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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 were strongly associated and are potential treatable traits of adult CRS., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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 FEV 1 , forced vital capacity [FVC], FEV 1 /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 analysis were female and 1065 (48·1%) were male. Six distinct cough subclasses were identified: 206 (9·3%) of 2213 participants had minimal cough, 1189 (53·7%) had cough with colds only, 305 (13·8%) had cough with allergies, 213 (9·6%) had intermittent productive cough, 147 (6·6%) had chronic dry cough, and 153 (6·9%) had chronic productive cough. Compared with people with minimal cough, and in contrast to other cough subclasses, people in the chronic productive cough and intermittent productive cough subclasses had worse lung function trajectories (FEV 1 persistent low trajectory 2·9%, 6·4%, and 16·1%; p=0·0011, p<0·0001; FEV 1 /FVC early low-rapid decline trajectory 2·9%, 12·1%, and 13·0%; p=0·012, p=0·0007) and a higher prevalence of cough (age 53 years 0·0%, 32·4% [26·1-38·7], and 50·3% [42·5-58·2]) and asthma (age 53 years 6·3% [3·7-10·6], 26·9% [21·3-33·3], and 41·7% [24·1-49·7]) from age 7 years to age 53 years., Interpretation: We identified potential treatable traits for six cough subclasses (eg, asthma, allergies, and active and passive smoking for productive cough). The required management of productive cough in primary care (eg, routine spirometry) might differ from that of dry cough if our findings are supported by other studies. Future population-based studies could apply our framework to address the heterogeneity and complexity of cough in the community., Funding: The National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, Victorian Asthma Foundation, Queensland Asthma Foundation, Tasmanian Asthma Foundation, The Royal Hobart Hospital Research Foundation, the Helen MacPherson Smith Trust, GlaxoSmithKline, and the China Scholarship Council., Competing Interests: Declaration of interests SCD, CJL, AJL, DSB, MJA, and JLP have investigator-initiated grants from GlaxoSmithKline. SCD, AJL, and MJA have investigator-initiated grants from Sanofi. SCD, JLP, CJL, DSB, and ABC are supported by the National Health and Medical Research Council of Australia (NHMRC). JLP is financially supported by the Australian Asthma Foundation, Craig Clifford Medical Trust, Helen McPherson Trust, and GlaxoSmithKline. AJL has received non-financial, technical support from Primus Pharmaceuticals. ABC has investigator-initiated grants from the NHMRC and the Australian Medical Research Future Fund; is a member of a data safety monitoring committee for GlaxoSmithKline, AstraZeneca, and Moderna; and was on the NHMRC Health Impact Committee, NHMRC Women in Science, and the European Respiratory Society Guideline Committee. JLP and SCD have an investigator-initiated grant from AstraZeneca. MJA has investigator-initiated grants from Pfizer and Boehringer-Ingelheim, was a consultant for Sanofi, received a speaker's fee from GlaxoSmithKline, and is an honorary member of the independent data monitoring committee for the NHMRC-funded Vietnam COPD Asthma and Prevention of Smoking 4 Trial via the Woolcock Institute. JZ is supported by The University of Melbourne and the China Scholarship Council joint PhD scholarship. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objective: Early-life risk factors for obstructive sleep apnoea (OSA) are poorly described, yet this knowledge may be critical to inform preventive strategies. We conducted the first study to investigate the association between early-life risk factors and OSA in middle-aged adults., Methods: Data were from population-based Tasmanian Longitudinal Health Study cohort (n = 3550) followed from 1st to 6th decades of life. Potentially relevant childhood exposures were available from a parent-completed survey at age 7-years, along with previously characterized risk factor profiles. Information on the primary outcome, probable OSA (based on a STOP-Bang questionnaire cut-off ≥5), were collected when participants were 53 years old. Associations were examined using logistic regression adjusting for potential confounders. Analyses were repeated using the Berlin questionnaire., Results: Maternal asthma (OR = 1.5; 95% CI 1.1-2.0), maternal smoking (OR = 1.2; 1.05, 1.5), childhood pleurisy/pneumonia (OR = 1.3; 1.04, 1.7) and frequent bronchitis (OR = 1.2; 1.01, 1.5) were associated with probable OSA. The risk-factor profiles of 'parental smoking' and 'frequent asthma and bronchitis' were also associated with probable OSA (OR = 1.3; 1.01, 1.6 and OR = 1.3; 1.01-1.9, respectively). Similar associations were found for Berlin questionnaire-defined OSA., Conclusions: We found novel temporal associations of maternal asthma, parental smoking and frequent lower respiratory tract infections before the age of 7 years with adult OSA. While determination of their pathophysiological and any causal pathways require further research, these may be useful to flag the risk of OSA within clinical practice and create awareness and vigilance among at-risk groups., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

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.

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., Competing Interests: Conflicts of interest: M.J. Abramson holds investigator-initiated grants for unrelated research from Pfizer, Boehringer Ingelheim and Sanofi; has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi; and has also received a speaker's fee from GSK. The other authors included in this study declare that they have no competing interests. All authors declare no support from any organisation or no financial relationship with any organisation that could appear to have influenced the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Grass pollen exposure is a risk factor for childhood asthma hospital attendances. However, its short-term influence on lung function, especially among those with other allergic conditions, has been less well-studied., Objective: To investigate this association in a population-based sample of children., Methods: Within the HealthNuts cohort, 641 children performed spirometry during the grass pollen season. Grass pollen concentration was considered on the day of testing (lag 0), up to 3 days before (lag 1-lag 3), and cumulatively (lag 0-3). We used linear regression to assess the relevant associations and examined potential interactions with current asthma, hay fever or eczema, and food allergy., Results: Associations were observed only in children with allergic disease (P value for interaction ≤ 0.1). In children with food allergy, grass pollen concentration was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV 1 /FVC) and lower mid-forced expiratory flows (FEF 25%-75% ) at all lags (eg, at lag 2, FEV 1 /FVC z-score = -0.50 [95% CI -0.80 to -0.20] and FEF 25%--75% z-score = -0.40 [-0.60 to -0.04] per 20 grains/m 3 pollen increase), and increased bronchodilator responsiveness (BDR) at lag 2 and lag 3 (eg, at lag 2, BDR = (31 [95% CI -0.005 to 62] mL). In children with current asthma, increasing grass pollen concentration was associated with lower FEF 25%-75% and increased BDR, whereas children with current hay fever or eczema had increased BDR only., Conclusions: A proactive approach needs to be enforced to manage susceptible children, especially those with food allergy, before high-grass pollen days., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic bronchitis in childhood is associated with a diagnosis of asthma and/or bronchiectasis a few years later, however, consequences into middle-age are unknown., Objective: To investigate the relationship between childhood bronchitis and respiratory-related health outcomes in middle-age., Design: Cohort study from age 7 to 53 years., Setting: General population of European descent from Tasmania, Australia., Participants: 3202 participants of the age 53-year follow-up (mean age 53, range 51-55) of the Tasmanian Longitudinal Health Study cohort who were born in 1961 and first investigated at age 7 were included in our analysis., Statistical Methods: Multivariable linear and logistic regression. The association between parent reported childhood bronchitis up to age 7 and age 53-year lung conditions (n=3202) and lung function (n=2379) were investigated., Results: Among 3202 participants, 47.5% had one or more episodes of childhood bronchitis, classified according to severity based on the number of episodes and duration as: 'non-recurrent bronchitis' (28.1%); 'recurrent non-protracted bronchitis' (18.1%) and 'recurrent-protracted bronchitis' (1.3%). Age 53 prevalence of doctor-diagnosed asthma and pneumonia (p-trend <0.001) and chronic bronchitis (p-trend=0.07) increased in accordance with childhood bronchitis severities. At age 53, 'recurrent-protracted bronchitis' (the most severe subgroup in childhood) was associated with doctor-diagnosed current asthma (OR 4.54, 95% CI 2.31 to 8.91) doctor-diagnosed pneumonia (OR=2.18 (95% CI 1.00 to 4.74)) and, paradoxically, increased transfer factor for carbon monoxide (z-score +0.51 SD (0.15-0.88)), when compared with no childhood bronchitis., Conclusion: In this cohort born in 1961, one or more episodes of childhood bronchitis was a frequent occurrence. 'Recurrent-protracted bronchitis', while uncommon, was especially linked to multiple respiratory outcomes almost five decades later, including asthma, pneumonia and raised lung gas transfer. These findings provide insights into the natural history of childhood 'bronchitis' into middle-age., Competing Interests: Competing interests: JP, AL, CL, DB, EHW, MJA and SCD have received an investigator-initiated grant from GlaxoSmithKline for unrelated research, and SCD holds a similar grant from AstraZeneca. MJA also holds investigator-initiated grants from Pfizer, Boehringer-Ingelheim and Sanofi for unrelated research; has undertaken an unrelated consultancy and received assistance with conference attendance from Sanofi; and received a speaker’s fee from GlaxoSmithKline. ABC is on independent data safety and monitoring boards for a SARs-COV2 vaccine (Moderna), an unlicensed RSV vaccine (GSK) and monoclonal antibody (AstraZeneca), where the monies are received by her institution. BRT serves on the medical advisory boards of Chiesi Australia and 4D Medical and has received an unrelated consultancy from GlaxoSmithKline and speaker fees from Mundipharma. AL has received investigational product (EpiCeram TM) free of charge from Primus Pharmaceuticals for use in unrelated research. DW has received consultancy fee from MSD for participation on an expert input forum, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The chronic respiratory non-communicable diseases, asthma and chronic obstructive pulmonary disease (COPD) are among the leading causes of global mortality and morbidity. Individuals suffering from these diseases are particularly susceptible to respiratory infections caused by bacterial and/or viral pathogens, which frequently result in exacerbation of symptoms, lung function decline, frequent hospital emergency visits and increased socioeconomic burden. Human rhinoviruses (HRV) remain the major viral pathogen group implicated in exacerbations of both asthma and COPD. The rhinoviral entry into the host lung epithelium is facilitated primarily by the adhesion site ("receptor") intercellular adhesion molecule-1 (ICAM-1), coincidentally expressed on the respiratory epithelium in these conditions. Multiple observations of increased airway ICAM-1 protein in asthmatics, smokers and smoking-related COPD have been recorded in the literature. However, the lack of robust therapies for COPD in particular has triggered a renewed interest in assessing receptor antagonism-based anti-viral strategies for treatment of intercurrent viral infections in those with pre-existing chronic lung diseases. Given the crucial role ICAM-1 plays in facilitating HRV adhesion and, thus, transmissibility to the host respiratory system, as well as the up-regulation of ICAM-1 by smoking, we summarize the role of HRV in smoking-induced COPD and especially highlight the role of ICAM-1 in epithelial viral adhesion and chronic lung disease progression. Further, the review also sheds light specifically on evolving precision therapeutic strategies in blocking ICAM-1 for preventing viral adhesion and exacerbations of COPD., (© 2022. The Author(s).)

