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Smoking cessation is an important screening component, but the evidence base to inform implementation is lacking. We report longitudinal smoking behavior in an Australian screening cohort and examine predictor variables associated with continued smoking.Healthy current or former smokers (quit less than 15 years and ≥30-pack year smoking history) aged 60-74 years underwent CT screening at baseline, year 1 and year 2. Participants received brief smoking cessation advice and generic Quitline materials. Smoking status was self-reported every 6 months for 5 years. Mediators of smoking behavior, adjusted for sociodemographic, health and scan variables were explored using logistic regression modeling.Two hundred thirty-five participants were analyzed. One hundred eight (46%) were current smokers at enrolment. At baseline, current smokers' mean Fagerström Test for Nicotine Dependence was 4.9, and they had higher levels of lung cancer-specific distress and passive smoke exposure than former smokers. At 36 months, 33% of baseline smokers achieved sustained (≥6 months) smoking abstinence. Five (4%) former smokers relapsed at any point during the study. Continued smoking was positively associated with greater nicotine dependence and smoking pack-years, and negatively associated with cardiovascular disease, stroke, and lung cancer family history.This study provides the first data on smoking cessation rates in Australian lung cancer screenees and supports screening as a teachable moment. We identify several factors that identify smokers who may require more intensive smoking cessation interventions and could be used to develop effective smoking cessation as part of lung cancer screening, tailored to individual risk profiles.

Objective A comprehensive digitalized program is a novel way to improve access to pulmonary rehabilitation for people with chronic obstructive pulmonary disease (COPD). This study aims to determine if a home-based pulmonary rehabilitation program supported by mobile health (mHealth) technology is equivalent to center-based pulmonary rehabilitation in terms of improvements in exercise capacity and health status in people with COPD. Methods This study is a prospective, multicenter, equivalence randomized controlled trial (RCT) with intention-to-treat analysis. A hundred participants with COPD will be recruited from 5 pulmonary rehabilitation programs. Following randomization, participants will be assigned in a concealed manner to receive either home-based pulmonary rehabilitation supported by mHealth or center-based pulmonary rehabilitation. Both programs will be 8 weeks and will include progressive exercise training, disease management education, self-management support, and supervision by a physical therapist. Co-primary outcome measures will be the 6-Minute Walk Test and the COPD Assessment Test. Secondary outcome measures will include the St George’s Respiratory Questionnaire, the EuroQol 5 Dimension 5 Level, the modified Medical Research Council dyspnea scale, the 1-minute sit-to-stand test, the 5 times sit-to-stand test, the Hospital Anxiety and Depression Scale, daily physical activity levels, health care utilization, and costs. Outcomes will be measured at baseline and at the end of the intervention. Participant experience will be assessed through semistructured interviews at the end of the intervention. Utilization of health care and costs will also be measured again after 12 months. Impact This study will be the first rigorous RCT to examine the effects of a home-based pulmonary rehabilitation program supported by mHealth technology that includes comprehensive clinical outcome evaluation, assessment of daily physical activity, a health economic analysis, and qualitative analysis. If findings demonstrate that there is equivalence in clinical outcomes, that the mHealth program costs the least amount (and is thus cost-effective), and that the mHealth program is acceptable to participants, such programs should be widely implemented to improve access to pulmonary rehabilitation.

Chronic obstructive pulmonary disease (COPD) was traditionally thought to be caused by tobacco smoking. However, recognition of the importance of non-smoking-related risk factors for COPD has increased over the past decade, with evidence on the burden, risk factors, and clinical presentations of COPD in never-smokers. About half of all COPD cases worldwide are due to non-tobacco-related risk factors, which vary by geographical region. These factors include air pollution, occupational exposures, poorly controlled asthma, environmental tobacco smoke, infectious diseases, and low socioeconomic status. Impaired lung growth during childhood, caused by a range of early-life exposures, is associated with an increased risk of COPD. Potential mechanisms for the pathogenesis of COPD in never-smokers include inflammation, oxidative stress, airway remodelling, and accelerated lung ageing. Compared with smokers who develop COPD, never-smokers with COPD have relatively mild chronic respiratory symptoms, little or no emphysema, milder airflow limitation, and fewer comorbidities; however, exacerbations can still be frequent. Further research-including epidemiological, translational, clinical, and implementation studies-is needed to address gaps in understanding and to advance potential solutions to reduce the burden of COPD in never-smokers.

