006). Estimates were similar between smokers and nonsmokers. There were no RCT data on incidence of fixed airflow obstruction. In the observational studies, ICS use was associated with improved pre-BD FEV1 in children and adults. There were limited observational data for post-BD outcomes.In patients with mild asthma, maintenance ICS are associated with modest, age-dependent improvements in long-term lung function, representing an added benefit to the broader clinical actions of ICS in asthma. There is currently insufficient evidence to determine whether treatment reduces incidence of fixed airflow obstruction in later life.

BACKGROUND: High surrounding greenness has many health benefits and might contribute to slower biological aging. However, very few studies have evaluated this from the perspective of epigenetics. OBJECTIVES: We aimed to evaluate the association between surrounding greenness and biological aging based on DNA methylation. METHODS: We derived Horvath's DNA methylation age (DNAmAge), Hannum's DNAmAge, PhenoAge, and GrimAge based on DNA methylation measured in peripheral blood samples from 479 Australian women in 130 families. Measures of DNAmAge acceleration (DNAmAgeAC) were derived from the residuals after regressing each DNAmAge metric on chronological age. Greenness was represented by satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) metrics within 300-, 500-, 1,000-, and 2,000-m buffers surrounding participant addresses. Greenness-DNAmAgeAC associations were estimated using a within-sibship design fitted by linear mixed effect models, adjusting for familial clustering and important covariates. RESULTS: Greenness metrics were associated with significantly lower DNAmAgeAC based on GrimAge acceleration, suggesting slower biological aging with higher greenness based on both NDVI and EVI in 300-2,000m buffer areas. For example, each interquartile range increase in NDVI within 1,000m was associated with a 0.59 (95% CI: 0.18, 1.01)-year decrease in GrimAge acceleration. Greenness was also inversely associated with three of the eight components of GrimAge, specifically, DNA methylation-based surrogates of serum cystatin-C, serum growth differentiation factor 15, and smoking pack years. Associations between greenness and biological aging measured by Horvath's and Hannum's DNAmAgeAC were less consistent, and depended on neighborhood socioeconomic status. No significant associations were estimated for PhenoAge acceleration. DISCUSSION: Higher surrounding greenness was associated with slower biological aging, as indicated by Gri