Thorax

Background: Heat exposure has been linked to chronic obstructive pulmonary disease (COPD) outcomes, but evidence on relative humidity and humidity-temperature interaction remains limited and inconsistent. Methods: We conducted a nationwide time-stratified case-crossover study of 473,494 COPD hospital admissions in England during the summer months (June-August) from 2003 to 2021. Case-control pairs were linked to high-resolution daily maximum temperature and relative humidity data derived from HadUK-Grid and ERA5-Land, respectively. Exposure-response relationships were modelled using distributed lag non-linear models. Joint effects were examined using interaction models, including linear interaction, temperature spline by humidity category, and fully categorical specifications. Analyses were stratified by age group, sex, and socioeconomic deprivation. Results: COPD admission risk increases steeply at higher temperatures following a J-shaped curve. The exposure-response for relative humidity is U-shaped with a relative risk of 1.08 (95% Confidence Intervals: 1.00 - 1.15) at the 99th relative humidity percentile. We find limited evidence of effect modification by socioeconomic deprivation for both exposures. An estimated 1,040 (95%CI: 820 - 1,270) summer COPD admissions per year are attributable to non-optimal temperatures and 910 (95%CI: 680 - 1,160) to relative humidity. Higher relative risks are observed with concurrent high temperature and high humidity, but the evidence is weak. Conclusion: High temperature and high relative humidity are associated with increased risk of COPD admission, with limited evidence of an interaction. Relative humidity should be considered alongside temperature in environmental risk assessment and targeted adaptation strategies, such as proactive heat-health advice for people living with COPD.

Background: Anxiety affects 22-56% of patients with COPD. It is independently associated with increased exacerbations, readmissions, and mortality. Medical hypnosis transiently alleviates state anxiety in severe COPD, and attenuates experimentally-induced dyspnoea in healthy volunteers. We aimed to assess the efficacy of hypnosis as adjunct therapy for anxiety during Pulmonary Rehabilitation (PR) versus an active comparator controlling for general motivation and relaxation. Methods. HYPNOBPCO_2 was a single-centre, phase 2, cluster-randomised, active-comparator, parallel-group, superiority trial done at Centre Hospitalier de Bligny, France. Adults +30 years with established COPD, mMRC dyspnoea grade +2, and +10 pack-years were eligible. Consecutive pulmonary rehabilitation cohorts (clusters) were randomly assigned (1:1) to medical hypnosis or structured relaxation, both adjunctive to a 4-week inpatient PR. The primary outcome was the six-item State-Trait Anxiety Inventory (STAI-6) at week 4, analysed in the intention-to-treat population. Secondary outcomes were sensory and affective dyspnoea (Multidimensional Dyspnea Profile sensory and affective sub-scales, COPD Assessment Test) and functional capacity (6-minute walk distance). A moderation analysis tested whether the hypnosis effect varied with baseline sensory and affective dyspnoea burden using Bayesian inference. This trial was registered prospectively (NCT04868357) and the protocol published. Findings. Between 27/09/2021 and 31/01/2024, 79 participants in 24 clusters were randomised (medical hypnosis n = 36, age 64.9 [8.3], 20 female; relaxation n = 43, age 67.4 [9.1], 23 female). Anxiety improved in both arms (deltaSTAI-6 = -5.72, posterior probability of reduction beyond MCID = 0.93). Medical hypnosis did not show an advantage over relaxation overall (deltaSTAI-6 = 0.95; posterior probability of reduction beyond MCID = 0.12). Medical hypnosis did show an advantage that scaled with baseline dyspnoea profile: in patients with high sensory and low affective burden, the predicted anxiety reduction relative to relaxation was larger and more probable (deltaSTAI-6 = -9.26; posterior probability of reduction beyond the 3-point MCID = 0.81). No clinically important safety issues were associated with either intervention and there were no deaths. Interpretation. Anxiety improved under both adjunctive mind-body interventions. The usefulness of hypnosis beyond relaxation was predicted by baseline dyspnoea profile, concentrating in patients with predominantly sensory burden. Future trials should focus on evaluating complementary interventions against burden phenotypes, ultimately paving the way for personalized interventions. Funding. Helebor Foundation; Agence Nationale de la Recherche.