Lung cancer is the commonest cause of cancer deaths worldwide. Although strongly associated with smoking, predisposition to lung cancer is also heritable, with multiple common risk variants identified. Rarely, dominantly inherited non-small-cell lung cancer (NSCLC) has been reported due to somatic mutations in EGFR/ErbB1 and ERBB2. Germline exome sequencing was performed in a multi-generation family with autosomal dominant NSCLC, including an affected child. Tumour samples were also sequenced. Full-length wild-type (wtErbB3) and mutant ERBB3 (mutErbB3) constructs were transfected into HeLa cells. Protein expression, stability, and subcellular localization were assessed, and cellular proliferation, pAkt/Akt and pERK levels determined. A novel germline variant in ERBB3 (c.1946 T > G: p.Iso649Arg), coding for receptor tyrosine-protein kinase erbB-3 (ErbB3), was identified, with appropriate segregation. There was no loss-of-heterozygosity in tumour samples. Both wtErbB3 and mutErbB3 were stably expressed. MutErbB3-transfected cells demonstrated an increased ratio of the 80 kDa form (which enhances proliferation) compared with the full-length (180 kDa) form. MutErbB3 and wtErbB3 had similar punctate cytoplasmic localization pre- and post-epidermal growth factor stimulation; however, epidermal growth factor receptor (EGFR) levels decreased faster post-stimulation in mutErbB3-transfected cells, suggesting more rapid processing of the mutErbB3/EGFR heterodimer. Cellular proliferation was increased in mutErbB3-transfected cells compared with wtErbB3 transfection. MutErbB3-transfected cells also showed decreased pAkt/tAkt ratios and increased pERK/tERK 30 min post-stimulation compared with wtErbB3 transfection, demonstrating altered signalling pathway activation. Cumulatively, these results support this mutation as tumorogenic. This is the first reported family with a germline ERBB3 mutation causing heritable NSCLC, furthering understanding of the ErbB family pathway in oncogenesis.

Hannah E O’Farrell, Rayleen V Bowman, Kwun M Fong, Ian A Yang Faculty of Medicine, the University of Queensland, Brisbane, QLD, AustraliaCorrespondence: Hannah E O’Farrell, Faculty of Medicine, the University of Queensland, Brisbane, QLD, Australia, Tel +61 07 3139 4110, Email hannah.ofarrell@uq.net.auPurpose: Molecular biomarkers for chronic obstructive pulmonary disease (COPD) severity have been difficult to identify. We aimed to assess extracellular vesicle miRNAs’ potential as a blood biomarker in discriminating disease severity in participants with COPD.Patients and Methods: Plasma extracellular vesicles (EVs) were obtained from two COPD cohorts (n = 20 during an exacerbation event, n = 20 during stable state), with varying disease severity (GOLD stages). The miRCURY LNA miRNA Serum/Plasma assay, specific to 179 targets, was used to evaluate EV miRNA expression. The miRNAs that were significantly dysregulated were further assessed for discriminatory power using ROC curve analysis, as well as their role in relevant biological pathways.Results: One miRNA was significantly dysregulated between moderate GOLD participants compared to severe/very severe GOLD participants, with an AUC of 0.798, p = 0.01 for miR-374b-5p. Five miRNAs were significantly dysregulated between exacerbating and stable COPD participants, with miR-223-3p resulting in the highest AUC (0.755, p = 0.006) for a single miRNA, with a combination of three miRNAs (miR-92b-3p, miR-374a-5p and miR-106b-3p) providing the highest discriminatory power (AUC 0.820, p = 0.001). The “cytokine–cytokine receptor interaction” (hsa04060 pathway) was the most significant KEGG pathway enriched for three out of the five miRNAs associated with COPD exacerbations.Conclusion: This initial small-scale study suggests that the bioactive cargo (miRNAs) in plasma EVs holds specific biological information for the severity of airflow obstruction and COPD exacerbations, warranting further investigation.Keywords: COPD, exacerbations, extracellular vesicles, miRNAs

Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease characterised by persistent respiratory symptoms and chronic airflow limitation on spirometry. COPD is highly prevalent and is associated with exacerbations and comorbid conditions. "COPD-X" provides quarterly updates in COPD care and is published by the Lung Foundation Australia and the Thoracic Society of Australia and New Zealand.The COPD-X guidelines (version 2.65) encompass 26 recommendations addressing: case finding and confirming diagnosis; optimising function; preventing deterioration; developing a plan of care; and managing an exacerbation.Both non-pharmacological and pharmacological strategies are included within these recommendations, reflecting the importance of a holistic approach to clinical care for people living with COPD to delay disease progression, optimise quality of life and ensure best practice care in the community and hospital settings when managing exacerbations. Several of the new recommendations, if put into practice in the appropriate circumstances, and notwithstanding known variations in the social determinants of health, could improve quality of life and reduce exacerbations, hospitalisations and mortality for people living with COPD.

Aims Population studies reporting contemporary long-term outcomes following catheter ablation of atrial fibrillation (AF) are sparse. We evaluated long-term clinical outcomes following AF ablation and examined variation in outcomes by age, sex, and the presence of heart failure. Methods and results We identified 30 601 unique patients (mean age 62.7 ± 11.8 years, 30.0% female) undergoing AF ablation from 2008 to 2017 in Australia and New Zealand using nationwide hospitalization data. The primary outcomes were all-cause mortality and rehospitalizations for AF or flutter, repeat AF ablation, and cardioversion. Secondary outcomes were rehospitalizations for other cardiovascular events. During 124 858.7 person-years of follow-up, 1900 patients died (incidence rate 1.5/100 person-years) with a survival probability of 93.0% (95% confidence interval (CI) 92.6–93.4%) by 5 years and 84.0% (95% CI 82.4–85.5%) by 10 years. Rehospitalizations for AF or flutter (13.3/100 person-years), repeat ablation (5.9/100 person-years), and cardioversion (4.5/100 person-years) were common, with respective cumulative incidence of 49.4% (95% CI 48.4–50.4%), 28.1% (95% CI 27.2–29.0%), and 24.4% (95% CI 21.5–27.5%) at 10 years post-ablation. Rehospitalizations for stroke (0.7/100 person-years), heart failure (1.1/100 person-years), acute myocardial infarction (0.4/100 person-years), syncope (0.6/100 person-years), other arrhythmias (2.5/100 person-years), and new cardiac device implantation (2.0/100 person-years) occurred less frequently. Elderly patients and those with comorbid heart failure had worse survival but were less likely to undergo repeat ablation, while long-term outcomes were comparable between the sexes. Conclusion Patients undergoing AF ablations had good long-term survival, a low incidence of rehospitalizations for stroke or heart failure, and about half remained free of rehospitalizations for AF or flutter, including for repeat AF ablation, or cardioversion.

The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a "poor" diet or protection against disease with a "healthy" diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut–lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut–lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.

Background: Accumulating evidence indicates early life exposure to air pollution, a suspected neurotoxicant, is negatively associated with children’s neurodevelopment. Objectives: To explore the role of multiple exposure periods to ambient particulate matter with diameter

Exposure to ambient air pollution may affect cognitive functioning and development in children. Unfortunately, there is little evidence available for low- and middle-income countries (LMICs), where air pollution levels are highest. We analysed the association between exposure to ambient fine particulate matter (≤2.5 μm [PM