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 (FEV 1 , forced vital capacity [FVC], FEV 1 /FVC ratio, forced expiratory flow at 25-75% of FVC [FEF 25-75% ], diffusing capacity for carbon monoxide [DLCO]) and COPD (post-bronchodilator FEV 1 /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 FEV 1 /FVC ratio (beta-coefficient -2·9% [95% CI -4·9 to -0·81]), FEV 1 (-190 mL [-339 to -40]), DLCO (-0·55 mmol/min/kPa [-0·97 to -0·13]), and FEF 25-75% (-339 mL/s [-664 to -14]). The association between very-to-moderate preterm birth and FEV 1 /FVC ratio was only significant among smokers (p interaction =0·0082). Similar findings were observed for moderate preterm birth when analysed as a separate group. Compared with term birth, late preterm birth was not associated with lower FEV 1 /FVC ratio or COPD., Interpretation: This is the first study to investigate the effect of prematurity on lung function into middle-age. Data show that very-to-moderate prematurity is associated with obstructive lung function deficits including COPD well into the sixth decade of life and that this effect is compounded by personal smoking., Funding: National Health and Medical Research Council (NHMRC) of Australia, European Union's Horizon 2020, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline., Competing Interests: Declaration of interests DSB, JLP, MJA, EHW, AJL, CJL, and SCD hold an investigator-initiated grant from GlaxoSmithKline for unrelated research. SCD holds an investigator-initiated grant from AstraZeneca for unrelated research. MJA holds investigator-initiated grants from Pfizer, Boehringer-Ingelheim, and Sanofi for unrelated research; has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi; and received a speaker's fee from GlaxoSmithKline. BRT has received unrelated speaker and consultancy fees from Chiesi, Mundipharma, and 4D medical. AJL has received non-financial support from Primus Pharmaceuticals for unrelated research. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2021 Asian Pacific Society of Respirology.)

Background: Experimental challenge studies have shown that pollen can have early and delayed effects on the lungs and airways. Here, we qualitatively and quantitatively synthesize the evidence of outdoor pollen exposure on various lung function and airway inflammation markers in community-based studies., Methods: Four online databases were searched: Medline, Web of Science, CINAHL and Google Scholar. The search strategy included terms relating to both exposure and outcomes. Inclusion criteria were human-based studies published in English that were representative of the community. Additionally, we only considered cross-sectional or short-term longitudinal studies which investigated pollen exposure by levels or season. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was conducted using random-effects models., Results: We included 27 of 6551 studies identified from the search. Qualitative synthesis indicated associations between pollen exposure and predominantly type-2 inflammation in both the upper and lower airways, but little evidence for lung function changes. People with ever asthma and/or seasonal allergic rhinitis (SAR) were at higher risk of such airway inflammation. Meta-analysis confirmed a positive relationship between pollen season, eosinophilia and eosinophil cationic protein (ECP) in people with ever SAR but the results between studies were highly variable. Heterogeneity was reduced after further subgrouping by age, and the forest plots indicated that eosinophilic airway inflammation to outdoor pollen exposure increased with age., Conclusion: Among people with ever asthma and ever SAR, exposure to increased ambient pollen triggers type-2 upper and lower airway inflammation rather than a non-specific or innate inflammation. These findings can lead to the formulation of specific pollen immunotherapy for susceptible individuals. Future research should be directed towards investigating lagged associations and effect modifications using larger and more generalized populations., Systematic Review Registration: CRD42020146981 (PROSPERO)., (© 2021 John Wiley & Sons Ltd.)

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 (FEV 1 ) 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 FEV 1 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 FEV 1 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., Competing Interests: Conflict of interest: D.J. Tan has nothing to disclose. Conflict of interest: D.S. Bui has nothing to disclose. Conflict of interest: X. Dai has nothing to disclose. Conflict of interest: C.J. Lodge has nothing to disclose. Conflict of interest: A.J. Lowe reports grants from National Health and Medical Research Council, during the conduct of the study. Conflict of interest: P.S. Thomas reports having participated in advisory board meetings for GSK and Astra Zeneca, unrelated to this work. Conflict of interest: D. Jarvis has nothing to disclose. Conflict of interest: M.J. Abramson reports grants from Pfizer and Boehringer Ingelheim, personal fees and non-financial support from Sanofi, and personal fees from GSK, outside the submitted work. Conflict of interest: E.H. Walters has nothing to disclose. Conflict of interest: J.L. Perret reports a travel grant from Boehringer-Ingelheim, outside the submitted work. Conflict of interest: S.C. Dharmage has nothing to disclose., (Copyright ©ERS 2021.)