Background Exposure to environmental tobacco smoke (ETS) negatively affects children`s health, but few studies examined parental smoking behaviour in families of children with respiratory diseases. We studied parental smoking prevalence, characteristics, and changes over one year among families in the Swiss Paediatric Airway Cohort (SPAC). Methods We included children aged 0-17 years referred to paediatric respiratory outpatient clinics in Switzerland from 2017 to 2024. Parents answered a questionnaire at the initial clinic visit and again after one year. We used multivariable logistic regression to explore the characteristics of mothers and fathers who smoked and assessed changes in smoking behavior over one year. Results Among 4,199 children (median age 9 years [IQR 5-12]), 31% were exposed to parental smoking at baseline (paternal smoking: 16%; maternal smoking: 6%; both parents smoking: 9%). Mothers were more likely to smoke if they had a lower education level (OR 2.0, 95%CI 1.6-2.5 for compulsory education vs university education), did not have Swiss nationality (OR 1.3, 1.0-1.6) and lived in a socially disadvantaged neighborhood (OR 1.3, 1.0-1.7). Similar associations were observed for fathers. In addition, fathers were more likely to smoke if they were unemployed (OR 2.0, 1.3-3.2 vs having a full-time job. The strongest predictor of smoking was having a partner who smoked, with ORs above 6 for both mothers and fathers. Parents of 2,338 children completed the one-year follow-up questionnaire. Data from 2226 mothers and 1895 fathers showed that among baseline smokers with follow-up data, 225 (78%) mothers and 382 (81%) of fathers continued smoking, and only 63 (22%) of mothers and 90 (19%) of fathers quit. Among baseline non-smokers, 47 (2%) mothers and 54 (3%) fathers started smoking. Conclusions One-third of children consulting respiratory specialists in Switzerland are exposed to parental smoking. ETS exposure was strongly associated with socio-economic factors. Even after visiting a specialized clinic, most parents continued to smoke. This highlights the urgent need for stronger national smoking policies and targeted support to help these parents quit and stay smoke-free.

Background: Randomized controlled trials have shown that computed tomographic (CT) screening reduces lung cancer mortality. Improved identification of at-risk groups, by leveraging non-smoking risk factors, could help refine screening selection. Aim: To evaluate polygenic risk scores (PRSs) and ambient air pollution (AAP) exposure for risk stratification in the NELSON lung cancer screening cohort. Methods: Two PRSs (PRS-McKay/PRS-Byun) and several AAPs (including nitrogen dioxide, ozone, and particulate matter [PM]) were assessed in the NELSON lung cancer screening trial (N=7,364). PRSs were validated in the Rotterdam Study (N=11,493). Associations with lung cancer, mortality, screening results, and discriminative ability to distinguish lung cancer were evaluated. Results: PRS-McKay and PRS-Byun were associated with lung cancer (odds ratio [OR] per SD [95%CI]: 1.22 [1.08-1.37] and 1.28 [1.13-1.44], respectively) and lung cancer-specific mortality (OR [95%CI]: 1.24 [1.05-1.47], for both), but not with non-lung cancer mortality (OR [95%CI]: 1.01 [0.94-1.10] and 1.03 [0.95-1.12], respectively). Exposure to PM2.5 was associated with lung cancer (OR [95%CI]: 1.11 [1.01-1.22]). PM constituents were associated with adenocarcinoma, particularly PM10 (OR [95%CI]: 1.16 [1.01-1.32]) and ultra-fine particles (OR [95%CI]: 1.16 [1.04-1.30]). PRS and AAP added modestly to the discriminative ability for lung cancer on top of pack-years, age, and sex (area under the curve [95%CI]: 0.659 [0.624-0.695] vs. 0.643 [0.608-0.679]). Conclusions: PRSs and exposure to PM were associated with lung cancer in a high-risk screening population. The primary potential of PRSs may reside in refining lung cancer screening selection toward individuals at higher risk of dying from lung cancer specifically.

Abstract Introduction Postal sputum sampling represents a potential strategy for patient-led, efficient, and regular sampling, yet little is known about the validity of posting samples for clinical and research purposes in bronchiectasis. This study aimed to validate postal sputum sampling for clinical and research applications in chronic P. aeruginosa infection. Methods Sputum was collected from 12 participants with bronchiectasis and known P. aeruginosa infection. Each sputum sample was divided into four aliquots: two were sent immediately for analysis with or without DNA-Shield (shield-fresh and non-shield-Fresh), while two were transported through the UK postal service, with or without DNA-Shield (shield-posted and non-shield-posted). All aliquots were sent at ambient temperature and subsequently processed for bacterial enumeration through selective culture, detailed antimicrobial susceptibility testing, quantitative PCR (qPCR), 16S microbiome sequencing, metabolomics, and proteomics. Results During postage, there was a median of four days (range, 2-7) between sample collection and processing. 7/12 patients were positive for P. aeruginosa by culture of fresh samples, with 100% agreement in posted samples. Postage did not affect cultured (p=0.81) or amplified load of P. aeruginosa (p=0.94), and no differences were observed in AST profiles across 140 isolates for P. aeruginosa cultured from fresh or posted samples. Metabolomics and proteomics revealed that variation between individuals was significantly greater than between fresh and posted samples, and no significant differences in microbial taxa were observed between samples. No differences were associated with the addition of DNA Shield by qPCR (p=0.19), however, freeze-thaw from -80{degrees}C increased amplified load (p=<0.01). Conclusions We found little evidence of an effect of postage on sputum positivity, recoverable load, AST profile, microbiome, proteome or metabolome in sputum samples. These data suggest postal sputum samples may be a valuable tool for clinical and research applications.