Exhaled nitric oxide fraction (FENO) values can be easily measured using portable analysers and are a surrogate marker of airway eosinophilia. FENO may be useful in diagnosing and monitoring conditions characterised by airway eosinophilia, i.e. asthma and possibly COPD. Many factors other than asthma and COPD affect FENO, especially atopy, which is associated with elevated FENO. One guideline recommends that FENO should be used as part of the diagnostic pathway for asthma diagnosis in adults and children aged >5 years. The role of FENO in monitoring asthma is even less clear, and most guidelines do not recommend its use outside of specialist asthma clinics. Currently, FENO is not recommended for diagnosis or monitoring of COPD. Although FENO is starting to find a place in the management of asthma in children and adults, considerably more research is required before the potential of FENO as an objective measurement in asthma and COPD can be realised. Key points For individuals aged ≥12 years, FENO is not recommended by all guidelines as a test to diagnose asthma (recommended only by the UK National Institute for Health and Care Excellence guideline for asthma symptoms, which are likely to respond to corticosteroid treatment). FENO may be used in conjunction with other investigations to diagnose asthma in 5–16-year-olds where there is diagnostic uncertainty, but further evidence is required. FENO is not recommended as a routine test to monitor all patients with asthma or to titrate asthma treatment. FENO is not recommended for routine clinical testing in adults with COPD. FENO may be useful to identify patients with COPD who could benefit from the use of inhaled corticosteroids (asthma–COPD overlap). Educational aims To understand what factors other than asthma and COPD affect FENO To understand the current controversies in the application of FENO to diagnosis and management of asthma in children To understand the current controversies in the application of FENO to diagnosis and management of asthma and COPD in adults, Exhaled nitric oxide fraction (FENO) may be a useful test for diagnosing asthma in adults and in children but is currently not recommended for monitoring all patients with asthma or COPD http://bit.ly/2lmjXpm

Greenspaces generate several perceived health benefits, including an overall improvement in the quality of life. However, little is known about the effects of greenspaces through pregnancy and early childhood in promoting health-related quality of life (HRQoL) among children.Participants were from the Mothers and their Children's Health Study (MatCH), a 2016/17 sub-study of a national prospective study since 1996 known as the Australian Longitudinal Study on Women's Health (ALSWH). Mothers (n=3,048) self-reported on their three youngest children aged under 13 years (n=5,799, mean=7.0 years, s.d=3.2 years) using the Pediatric Quality of Life Inventory (PedsQL) to measure their HRQoL. Since 1996, annual exposure to green and non-green vegetation was measured using two remote sensing indicators: Normalized Difference Vegetation Index (NDVI) and fractional cover of non-photosynthetic vegetation (fNPV), respectively, for 100 m and 500 m buffer zone around maternal residential address. Multiple exposure windows were calculated including during pregnancy, the first year of life and child's lifetime exposure. Generalised estimating equations (GEE) models, adjusting for potential confounders, were used for analyses.A 1 standard deviation increase in NDVI greenness within 500 m buffer around the home at early life and during childhood was positively associated with higher HRQoL in the total scores and psychological health summary scores in the crude model only. No association was found between fNPV (non-green vegetation) at 100 m and 500 m circular buffers and children's HRQoL. The overall findings from our models remained consistent based on a series of sensitivity analyses, including the impact of maternal residential mobility status and geocoding method on the effect estimates.Our study revealed that surrounding residential greenspace was not associated with children's HRQoL. Further longitudinal studies are required to better understand the influence of greenspace at different periods of exposure on the health and wellbeing of children.

BACKGROUND AND AIM: Household air pollution (HAP) is a leading cause of environmental pollution and health burden. Many countries in Africa cook with polluting fuels (main cause of HAP). Women’s em...

Exacerbations are serious complications of chronic obstructive pulmonary disease (COPD) that often require acute care from pre-hospital and emergency department (ED) services. Despite being a frequent cause of emergency presentations, gaps remain in both literature and practice for emergency care pathways of COPD exacerbations. This review seeks to address these gaps and focuses on the literature of pre-hospital and ED systems of care and how these intersect with patients experiencing an exacerbation of COPD. The literature in this area is expanding rapidly; however, more research is required to further understand exacerbations and how they are addressed by emergency medical services worldwide. For the purpose of this review, the pre-hospital domain includes ambulance and other emergency transport services, and encompasses medical interventions delivered prior to arrival at an ED or hospital. The ED domain is defined as the area of a hospital or free-standing centre where patients arrive to receive emergent medical care prior to admission. In many studies there is a significant overlap between these two domains and frequent intersection and collaboration between services. In both of these domains, for the management of COPD exacerbations, several overarching themes have been identified in the literature. These include: the appropriate delivery of oxygen in the emergency setting; strategies to improve the provision of care in accordance with diagnostic and treatment guidelines; strategies to reduce the requirement for emergency presentations; and, technological advances including machine learning which are helping to improve emergency healthcare systems.

