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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: 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.)

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.)

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.)

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 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: 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: 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.

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.

Background: Some aspects of diet are relatively newly recognized potential risk factors for asthma, but the evidence to date is conflicting., Objective: The goal was to determine whether the food and nutrient intakes of adults with asthma differ from those of adults without asthma., Design: This was a community-based, cross-sectional study of 1601 young adults ( +/- SD age: 34.6 +/- 7.1 y) who were initially recruited by random selection from the federal electoral rolls in Melbourne in 1999. Subjects completed a detailed respiratory questionnaire, a validated semiquantitative food-frequency questionnaire, skin-prick testing, and lung function tests, including a methacholine challenge test for bronchial hyperreactivity (BHR). A total of 25 nutrients and 47 food groups were analyzed by using multiple logistic regression with alternate definitions of asthma and atopy as the outcomes., Results: Whole milk appeared to protect against current asthma (odds ratio: 0.66; 95% CI: 0.46, 0.97), doctor-diagnosed asthma (0.73; 0.54, 0.99), BHR (0.68; 0.48, 0.92), and atopy (0.71; 0.54, 0.94). Conversely, soy beverage was associated with an increased risk of current asthma (2.05; 1.19, 3.53), doctor-diagnosed asthma (1.69; 1.04, 2.77), and BHR (1.65; 1.00, 2.71). Apples and pears appeared to protect against current asthma (0.83; 0.71, 0.98), asthma (0.88; 0.78, 1.00), and BHR (0.88; 0.77, 1.00)., Conclusions: The consumption of dairy products, soy beverages, and apples and pears, but not of nutrients per se, was associated with a range of asthma definitions. Dietary modification after diagnosis is one possible explanation for this finding. Intervention studies using whole foods are required to ascertain whether such modifications of food intake could be beneficial in the prevention or amelioration of asthma.

11beta-hydroxysteroid dehydrogenases (11beta-HSD) are responsible for the conversion of bioactive glucocorticoids to and from inactive metabolites. 11beta-HSD2 is generally considered a high-affinity inactivator of natural glucocorticoids, although its activity with synthetic compounds in vivo is unknown. Inhaled corticosteroids (ICS) remain the primary antiinflammatory agents for treating asthma, but little is known about their metabolism in the lung. The aims of this study were to determine whether the 11beta-HSD2 enzyme can be localized to human airway tissue and whether differential expression of this enzyme relates to asthma severity and ICS needs. We studied airway biopsy specimens from 22 asthmatic subjects, in two groups: (1) a group not treated with ICS (n = 7); and (2) a group treated with ICS (range: 200 to 1,500 microg/d; n = 15). A control population consisted of nine nonasthmatic subjects. Immunostaining was done with an immunopurified antibody to human 11beta-HSD2. Immunoreactivity was generally localized to the endothelium of vessels in the lamina propria and to airway epithelium both in asthmatic patients and nonasthmatic controls. There was a statistically significant inverse relationship between the ICS dose required for effective treatment and the extent of epithelial 11beta-HSD2 staining (r = -0.44; p = 0.04). This is consistent with 11beta-HSD2 acting as an oxidoreductase that regenerates rather than inactivates ICS. This study suggests that glucocorticoid sensitivity in the lung is not determined by ICS breakdown, but may be related to 11beta-HSD2 sustaining the activation of synthetic glucocorticoids.

Background Despite the challenges of diagnosing and managing adult patients with chronic cough, a systematic synthesis of evidence on aetiological risk factor is lacking. Methods We systematically searched PUBMED and EMBASE to synthesize the current evidence for longitudinal associations between various risk factors and chronic cough in the general adult population, following the meta-analysis of observation studies in epidemiology (MOOSE) guidelines. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Fixed-effect meta-analysis was conducted where appropriate. Results Of 26 eligible articles, 16 domains of risk factors were assessed. There was consistent evidence that asthma (pooled adjusted OR (aOR) = 3.01; 95%CI: 2.33-3.70; I2=0%, number of articles (N)=3) and low education levels/socioeconomic status (SES) (pooled aOR=1.46; 95%CI: 1.20-1.72; I2=0%; N = 3) were associated with an increased risk of chronic cough after adjusting for smoking and other confounders. While continuous smoking was associated chronic cough (aOR =1.81; 95%CI: 1.36,2.26; I2=57%; N = 3), there was too little evidence to draw conclusions for occupational exposures, outdoor air pollution, early-life exposures, diet, snoring and other chronic conditions. Conclusions Asthma, persistent smoking and lower education/SES were associated with increased risk of chronic cough. Longitudinal associations between other factors frequently mentioned empirically need further investigation. Key messages Our systematic review found asthma, smoking and lower education to be associated with adult chronic cough. More longitudinal studies are needed to understand other potential risk factors for adult chronic cough. [ABSTRACT FROM AUTHOR]