Abstract Background Fibrotic interstitial lung disease (F-ILD) has high mortality. Evidence suggests short telomere causality and sex hormone interactions. STARSHIP aimed to assess feasibility for future F-ILD sex hormone trials. Methods Leukocyte telomere length (LTL), complete blood count, sex hormone (testosterone and oestrogen), sex hormone binding globulin (SHBG) and albumin concentrations were determined in 102 F-ILD outpatients (age 49-89, male N=80 [78%]) and age/sex-matched controls (ASMCs). Patients undertook routine pulmonary function tests, 93 (91%) participated in bespoke telephone interviews. Survival was assessed at median 33 (28-39) months. Results 77/79 (97.4%) male patients had haemoglobin and haematocrit below the upper reference limit. Mean LTL was shorter for patients than ASMCs (4.57kb [95%CI:4.46-4.69] vs 4.78kb [95%CI:4.67-4.89]; p<0.006). SHBG concentrations were higher for patients. Mean bioavailable testosterone was lower for N=80 male patients than ASMCs (4.95nmol/L [95%CI:4.50-5.41] vs 6.40nmol/L [95%CI:5.82-6.98]; p<0.0001). Post-menopausal oestrogen concentrations were low for female patients and controls. Mean free androgen index (FAI) was low for female patients but not ASMCs (mean 0.51 [95%CI:0.35-0.67] vs 1.23 [95%CI:0.77-1.69]; p=0.0036, N=22). Age/BMI-adjusted bioavailable testosterone concentration in male patients correlated with both DLCO% (=3.31, p=2.4x10-4) and FVC% (=2.76, p=0.0030). FVC% associated with FAI in females (=34.3, p=0.0029). In all-confounder-adjusted Cox analysis, low free testosterone associated with mortality (HR=2.66, p=0.023, N=77) in male patients. Lower FAI (adjusted for age/lung function) suggested similar effects but more studies needed for females (HR=3.59, p=0.22, N=18). Conclusions ILD patients have low sex hormones concentration(s), which associated with reduced lung function and survival. Sex hormone supplementation studies are needed.

Background There is growing interest in tuberculosis (TB) community screening and detection of asymptomatic TB (aTB). We explored how setting and screening approach influence the relationship between reported symptoms and underlying disease severity and infectiousness. Methods We compared markers of TB severity and infectiousness (computer-aided detection [CAD, CAD4TBv5] scores derived from chest radiographs and trace vs exceeding trace Xpert MTB/RIF Ultra results) among people diagnosed with aTB or symptomatic TB (sTB) through a community survey, and those diagnosed with aTB or sTB in clinics in the same South African community. We evaluated how variation in screening algorithms influence the relative severity of community-diagnosed aTB vs sTB, and estimated the TB prevalence and severity among people not eligible for testing in the survey (CAD score <25 and no reported symptoms). Results People with clinic-diagnosed sTB had higher CAD scores and a greater proportion of Xpert results exceeding trace than those with community-diagnosed sTB, whereas differences between community-diagnosed aTB and sTB were minimal. Under a hypothetical community universal Xpert testing strategy, people detected with sTB may have more severe disease on average than people detected with aTB. In contrast, restricting testing to people with CAD scores [&ge;]50 and/or reported symptoms would have resulted in higher CAD scores among those diagnosed with aTB than sTB. Conclusions Screening algorithm design and context influence the spectrum of TB disease detected. Community screening approaches where testing is based on symptoms and/or a threshold CAD score may identify aTB that is on average more severe than sTB.