Pharmacological treatment of patients with chronic obstructive pulmonary disease (COPD) aims to reduce disease burden and prevent future risk, especially exacerbations, hospitalizations, decline of lung function and quality of life, and mortality. This review will describe the basic pharmacology of the different classes of agents, followed by the effects they exert in patients with COPD, and the side effects. Targets for pharmacological treatments include airway smooth muscle contraction, inflammation, mucus production, alpha-1-antitrypsin deficiency and respiratory infection. Inhaled bronchodilators are the mainstay, with methylxanthines as secondary choice agents. Anti-inflammatory therapy can be administered as corticosteroids, phosphodiesterase inhibitor, and long-term macrolides such as azithromycin. Mucus production is addressed by use of mucolytics. In some countries, alpha-1-antitrypsin augmentation therapy is available for severe alpha-1-antitrypsin deficiency. The treatment of bacterial infection and/or colonization can be attempted with antibiotics; there is a dire need for effective anti-viral agents for the common viruses causing exacerbations of COPD. Since clinicians need to choose medications for their individual patients, algorithms for how to choose and change medication are increasingly being presented with more elements of treatable traits and personalized medicine.

BACKGROUND: Culture-independent methods such as quantitative polymerase chain reaction (qPCR) are more sensitive for detecting pathogens than conventional culture. This study aimed to test the clinical potential of a multiple target qPCR array in identifying sputum pathogens, compared to traditional culture. METHODS: Forty chronic obstructive pulmonary disease (COPD) patients provided spontaneous sputum and blood samples during an exacerbation event (n=25 patients) and in stable state (n=15 patients). Sputum was processed and analysed by microscopy, culture and sensitivity testing (MCS) to identify living microbial isolates, and multiple target qPCR (44 targets for bacterial and fungal pathogens and antibiotic resistance genes), and 16S rRNA gene sequencing. RESULTS: Six microbial isolates (5 bacterial, 1 fungal) were cultured from 20 exacerbation and 10 stable patient sputum samples. Four of these microbial isolates had their presence in patient sputum confirmed by qPCR. All bacterial targets detected by qPCR were further confirmed by 16S rRNA gene sequencing at a genus level. qPCR identified significantly more bacterial pathogens than culture (P

In clinical assessments, the correlation between atmospheric air pollution and respiratory damage is highly complicated. Epidemiological studies show that atmospheric air pollution is largely responsible for the global proliferation of pulmonary disease. This is particularly significant, since most Computational Fluid Dynamics (CFD) studies to date have used monodisperse particles, which may not accurately reflect realistic inhalation patterns, since atmospheric aerosols are mostly polydisperse. The aim of this study is to investigate the anatomy and turbulent effects on polydisperse particle transport and deposition (TD) in the upper airways. The Euler-Lagrange approach is used for polydisperse particle TD prediction in both laminar and turbulent conditions. Various anatomical models are adopted to investigate the polydisperse particle TD under different flow conditions. Rossin-Rammler diameter distribution is used for the distribution of the initial particle diameter. The numerical results illustrate that airflow rate distribution at the right lung of a realistic model is higher than a non-realistic model. The CFD study also shows that turbulence effects on deposition are higher for larger diameter particles than with particles of smaller diameter. A significant amount of polydisperse particles are also shown to be deposited at the tracheal wall for CT-based model, whereas particles are mostly deposited at the carinal angle for the non-realistic model. A comprehensive, polydisperse particle TD analysis would enhance understanding of the realistic deposition pattern and decrease unwanted therapeutic aerosol deposition at the extrathoracic airways.

