User experience testing of the mobile pulmonary rehabilitation (m-PR™) app in people with chronic obstructive pulmonary disease.

Objective: Mobile health (mHealth) technologies are emerging to support the delivery of pulmonary rehabilitation (PR). This study aimed to explore the ease of use, satisfaction and acceptability of an Australian mobile pulmonary rehabilitation app (m-PR™) in people with chronic obstructive pulmonary disease (COPD). Methods: In this mixed methods observational study, participants with COPD were recruited following PR assessment. Participants were educated on m-PR™ which contained symptom monitoring, individualised exercise training with exercise videos, education videos, goal setting, health notifications and medication action plan. Participants used m-PR™ for 4-8 weeks. At baseline, participants were surveyed to assess level of technology engagement. At follow-up, participants completed the system usability survey (SUS), a satisfaction survey and a semi-structured interview. Results: Fifteen participants (mean age 70 [SD 10] years, 53% female) completed the study. Technology usage was high with 73% (n = 11) self-rating their technology competence as good or very good. The SUS score of 71 (SD 16) demonstrated above average perceived usability of m-PR™. The satisfaction survey indicated that 67% (n = 10) enjoyed m-PR™ and 33% (n = 5) were neutral. Most participants found the different m-PR™ components somewhat easy or very easy to use (range 69-100%) and somewhat helpful or very helpful (range 76-100%). Interview responses revealed that m-PR™ elicited divergent feelings among participants, who reported both positive and negative feelings towards the app's features, the effort required to use it and data security. Conclusion: The majority of participants found m-PR™ enjoyable, easy to use and helpful in managing their COPD. Further research is warranted to understand the effectiveness of mHealth to deliver PR.

Long-term outcomes after hospitalization for atrial fibrillation or flutter.

BACKGROUND AND AIMS: Atrial fibrillation (AF) and flutter are common causes of hospitalizations but contemporary long-term outcomes following these episodes are uncertain. This study assessed outcomes up to 10 years after an acute AF or flutter hospitalization. METHODS: Patients hospitalized acutely with a primary diagnosis of AF or flutter from 2008-17 from all public and most private hospitals in Australia and New Zealand were included. Kaplan-Meier methods and flexible parametric survival modelling were used to estimate survival and loss in life expectancy, respectively. Competing risk model accounting for death was used when estimating incidence of non-fatal outcomes. RESULTS: A total of 260 492 adults (mean age 70.5 ± 14.4 years, 49.6% female) were followed up for 1 068 009 person-years (PY), during which 69 167 died (incidence rate 6.5/100 PY) with 91.2% survival at 1 year, 72.7% at 5 years, and 55.2% at 10 years. Estimated loss in life expectancy was 2.6 years, or 16.8% of expected life expectancy. Re-hospitalizations for heart failure (2.9/100 PY), stroke (1.7/100 PY), and myocardial infarction (1.1/100 PY) were common with respective cumulative incidences of 16.8%, 11.0%, and 7.1% by 10 years. Re-hospitalization for AF or flutter occurred in 21.3% by 1 year, 35.3% by 5 years, and 41.2% by 10 years (11.6/100 PY). The cumulative incidence of patients undergoing catheter ablation of AF was 6.5% at 10 years (1.2/100 PY). CONCLUSIONS: Patients hospitalized for AF or flutter had high death rates with an average 2.6-year loss in life expectancy. Moreover, re-hospitalizations for AF or flutter and related outcomes such as heart failure and stroke were common with catheter ablation used infrequently for treatment, which warrant further actions.

Azithromycin Induced Asthma Remission in Adults With Persistent Uncontrolled Asthma: A Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Asthma remission is a potential treatment goal. RESEARCH QUESTION: Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared with placebo? STUDY DESIGN AND METHODS: This secondary analysis used data from the AMAZES clinical trial-a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids during the previous 6 months evaluated at 12 months and a 5-item Asthma Control Questionnaire score ≤ 1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (postbronchodilator FEV1 ≥ 80% or postbronchodilator FEV1 ≤ 5% decline from baseline) and complete remission (sputum eosinophil count < 3% plus the aforementioned criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. RESULTS: A total of 335 participants (41.5% male; median age, 61.01 years; quartile 1-3, 51.03-68.73) who completed the 12-month treatment period were included in the analysis. Twelve months of treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; P = .032) and clinical remission plus lung function criteria (50.8% vs 37.1%; P = .029) compared with placebo, respectively. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; P = .058). Sensitivity analyses supported these findings. Baseline factors (eg, better asthma-related quality of life, absence of oral corticosteroid burst in the previous year) predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. INTERPRETATION: Adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.

Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Biologics (mepolizumab and omalizumab) induced remission in severe asthma patients.

BACKGROUND: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

Biomarkers of lung cancer for screening and in never-smokers-a narrative review.

Background and Objective: Lung cancer is the leading cause of cancer-related mortality worldwide, partially attributed to late-stage diagnoses. In order to mitigate this, lung cancer screening (LCS) of high-risk patients is performed using low dose computed tomography (CT) scans, however this method is burdened by high false-positive rates and radiation exposure for patients. Further, screening programs focus on individuals with heavy smoking histories, and as such, never-smokers who may otherwise be at risk of lung cancer are often overlooked. To resolve these limitations, biomarkers have been posited as potential supplements or replacements to low-dose CT, and as such, a large body of research in this area has been produced. However, comparatively little information exists on their clinical efficacy and how this compares to current LCS strategies. Methods: Here we conduct a search and narrative review of current literature surrounding biomarkers of lung cancer to supplement LCS, and biomarkers of lung cancer in never-smokers (LCINS). Key Content and Findings: Many potential biomarkers of lung cancer have been identified with varying levels of sensitivity, specificity, clinical efficacy, and supporting evidence. Of the markers identified, multi-target panels of circulating microRNAs, lipids, and metabolites are likely the most clinically efficacious markers to aid current screening programs, as these provide the highest sensitivity and specificity for lung cancer detection. However, circulating lipid and metabolite levels are known to vary in numerous systemic pathologies, highlighting the need for further validation in large cohort randomised studies. Conclusions: Lung cancer biomarkers is a fast-expanding area of research and numerous biomarkers with potential clinical applications have been identified. However, in all cases the level of evidence supporting clinical efficacy is not yet at a level at which it can be translated to clinical practice. The priority now should be to validate existing candidate markers in appropriate clinical contexts and work to integrating these into clinical practice.

Telomere biology disorder presenting acutely with pulmonary fibrosis and hepatopulmonary syndrome in a young adult male.

A 33-year-old man presented with acute dyspnoea and profound hypoxaemia, and had clubbing, greying of hair, orthodeoxia and fine inspiratory crackles. CT chest showed established pulmonary fibrosis in a usual interstitial pneumonia pattern. Additional investigations revealed a small patent foramen ovale, pancytopenia, and oesophageal varices and portal hypertensive gastropathy from liver cirrhosis. Telomere length testing demonstrated short telomeres (<1st percentile), confirming the diagnosis of a telomere biology disorder. An interstitial lung disease gene panel identified a pathogenic variant in TERT (c.1700C>T, p.(Thr567Met)) and a variant of uncertain significance in PARN (c.1159G>A, p.(Gly387Arg)). Combined lung and liver transplantation was deemed not suitable due to frailty and severe hepatopulmonary syndrome, and he died 56 days after presentation. Early recognition of the short telomere syndrome is important, and its multi-organ involvement poses challenges to management. Genetic screening may be important in younger patients with pulmonary fibrosis or in unexplained liver cirrhosis.

Vertebral CT attenuation outperforms standard clinical fracture risk prediction tools in detecting osteoporotic disease in lung cancer screening participants.