Objectives Genetic testing is increasingly used in the diagnosis and management of respiratory conditions, including pulmonary fibrosis (PF). The perspectives of people with PF and healthcare professionals (HCP) on the use of genetic testing remain largely unexplored. Methods A qualitative study was undertaken. People living with PF, their caregivers, and HCP were invited to undertake a semi-structured interview. Interviews were conducted via videoconference or telephone, audio-recorded, and transcribed verbatim. Data were analysed by two researchers using inductive thematic analysis. Results Thirty-eight participants; 15 people living with PF, 1 caregiver, and 22 HCPs were interviewed. Analysis revealed three key themes. Genetic testing in PF was valued by all groups; people with PF wanted testing now, whilst respiratory physicians were cautious, citing their uncertainty regarding clinical value. All groups desired more information and support; people with PF desired a better understanding of terminology, whilst genetic counsellors wanted to better understand PF. No single model for returning genetic results in PF was identified, however resources, multidisciplinary care, and timely return of results was considered important. Conclusion Genetic testing is valued by people with PF and their HCP, but uncertainties remain regarding whether it should be offered and how results should be best communicated.

Tuberculosis (TB) is increasingly recognised as a spectrum of infection and disease, yet the prevalence of viable, asymptomatic Mycobacterium tuberculosis (M.tb) infection remains uncertain. Subclinical Tuberculosis (scTB), defined as microbiologically confirmed M.tb infection in the absence of recognised symptoms, is under detected by symptom, sputum and imaging-based approaches. We conducted postmortem examinations of 94 adults who died from non-infectious causes, none of whom were clinically suspected of TB or reported TB related symptoms prior to death. Lung and extrapulmonary tissues were cultured for M.tb. Viable M.tb was confirmed in six individuals, corresponding to a prevalence of 6.4% (95% CI: 2.4 to 13.4%). These findings provide direct tissue-based evidence that viable, asymptomatic M.tb infection can persist beyond the reach of conventional clinical detection. Our data suggest that a biologically active reservoir of infection may exist undetected within high-burden settings, with implications for surveillance strategies aimed at TB elimination.

Background Tuberculosis remains the leading infectious cause of death worldwide. In the WHO African region, declining incidence has coincided with antiretroviral therapy (ART) scale-up, though whether this reflects reduced progression to disease or reduced transmission is unclear. We evaluated how ART and symptom status influence within-household Mycobacterium tuberculosis complex (MTBC) transmission risk. Methods We conducted a case-contact household study in rural South Africa, enrolling index adults with bacteriologically-confirmed pulmonary tuberculosis. MTBC immunoreactivity was measured in all child household contacts (aged 2-14 years) as a proxy measure of within-household transmission. We assessed the influence of index person ART status and symptom status, and explored effect-measure modification of the association between index person HIV status and transmission risk by sex. Results Among 755 child contacts of 296 index persons, effective ART was not associated with within-household MTBC transmission risk (risk ratio [RR], 1.07; 95% CI, 0.66-1.74). Among PLHIV engaged in ART care, WHO TB four-symptom screen (WHO4SS) status was not associated with transmission risk (RR, 0.80; 95% CI, 0.43-1.47), although absence of reported cough reduced risk (RR, 0.61; 95% CI, 0.38-0.96). A pronounced interaction between sex and HIV status was observed: HIV-negative women had the highest within-household MTBC transmission risk (30.5% vs. 14.3% in women with HIV) whereas risks were similar between HIV-positive and HIV-negative men. Conclusions We found no evidence that effective ART or WHO4SS status influenced within-household MTBC transmission risk, though confidence intervals were wide. Absence of reported cough was associated with lower risk, and transmission risk was highest among child contacts of HIV-negative women. These findings suggest reported cough is a useful marker of transmission risk and that routine tuberculosis screening within ART care may reduce transmission from PLHIV; intensified efforts are nonetheless needed to achieve earlier tuberculosis detection in HIV-negative individuals.

Purpose To evaluate the implementation characteristics of a commercially available chest radiography artificial intelligence (AI) system in a large real-world health check-up cohort using workflow-level, lesion-specific, and exploratory retrospective lung cancer case analyses. Methods This retrospective single-centre study included 298,991 consecutive health check-up chest radiographs from 114,866 individuals obtained between 2019 and 2023 and interpreted under routine double reading by board-certified radiologists. A commercially available AI system was evaluated using two prespecified thresholds: positivity in any of ten findings for the all-score analysis and positivity for nodule or mass for the nodule-focused analysis, both at a manufacturer-recommended score threshold of 15. Because routine radiologist judgement rather than universal CT or pathologic verification served as the reference framework, the primary analyses were interpreted as radiologist-referenced operational concordance analyses. Results Radiologist-referenced sensitivity and specificity were 72.0% and 79.6%, respectively, in the all-score analysis and 87.1% and 91.8%, respectively, in the nodule-focused analysis. Negative predictive values were 99.0% and 100.0%, respectively. Among 48 histopathologically confirmed lung cancer cases, retrospective timeline analyses showed earlier AI positivity than routine radiologist positivity in a subset of cases. These findings should be interpreted as exploratory observations and do not establish prospective clinical benefit. Conclusion In a large health check-up cohort, chest radiography AI demonstrated stable concordance with routine radiologist judgement and high sensitivity for radiologist-reported pulmonary nodules and masses. Exploratory retrospective analyses showed earlier AI positivity in a subset of histopathologically confirmed lung cancer cases, supporting further prospective evaluation of AI-assisted health check-up workflows.