Rationale: The macrolide antibiotic azithromycin reduces exacerbations in adults with persistent symptomatic asthma. However, owing to the pleotropic properties of macrolides, unintended bacteriological consequences such as augmented pathogen colonization or dissemination of antibiotic-resistant organisms can occur, calling into question the long-term safety of azithromycin maintenance therapy.Objectives: To assess the effects of azithromycin on the airway microbiota, pathogen abundance, and carriage of antibiotic resistance genes.Methods: 16S rRNA sequencing and quantitative PCR were performed to assess the effect of azithromycin on sputum microbiology from participants of the AMAZES (Asthma and Macrolides: The Azithromycin Efficacy and Safety) trial: a 48-week, double-blind, placebo-controlled trial of thrice-weekly 500 mg oral azithromycin in adults with persistent uncontrolled asthma. Pooled-template shotgun metagenomic sequencing, quantitative PCR, and isolate whole-genome sequencing were performed to assess antibiotic resistance.Measurements and Main Results: Paired sputum samples were available from 61 patients (n = 34 placebo, n = 27 azithromycin). Azithromycin did not affect bacterial load (P = 0.37) but did significantly decrease Faith's phylogenetic diversity (P = 0.026) and Haemophilus influenzae load (P < 0.0001). Azithromycin did not significantly affect levels of Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, or Moraxella catarrhalis. Of the 89 antibiotic resistance genes detected, five macrolide resistance genes and two tetracycline resistance genes were increased significantly.Conclusions: In patients with persistent uncontrolled asthma, azithromycin reduced airway H. influenzae load compared with placebo but did not change total bacterial load. Macrolide resistance increased, reflecting previous studies. These results highlight the need for studies assessing the efficacy of nonantibiotic macrolides as a long-term therapy for patients with persistent uncontrolled asthma.

Diesel emissions contain high levels of particulate matter (PM) which can have a severe effect on the airways. Diesel PM can be effectively reduced with the substitution of diesel fuel with a biofuel such as vegetable oil. Unfortunately, very little is known about the cellular effects of these alternative diesel emissions on the airways. The aim of this study was to test whether coconut oil substitution in diesel fuel reduces the adverse effect of diesel emission exposure on human bronchial epithelial cells. Human bronchial epithelial cells were cultured at air-liquid interface for 7 days and exposed to diesel engine emissions from conventional diesel fuel or diesel fuel blended with raw coconut oil at low (10%), moderate (15%) and high (20%) proportions. Cell viability, inflammation, antioxidant production and xenobiotic metabolism were measured. Compared to conventional diesel, low fractional coconut oil substitution (10% and 15%) reduced inflammation and increased antioxidant expression, whereas higher fractional coconut oil (20%) reduced cell viability and increased inflammation. Therefore, cellular responses after exposure to alternative diesel emission are dependent on fuel composition.

We report the prevalence and progression of incidentally-detected interstitial lung abnormalities (ILA) in the Queensland Lung Cancer Screening Study (QLCSS) cohort. 256 volunteers aged 60-74, with ≥30 pack years smoking history and FEV1≥50% predicted underwent low dose Computed Tomography (CT) chest screening. Electronic search of baseline (T0) and two year follow-up (T2) CT reports identified candidate cases using Fleischner Society interstitial terminology. Candidate CTs were reviewed in a randomised order by two experienced radiologists and a senior respiratory medicine trainee blinded to the existing reports. Scans were evaluated for the presence and extent of ILA using an in-house score, and graded for progression. ILAs were detected in 20/256 baseline cases (7.8%) with no incident cases detected at T2 surveillance imaging. Of these twenty cases, nine (45%) had reticulation, eighteen (90%) had ground glass change, one had traction bronchiectasis and one had randomly distributed nodularity. Seven cases with ground glass changes also had areas of reticulation, and only two had reticulation alone. All ILAs were graded as minor except for the traction bronchiectasis which was moderate. Only one case progressed on T2 imaging. ILAs were associated with the presence of auscultatory crackles (50%vs11.6%, p=0.001) and a lesser degree of emphysema (mean % volumetric emphysema 6.7%vs9.8%, p=0.009). No relationship was observed between baseline and serial lung function parameters. ILAs are frequent incidental findings in lung cancer screening. In the majority of cases these abnormalities do not appear to change significantly over a two-year period of surveillance. This article is protected by copyright. All rights reserved.

Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.