Introduction: We investigated if long-term household air pollution (HAP) is associated with asthma and lung function decline in middle-aged adults, and whether these associations were modified by glutathione S -transferase (GST) gene variants, ventilation and atopy., Materials and Methods: Prospective data on HAP (heating, cooking, mould and smoking) and asthma were collected in the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n=3314). Subsamples had data on lung function (n=897) and GST gene polymorphisms (n=928). Latent class analysis was used to characterise longitudinal patterns of exposure. Regression models assessed associations and interactions., Results: We identified seven longitudinal HAP profiles. Of these, three were associated with persistent asthma, greater lung function decline and % reversibility by age 53 years compared with the "Least exposed" reference profile for those who used reverse-cycle air conditioning, electric cooking and no smoking. The "All gas" (OR 2.64, 95% CI 1.22-5.70), "Wood heating/smoking" (OR 2.71, 95% CI 1.21-6.05) and "Wood heating/gas cooking" (OR 2.60, 95% CI 1.11-6.11) profiles were associated with persistent asthma, as well as greater lung function decline and % reversibility. Participants with the GSTP1 Ile/Ile genotype were at a higher risk of asthma or greater lung function decline when exposed compared with other genotypes. Exhaust fan use and opening windows frequently may reduce the adverse effects of HAP produced by combustion heating and cooking on current asthma, presumably through increasing ventilation., Conclusions: Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation., Competing Interests: Conflict of interest: X. Dai has nothing to disclose. Conflict of interest: D.S. Bui has nothing to disclose. Conflict of interest: J.L. Perret reports grants from the National Health and Medical Research Council of Australia and Asthma Foundation, during the conduct of the study; grants from Boehringer Ingelheim, outside the submitted work. Conflict of interest: A.J. Lowe reports grants from the National Health and Medical Research Council of Australia, during the conduct of the study. Conflict of interest: P.A. Frith has nothing to disclose. Conflict of interest: G. Bowatte has nothing to disclose. Conflict of interest: P.S. Thomas has nothing to disclose. Conflict of interest: G.G. Giles has nothing to disclose. Conflict of interest: G.S. Hamilton has nothing to disclose. Conflict of interest: H. Tsimiklis has nothing to disclose. Conflict of interest: J. Hui has nothing to disclose. Conflict of interest: J. Burgess has nothing to disclose. Conflict of interest: A.K. Win has nothing to disclose. Conflict of interest: M.J. Abramson reports grants from Pfizer and Boehringer Ingelheim, personal fees for consultancy from Sanofi, outside the submitted work. Conflict of interest: E.H. Walters has nothing to disclose. Conflict of interest: S.C. Dharmage has nothing to disclose. Conflict of interest: C.J. Lodge has nothing to disclose., (Copyright ©ERS 2021.)

Introduction: Adult spirometry following community-acquired childhood pneumonia has variably been reported as showing obstructive or non-obstructive deficits. We analysed associations between doctor-diagnosed childhood pneumonia/pleurisy and more comprehensive lung function in a middle-aged general population cohort born in 1961., Methods: Data were from the prospective population-based Tasmanian Longitudinal Health Study cohort. Analysed lung function was from ages 7 years (prebronchodilator spirometry only, n=7097), 45 years (postbronchodilator spirometry, carbon monoxide transfer factor and static lung volumes, n=1220) and 53 years (postbronchodilator spirometry and transfer factor, n=2485). Parent-recalled histories of doctor-diagnosed childhood pneumonia and/or pleurisy were recorded at age 7. Multivariable linear and logistic regression were used., Results: At age 7, compared with no episodes, childhood pneumonia/pleurisy-ever was associated with reduced FEV 1 :FVC for only those with current asthma (beta-coefficient or change in z-score=-0.20 SD, 95% CI -0.38 to -0.02, p=0.028, p interaction=0.036). At age 45, for all participants, childhood pneumonia/pleurisy-ever was associated with a restrictive pattern: OR 3.02 (1.5 to 6.0), p=0.002 for spirometric restriction (FVC less than the lower limit of normal plus FEV 1 :FVC greater than the lower limit of normal); total lung capacity z-score -0.26 SD (95% CI -0.38 to -0.13), p<0.001; functional residual capacity -0.16 SD (-0.34 to -0.08), p=0.001; and residual volume -0.18 SD (-0.31 to -0.05), p=0.008. Reduced lung volumes were accompanied by increased carbon monoxide transfer coefficient at both time points (z-score +0.29 SD (0.11 to 0.49), p=0.001 and +0.17 SD (0.04 to 0.29), p=0.008, respectively)., Discussion: For this community-based population, doctor-diagnosed childhood pneumonia and/or pleurisy were associated with obstructed lung function at age 7 for children who had current asthma symptoms, but with evidence of 'smaller lungs' when in middle age., Competing Interests: Competing interests: CFM has directed speaker fees to her institution from Menarini and AstraZeneca. MJA has received investigator-initiated grants for unrelated research from Pfizer and Boehringer Ingelheim, and an unrelated consultancy from Sanofi. BRT has received speaker fees from Mundipharma Australia and AstraZeneca. ABC has received other fees from GlaxoSmithKline. JLP has received a travel grant from Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim : To identify the level of non-pharmacological care received by middle-aged adults with current asthma in Australia and to identify its association with clinical measures. Methods : The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort first studied in 1968 ( n  = 8583). In 2010, when participants were aged 49 years, a stratified sample enriched for asthma and bronchitis underwent clinical assessments including respiratory questionnaires and lung function testing ( n  = 836). Current asthma was defined as self-reported asthma symptoms and/or healthcare utilization in the last 12 months. Multivariable linear regression and log-binomial models were used to assess the relevant associations. Results : Of the entire TAHS cohort, 15.6% (95% CI 13.4-18.2%) had current asthma. Of these, 37.9% (95% CI 30.5-45.9%) had seen a general practitioner for their asthma and 16.5% (95% CI 11.5-23.1%) had discussed their asthma with a pharmacist in the last 12 months. Written asthma action plans (AAPs) were reported by 17.9% (95% CI 12.9-23.2%), verbal AAPs by 53.8% (95% CI 45.9-61.6%) and doctor-assessments of inhaler technique by 42.7% (95% CI 35.2-50.5%). Adults with asthma of greater severity were more likely to have received verbal AAPs (p-trend =0.02). In contrast, adults with lower spirometry were more likely to have received verbal AAPs ( p  = 0.04), written AAPs ( p  = 0.001) and education on inhaler technique ( p  = 0.04). Conclusion : Despite an established evidence base and recommendations in local and international guidelines, non-pharmacological asthma management remains sub-optimal in the middle-aged adult asthma population.

Background and Objective: Obstructive sleep apnoea (OSA) and asthma are associated, and nocturnal breathing difficulty that is usually identified as asthma-like symptoms can be present in both conditions. We investigated how nocturnal asthma-like symptoms (NAS) and bronchial hyper-reactivity (BHR) contribute to the association between OSA risk and current asthma, which is currently unknown but a clinically important question., Methods: We used data from 794 middle-aged participants in a population-based cohort who provided information on OSA risk (defined by a STOP-Bang questionnaire score of at least 3), current asthma and NAS, and underwent methacholine bronchial challenge testing. Using regression models, we examined the association between OSA risk and current asthma-NAS subgroups and investigated any effect modification by BHR., Results: The participants were aged 50 years (49.8% male). OSA risk was associated with NAS with or without current asthma (odds ratio (OR): 2.6; 95% CI = 1.3-5.0; OR: 4.2; 95% CI = 1.1-16.1, respectively), but not with current asthma in the absence of NAS. BHR was associated with current asthma with or without NAS (OR: 2.9; 95% CI = 1.4-5.9; OR: 3.4; 95% CI = 2.0-7.0, respectively) but not with NAS in the absence of current asthma. The associations between OSA risk and current asthma were neither modified nor mediated by BHR., Conclusion: Our findings suggest that some of the nocturnal symptoms perceived as asthma may be OSA symptoms. Patients with nocturnal asthma symptoms should be considered for possible OSA., (© 2019 Asian Pacific Society of Respirology.)

Background: Markers of microbial exposure are thought to be associated with risk of allergic sensitization; however, the associations are inconsistent and may be related to gene-environment interactions., Objective: To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship., Methods: We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi-level mixed-effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random-effects meta-analysis., Results: CD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta-analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455-SNP (P = 0.001) but not with the rs2569190-SNP (P = 0.60). The pooled meta-analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455-C-allele than the T-allele (OR = 0.83 vs 1.05, respectively)., Conclusion and Clinical Relevance: Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals., (© 2018 John Wiley & Sons Ltd.)