ABSTRACT Background: Corticosteroids reduce mortality in severe COVID-19 requiring oxygen or invasive mechanical ventilation, yet emerging data suggest that SARS-CoV-2-associated acute lung injury is biologically heterogeneous and that treatment response may vary across molecularly defined disease states. Lung-derived molecular endotypes of severe COVID-19-associated acute lung injury have been described, but direct molecular profiling is not routinely available at the bedside. We evaluated whether a clinical predictor of previously defined lung molecular endotype identifies heterogeneity in corticosteroid treatment effect among mechanically ventilated patients with COVID-19. Methods: We utilized a single-center cohort of 5,000 patients with COVID-19 treated at the University of North Carolina Hospital between January 1, 2020, and December 31, 2022, to emulate a target trial assessing the effect of corticosteroid receipt on mortality, length of stay, and incident organ support. Confounding was addressed through inverse probability of treatment weighting (IPTW). Outcomes for severely ill patients requiring mechanical ventilation were compared to the RECOVERY trial results, with subsequent moderation analysis and stratified analysis by clinically predicted lung molecular endotype and vaccination status. The primary outcome was 28-day mortality. Secondary Outcomes were time to discharge alive and progression to additional organ support. Results: This emulated target trial showed a directionally favorable but non-statistically significant association between corticosteroid treatment and reduced 28-day mortality in patients requiring mechanical ventilation for SARS-CoV-2 infection. A clinical predictor of lung molecular endotype moderated the effect of corticosteroids on 28-day mortality (p-value for interaction 0.038) and identified distinct predicted endotype-specific treatment effect. Corticosteroid treatment was associated with lower 28-day mortality in the predicted Hyper-Inflammatory endotype (OR 0.62, 95% CI 0.39, 0.99) but not in the predicted Metabolic Dysregulation endotype (OR 1.15, 95% CI 0.82, 1.61). We did not detect significant effect modification by vaccination status (p-value for interaction 0.65), although inference was limited by the small, vaccinated subgroup (28-mortality OR 0.78, 95% CI 0.37, 1.65 in vaccinated vs 0.94, 95% CI 0.70, 1.26 in unvaccinated). Conclusions: In this target trial emulation of mechanically ventilated patients with severe COVID-19, corticosteroid treatment showed a directionally favorable but non-statistically significant association with reduced 28-day mortality in the overall cohort. However, a clinical predictor of lung molecular endotype identified significant heterogeneity in treatment effect, with benefit concentrated in the predicted Hyper-Inflammatory endotype and no apparent benefit in the predicted Metabolic Dysregulation endotype. These findings support prospective validation of clinically deployable endotype-guided corticosteroid treatment strategies in acute lung injury and ARDS.

ABTRACT Background Children from low- and middle-income countries are particularly vulnerable to air pollution, a major environmental health risk, due to the immaturity of their lungs and their proximity to sources of household pollution. This study aimed to investigated the effect of exposure to biomass combustion through domestic and maternal occupational activities on respiratory health of children living in disadvantaged urban areas of Abidjan, Cote dIvoire. Methods Between February and December 2023, we conducted a cross-sectional observational study among children <16 years from households of women using biomass fuel for cooking (Group (G) 1), engaged in occupational fish smoking activities (G2), or primarily using gas for domestic cooking (G3). We assessed reported respiratory symptoms through standardized questionnaires and the presence of lung function impairments (LFI) though pulmonary function tests (spirometry and Rint). We assessed the association between study groups and key covariates with respiratory symptoms and LFI using mixed-effects regression models. Results Of 210 children enrolled - 119 (56.8%) female, median age 9 (6-12) years, 82 (39.0%) in G1, 47 (22.4%) in G2, and 81 (38.6%) in G3 - 15 (7.1%) reported wheezing in the last 12 months, 82 (39.0%) reported dry cough at night, 9 (4.9%) presented with dyspnea and 5 (2.7%) had chest pain on clinical examination, for an overall proportion of children with reported respiratory symptoms of 43.8% (92/210). Of 176 children who underwent pulmonary function testing, 59 (33.5%) had LFI detected, including 34 (45.9%) in G1, 8 (22.2%) in G2, and 17 (25.8%) in G3 (p = 0.011). Study group was associated with respiratory symptoms (G1 vs G3; aOR 3.82, 95% CI 1.68-8.68; p < 0.001), as well as with LFI (p = 0.042). Girls were at greater risk of LFI than boys (aOR 2.69, 95% CI 1.24-5.80; p = 0.012). Children whose mothers used charcoal or wood as cooking fuel had higher odds of respiratory symptoms (OR 2.61, 95% CI 1.22-5.58; p = 0.013) but no association was found with LFI (p = 0.459) compared with unexposed children. Conclusion Respiratory symptoms and lung function impairments were highly prevalent among children living disadvantaged, especially when mothers cook with wood or charcoal. Targeted maternal awareness and broader interventions to reduce household air pollution in disadvantaged urban areas are urgently needed to protect long-term respiratory health.