Exposure to greenspaces has beneficial effects on children's mental health and development. This study explores the association between residential exposure to greenspace and early childhood development and academic outcomes.Children were from Mothers and their Children's Health (MatCH) study, a sub-study of the Australian Longitudinal Study on Women's Health. We obtained data on early childhood development from the Australian Early Development Census (AEDC), a population-wide census data (n = 936 children, mean age: 5.3, SD: 0.5 years). Academic performance relative to the national minimum standard (NMS) (i.e., in reading, writing, grammar and punctuation, spelling, and numeracy) of children with Year 3 and 5 data were from the 'National Assessment Program - Literacy and Numeracy' (NAPLAN) (n = 1679 children). Annual exposure to green and non-green vegetation was measured using the Normalized Difference Vegetation Index (NDVI) and fractional cover of non-photosynthetic vegetation (fNPV), respectively, within 100 m and 500 m buffer zone of maternal residential address. We calculated greenspace exposure at the year of test and average exposure throughout childhood. Greenspace exposures were standardised and odds ratio (ORs) with 95% confidence intervals (95% CI) were estimated using generalised estimating equation models, adjusting for potential confounders.Exposure to fNPV within 500 m buffer of homes at the year of test and during child's lifetime was associated with academic scores below/at NMS at Year 3 (baseline) and Year 5 (follow-up) for the domains of reading, writing, and grammar and punctuation. Surrounding residential greenness was not significantly associated with NAPLAN scores. No association was found between residential greenspace and developmental vulnerability on one or more AEDC domains across both exposure windows.Our study revealed that long-term and short-term exposure to non-green vegetation around homes is linked to poor academic performance in children. Further research on fNPV is required to verify these findings, with additional longitudinal studies.

Lung cancer remains the leading cause of cancer related mortality worldwide. We aimed to test whether a simple blood biomarker (extracellular vesicle miRNAs) can discriminate between cases with and without lung cancer. Methods: plasma extracellular vesicles (EVs) were isolated from four cohorts (n = 20 in each): healthy non-smokers, healthy smokers, lung cancer, and stable COPD participants. EV miRNA expression was evaluated using the miRCURY LNA miRNA Serum/Plasma assay for 179 specific targets. Significantly dysregulated miRNAs were assessed for discriminatory power using ROC curve analysis. Results: 15 miRNAs were differentially expressed between lung cancer and healthy non-smoking participants, with the greatest single miRNA being miR-205-5p (AUC 0.850), improving to AUC 0.993 in combination with miR-199a-5p. Moreover, 26 miRNAs were significantly dysregulated between lung cancer and healthy smoking participants, with the greatest single miRNA being miR-497-5p (AUC 0.873), improving to AUC 0.953 in combination with miR-22-5p, 14 miRNAs were significantly dysregulated between lung cancer and stable COPD participants, with the greatest single miRNA being miR-27a-3p (AUC 0.803), with two other miRNAs (miR-106b-3p and miR-361-5p) further improving discriminatory power (AUC 0.870). Conclusion: this case control study suggests miRNAs in EVs from plasma holds key biological information specific for lung cancer and warrants further prospective assessment.

Access to clean and affordable energy is vital for health, well-being, and socio-economic development. This critical service remains unrealised in many African countries. Women's empowerment is known to promote healthcare service use, child nutrition and agricultural productivity. In Africa, however, little is known about the relationship between women's empowerment and household fuel use, and if it varies between countries. Therefore, we assessed the cross-sectional associations between women's empowerment and cooking fuel use in 31 African countries. We analysed individual-level data from the Demographic and Health Surveys, conducted between 2003 and 2018 (n= 264 269 [women-household pairs]). We used a novel, Africa-specific index (Survey-based Women's emPowERment index), including three domains of empowerment: decision-making, attitude to violence, and social independence. Hierarchical logistic regression models assessed the associations between women's empowerment domains and the type of fuel used in the household ('clean': electricity, liquefied petroleum gas, biogas or natural gas; 'polluting': solid fuels or kerosene). Results were adjusted for household- and area-level covariates, and expressed as odds ratios (OR). The 31 country-specific estimates were combined using meta-analysis. Approximately 43 778 (14.5%) of households used clean fuels. Overall, between 12/31 and 22/31 country-level estimates showed a significant association between a one standard deviation increase in empowerment domains (higher scores indicate greater empowerment), and higher odds of using clean fuel as primary energy source for cooking. The random-effect meta-analytic estimates showed that increased empowerment was associated with higher odds of using clean fuel for attitude to violence (OR = 1.22; 95% CI: 1.12–1.33), social independence (OR = 1.34; 95% CI: 1.28–1.42), and decision-making (OR = 1.10; 95% CI: 1.05–1.15). These findings suggest that empowering women, in addition to being crucial in its own right, has potential to accelerate transitions to clean fuel in Africa, although these associations are not uniform at national-scale.