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BACKGROUND: Cough is a common yet heterogeneous condition. Little is known about the characteristics and course of cough in general populations. We aimed to investigate cough subclasses, their characteristics from childhood across six decades of life, and potential treatable traits in a community-based cohort. METHODS: For our analysis of the Tasmanian Longitudinal Health Study (TAHS), a prospective, community-based cohort study that began on Feb 23, 1968, and has so far followed up participants in Tasmania, Australia, at intervals of 10 years from a mean age of 7 years to a mean age of 53 years, we used data collected as part of the TAHS to distinguish cough subclasses among current coughers at age 53 years. For this analysis, participants who answered Yes to at least one cough-related question via self-report questionnaire were defined as current coughers and included in a latent class analysis of cough symptoms; participants who answered No to all nine cough-related questions were defined as non-coughers and excluded from this analysis. Two groups of longitudinal features were assessed from age 7 years to age 53 years: previously established longitudinal trajectories of FEV1, forced vital capacity [FVC], FEV1/FVC ratio, asthma, and allergies-identified via group-based trajectory analysis or latent class analysis-and symptoms at different timepoints, including asthma, current productive cough, ever chronic productive cough, current smoking, and second-hand smoking. FINDINGS: Of 8583 participants included at baseline in the TAHS, 6128 (71·4%) were traced and invited to participate in a follow-up between Sept 3, 2012, and Nov 8, 2016; 3609 (58·9%) of these 6128 returned the cough questionnaire. The mean age of participants in this analysis was 53 years (SD 1·0). 2213 (61·3%) of 3609 participants were defined as current coughers and 1396 (38·7%) were categorised as non-coughers and excluded from the latent class analysis. 1148 (51·9%) of 2213 participants in this ana

INTRODUCTION: Evidence on the early life risk factors of adult CRS, and the history of asthma and allergies across the life course, is limited. AIM: To investigate relationships between respiratory infective/allergic conditions in childhood, and asthma and allergies across the life course and CRS in middle age. METHODS: Data were from the population-based Tasmanian Longitudinal Health Study (TAHS) cohort, first studied in 1968 when aged 6-7 years (n = 8583) and serially followed into middle age (n = 3609). Using a well-accepted epidemiological definition, participants were assigned a CRS-severity subtype at age 53: no sinusitis/CRS (reference); past doctor diagnosis only; current symptoms without doctor diagnosis; and doctor-diagnosed CRS with current symptoms. Relationships with infective/allergic respiratory illnesses at age 7, and previously published asthma-allergy trajectories from 7 to 53 years, were examined using multinominal regression. RESULTS: In middle age, 5.8% reported current CRS symptoms with 2.5% doctor-diagnosed. Childhood conditions associated with symptomatic doctor-diagnosed CRS included frequent head colds (multinomial odds ratio [mOR] = 2.04 (95% confidence interval [95% CI]: 1.24, 3.37)), frequent tonsillitis (mOR = 1.61 [95% CI: 1.00, 2.59]) and current childhood asthma (mOR = 2.23 [95% CI: 1.25, 3.98]). Life course trajectories that featured late-onset or persistent asthma and allergies were associated with all CRS subtypes in middle age; early-onset persistent asthma and allergies (mOR = 6.74, 95% CI: 2.76, 16.4); late-onset asthma allergies (mOR = 15.9, 95% CI: 8.06, 31.4), and late-onset hayfever (mOR = 3.02, 95% CI: 1.51, 6.06) were associated with symptomatic doctor-diagnosed CRS. CONCLUSION: Current asthma, frequent head colds and tonsillitis at age 7 could signal a susceptible child who is at higher risk for CRS in mid-adult life and who might benefit from closer monitoring and/or proactive management. Concurrent asthma and allergies

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.

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.

BACKGROUND AND OBJECTIVES: While adult chronic cough has high burden, its phenotypes, particularly those without aetiologically related underlying conditions, are understudied. We investigated the prevalence, lung function and comorbidities of adult chronic cough phenotypes. METHODS: Data from 3608 participants aged 53 years from the Tasmanian Longitudinal Health Study (TAHS) were included. Chronic cough was defined as cough on most days for >3 months in a year. Chronic cough was classified into "explained cough" if there were any one of four major cough-associated conditions (asthma, COPD, gastroesophageal reflux disease or rhinosinusitis) or "unexplained cough" if none were present. Adjusted regression analyses investigated associations between these chronic cough phenotypes, lung function and non-respiratory comorbidities at 53 years. RESULTS: The prevalence of chronic cough was 10% (95%CI 9.1,11.0%) with 46.4% being "unexplained". Participants with unexplained chronic cough had lower FEV1/FVC (coefficient: -1.2% [95%CI:-2,3, -0.1]) and increased odds of comorbidities including obesity (OR=1.6 [95%CI: 1.2, 2.3]), depression (OR=1.4 [95%CI: 1.0, 2.1]), hypertension (OR=1.7 [95%CI: 1.2, 2.4]) and angina, heart attack or myocardial infarction to a lesser extent, compared to those without chronic cough. Participants with explained chronic cough also had lower lung function than both those with unexplained chronic cough and those without chronic cough. CONCLUSIONS: Chronic cough is prevalent in middle-age and a high proportion is unexplained. Unexplained cough contributes to poor lung function and increased comorbidities. Given unexplained chronic cough is not a symptom of major underlying respiratory conditions it should be targeted for better understanding in both clinical settings and research.