Background: Asthma and allergic diseases are heterogeneous. Measurement of biomarkers in exhaled breath condensate (EBC) may help to discriminate between different phenotypes and may assist with clinical prognostication., Objectives: We aimed to assess associations between total nitric oxide products (NO x ) in EBC and different allergic phenotypes and lung function in young and middle-aged adults., Methods: Cross-sectional analyses were nested within two Australian longitudinal studies, the Melbourne Atopy Cohort Study (MACS, mean age 17.8 years) and the Tasmanian Longitudinal Health Study (TAHS, mean age 49.4 years). Levels of EBC NO x were determined by Griess-reaction fluorescent method. Associations were assessed between EBC NO x and different allergic phenotypes, lung function and airway reactivity., Results: Atopy, with or without asthma or rhinitis, was associated with increased EBC NO x levels particularly in individuals with poly-aero-sensitization. These findings were generally consistent across the two age groups. In the older cohort, use of ICS in the previous 12 months masked the association between sensitization and EBC NO x (OR = 0.64, 95% CI = 0.21-1.96, p for interaction = 0.05)., Conclusions and Clinical Relevance: In these population-based samples, EBC NO x was most strongly associated with atopic sensitization, rather than either current asthma or rhinitis, possibly indicating underlying increased airway inflammation associated with atopy. Therefore, EBC NO x could be a key predictor of atopy in both young and middle-aged adults, regardless of the presence of concomitant asthma or rhinitis., (© 2018 John Wiley & Sons Ltd.)

Objective: Atopy is associated with asthma, but cross-sectional studies suggest this association may be weaker in older adults. It remains unclear if atopy predicts asthma later in adult life. We aimed to investigate whether atopy in young adults predicted asthma 20 years later and to quantify the contemporaneous relationship of atopy and asthma as adults age., Methods: Participants of the European Community Respiratory Health Survey (ECRHS) in Melbourne aged 20-44 years were followed for 20 years and completed questionnaires, skin prick tests (SPT) and allergen specific immunoglobulin E measurement at a baseline and two subsequent surveys. Using logistic regression and generalized estimating equations, we tested if atopy at baseline predicted current asthma later in life and estimated the association between current atopy measured at each survey and current asthma, while adjusting for potential confounders., Results: The analysis included 220 participants: 50.9% male. Mean (SD) age at baseline was 35.7 (5.7) years. Asthma and atopy prevalence remained stable over 20 years. Baseline atopy (SPT) was associated with current asthma (OR 9.74, 95%CI 4.22, 22.5) over 20 years, and current atopy (SPT) with concurrent asthma (3.12; 1.70, 5.74)., Conclusions: Atopy remains strongly associated with current asthma in 40 to 64 year-old adults, both prospectively and contemporaneously, but the prospective association is stronger.

Background and Objective: Chronic obstructive pulmonary disease (COPD) has potential origins in childhood but an association between childhood measles and post-bronchodilator (BD) airflow obstruction (AO) has not yet been shown. We investigated whether childhood measles contributed to post-BD AO through interactions with asthma and/or smoking in a non-immunized middle-aged population., Methods: The population-based Tasmanian Longitudinal Health Study (TAHS) cohort born in 1961 (n = 8583) underwent spirometry in 1968 before immunization was introduced. A history of childhood measles infection was obtained from school medical records. During the fifth decade follow-up (n = 5729 responses), a subgroup underwent further lung function measurements (n = 1389). Relevant main associations and interactions by asthma and/or smoking on post-BD forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC; continuous variable) and AO (FEV 1 /FVC < lower limit of normal) were estimated by multiple regression., Results: Sixty-nine percent (n = 950) had a history of childhood measles. Childhood measles augmented the combined adverse effect of current clinical asthma and smoking at least 10 pack-years on post-BD FEV 1 /FVC ratio in middle age (z-score: -0.70 (95% CI: -1.1 to -0.3) vs -1.36 (-1.6 to -1.1), three-way interaction: P = 0.009), especially for those with childhood-onset asthma. For never- and ever-smokers of <10 pack-years who had current asthma symptoms, compared with those without childhood measles, paradoxically, the odds for post-BD AO was not significant in the presence of childhood measles (OR: 12.0 (95% CI: 3.4-42) vs 2.17 (0.9-5.3))., Conclusion: Childhood measles infection appears to compound the associations between smoking, current asthma and post-BD AO. Differences between asthma subgroups provide further insight into the complex aetiology of obstructive lung diseases for middle-aged adults., (© 2018 Asian Pacific Society of Respirology.)

Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without ICS. LABAs clearly demonstrate effective bronchodilatation and steroid-sparing activity, but long-term treatment can lead to tolerance of their bronchodilator effects. There are also concerns with regard to the effects of LABAs on bronchial hyperresponsiveness (BHR), where long-term use is associated with increased BHR and loss of bronchoprotection. A complicating factor is that formoterol and salmeterol are both chiral compounds, usually administered as 50:50 racemic (rac-) mixtures of two enantiomers. The chiral nature of these compounds has been largely forgotten in the debate regarding LABA safety and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from the short-acting β2-agonist (SABA) salbutamol. Supportive clinical findings include the fact that patients in emergency departments who demonstrate a blunted response to salbutamol are more likely to benefit from (R)-salbutamol than rac-salbutamol, and resistance to salbutamol appears to be a contributory mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue.

Background and Aims: Traffic Related Air Pollution (TRAP) exposure is known to exacerbate existing respiratory diseases. We investigated longer term effects of TRAP exposure for individuals with or without existing asthma, and with or without lower lung function., Methods: Associations between TRAP exposure and asthma (n = 689) and lung function (n = 599) were investigated in the prospective Tasmanian Longitudinal Health Study (TAHS). TRAP exposure at age 45 years was measured using two methods based on residential address: mean annual NO 2 exposure; and distance to nearest major road. Adjusted multinomial logistic regression was used to model the association between exposure to TRAP at 45 years and changes in asthma and lung function, using three follow ups of TAHS (45, 50 and 53 years)., Results: For those who never had asthma by 45, living <200 m from a major road was associated with increased odds of new asthma that persisted from 50 to 53 years (adjusted Odds Ratio [aOR] 5.20; 95% CI 1.07, 25.4). Asthmatic participants at 45 had an increased risk of persistent asthma up to 53 years if they were living <200 m from a major road, compared with asthmatic participants living >200 m from a major road (aOR = 5.21; 95% CI 1.54, 17.6)., Conclusion: For middle aged adults, living <200 m for a major road (a marker of TRAP exposure) influences both the development and persistence of asthma. These findings have public health implications for asthma prevention strategies in primary and secondary settings., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Current evidence concerning the impact of exposure to traffic-related air pollution (TRAP) on adult respiratory morbidity mainly comes from cross-sectional studies. We sought to establish more robust measures of this association and potential gene-environment interactions using longitudinal data from an established cohort study.Associations between measures of TRAP (nitrogen dioxide (NO 2 ) and distance to major roads) and wheeze, asthma prevalence and lung function were investigated in participants of the Tasmanian Longitudinal Health Study at 45- and 50-year follow-ups. Generalised estimating equations were used to quantify associations and the potential modifying effect of glutathione S -transferase gene variants.Living <200 m from a major road was associated with increased prevalence of current asthma and wheeze, and lower lung function. The association between living <200 m from a major road and current asthma and wheeze was more marked for carriers of the GSTT1 null and GSTP1 val / val or ile / val genotypes. Over the 5-year period, higher NO 2 exposures were associated with increased current asthma prevalence. Higher NO 2 exposure was associated with lower forced vital capacity for carriers of the GSTT1 null genotype.TRAP exposures were associated with increased risk of asthma, wheeze and lower lung function in middle-aged adults. The interaction with the GSTT1 genotype suggests that deficient antioxidant mechanisms may play a role in these adverse health effects., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Background: Perinatal events can influence the development of asthma in childhood but current evidence is contradictory concerning the effects on life-time asthma risk., Objective: To assess the relationship between birth characteristics and asthma from childhood to adulthood., Methodology: All available birth records for the Tasmanian Longitudinal Health Study (TAHS) cohort, born in 1961 were obtained from the Tasmanian State Archives and Tasmanian hospitals. Low birth weight (LBW) was defined as less than 2500 grams. Preterm birth was defined as delivery before 37 weeks' gestation. Small for gestational age (SGA) was defined as a birth weight below the 10 th percentile for a given gestational age. Multivariate logistic and cox regression were used to examine associations between birth characteristics and lifetime risk of current and incident asthma, adjusting for confounders., Results: The prevalence of LBW was 5.2%, SGA was 13.8% and preterm was 3.3%. LBW (OR = 1.65, 95%CI 1.12,2.44) and preterm birth (OR = 1.81, 95%CI 0.99, 3.31) were both associated with an increased risk of current asthma between the ages of 7 to 43 years. There was no association between SGA and current asthma risk. However, SGA was associated with incident asthma (HR = 1.32, 95%CI 1.00, 1.74), and there was an interaction with sex (p value = 0.08), with males having a greater risk of incident asthma (HR = 1.70, 95%CI 1.16-2.49) than females (HR = 1.04, 95%CI 0.70-1.54)., Conclusions: Preterm birth and LBW were associated with an increased risk of current asthma into middle-age. These findings are the first to demonstrate the continuing impact of these characteristics on asthma risk into middle-age.

