Paul D. Robinson

There are errors in the author affiliations. The correct affiliations are as follows: Chi Yan Hui1, Kathleena Condon2, Shailesh Kolekar3, Nicola Roberts4, Katherina Bernadette Sreter5, Sami O. Simons6, Carlos Figueiredo7, Zoe McKeough8, Hani Salim9, Aleksandra Gawlik-Lipinski10, Apolline Gonsard11, Ayşe Önal Aral12, Anna Vanoverschelde13, Matthew Armstrong14, Dario Kohlbrenner15, Cátia Paixão16, Patrick Stafler17, Efthymia Papadopoulou18, Adrian Paul Rabe19, Milan Mohammad20, Izolde Bouloukaki21, Shirley Quach22, Malek Chaabouni23, Georgios Kaltsakas24, Kate Loveys25, Tonje Reier-Nilsen26, Anthony Paulo Sunjaya27, Paul Robinson2, Hilary Pinnock1, Amy Hai Yan Chan28 1 Allergy and Respiratory Research Group, Usher Institute, The University of Edinburgh, Edinburgh, United Kingdom, 2 Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia, 3 Department of Respiratory Medicine, Zealand University Roskilde Hospital, Institute of Clinical Medicine Copenhagen University, Copenhagen, Denmark, 4 School of Health and Social Care, Edinburgh Napier University, Edinburgh, United Kingdom, 5 Department of Pulmonology, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia, 6 Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, Netherlands, 7 Department of Pulmonology, Hospital de Santa Marta, Lisbon, Portugal, 8 Discipline of Physiotherapy, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia, 9 Department of Family Medicine, Faculty of Medicine & Health Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia, 10 Department of Respiratory Medicine, University of Leicester, Leicester, United Kingdom, 11 Department of Pediatric Pulmonology and Allergology, University Hospital Necker-Enfants Malades, APHP, Paris, France, 12 Pulmonary Diseases Clinic, Ankara Go¨lbaşı State Hospital, Ankara, Turkey, 13 Hospital Outbreak Support Team (HOST), H.uni network, Brussels, Belgium, 14 Department of Rehabilitation & Sports Science, Bournemouth University, Bournemouth, England, United Kingdom, 15 Faculty of Medicine, University of Zurich, Zurich, Switzerland, 16 Respiratory Research and Rehabilitation Laboratory (Lab3R), School of Health Sciences (ESSUA), University of Aveiro, Aveiro, Portugal, 17 Pulmonary Institute, Schneider Children’s Medical Center of Israel, Petach Tikvah, Israel, 18 Pulmonology Department, General Hospital of Thessaloniki, Thessaloniki, Greece, 19 Department of Primary Care and Public Health, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom, 20 Centre for Physical Activity Research, Copenhagen University Hospital, Copenhagen, Denmark, 21 Department of Social Medicine, School of Medicine, University of Crete, Crete, Greece, 22 School of Rehabilitation Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada, 23 Department of Internal Medicine II—Pulmonology Section, Asklepios Klinik Altona, Hamburg, Germany, 24 Centre for Human and Applied Physiological Sciences (CHAPS), King’s College London, London, United Kingdom, 25 Department of Paediatrics: Child and Youth Health, The University of Auckland School of Medicine, Grafton, Auckland, New Zealand, 26 The Norwegian Sports Medicine Centre, Oslo, Norway, 27 Respiratory Division, The George Institute for Global Health, Sydney, Australia, 28 School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.

Lung cancer screening (LCS) reduces lung cancer-related mortality; however, uptake remains low compared with other cancer screening programmes. In this observational study, we report the impact of timed appointments and reminders on participation in our regional LCS programme.Initial uptake of timed appointments was 53.0% (n=17 274/32 593), higher than previously reported in the UK, while initial uptake of open invitations was 29.8% (n=10 246/34 371). Among initial non-responders, 17.5% (n=4263/24 400) completed triage following a reminder. The increased participation following reminders only partially offset the significant difference in initial uptake between the two appointment types.Timed appointments and reminders are strongly advocated to increase participation in national LCS programmes.