We evaluated aggregated, privacy-preserving smartphone-detected nocturnal cough activity from the Sleep Cycle application as a potential syndromic surveillance signal in England. Weekly cough metrics from January 2023 to January 2026 were compared with UK Health Security Agency indicators: NHS 111 acute respiratory infection (ARI) triage calls, influenza and COVID-19 PCR positivity, and hospital admission rates for influenza, COVID-19, and respiratory syncytial virus. We evaluated total cough counts alongside two population-normalised metrics, coughs per user and coughs per hour of sleep, and assessed temporal relationships nationally and regionally using cross-correlation with prewhitening. The strongest and most consistent associations were observed for NHS 111 ARI triage calls, where population-normalised cough metrics showed raw national correlations of approximately 0.95 and retained prewhitened correlations above 0.55 at lag 0. This indicates that nocturnal cough activity closely tracks short-term variation in an established syndromic surveillance indicator, beyond shared seasonality, long-term trends, and autocorrelation. Similar near-contemporaneous patterns were observed across regions. Population-normalised cough metrics also showed epidemiologically plausible leading associations with pathogen-specific indicators: coughs per hour of sleep peaked one week before influenza PCR positivity, while both coughs per user and coughs per hour of sleep peaked one week before COVID-19 PCR positivity. Hospital-based indicators showed weaker and more heterogeneous relationships, but the normalised cough metrics still showed plausible temporal alignment with influenza and COVID-19 admissions, including contemporaneous associations with influenza admissions and short leading associations with COVID-19 admissions. In contrast, unnormalised total cough counts produced less stable and often non-interpretable lag structures, consistent with sensitivity to variation in observation volume. These findings suggest that passive, near-real-time nocturnal cough monitoring can provide a population-level signal of respiratory symptom burden, with greatest utility as a broad syndromic indicator that complements surveillance sources affected by healthcare-seeking behaviour, laboratory turnaround times, backfilling, and reporting delays.

Background Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in critical care, affecting 20-36% of mechanically ventilated patients. Early prediction is hampered by the absence of a reliable, objective diagnostic standard. We developed ADVISE (Automated Dudley Ventilation Infection Series Evaluation), a machine learning model to predict physiological deterioration consistent with developing VAP using routinely collected electronic health record data from a UK NHS intensive care unit. Methods Retrospective observational study of admissions at Russell's Hall Hospital ICU (2008-2026). Following National Data Opt-Out exclusion (158 admissions, 4.2%), 3,566 admissions generated 33,208 candidate 48-hour observation blocks. Six temporal variables - FiO2, ventilator mode, P:F ratio, procalcitonin (PCT), secretion amount, and secretion description - were extracted across the baseline window (hours 1-24). A composite VAP-surrogate outcome required concurrent P:F ratio decline (>=5%) and PCT rise (>=0.5 ng/mL) across the outcome window (hours 25-48). After sequential quality filters, 2,134 blocks (18 positive, 0.84% prevalence) were retained. An XGBoost classifier was trained using nested 5-fold cross-validation with scale_pos_weight=114.0 and ROC-based hyperparameter optimisation on 1,495 training blocks, evaluated on 639 held-out test blocks. Performance was assessed via AUROC, AUPRC, and calibration (Brier score). Bootstrap resampling (1,000 iterations) generated 95% confidence intervals. Results On the held-out test set (n=639, 5 positive outcomes), ADVISE achieved AUROC 0.874 [95% CI: 0.771-0.939] and AUPRC 0.031 [0.008-0.069], representing a 4.0-fold improvement over the no-skill baseline. Nested cross-validation mean AUROC was 0.844 +/- 0.078 (range 0.716-0.915). At the Youden-optimal threshold, sensitivity was 0% with specificity 97.8%, reflecting extreme class imbalance (0.78% test prevalence). A threshold targeting 80% sensitivity achieved sensitivity 80.0% [33.3-100.0%], specificity 87.4% [84.8-89.9%], positive predictive value 4.8% [1.1-9.9%], and negative predictive value 99.8% [99.4-100.0%], detecting 4 of 5 VAP cases with approximately 80 false alarms (12.6% false positive rate). Brier score was 0.0078. Feature importance identified baseline P:F ratio as the dominant predictor (41.3% total gain), followed by ventilator mode (26.1%), secretion amount (13.2%), secretion description (9.1%), procalcitonin (5.9%), and FiO2; (4.5%). Conclusions ADVISE demonstrates that baseline oxygenation trajectory and ventilatory support patterns - derived exclusively from routinely charted ICCA variables - can identify admissions at risk of VAP-related physiological deterioration with meaningful discrimination (AUROC 0.874) despite severe class imbalance. The 80% sensitivity operating point offers a clinically actionable alert rate (12.6% FPR), supporting integration into existing ICU workflows. This proof-of-concept study establishes feasibility; multi-site prospective validation is required before clinical deployment.