OBJECTIVES: Compare accuracy of vertebral Hounsfield Unit (VHU) attenuation and FRAX and Garvan Fracture Risk Calculators in identifying low bone mineral density (BMD) and prevalent vertebral compression fractures (VF) in lung cancer screening (LCS) participants. METHODS: Baseline CT scans from a single site of the International Lung Screen Trial were analysed. BMD was measured using VHU (of the most caudally imaged vertebra) and quantitative CT (QCT) (low BMD defined as <110 HU and <120 mg/cm3, respectively). Prevalent VF were classified semi-quantitatively. 10-year FRAX and Garvan fracture risks were calculated using dual energy X-ray absorptiometry (DXA) femoral neck T-score where available. Discrimination was assessed by area under receiver-operating characteristic curves (AUC). RESULTS: 535 LCS participants were included; 41% had low VHU-BMD, 56% had low QCT-BMD and 10% had ≥1 VF with ≥25% vertebral height loss. VHU demonstrated 94% specificity and 70% sensitivity in identifying low QCT-BMD. VHU was superior to fracture risk tools in discriminating low QCT-BMD (AUC: VHU 0.94 vs FRAX 0.67, Garvan 0.64 [p < 0.05]). In 64 participants with recent DXA scans, VHU was superior to FRAXT-score and GarvanT-score in discriminating low QCT-BMD (AUC: VHU 0.99, FRAXT-score 0.71, GarvanT-score 0.71 [p < 0.05]). VHU was non-inferior to FRAXT-score and GarvanT-score in discriminating VF (AUC: VHU 0.65, FRAXT-score 0.53, GarvanT-score 0.61). CONCLUSIONS: VHU outperforms clinical risk calculators in detecting low BMD and discriminates prevalent VF equally well as risk calculators with T-scores, yet is significantly simpler to perform. ADVANCES IN KNOWLEDGE: VHU measurement could aid osteoporosis assessment in high-risk smokers undergoing LCS.

Freedom from atrial arrhythmia and other clinical outcomes at 5 years and beyond after catheter ablation of atrial fibrillation: a systematic review and meta-analysis.

AIMS: Catheter ablation of atrial fibrillation (AF) is now a mainstream procedure although long-term outcomes are uncertain. We performed a systematic review and meta-analysis of procedural outcomes at 5 years and beyond. METHODS AND RESULTS: We searched PubMed and Embase and after the screening, identified 73 studies (67 159 patients) reporting freedom from atrial arrhythmia, all-cause death, stroke, and major bleeding at ≥5 years after AF ablation. The pooled mean age was 59.7y, 71.5% male, 62.2% paroxysmal AF, and radiofrequency was used in 78.1% of studies. Pooled incidence of freedom from atrial arrhythmia at 5 years was 50.6% (95%CI 45.5-55.7%) after a single ablation and 69.7% [95%CI (confidence interval) 63.8-75.3%) after multiple procedures. The incidence was higher among patients with paroxysmal compared with non-paroxysmal AF after single (59.7% vs. 33.3%, p = 0.002) and multiple (80.8% vs. 60.6%, p < 0.001) ablations but was comparable between radiofrequency and cryoablation. Pooled incidences of other outcomes were 6.0% (95%CI 3.2-9.7%) for death, 2.4% (95%CI 1.4-3.7%) for stroke, and 1.2% (95%CI 0.8-2.0%) for major bleeding at 5 years. Beyond 5 years, freedom from arrhythmia recurrence remained largely stable (52.3% and 64.7% after single and multiple procedures at 10 years), while the risk of stroke and bleeding increased over time. CONCLUSION: Nearly 70% of patients having multiple ablations remained free from atrial arrhythmia at 5 years, with the incidence slightly decreasing beyond this period. Risk of death, stroke, and major bleeding at 5 years were low but increased over time, emphasizing the importance of long-term thromboembolism prevention and bleeding risk management.

Mobile Health Pulmonary Rehabilitation Compared to a Center-Based Program for Cost-Effectiveness and Effects on Exercise Capacity, Health Status, and Quality of Life in People With Chronic Obstructive Pulmonary Disease: A Protocol for a Randomized Controlled Trial.

OBJECTIVE: The use of digital health is a novel way to improve access to comprehensive 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 semi-structured interviews at the end of the intervention. Utilization of health care and costs will 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.

Inhaled corticosteroids versus placebo for stable chronic obstructive pulmonary disease.