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: 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: 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

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: 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

Respiratory diseases such as asthma, allergic rhinitis (AR) and chronic obstructive pulmonary disease (COPD) affect millions worldwide and pose a significant global public health burden. Over the years, changes in land use and climate have increased pollen quantity, allergenicity and duration of the pollen season, thus increasing its impact on respiratory disease. Many studies have investigated the associations between short-term ambient pollen (i.e., within days or weeks of exposure) and respiratory outcomes. Here, we reviewed the current evidence on the association between short-term outdoor pollen exposure and thunderstorm asthma (TA), asthma and COPD hospital presentations, general practice (GP) consultations, self-reported respiratory symptoms, lung function changes and their potential effect modifiers. The literature suggests strong evidence of an association between ambient pollen concentrations and almost all respiratory outcomes mentioned above, especially in people with pre-existing respiratory diseases. However, the evidence on sub-clinical lung function changes, COPD, and effect modifiers other than asthma, hay fever and pollen sensitisation are still scarce and requires further exploration. Better understanding of the implications of pollen on respiratory health can aid healthcare professionals to implement appropriate management strategies.

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: 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: Eczema is a chronic inflammatory skin disease. Domestic water with high mineral content (hard water) is a risk factor for eczema in children, but this association has not been assessed in adults. OBJECTIVES: To examine the association between domestic hard water supply and eczema prevalence and incidence in adults aged 40-69 years and the contextual effect in eczema outcomes by postcode in adults in the UK. METHODS: We used data from the UK Biobank study collected in 2006-10 (baseline) and 2013-14 (follow-up). Eczema prevalence at baseline (2006-10) and at follow-up (2013-14) and incidence (new onset between baseline and follow-up) were determined from the touchscreen questionnaires and nurse-led interviews. Domestic hard water information was obtained in 2005 and 2013 from the local water supply companies in England, Wales and Scotland as CaCO3 concentrations. We fitted multilevel logistic regression models with random intercepts for postcode areas to examine the effect of domestic hard water on eczema outcomes, and we measured components of variance. RESULTS: In total, 306 531 participants with a mean age of 57 years nested across 7642 postcodes were included in the baseline analysis, and 31 036 participants nested across 3695 postcodes were included in the follow-up analysis. We observed an increase in the odds of eczema at baseline [odds ratio (OR) 1·02, 95% confidence interval (CI) 1·01-1·04] per 50 mg L-1 of CaCO3 increase. Furthermore, exposure to domestic hard water (> 200 mg L-1 of CaCO3 ) was associated with increased odds of prevalent eczema at baseline (OR 1·12, 95% CI 1·04-1·22). Moreover, there was a significant linear trend (P < 0·001) in which increasing levels of hard water increased eczema prevalence risk. No association was observed with incident eczema or eczema at follow-up. The intraclass correlation coefficient for postcode was 1·6% (95% CI 0·7-3·4), which remained unexplained by area-level socioeconomic measures. CONCLUSIONS: Incr

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.

Further analyses to clarify the clinical and public health messages for early-life upper respiratory tract infections are suggested to better inform parents and the healthcare professionals who look after these children in the general community https://bit.ly/3xAWxz0

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.

The profound effect of COVID-19 pandemic has not eluded Vietnam, a lower-middle-income country that borders China, the country where the outbreak originated. Currently facing a second wave, Vietnam experienced several months of insignificant community-transmission, when the epidemic was effectively under control. This paper provides an account of the policies developed by the national COVID-19 response team during the first wave, from January to July 2020. Three key components were identified, including (i) the timely and decisive responses from the national and local authorities in the early phase of the pandemic, (ii) a society-wide approach, supported by an effective risk communication strategy which managed to gain the public trust, and (iii) an effective preventive medicine and infectious disease control system, residing in early case identification, strict isolation, effective contact tracing and compulsory quarantine of close contacts. While several other important components of the health system, such as financing and human resources remain largely under-explored, the results of this study show that a mixture of measures may lead to an effective epidemic management.

The aim of this study was to investigate the impact of biomass fuel for cooking on adverse fetal growth outcomes in Sri Lanka. A cross-sectional study of mothers recruited at maternity clinics in rural communities in Sri Lanka's Central Province was undertaken. Data pertaining to household air pollution and fetal growth parameters were collected using an interviewer-administered questionnaire. Logistic regression models, adjusted for potential confounders, were used to evaluate the impact of biomass fuel for cooking on low birth weight (LBW) and small for gestational age (SGA) parameters. Findings showed that exposure to biomass cooking fuels during pregnancy was associated with an increased risk of LBW adjusted odds ratio (aOR) 2.74 (95% CI 1.08-6.96) and SGA (aOR: 1.87, 95% CI 1.03-3.41) compared with the use of clean energy. The risk of LBW was highest for traditional biomass stoves compared to improved biomass stoves (aOR: 3.23, 95% 1.17-8.89) and biomass use in kitchens without a chimney compared to kitchens with a chimney (aOR: 4.63, 95% 1.54-13.93). Similar trends were observed for SGA.