Males incur greater risk of tuberculosis (TB) than females, but the contribution of sex-associated immune differences remains unclear. We addressed this using sex-stratified transcriptomic analyses across four independent studies spanning active pulmonary TB, subclinical TB and latent infection, in peripheral blood, bronchoalveolar lavage (BAL) and by using the tuberculin skin test (TST) as a standardised in vivo antigenic challenge. In blood of active TB patients, expression of TNF- and type I interferon-regulated signatures, genome-wide gene expression, and performance of leading host-response biomarkers of TB were comparable between sexes. Similarly, blood transcriptomic biomarkers showed no meaningful sex-related differences for predicting asymptomatic or incident TB. In the TST of people with latent infection, bulk and single-cell RNA sequencing identified only limited differences, largely restricted to sex chromosome-linked transcripts, with no consistent evidence of dimorphism in immune-regulated pathways. Single-cell RNA sequencing of BAL samples identified reduced abundance of B cells in male TB patients, with gene expression differences again largely restricted to sex chromosome-linked transcripts. These findings suggest that canonical immune responses associated with TB are broadly similar between the sexes, and that increased TB risk among males more likely reflects differential exposure rather than intrinsic immunological susceptibility.

Urban air pollution remains a significant public health concern, contributing to premature deaths and adverse health outcomes. However, there is little causal research evaluating the effectiveness of policies designed to improve air quality. This study assesses the impact of all three stages of London's Ultra Low Emission Zone (ULEZ) on air pollution, via PM2.5 levels, and respiratory health, via prescription records for bronchodilator and respiratory corticosteroid medications. Analyses are at general practice level, using a generalised synthetic control method to estimate causal impacts. Stage 1 was associated with a statistically significant but negligible 0.77% reduction in PM2.5 levels, with no corresponding change in prescribing. Stage 2 produced a paradoxical 2.69% increase in PM2.5, alongside a 4.44% decrease in inhaled corticosteroid quantity but a 12.51% increase in average daily quantity (ADQ) usage, suggesting a worsening of disease severity among existing patients. Stage 3 yielded a 2.69% PM2.5 reduction and a modest 2.18% decrease in bronchodilator ADQ usage. Spillover effects beyond the ULEZ boundary were statistically significant, but negligible. We find overall that the ULEZ had minimal effects on both air quality and respiratory prescribing across all three stages. These findings provide new insights into the effectiveness of ULEZ policies in reducing air pollution and its associated health impacts, suggesting the zone's effects are considerably smaller than previously reported, and that integration with broader policy measures may be necessary to achieve meaningful public health gains.