BACKGROUND: The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much uncertainty. COPD clinical guidelines currently recommend selective use of ICS. ICS are not recommended as monotherapy for people with COPD, and are only given in combination with long-acting bronchodilators due to greater efficacy of combination therapy. Incorporating and critiquing newly published placebo-controlled trials into the monotherapy evidence base may help to resolve ongoing uncertainties and conflicting findings about their role in this population. OBJECTIVES: To evaluate the benefits and harms of inhaled corticosteroids, used as monotherapy versus placebo, in people with stable COPD, in terms of objective and subjective outcomes. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was October 2022. SELECTION CRITERIA: We included randomised trials comparing any dose of any type of ICS, given as monotherapy, with a placebo control in people with stable COPD. We excluded studies of less than 12 weeks' duration and studies of populations with known bronchial hyper-responsiveness (BHR) or bronchodilator reversibility. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our a priori primary outcomes were 1. exacerbations of COPD and 2. quality of life. Our secondary outcomes were 3. all-cause mortality, 4. lung function (rate of decline of forced expiratory volume in one second (FEV1)), 5. rescue bronchodilator use, 6. exercise capacity, 7. pneumonia and 8. adverse events including pneumonia. ]. We used GRADE to assess certainty of evidence. MAIN RESULTS: Thirty-six primary studies with 23,139 participants met the inclusion criteria. Mean age ranged from 52 to 67 years, and females were 0% to 46% of participants. Studies recruited across the severities of COPD. Seventeen studies were of duration longer than three months and up to six months and 19 studies were of duration longer than six months. We judged the overall risk of bias as low.  Long-term (more than six months) use of ICS as monotherapy reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: rate ratio 0.88 exacerbations per participant per year, 95% confidence interval (CI) 0.82 to 0.94; I2 = 48%, 5 studies, 10,097 participants; moderate-certainty evidence; pooled means analysis: mean difference (MD) -0.05 exacerbations per participant per year, 95% CI -0.07 to -0.02; I2 = 78%, 5 studies, 10,316 participants; moderate-certainty evidence). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60; I2 = 0%; 5 studies, 2507 participants; moderate-certainty evidence; minimal clinically importance difference 4 points). There was no evidence of a difference in all-cause mortality in people with COPD (odds ratio (OR) 0.94, 95% CI 0.84 to 1.07; I2 = 0%; 10 studies, 16,636 participants; moderate-certainty evidence). Long-term use of ICS  reduced the rate of decline in FEV1 in people with COPD (generic inverse variance analysis: MD 6.31 mL/year benefit, 95% CI 1.76 to 10.85; I2 = 0%; 6 studies, 9829 participants; moderate-certainty evidence; pooled means analysis: 7.28 mL/year, 95% CI 3.21 to 11.35; I2 = 0%; 6 studies, 12,502 participants; moderate-certainty evidence). ADVERSE EVENTS: in the long-term studies, the rate of pneumonia was increased in the ICS group, compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.38, 95% CI 1.02 to 1.88; I2 = 55%; 9 studies, 14,831 participants; low-certainty evidence). There was an increased risk of oropharyngeal candidiasis (OR 2.66, 95% CI 1.91 to 3.68; 5547 participants) and hoarseness (OR 1.98, 95% CI 1.44 to 2.74; 3523 participants). The long-term studies that measured bone effects generally showed no major effect on fractures or bone mineral density over three years. We downgraded the certainty of evidence to moderate for imprecision and low for imprecision and inconsistency. AUTHORS' CONCLUSIONS: This systematic review updates the evidence base for ICS monotherapy with newly published trials to aid the ongoing assessment of their role for people with COPD. Use of ICS alone for COPD likely results in a reduction of exacerbation rates of clinical relevance, probably results in a reduction in the rate of decline of FEV1 of uncertain clinical relevance and likely results in a small improvement in health-related quality of life not meeting the threshold for a minimally clinically important difference. These potential benefits should be weighed up against adverse events (likely to increase local oropharyngeal adverse effects and may increase the risk of pneumonia) and probably no reduction in mortality. Though not recommended as monotherapy, the probable benefits of ICS highlighted in this review support their continued consideration in combination with long-acting bronchodilators. Future research and evidence syntheses should be focused in that area.

A cross-sectional analysis of ambient fine particulate matter (PM2.5) exposure and haemoglobin levels in children aged under 5 years living in 36 countries.

