BMJ Open Respiratory Research

Abstract Importance: Socially vulnerable patients have a high burden of obstructive sleep apnea, but the stage of the referral pathway at which access barriers arise is uncertain. Objective: To determine whether area-level social deprivation was associated with appointment scheduling, wait time, cancellations, or no-shows among adults referred for specialist obstructive sleep apnea care. Design: This was a cross-sectional study evaluating patients referred from December 1, 2016 through November 30, 2019. Data were analyzed from January 30, 2026 to May 16, 2026. Setting: Foothills Medical Centre Sleep Centre in Calgary, Canada. Participants: Adults referred to a tertiary academic sleep centre in Calgary, Alberta, Canada. Eligible patients had valid provincial health insurance and either a scheduled clinic appointment or home sleep apnea test data available. Exposures: Quintiles of the four Canadian Index of Multiple Deprivation domains: residential instability, economic dependency, ethnocultural composition, and situational vulnerability. Main Outcomes and Measures: The primary outcome was receipt of a scheduled specialist appointment. Secondary outcomes were time from referral to the first attended appointment and number of appointment cancellations or no-shows. Results: Among 3111 patients (mean [SD] age, 53.7 [14.3] years; 40.7% female), 1766 (56.7%) were scheduled and 1647 (52.9%) attended an appointment. Each quintile increase in situational vulnerability was associated with lower odds of scheduling (adjusted odds ratio [95% confidence interval] 0.86 [0.81-0.92]), whereas each quintile increase in ethnocultural composition was associated with higher odds (adjusted odds ratio [95% confidence interval] 1.32 [1.22-1.43]). Residential instability and economic dependency were not associated with scheduling. No deprivation domain was associated with time to the first attended appointment, cancellations, or no-shows. Conclusions and Relevance: In this cohort, area-level deprivation was associated with whether patients were scheduled for an appointment but not with wait time or missed visits after scheduling. These findings suggest that equity interventions should focus on completion of referral and scheduling processes.

Objectives: Acute hypercapnic respiratory failure (AHRF) is a common cause of hospitalization among adults with chronic respiratory and sleep-related disorders. We evaluated whether admission to hospitals with an on-site American Academy of Sleep Medicine (AASM)-accredited sleep facility was associated with length of stay (LOS) and hospitalization cost among adults admitted with AHRF. Methods: We conducted a retrospective cohort study using the Healthcare Cost and Utilization Project New York State Inpatient Database from 2017 to 2021. Adults admitted to hospitals outside New York City were included because hospital density, referral patterns, and access to specialty services differ from those in New York City. Hospitals were classified by the presence of an on-site AASM-accredited sleep facility, used as a structural proxy for institutional sleep medicine capacity. LOS and hospitalization cost were log10-transformed before analysis. We used bivariate analyses and hierarchical multivariable linear regression models adjusting for demographic, clinical, socioeconomic, and hospital-level covariates. Results: A total of 3,247 adults met inclusion criteria. In unadjusted analyses, admission to hospitals with an on-site AASM-accredited sleep facility was associated with shorter LOS and lower hospitalization cost. After adjustment, sleep facility status was not independently associated with either outcome and did not improve model fit. Greater comorbidity burden was the strongest independent predictor of both longer LOS and higher cost. Housing instability and race categorized as other than White were also associated with higher resource use. Chronic obstructive pulmonary disease was independently associated with shorter LOS and lower cost. Conclusions: Among adults hospitalized with AHRF, LOS and hospitalization cost were more strongly associated with comorbidity burden and socioeconomic disadvantage than with the presence of an on-site AASM-accredited sleep facility. These findings suggest that accreditation status alone may not capture inpatient sleep medicine processes most relevant to acute respiratory care.

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.

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.