Rationale: The burden of chronic obstructive pulmonary disease (COPD) is increasing, yet there are limited data on early life risk factors., Objectives: To investigate the role of childhood lung function in adult COPD phenotypes., Methods: Prebronchodilator spirometry was performed for a cohort of 7-year-old Tasmanian children (n = 8,583) in 1968 who were resurveyed at 45 years, and a selected subsample (n = 1,389) underwent prebronchodilator and post-bronchodilator spirometry. For this analysis, COPD was spirometrically defined as a post-bronchodilator FEV 1 /FVC less than the lower limit of normal. Asthma-COPD overlap syndrome (ACOS) was defined as the coexistence of both COPD and current asthma. Associations between childhood lung function and asthma/COPD/ACOS were examined using multinomial regression., Measurements and Main Results: At 45 years, 959 participants had neither current asthma nor COPD (unaffected), 269 had current asthma alone, 59 had COPD alone, and 68 had ACOS. The reweighted prevalence of asthma alone was 13.5%, COPD alone 4.1%, and ACOS 2.9%. The lowest quartile of FEV 1 at 7 years was associated with ACOS (odds ratio, 2.93; 95% confidence interval, 1.32-6.52), but not COPD or asthma alone. The lowest quartile of FEV 1 /FVC ratio at 7 years was associated with ACOS (odds ratio, 16.3; 95% confidence interval, 4.7-55.9) and COPD (odds ratio, 5.76; 95% confidence interval, 1.9-17.4), but not asthma alone., Conclusions: Being in the lowest quartile for lung function at age 7 may have long-term consequences for the development of COPD and ACOS by middle age. Screening of lung function in school age children may identify a high-risk group that could be targeted for intervention. Further research is needed to understand possible modifiers of these associations and develop interventions for children with impaired lung function.

Asthma phenotypes based on age-of-onset may be differently influenced by the interaction between variation in toll-like receptor (TLR)/CD14 genes and environmental microbes. We examined the associations between single-nucleotide polymorphisms (SNP) in the TLR/CD14 genes and asthma, and their interaction with proxies of microbial exposure (childhood farm exposure and childhood rural environment). Ten SNPs in four genes (TLR2, TLR4, TLR6, CD14) were genotyped for 1,116 participants from the Tasmanian Longitudinal Health Study (TAHS). Using prospectively collected information, asthma was classified as never, early- (before 13 years) or late-onset (after 13 years). Information on childhood farm exposure/childhood rural environment was collected at baseline. Those with early-onset asthma were more likely to be males, had a family history of allergy and a personal history of childhood atopy. We found significant interaction between TLR6 SNPs and childhood farm exposure. For those with childhood farm exposure, carriers of the TLR6-rs1039559 T-allele (p-interaction = 0.009) and TLR6-rs5743810 C-allele (p-interaction = 0.02) were associated with lower risk of early-onset asthma. We suggest the findings to be interpreted as hypothesis-generating as the interaction effect did not withstand correction for multiple testing. In this large, population-based longitudinal study, we found that the risk of early- and late-onset asthma is differently influenced by the interaction between childhood farming exposure and genetic variations.

Background: Differences between early-onset and late-onset adult asthma have not been comprehensively described using prospective data., Aims: To characterise the differences between early-onset and late-onset asthma in a longitudinal cohort study., Methods: The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort. Respiratory histories and spirometry were first performed in 1968 when participants were aged 7 (n=8583). The cohort was traced and resurveyed from 2002 to 2005 (n=5729 responses) and a sample, enriched for asthma and bronchitis participated in a clinical study when aged 44 (n=1389)., Results: Of the entire TAHS cohort, 7.7% (95% CI 6.6% to 9.0%) had early-onset and 7.8% (95% CI 6.4% to 9.4%) late-onset asthma. Atopy and family history were more common in early-onset asthma while female gender, current smoking and low socioeconomic status were more common in late-onset asthma. The impact on lung function of early-onset asthma was significantly greater than for late-onset asthma (mean difference prebronchodilator (BD) FEV 1 /FVC -2.8% predicted (-5.3 to -0.3); post-BD FEV 1 FVC -2.6% predicted (-5.0 to -0.1)). However, asthma severity and asthma score did not significantly differ between groups. An interaction between asthma and smoking was identified and found to be associated with greater fixed airflow obstruction in adults with late-onset asthma. This interaction was not evident in adults with early-onset disease., Conclusions: Early-onset and late-onset adult asthma are equally prevalent in the middle-aged population. Major phenotypic differences occur with asthma age-of-onset; while both share similar clinical manifestations, the impact on adult lung function of early-onset asthma is greater than for late-onset asthma., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background and Objective: Personal smoking is widely regarded to be the primary cause of chronic bronchitis (CB) in adults, but with limited knowledge of contributions by other factors, including current asthma. We aimed to estimate the independent and relative contributions to adult CB from other potential influences spanning childhood to middle age., Methods: The population-based Tasmanian Longitudinal Health Study cohort, people born in 1961, completed respiratory questionnaires and spirometry in 1968 (n=8,583). Thirty-seven years later, in 2004, two-thirds responded to a detailed postal survey (n=5,729), from which the presence of CB was established in middle age. A subsample (n=1,389) underwent postbronchodilator spirometry between 2006 and 2008 for the assessment of chronic airflow limitation, from which nonobstructive and obstructive CB were defined. Multivariable and multinomial logistic regression models were used to estimate relevant associations., Results: The prevalence of CB in middle age was 6.1% (95% confidence interval [CI]: 5.5, 6.8). Current asthma and/or wheezy breathing in middle age was independently associated with adult CB (odds ratio [OR]: 6.2 [95% CI: 4.6, 8.4]), and this estimate was significantly higher than for current smokers of at least 20 pack-years (OR: 3.0 [95% CI: 2.1, 4.3]). Current asthma and smoking in middle age were similarly associated with obstructive CB, in contrast to the association between allergy and nonobstructive CB. Childhood predictors included allergic history (OR: 1.3 [95% CI: 1.1, 1.7]), current asthma (OR: 1.8 [95% CI: 1.3, 2.7]), "episodic" childhood asthma (OR: 2.3 [95% CI: 1.4, 3.9]), and parental bronchitis symptoms (OR: 2.5 [95% CI: 1.6, 4.1])., Conclusion: The strong independent association between current asthma and CB in middle age suggests that this condition may be even more influential than personal smoking in a general population. The independent associations of childhood allergy and asthma, though not childhood bronchitis, as clinical predictors of adult CB raise the possibility of some of this burden having originated in childhood.