Low haemoglobin (Hb) concentrations and anaemia in children have adverse effects on development and functioning, some of which may have consequences in later life. Exposure to ambient air pollution is reported to be associated with anaemia, but there is little evidence specific to low- and middle-income countries (LMICs), where childhood anaemia prevalence is greatest. We aimed to determine if long-term ambient fine particulate matter (≤2.5 µm in aerodynamic diameter [PM2.5]) exposure was associated with Hb levels and the prevalence of anaemia in children aged <5 years living in 36 LMICs. We used Demographic and Health Survey data, collected between 2010 and 2019, which included blood Hb measurements. Satellite-derived estimates of annual average PM2.5 was the main exposure variable, which was linked to children's area of residence. Anaemia was defined according to standard World Health Organization guidelines (Hb < 11 g/dL). The association of PM2.5 with Hb levels and anaemia prevalence was examined using multivariable linear and logistic regression models, respectively. We examined whether the effects of ambient PM2.5 were modified by a child's sex and age, household wealth index, and urban/rural place of residence. Models were adjusted for relevant covariates, including other outdoor pollutants and household cooking fuel. The study included 154,443 children, of which 89,904 (58.2%) were anaemic. The country-level prevalence of anaemia ranged from 15.8% to 87.9%. Mean PM2.5 exposure was 33.0 (±21.6) µg/m3. The adjusted model showed that a 10 µg/m3 increase in annual PM2.5 concentration was associated with greater odds of anaemia (OR = 1.098 95% CI: 1.087, 1.109). The same increase in PM2.5 was associated with a decrease in average Hb levels of 0.075 g/dL (95% CI: 0.081, 0.068). There was evidence of effect modification by household wealth index and place of residence, with greater adverse effects in children from lower wealth quintiles and children in rural areas. Exposure to annual PM2.5 was cross-sectionally associated with decreased blood Hb levels, and greater risk of anaemia, in children aged <5 years living in 36 LMICs.

An epithelial-to-mesenchymal transition induced extracellular vesicle prognostic signature in non-small cell lung cancer.

Despite significant therapeutic advances, lung cancer remains the leading cause of cancer-related death worldwide1. Non-small cell lung cancer (NSCLC) patients have a very poor overall five-year survival rate of only 10-20%. Currently, TNM staging is the gold standard for predicting overall survival and selecting optimal initial treatment options for NSCLC patients, including those with curable stages of disease. However, many patients with locoregionally-confined NSCLC relapse and die despite curative-intent interventions, indicating a need for intensified, individualised therapies. Epithelial-to-mesenchymal transition (EMT), the phenotypic depolarisation of epithelial cells to elongated, mesenchymal cells, is associated with metastatic and treatment-refractive cancer. We demonstrate here that EMT-induced protein changes in small extracellular vesicles are detectable in NSCLC patients and have prognostic significance. Overall, this work describes a novel prognostic biomarker signature that identifies potentially-curable NSCLC patients at risk of developing metastatic NSCLC, thereby enabling implementation of personalised treatment decisions.

Active screening for lung cancer increases smoking abstinence in Australia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A cross-sectional analysis of long-term exposure to ambient air pollution and cognitive development in children aged 3-4 years living in 12 low- and middle-income countries.

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 [PM2.5]) and cognitive development indicators in a cross-sectional analysis of children (aged 3-4 years) in 12 LMICs. We linked Demographic and Health Survey data, conducted between 2011 and 2018, with global estimates of PM2.5 mass concentrations to examine annual average exposure to PM2.5 and cognitive development (literacy-numeracy and learning domains) in children. Cognitive development was assessed using the United Nations Children's Fund's early child development indicators administered to each child's mother. We used multivariable logistic regression models, adjusted for individual- and area-level covariates, and multi-pollutant models (including nitrogen dioxide and surface-level ozone). We assessed if sex and urban/rural status modified the association of PM2.5 with the outcome. We included 57,647 children, of whom, 9613 (13.3%) had indicators of cognitive delay. In the adjusted model, a 5 µg/m3 increase in annual all composition PM2.5 was associated with greater odds of cognitive delay (OR = 1.17; 95% CI: 1.13, 1.22). A 5 µg/m3 increase in anthropogenic PM2.5 was also associated with greater odds of cognitive delay (OR = 1.05; 95% CI: 1.00, 1.10). These results were robust to several sensitivity analyses, including multi-pollutant models. Interaction terms showed that urban-dwelling children had greater odds of cognitive delay than rural-dwelling children, while there was no significant difference by sex. Our findings suggest that annual average exposure to PM2.5 in young children was associated with adverse effects on cognitive development, which may have long-term consequences for educational attainment and health.

Longitudinal risk of death, hospitalizations for atrial fibrillation, and cardiovascular events following catheter ablation of atrial fibrillation: a cohort study.

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.

Plasma Extracellular Vesicle miRNA Profiles Distinguish Chronic Obstructive Pulmonary Disease Exacerbations and Disease Severity.

Purpose: 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.

COPD-X Australian guidelines for the diagnosis and management of chronic obstructive pulmonary disease: 2022 update.

INTRODUCTION: 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. MAIN RECOMMENDATIONS: 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. CHANGES IN MANAGEMENT AS A RESULT OF THESE GUIDELINES: 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.