Introduction Hospitalised community-acquired pneumonia (CAP) is heterogeneous in aetiology, severity, and outcome. Phenotyping and endotyping approaches offer potential to stratify patients biologically and guide targeted therapy, but require well-characterised cohorts with linked biosamples. We describe the PARIS (Pneumonia: Acute Respiratory Infection +/- Sepsis) study: a prospective observational cohort of hospitalised patients with pneumonia, designed to characterise functional outcomes and to provide a biobank for translational immunological research. Methods Adults admitted with CAP to a single NHS district general hospital were enrolled within 24 hours of admission between December 2020 and March 2022. Clinical, functional, and physiological data were collected at enrolment, hospital discharge, and 6-8 week follow-up. Serial blood samples were collected for flow cytometry, transcriptomics, pathogen DNA detection, and plasma biobanking. Results Forty-seven patients were enrolled (15 without and 32 with sepsis [SOFA >=2] at enrolment); 87% met sepsis criteria by 24 hours post enrolment. Most patients (30/47, 64%) were managed as COVID-19, microbiologically confirmed in 27. Mean age was 57 years (SD 16), 70% were male, and baseline comorbidity burden was low. Severity was moderate (median NEWS2 4 at enrolment, rising to 6 by 24 hours post enrolment; p<0.001). Mortality was 4/47 (8.5%), with 44/47 (94%) alive at hospital discharge. Median length of stay was 8 days (IQR 5.5-11). Translational samples were collected from the majority: fresh flow cytometry (44/47, 94%), transcriptomics from the sepsis subgroup (31/32, 97%), pathogen DNA sampling (35 samples received across study timepoints; see Table 5), and stored plasma (29/47, 62%). The primary outcome of functional decline (Barthel score decrease >=1.85) occurred in only 1/29 patients with paired assessments (3.4%). Persistent CRP elevation (>3 mg/L) at 6-8 week follow-up was present in 16/31 (52%) survivors with available data. Conclusions The PARIS cohort provides a well-characterised clinical platform and linked biobank to support translational studies of pneumonia and sepsis. The low rate of functional decline reflects the younger, lower-comorbidity, COVID-predominant population recruited. Primary protocol endpoints were not achieved owing to pandemic-related disruption. Data and samples underpin a programme of linked translational studies.

Background and Objectives: Area-based hypoxic burden, termed as hypoxic dip area (HDA) has been studied as a novel obstructive sleep apnea (OSA) metric that may better characterize intermittent hypoxemia in OSA and thereby better predict outcomes. However, to be of use in routine clinical care, a physiological normative value is necessary. Here we attempt to use several large cohorts to establish a percentile-based threshold that can classify individuals with normal vs. abnormal physiological profiles. Methods: Data from 10 cohorts (EPISONO, FINS, Dayfun, MrOS, MESA, SHHS, APPLES, WSC, CFS, and AIRS [Mount Sinai Clinical Cohort]; n=14,031 subjects) were included. HDA was defined as the area bounded by SpO2 nadirs ([&ge;]2% desaturation) flanking left/right peaks. The 97.5th percentile of HDA among asymptomatic subjects (n=136) from EPISONO, FINS, and DAYFUN (aged 20-52 years; 46 [33.8%] male) was used to define normal and elevated HDA levels. Physiological features, clinical comorbidities, and incident cardiovascular disease (CVD) events and mortality were compared between normal/elevated HDA groups. Sensitivity analyses were conducted using age-, sex-, and BMI-adjusted threshold derived from multivariable regression model. Results: The 97.5% percentile cutoff of HDA was 8.6%min/h, classifying 4,500 individuals as normal HDA and 9,531 as elevated HDA. Individuals with elevated HDA ([&ge;]8.6%min/h) demonstrated greater nocturnal hypoxemia (lower baseline SpO2, higher T90, T85, T80 and oxygen desaturation index), higher AHI (apnea-hypopnea index) and arousal index, and greater daytime sleepiness as well as a higher prevalence of lifetime CVD and hypertension across cohorts. Elevated HDA was related with a higher prevalence of incident CVD events and mortality in unadjusted analyses, although these associations were attenuated after adjustment for confounding factors. Results were similar using alternative thresholds derived from multivariable regression analyses. Conclusions: A physiologically derived cutoff of 8.6% min/h for HDA effectively distinguishes physiological profiles across respiratory, arousal, and oxygenation domains and generalizes across multiple cohorts. Those with elevated HDA had a higher prevalence of incident CVD outcomes, although observed relationships were attenuated after further adjustment. Our findings provide a physiologically interpretable threshold for HDA that can be readily used in clinical use.