Background: Tuberculosis (TB) preventive treatment is a key component of TB control in low-incidence settings, but uptake remains low. Objective: To explore factors influencing patient decisions to accept or decline preventive treatment for TB infection. Design: Qualitative study using semi-structured interviews, analysed with the Theoretical Domains Framework (TDF). Setting: Routine clinical TB prevention services at two hospitals in London, UK. Participants: Adults (18+) diagnosed with TB infection and offered preventive treatment. Methods: Semi-structured interviews were audio-recorded and transcribed verbatim. The TDF was applied to analyse transcripts using a combined inductive thematic analysis and deductive framework approach. Themes were also mapped to the Capability, Opportunity and Motivation model of Behaviour (COM-B) domains. Results: Twenty-five participants (median age 34 years; 64% male) were included; 56% accepted treatment, 28% declined, and 16% were undecided. Influences on decision-making mapped to 12 of 14 TDF domains. Facilitators of treatment acceptance included perceived risk of TB (beliefs about consequences), desire to protect others' health (social influences and goals), confidence in treatment adherence (beliefs about capabilities), and routine integration strategies (behavioural regulation). Barriers to treatment acceptance included low perceived individual risk and doubts about necessity or effectiveness (beliefs about consequences), concerns about side effects and treatment burden (environmental context and resources) and anticipated stigma (social influences). Knowledge had a mixed influence, primarily shaping perceived necessity, but did not determine decisions alone. Social, environmental and emotional factors further influenced decisions, with participants balancing anticipated benefits against perceived burden and uncertainty across multiple interacting domains. Conclusions: Decisions to accept preventive TB treatment are driven by interacting capability, opportunity and motivation factors rather than knowledge alone. Interventions to improve shared decision making should address perceived risk, treatment burden, self-efficacy and social influences.

Introduction: Childrens exposure to second hand tobacco smoke is a preventable global public health issue, yet there is no consensus on how best to support families to create a smoke free home. This pilot randomised controlled trial tested the feasibility of use of free nicotine replacement therapy combined with telephone delivered support to reduce childrens exposure to second hand smoke in the home, and inform a future full scale trial. Methods: Parents and carers aged 18 and over, who smoke in the home and care for one or more children aged 0 to 16 years were recruited through existing initiatives and social media. Participants were randomised to either the intervention or control arm. Group A received free posted to home nicotine replacement therapy, alongside fortnightly telephone calls to support smoking abstinence in the home. Group B were signposted to the Scottish Government Take it Right Outside website which provides interactive advice on creating a smoke free home. To measure second-hand smoke levels, participants installed an air quality monitor in their living room for 7 days to measure fine particulate matter at baseline and 12 week follow-up. Results: Approximately one-quarter (27 of 100) of the intended sample size was recruited. Median fine particulate matter concentrations reduced in both the intervention (by 36mg per cubic metre) and control (by 16mg per cubic metre) groups. Retention rates and adherence rates to nicotine replacement therapy were 70 percent and above, with no risks and or safety concerns reported, suggesting this approach is feasible and acceptable to participants. The estimated cost of delivering this 12 week intervention was two hundred and forty four pounds per individual. Conclusions: Although recruitment rates were insufficient to recommend progression to a larger trial to test effectiveness of this approach in Scotland, this study could inform trial development in other countries where smoking in the home is commonplace. Insights regarding the alignment of smoke free home interventions with broader smoking cessation initiatives could inform future policy and public health approaches.

Background: Monitoring Pseudomonas aeruginosa (P. aeruginosa) infection in people with cystic fibrosis (pwCF) is essential for early detection, targeted treatment, and prevention of chronification. Sputum culture is the current standard, yet many patients, particularly those receiving CFTR modulator therapy, struggle to expectorate sputum. Microbial aerosols from the respiratory tract offer a non-invasive alternative. This proof-of-principle study assessed the accuracy and feasibility of the AveloMask, a novel breath aerosol collection kit paired with qPCR detection. Methods: Adult pwCF and bronchiectasis patients attending routine monitoring visits and healthy controls were enrolled in a cross-sectional study. Participants wore the mask for 30 minutes, followed by 20 instructed coughs. Mask filters were tested with a triplex qPCR assay targeting P. aeruginosa specific ecfX and gyrB, and human RPP30 as an endogenous control. Accuracy was evaluated using a composite reference standard (sputum culture and PCR). Results: Of 25 patients enrolled, 23 were included in the analyses. Sensitivity was 12/19 (63.2%) for breath qPCR versus 15/19 (78.9%) for sputum culture. Breath qPCR missed 5 cases detected by sputum culture but detected 2 sputum culture-negative/qPCR-positive cases. Specificity of breath qPCR was 100% in 4 patients and 15 healthy controls. RPP30 was detected in all mask samples. AveloMask was perceived as easy to use, with many patients preferring it over sputum collection. Discussion: Mask-based breath collection demonstrated promising diagnostic accuracy for detection of P. aeruginosa. Breath sampling may complement or partially substitute sputum-based diagnostics, especially in patients unable to expectorate. Further studies are needed to define its clinical role.