Environmentally persistent free radicals (EPFRs) are combustion products present in substantial numbers on atmospheric particulate matter with half-lives of days to years. The mechanisms linking EPFR exposure and respiratory diseases are unclear, but likely involve oxidative stress. We investigated the mechanisms by which EPFR exposure impact on well-differentiated primary human nasal epithelial cells from subjects sensitive or resistant to oxidant stressors, cultured at an air-liquid interface. We found that EPFR exposure induced mitochondrial reactive oxygen species (mtROS) production; increased mitochondrial DNA copy number; down-regulated mucus production gene, Mucin-5AC (MUC5AC); up-regulated detoxifying gene, cytochrome P450 1A1 (CYP1A1), nuclear factor erythroid 2-related factor 2 (NRF2)-regulated antioxidant pathways including Sirtuin 1 (SIRT1)-Forkhead box O3 (FOXO3), mitophagy, PTEN-induced kinase 1 (PINK1), apoptosis, cyclin-dependent kinase inhibitor p21 (p21), and inflammation, C-C motif chemokine ligand 5 (CCL5). These results indicate that the well-differentiated respiratory epithelium can respond and activate redox reactions when exposed to sublethal concentrations of EPFRs. Increased susceptibility to EPFR exposure is conferred by failure to upregulate the mucin gene, MUC5AC, expression. Pre-treatment with astaxanthin prevented most of the negative impacts caused by EPFRs. Our results demonstrate that EPFRs can induce oxidative stress and cause damage to respiratory epithelium. A dietary antioxidant, astaxanthin, protected cells from EPFR-induced oxidant stress.

Background: Oscillometry may provide the feasible and sensitive tool for objective remote monitoring of paediatric asthma. Methods: Observational study of school-aged healthy, well-controlled and poorly-controlled asthma performing daily home-based oscillometry for 3-4 months, alongside objective measures of asthma control (Asthma Control Questionnaire weekly and Asthma Control Test monthly), medication use and exacerbations. Day-to-day variability calculated as coefficient of variation (CV) for resistance at 5 Hz (R5), reactance at 5 Hz (X5) and area under reactance curve (AX). Our objective was to examine feasibility, whether day-to-day variability was increased in asthma and correlations with asthma control and exacerbation burden. Clinical exacerbation patterns were examined using principal component analysis and k-means clustering of oscillometry, symptoms, breathing parameters and adherence. Results: Feasibility was 74.9±16.0% in health (n=13, 93.7±16.2 days) and 80.6±12.9% in asthma (n=42, 101.6±24.9 days; 17 well-controlled and 27 poorly-controlled asthma). Increased day-to-day variability in all oscillometry indices occurred in asthma versus health (all p≤0.002), with CV R5 the best discriminator (area under receiver operating characteristics curve 0.88, p<0.001). CV R5 increased during exacerbation and correlated with all asthma control measures and exacerbation burden. Correlations remained when examining non-exacerbation oscillometry data. Two exacerbation patterns were found based on oscillometry data in the pre-exacerbation period, characterised by severity of impairment of R5, X5, AX and CV R5 (n=12, more severe). Findings were similar using post-exacerbation period oscillometry data (n=8, more severe). Symptoms did not differ across exacerbation patterns. Conclusions: Home-based oscillometry monitoring was highly feasible over extended periods in school-aged asthmatics. Day-to-day oscillometry variability was increased in asthma compared with health, reflected asthma control and exacerbation burden and identified differing exacerbation patterns.

Improved maternal asthma management in pregnancy may reduce recurrent bronchiolitis and wheeze outcomes in infancy. We assessed whether infant bronchiolitis and wheeze outcomes are influenced by inflammation-guided management intervention, inhaled corticosteroid (ICS) use or exacerbations in pregnancy. A randomised controlled trial (RCT) secondary analysis and observational cohort analysis using the same study population was carried out. Pregnant women (12-23 weeks' gestation) from six centres in Australia were recruited and randomised to inflammation-guided asthma management or usual care between 2013 and 2023. ICS use and asthma exacerbations were reported during pregnancy and postnatally. When infants were 6 (n=691) and 12 (n=606) months of age, respiratory information was collected from parents and medical records. Associations for the RCT and observational analyses were assessed with logistic regression. Guided asthma management in pregnancy was not associated with bronchiolitis or wheeze-related outcomes, for example for recurrent bronchiolitis at 12 months, the intervention OR was 1.04 (95% CI 0.62-1.73). In the observational analyses, ICS use in pregnancy was not associated with respiratory outcomes; however, asthma exacerbations in pregnancy were associated with at least one bronchiolitis episode (adjusted odds ratio (adjOR) 2.20, 95% CI 1.28-3.76) or croup episode (adjOR 4.34, 95% CI 1.89-9.96) at 6 months, and wheeze (adjOR 1.80, 95% CI 1.14-2.84) and increasing wheeze episodes at 12 months (adjOR 1.81, 95% CI 1.17-2.79). Although there was no evidence that guided asthma management or ICS use in pregnancy reduces infant bronchiolitis or wheeze, maternal asthma exacerbations are an important risk factor for these outcomes. Further research is needed to reduce exacerbations in pregnancy.