Background and Objective: The role of indoor air pollution as a risk factor for asthma and respiratory symptoms in middle age is unclear. We investigated associations between indoor air pollution sources and (i) asthma phenotypes and (ii) asthma-related respiratory symptoms in middle-aged adults., Methods: Subjects (n = 5729) who participated in the 2004 survey of the Tasmanian Longitudinal Health Study completed respiratory and home environment questionnaires. Associations between indoor air pollution sources, and asthma phenotypes and asthma-related respiratory symptoms were estimated., Results: Recent mould in the home was associated with current asthma (odds ratio (OR) 1.26; 95% confidence interval 1.06-1.50), wheeze (OR 1.34; 1.17-1.54) and nocturnal chest tightness (OR 1.30; 1.12-1.51). Stratified by atopy and gender, recent mould was associated with current non-atopic asthma only in males (OR 3.73; 1.29-10.80). More rooms affected by mould were associated with significant trends for current asthma, wheeze and nocturnal chest tightness. Home environmental tobacco smoke was associated with doctor-diagnosed asthma (OR 1.25; 1.02-1.53), wheeze (OR 1.69; 1.41-2.03), nocturnal chest tightness (OR 1.54; 1.26-1.88), with current asthma only in non-smokers (OR 2.09; 95%: 1.30-3.35) and with current asthma only in males (OR 1.74; 95%: 1.25-2.42). Among heating appliances, reverse cycle air conditioning was negatively associated with doctor-diagnosed asthma (OR 0.84; 0.70-1.00). Neither electric nor gas stove use was associated with either asthma phenotype or with asthma-related respiratory symptoms., Conclusions: In middle age, reducing home exposure to mould and environmental tobacco smoke might reduce asthma and asthma-related respiratory symptoms., (© 2014 The Authors. Respirology © 2014 Asian Pacific Society of Respirology.)

Background: Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti-IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add-on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE-mediated asthma who require continuous or frequent treatment with oral corticosteroids., Objectives: To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children., Search Methods: We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites., Selection Criteria: Randomised controlled trials examining anti-IgE administered in any manner for any duration. Trials with co-interventions were included, as long as they were the same in each arm., Data Collection and Analysis: Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources., Main Results: In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti-IgE treatment as an adjunct to treatment with corticosteroids.For participants with moderate or severe asthma who were receiving background inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab-treated participants compared with those given placebo (weighted mean difference (WMD) -118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI -154 to -84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63).Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta2-agonist medication compared with placebo (mean difference (MD) -0.39 puffs per day, 95% CI -0.55 to -0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD -0.58, 95% CI -0.84 to -0.31) and severe (MD -0.30, 95% CI -0.49 to -0.10) asthma subgroups on a background therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a background therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab).To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived., Authors' Conclusions: Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone-sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research.

Background and Objective: The impact of ambient wood smoke and traffic-related air pollution on adult asthma has not been well studied. This paper aims to investigate associations between exposure to ambient wood smoke, traffic-related air pollution and current asthma/asthma severity in middle age, and whether any associations are modified by atopic status., Methods: Using data from the Tasmanian Longitudinal Health Study, associations between ambient wood smoke and two indices of traffic-related air pollution (frequency of heavy vehicles near the home and frequency of intense traffic noise) and current asthma/asthma severity were investigated. Unconditional logistic regression to examine current asthma and ordinal logistic regression to examine asthma severity was used., Results: For asthmatics, both exposure to ambient wood smoke (odds ratio 1.11; 95% confidence interval 1.02-1.20) and being frequently exposed to heavy vehicles (odds ratio 1.80; 95% confidence interval 1.09-2.96) were associated with increased asthma severity. Neither association varied by atopic status., Conclusions: In middle-aged adults, ambient wood smoke and traffic pollution were associated with increased asthma severity. These findings suggest that avoiding or limiting exposure to traffic pollution and wood smoke may help to reduce asthma. Future studies to replicate this finding are recommended and should examine specific biological mechanisms for this effect., (© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.)

Background: The atopic march hypothesis proposes that eczema precedes the development of asthma and allergic rhinitis., Objective: We sought to assess the evidence for a causal effect of infantile eczema on childhood hay fever, asthma, or both., Methods: We used parental reports on infantile eczema and childhood asthma and hay fever for 3778 pairs of 7-year-olds matched to their sibling closest in age within 2 years from the Tasmanian Longitudinal Health Study. We analyzed paired sibling data using a logistic regression model that allowed inference about a causal effect of a familial predictor on a child's outcome by examining the change in association with their cosibling's predictor after adjusting for their own predictor status., Results: Siblings were concordant for infantile eczema (tetrachoric correlation, 0.40). For having both hay fever and asthma by age 7 years, the association with cosibling's eczema was an odds ratio (OR) of 1.98 (95% CI, 1.37-2.86), which reduced after adjusting for own eczema to an OR of 1.65 (95% CI, 1.17-2.34). For having hay fever only, the association with cosibling's eczema was an OR of 1.68 (95% CI, 1.22-2.31) before and an OR of 1.59 (95% CI, 1.19-2.14) after adjusting for own eczema. There was no association between having asthma only and cosibling's eczema (OR, 1.00; 95% CI, 0.77-1.30)., Conclusions: Eczema in infancy might have a causal effect on hay fever in children with and perhaps without asthma. The association of infantile eczema on asthma in children without hay fever, which might be early transient wheeze, is unlikely to be causal or familial. These findings have implications for hay fever prevention., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Few studies have examined common childhood infections and adult asthma. We examined associations between childhood infectious diseases, childhood pneumonia, and current, persisting, and incident asthma to middle age., Methods: We analyzed data from the Tasmanian Longitudinal Health Study (TAHS). A history of pneumonia was ascertained from their parents when the TAHS participants were 7 years old. Measles, rubella, mumps, chickenpox, diphtheria, and pertussis were identified from school medical records. Associations with current, persisting, or incident asthma were examined using regression techniques., Results: Greater infectious diseases load was negatively associated with persisting asthma at all ages. Individually, pertussis (adjusted OR [aOR], 0.53; 95% CI, 0.28-1.00) was negatively associated with asthma persisting to age 13 years, chickenpox (aOR, 0.58; 95% CI, 0.38-0.88) was negatively associated with asthma persisting to age 32 years, and rubella was negatively associated with asthma persisting to ages 32 (aOR, 0.61; 95% CI, 0.31-0.96) and 44 years (aOR 0.53; 95% CI, 0.35-0.82). Pertussis was associated with preadolescent incident asthma (adjusted hazard ratio [aHR], 1.80; 95% CI, 1.10-2.96), whereas measles was associated with adolescent incident asthma (aHR, 1.66; 1.06-2.56). Childhood pneumonia was associated with current asthma at ages 7 (aOR, 3.12; 95% CI, 2.61-3.75) and 13 years (aOR, 1.32; 95% CI, 1.00-1.75), an association stronger in those without than those with eczema (aOR, 3.46; 95% CI, 2.83-4.24 vs aOR, 2.08; 95% CI, 1.38-3.12)., Conclusions: Overall, childhood infectious diseases protected against asthma persisting in later life, but pertussis and measles were associated with new-onset asthma after childhood. Measles and pertussis immunization might lead to a reduction in incident asthma in later life.

Objective: To examine asthma remission from childhood to middle age., Methods: This was a population-based cohort study. In 1968 the Tasmanian Longitudinal Health Study enrolled 8583 7-year-old Tasmanian schoolchildren who were re-surveyed in 2004. Those reporting ever having asthma when last surveyed completed another questionnaire in 2007 ascertaining age at last asthma attack and asthma medication use. The main outcome measure was asthma remission, defined as no asthma attack for 2 years and no current asthma medication use, or no self-reported asthma in adult life but with parent-reported childhood asthma., Results: Of 5729 respondents to the 2004 survey, 1238 self-reported asthma. A further 573 denied asthma, but had parent-reported childhood asthma, giving a study sample of 1811. Asthma had remitted in 1177 (65.0%) of whom 649 (55.1%) were male. Childhood (OR 0.38, 95% CI 0.25 to 0.58) and later-onset allergic rhinitis (0.42, 0.29 to 0.63), childhood (0.66, 0.47 to 0.94) and later-onset eczema (0.66, 0.47 to 0.92), maternal asthma (0.66, 0.47 to 0.92) and childhood chronic bronchitis (0.56, 0.41 to 0.76) were negatively associated with remission. There was weaker evidence for a negative association between passive smoking (0.75, 0.54 to 1.04) and lower socio-economic status (p-trend 0.09) and remission. Childhood-onset asthma (3.76, 2.58 to 5.49) was more likely to remit than adult-onset asthma. Adult smoking was positively associated with remission in childhood-onset asthma (1.49, 1.06 to 2.09). Sex did not influence remission., Conclusion: While inherited factors cannot be changed, the effect of allergic rhinitis or eczema on asthma remission might be altered by early, aggressive treatment. Every effort should be made to lessen passive exposure to tobacco smoke.