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.

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

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: The relationship between asthma and coronavirus disease 2019 (COVID-19) risk is not clear and may be influenced by level of airway obstruction, asthma medication and known COVID-19 risk factors. We aimed to investigate COVID-19 risk in people with asthma. METHODS: We used UK Biobank data from all participants tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n=107 412; 17 979 test positive). Questions at baseline defined ever asthma and asthma medications. Baseline forced expiratory volume in 1 s (FEV1) was categorised into quartiles. Logistic regression modelled relationships between asthma, and asthma categories (age at onset, medications, FEV1 quartiles), and risk of SARS-CoV-2 positive test. We investigated modification by sex, ethnic group, smoking and body mass index. RESULTS: There was a reduced risk of a positive test associated with early-onset asthma (<13 years) (OR 0.91, 95% CI 0.84-0.99). This was found for participants with early-onset asthma who were male (OR 0.87, 95% CI 0.78-0.98), nonsmokers (OR 0.87, 95% CI 0.78-0.98), overweight/obese (OR 0.85, 95% CI 0.77-0.93) and non-Black (OR 0.90, 95% CI 0.82-0.98). There was increased risk amongst early-onset individuals with asthma in the highest compared to lowest quartile of lung function (1.44, 1.05-1.72). CONCLUSION: Amongst male, nonsmoking, overweight/obese and non-Black participants, having early-onset asthma was associated with lower risk of a SARS-CoV-2 positive test. We found no evidence of a protective effect from asthma medication. Individuals with early-onset asthma of normal weight and with better lung function may have lifestyle differences placing them at higher risk. Further research is needed to elucidate the contribution of asthma pathophysiology and different health-related behaviour, across population groups, to the observed risks.

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.

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.

Bronchodilator reversibility (BDR) is often used as a diagnostic test for adult asthma. However, there has been limited assessment of its diagnostic utility. We aimed to determine the discriminatory accuracy of common BDR cut-offs in the context of current asthma and asthma-COPD overlap (ACO) in a middle-aged community sample. The Tasmanian Longitudinal Health Study is a population-based cohort first studied in 1968 (n=8583). In 2012, participants completed respiratory questionnaires and spirometry (n=3609; mean age 53 years). 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. Area under the ROC curve (AUC) was highest when BDR was expressed as change in forced expiratory volume in 1 s (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 categorical cut-offs examined, the European Respiratory Society/American Thoracic Society threshold (≥12% from baseline and ≥200 mL) was assessed as providing the best balance between positive and negative likelihood ratios (LR+ and LR-, respectively), with corresponding sensitivities and specificities of 9% and 97%, respectively, for current asthma (LR+ 3.26, LR- 0.93), and 47% and 97%, respectively, for ACO (LR+ 16.05, LR- 0.55). With a threshold of ≥12% and ≥200 mL from baseline, a positive BDR test provided a clinically meaningful change in the post-test probability of disease, whereas a negative test did not. BDR was more useful as a diagnostic test in those with co-existent post-bronchodilator airflow obstruction (ACO).

PURPOSE: To study changes in lung function among individuals with a risk of obstructive sleep apnoea (OSA), and if asthma affected this relationship. METHODS: We used data from the European Community Respiratory Health Survey II and III, a multicentre general population study. Participants answered questionnaires and performed spirometry at baseline and 10-year follow-up (n = 4,329 attended both visits). Subjects with high risk for OSA were identified from the multivariable apnoea prediction (MAP) index, calculated from BMI, age, gender, and OSA symptoms at follow-up. Asthma was defined as having doctor's diagnosed asthma at follow-up. Primary outcomes were changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from baseline to follow-up. RESULTS: Among 5108 participants at follow-up, 991 (19%) had a high risk of OSA based on the MAP index. Participants with high OSA risk more often had wheeze, cough, chest tightness, and breathlessness at follow-up than those with low OSA risk. Lung function declined more rapidly in subjects with high OSA risk (low vs high OSA risk [mean ± SD]: FEV1 = - 41.3 ± 24.3 ml/year vs - 50.8 ± 30.1 ml/year; FVC = - 30.5 ± 31.2 ml/year vs - 45.2 ± 36.3 ml/year). Lung function decline was primarily associated with higher BMI and OSA symptoms. OSA symptoms had a stronger association with lung function decline among asthmatics, compared to non-asthmatics. CONCLUSION: In the general population, a high probability of obstructive sleep apnoea was related to faster lung function decline in the previous decade. This was driven by a higher BMI and more OSA symptoms among these subjects. The association between OSA symptoms and lung function decline was stronger among asthmatics.

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

BACKGROUND: Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade. METHODS: We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD. FINDINGS: Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, ac