Background: The evidence on whether the atopic march observed in childhood (ie, the progression from eczema to allergic rhinitis and asthma) extends to adulthood is sparse, and there is no evidence on whether the progression leads to a specific phenotype of asthma., Objective: We sought to assess whether childhood eczema and rhinitis are risk factors for specific phenotypes of adult asthma., Methods: Participants of the Tasmanian Longitudinal Health Study recruited in 1968 (age range, 6.0-7.0 years) were followed up at age 44 years. The risk of current atopic or nonatopic asthma in middle age characterized by sensitization to aeroallergens given childhood eczema, rhinitis, or both was calculated by using multinomial logistic regression., Results: No association was found between childhood eczema or rhinitis and nonatopic adult asthma. In contrast, childhood eczema and rhinitis in combination predicted both new-onset atopic asthma by middle age (adjusted multinomial odds ratio [aMOR], 6.3; 95% CI, 1.7-23.2) and the persistence of childhood asthma to adult atopic asthma (aMOR, 11.7; 95% CI, 3.6-37.9). Participants with childhood eczema alone were at increased risk of new-onset atopic asthma (aMOR, 4.1; 95% CI, 1.9-8.8), whereas rhinitis alone predicted the persistence of childhood asthma to atopic asthma (aMOR, 2.7; 95% CI, 1.3-5.6). Of all asthma, 29.7% of persistent atopic asthma and 18.1% of new-onset atopic asthma could be attributed to having childhood eczema and rhinitis., Conclusion: Childhood eczema and rhinitis are strongly associated with the incidence and persistence of adult atopic asthma., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background and Objective: Attacks of fatal asthma have been shown to be either of short duration or long duration and associated with differing degrees of smooth muscle contraction, luminal mucus deposition and ratios of eosinophils to neutrophils in the airway wall. We hypothesized that this bimodal distribution might be related to airway mast cell degranulation., Methods: Airway sections from cases of fatal asthma in the second Victorian asthma mortality study and from cases coming to coronial autopsy in Perth were examined. Tryptase-positive mast cells, numbers of intact and degranulated mast cells, post-mortem blood salbutamol levels and airway dimensions were measured., Results: Although the total number of mast cells were similar, the ratio of degranulated to intact mast cells (D/I) was significantly increased in the smooth muscle (P < 0.05) and outer airway wall (P < 0.001), in short-duration cases compared with long-duration cases. Proportional muscle shortening was significantly increased (P < 0.05) in short-duration cases (17 +/- 7%) compared with long-duration cases (11 +/- 7%). Blood salbutamol levels were related to the total airway wall mast cell D/I ratio for all cases combined (r = 0.57, P = 0.01)., Conclusions: The duration of a fatal attack of asthma may be partly determined by the degranulation of mast cells.

Background: The association between eczema and asthma is well documented, but the temporal sequence of this association has not been closely examined., Objectives: To examine the association between childhood eczema and asthma incidence from preadolescence to middle age, and between childhood eczema and asthma persisting to middle age. A further aim was to examine any effect modification by nonallergic childhood exposures on the association between childhood eczema and both childhood asthma and later life incident asthma., Methods: Data were gathered from the 1968, 1974, and 2004 surveys of the Tasmanian Longitudinal Health Study. Multivariable logistic regression examined the association between childhood eczema and childhood asthma. Cox regression examined the association between childhood eczema and asthma incidence in preadolescence, adolescence, and adult life. Binomial regression examined the association between childhood eczema and childhood asthma persisting to age 44 years., Results: Childhood eczema was significantly associated with childhood asthma and with incident asthma in preadolescence (hazard ratio [HR], 1.70; 95% CI, 1.05-2.75), adolescence (HR, 2.14; 95% CI, 1.33-3.46), and adult life (HR, 1.63; 95% CI, 1.28-2.09). Although childhood eczema was significantly associated with asthma persisting from childhood to middle age (relative risk, 1.54; 95% CI, 1.17-2.04), this association was no longer evident when adjusted for allergic rhinitis., Conclusion: Childhood eczema increased the likelihood of childhood asthma, of new-onset asthma in later life and of asthma persisting into middle age.

Objectives: To use community pharmacy medication records to identify patients whose asthma may not be well managed and then implement and evaluate a multidisciplinary educational intervention to improve asthma management., Design, Setting and Participants: We used a multisite controlled study design. Forty-two pharmacies throughout Tasmania ran a software application that "data-mined" medication records, generating a list of patients who had received three or more canisters of inhaled short-acting beta(2)-agonists in the preceding 6 months. The patients identified were allocated to an intervention or control group. Pre-intervention data were collected for the period May to November 2006 and post-intervention data for the period December 2006 to May 2007., Intervention: Intervention patients were contacted by the community pharmacist via mail, and were sent educational material and a letter encouraging them to see their general practitioner for an asthma management review. Pharmacists were blinded to the control patients' identities until the end of the post-intervention period., Main Outcome Measure: Dispensing ratio of preventer medication (inhaled corticosteroids [ICSs]) to reliever medication (inhaled short-acting beta(2)-agonists)., Results: Thirty-five pharmacies completed the study, providing 702 intervention and 849 control patients. The intervention resulted in a threefold increase in the preventer-to-reliever ratio in the intervention group compared with the control group (P < 0.01) and a higher proportion of patients in the intervention group using ICS therapy than in the control group (P < 0.01)., Conclusions: Community pharmacy medication records can be effectively used to identify patients with suboptimal asthma management, who can then be referred to their GP for review. The intervention should be trialled on a national scale to determine the effects on clinical, social, emotional and economic outcomes for people in the Australian community, with a longer follow-up to determine sustainability of the improvements noted.

Background: The potential for tolerance to develop to zafirlukast, a cysteinyl leukotriene (CysLT) receptor antagonist (LRA) in persistent asthma, has not been specifically examined., Objective: To look for any evidence of tolerance and potential for short-term clinical worsening on LRA withdrawal. Outcome measures included changes in; airway hyperresponsiveness to inhaled methacholine (PD20FEV1), daily symptoms and peak expiratory flows (PEF), sputum and blood cell profiles, sputum CysLT and prostaglandin (PG)E2 and exhaled nitric oxide (eNO) levels., Methods: A double blind, placebo-controlled study of zafirlukast, 20 mg twice daily over 12 weeks in 21 asthmatics taking beta2-agonists only (Group I), and 24 subjects treated with ICS (Group II)., Results: In Group I, zafirlukast significantly improved morning PEF and FEV1compared to placebo (p < 0.01), and reduced morning waking with asthma from baseline after two weeks (p < 0.05). Similarly in Group II, FEV1 improved compared to placebo (p < 0.05), and there were early within-treatment group improvements in morning PEF, beta2-agonist use and asthma severity scores (p < 0.05). However, most improvements with zafirlukast in Group I and to a lesser extent in Group II deteriorated toward baseline values over 12 weeks. In both groups, one week following zafirlukast withdrawal there were significant deteriorations in morning and evening PEFs and FEV1 compared with placebo (p < or = 0.05) and increased nocturnal awakenings in Group II (p < 0.05). There were no changes in PD20FEV1, sputum CysLT concentrations or exhaled nitric oxide (eNO) levels. However, blood neutrophils significantly increased in both groups following zafirlukast withdrawal compared to placebo (p = 0.007)., Conclusion: Tolerance appears to develop to zafirlukast and there is rebound clinical deterioration on drug withdrawal, accompanied by a blood neutrophilia.

Background: The association between allergic rhinitis and asthma is well documented, but the temporal sequence of this association has not been closely examined., Objective: We sought to assess the associations between childhood allergic rhinitis and (1) asthma incidence from preadolescence to middle age and (2) asthma persistence to middle age., Methods: Data were gathered from the 1968, 1974, and 2004 surveys of the Tasmanian Asthma Study. Cox regression was used to examine the association between childhood allergic rhinitis and asthma incidence in preadolescence, adolescence, and adult life. Binomial regression was used to examine the association between childhood allergic rhinitis and asthma beginning before the age of 7 years and persisting at age 44 years., Results: Childhood allergic rhinitis was associated with a significant 2- to 7-fold increased risk of incident asthma in preadolescence, adolescence, or adult life. Childhood allergic rhinitis was associated with a 3-fold increased risk of childhood asthma persisting compared with remitting by middle age., Conclusions: Childhood allergic rhinitis increased the likelihood of new-onset asthma after childhood and the likelihood of having persisting asthma from childhood into middle age., Clinical Implications: Asthma burden in later life might be reduced by more aggressive treatment of allergic rhinitis in early life.

In this narrative review the scientific rationale for the development of a therapeutic modality for asthma based on decreasing the circulating and cell-bound levels of immunoglobulin-E (IgE) is outlined. The one drug that has so far entered clinical practice to do this is a humanised monoclonal antibody to the Fc portion of the IgE molecule, omalizumab. It is highly effective in reducing IgE blood levels and its established mode of delivery is by subcutaneous injection. The clinical trial development of omalizumab is reviewed and the published data and claims for its efficacy and role in clinical practice is critically appraised. The target group of omalizumab has become focused on severe asthmatics who are still symptomatic after being administered with high-dose inhaled corticosteroids plus long-acting beta-agonists. The strongest evidence for effect is in those with frequent severe exacerbations.

Purpose: To assess misclassification in adults reporting childhood asthma., Methods: The Tasmanian Asthma Survey commenced in 1968 when 8,583 7-year-old children attending school in Tasmania (participants) were studied. In 1991-1993, a stratified sample of 1,494 participants was studied. Their recall of childhood asthma was compared to their parents' prospectively gathered report., Results: Where participants had childhood asthma, those with current asthma, severe eczema, or hay fever were less likely to misclassify while females were more likely to misclassify. Where participants had no childhood asthma, misclassification was associated with current asthma, hay fever, or allergies., Conclusions: Retrospective self-assessment of childhood asthma is unreliable.

Anatomical dead space measured by the Fowler method (VDF) is the sum of 2 serial volume compartments (VDF = VDp1 + VDp2). VDF has been shown to increase linearly with end-inspiratory lung volume (EILV) and the gradient of the relationship (DeltaVDF) has been used as an index of airway distensibility. The aim of this study was to partition VDF into its serial compartments VDp1 and VDp2 to test the hypothesis that, given the greater distensibility of distal airways, VDp2 would demonstrate greater volume dependence than VDp1. The relationships between each measure of VD (VDF, VDp1, and VDp2) and EILV were studied in 16 healthy subjects and 16 mildly asthmatic subjects. Significant (p < 0.05) linear relationships were obtained between each measure of VD and EILV in both subject groups. Changes in VDp1 with EILV (DeltaVDp1) accounted for 78.6% +/- 5.6% (mean +/- SEM) and 72.6% +/- 6.3% of DeltaVDF in the healthy and asthmatic groups, respectively. DeltaVDp1 was greater in the healthy subjects than in asthmatic subjects (18.4 versus 13.1 mL/L, p = 0.005). We conclude that in both asthmatic and healthy subjects, the major component of DeltaVDF was DeltaVDp1 and not DeltaVDp2, as originally hypothesized. We believe our results are reflecting the degree of asynchronous airway emptying.

Rationale: Increased vascularity is a feature of airway remodeling in asthma with the potential to contribute to a number of functional abnormalities in this chronic disease. Although various growth factors have been implicated in modulating vascularity, the important contributors in vivo are still being elucidated. The most likely candidate is vascular endothelial growth factor (VEGF)., Objectives: We have examined VEGF and its receptors, VEGFR1 and VEGFR2, and angiopoietin-1 (Ang1) in the airways of subjects with asthma and contrasted these results with findings in normal control subjects. We aimed to explore whether these powerful angiogenic factors were expressed at elevated levels in asthmatic airways., Methods: We obtained biopsy and bronchoalveolar lavage samples from 35 subjects with mild to moderate asthma and from 22 normal control subjects., Measurements: We performed immunohistochemistry and image analysis to obtain quantitative measures of VEGF, VEGFR1, VEGFR2, and Ang1 staining in airway biopsies, and ELISA to assess VEGF concentration in the bronchoalveolar lavage fluid., Results: VEGF staining and VEGF levels in bronchoalveolar lavage fluid were elevated in the airways of subjects with asthma and were related to the number of vessels; Ang1 staining was similarly increased. VEGFR1 was slightly higher in subjects with asthma and the VEGFR1:VEGFR2 ratio was significantly higher in subjects with asthma. We observed angiogenic sprouts (i.e., early-forming vascular structures) that were increased in number in subjects with asthma., Conclusions: Our findings suggest that VEGF, its receptors, and Ang1 are likely to be important in vascular changes in the airways of patients with asthma. Further, there are observable structures in the vessel walls of asthmatic airways that could present ongoing evidence of increased angiogenic activity.

Objective: To trace all participants 36 years after the original Tasmanian Asthma Study (TAS)., Methods: In 1968, the TAS investigated asthma in 8,583 children who were born in 1961. We attempted to trace these participants in 2002-04 using names, dates of birth and gender. Current addresses were sought by computer linkage to the Commonwealth Electoral Roll, the Medicare database and the Tasmanian marriage records. Computer linkage was conducted with the National Death Index (NDI). Siblings of participants were also linked to the Commonwealth Electoral Roll and those identified were sent a letter requesting the participant's address. The Australian Twin Registry (ATR) and the 1991-93 TAS substudy were used to locate participant addresses., Results: After three rounds of electoral roll linkage, 56% of all cohort members were traced. Name changes were identified for 49% of the 3,477 females not initially matched to the electoral roll using linkage to marriage records. NDI linkage yielded a 0.7% match. Medicare linkage identified addresses for 27% of the 1,982 remaining participants. Writing to siblings located 60% of 1,661 participants. One hundred and eighty-three participants were matched to the 1991-93 TAS and 23 twins matched to the ATR. Overall, 81.5% of the cohort members were identified., Conclusions: With these methods, we have been able to trace a possible address for a large portion of the original participants, with the electoral roll linkage being the most useful., Implications: It is possible to trace Australians for follow-up studies using electronic linkage, although without unique identifiers it is labour and resource intensive and requires matching to several databases.

The beta(2)-adrenergic receptor (beta(2)AR) is a transmembrane protein expressed by airway smooth muscle cells. In vitro studies have shown that polymorphisms at amino acid positions 16 and 27 alter receptor function. The aim of this study was to examine the associations between the beta ( 2 ) AR polymorphisms and risks of asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in a sample of adults. Participants were part of a cross-sectional population-based study of risk factors for respiratory disease. A total of 1,090 Caucasian participants completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of gas transfer. Genotyping for beta ( 2 ) AR polymorphisms at positions 16 and 27 was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Haplotype frequencies for the two polymorphisms were estimated using the E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR 5.13; 95% CI 1.40,18.8), asthma (2.44; 1.12,5.31) and symptoms of wheeze (1.84; 1.02,3.35). The Gln27 homozygotes had an increased risk of asthma (2.08; 1.05,4.13) and bronchial hyperreactivity (BHR) (1.92; 1.07,3.46). The Arg16/Gln27 haplotype was associated with asthma (1.63; 1.12,2.38) and COPD (2.91; 1.42,5.94). The Arg16/Gln27 beta(2)AR haplotype is important in COPD, asthma and BHR, and may be associated with more severe respiratory symptoms in middle-aged and older adults.