Introduction Acute lower respiratory tract disease (aLRTD) is a leading cause of hospitalisation and death, particularly in older adults and adults with comorbidities, with acute lower respiratory tract infection (aLRTI; pneumonia and non-pneumonic LRTI) being a major component. Non-pulmonary complications and functional decline after aLRTI are recognised, but their pathogen-specific burden is poorly described. We aimed to quantify renal, hepatic, thromboembolic and functional complications, and mortality, after aLRTI hospitalisation, by clinical phenotype and pathogen. Methods We conducted a cohort study of adults (>18 years) admitted with aLRTD to two hospitals in Bristol, UK (01 August 2022-31 July 2024). aLRTD was classified as pneumonia, non-pneumonic LRTI (NP-LRTI) or no diagnosis of aLRTI. Pathogens were identified from standard-of-care and research microbiology. Outcomes were acute kidney injury (AKI), acute liver dysfunction, venous thromboembolism (VTE), in-hospital falls, reduced mobility at discharge, increased care requirements, and 30-day and 1-year mortality. Analyses were descriptive. Results Among 246,797 adult admissions, 21,456 aLRTD hospitalisations were included: 10,239 (47.7%) pneumonia, 7,742 (36.1%) NP-LRTI and 3,475 (16.2%) with no evidence of aLRTI. Of 19,152 tested aLRTD admissions, 8,503 (44.4%) had a positive microbiological/virological test, yielding 9,204 pathogen detections; 1,194 (6.2%) had co-infections, and SARS-CoV-2 was most frequent, with influenza the second most common in pneumonia and NP-LRTI. Pneumonia had greater severity than NP-LRTI and no diagnosis of aLRTI (median length of stay 6 vs 4 vs 4 days; ICU admission 3.4% vs 0.7% vs 0.5%, respectively). Overall, 22.2% developed AKI, 6.1% acute liver dysfunction, 0.6% DVT and 2.4% PE; 1.8% had a fall, 11.5% reduced mobility, and 16.6% required increased care at discharge. 30-day and 1-year mortality were highest for pneumonia (14.0% and 32.0%, respectively). Pathogen-specific analyses showed longer stays and higher complications and mortality rates for SARS-CoV-2 and Streptococcus pneumoniae, and shorter stays with lower complication and mortality rates for influenza and Haemophilus influenzae. Conclusions Non-cardiovascular complications and functional decline after aLRTI were common, particularly in pneumonic and SARS-CoV-2 or pneumococcal disease. These findings support routine surveillance for renal, hepatic, thromboembolic events, early mobilisation and rehabilitation, and consideration of multi-system outcomes when evaluating public health and economic value of vaccines and therapies.

Background: Aging has a critical role in lung changes and the outcome of lung disease. Several lung aging equations have been proposed to measure deviation from physiological aging of the respiratory system. In this study, we aimed to develop a single measure of accelerated lung aging and show its application as a measure of lung aging. Method: We used a pre-bronchodilator pulmonary function test (PFT) from NHANES adult participants recruited from 2007 to 2011. We applied Klemera-Dubal Method (KDM) to four PFT measurements, FEV1, FVC, FEF25-75, and PEF, to calculate a measure of lung biological aging. Physiological Aging of the Respiratory System (PARS) was calculated from the residual method vs. chronological age. We tested the construct validity of PARS by measuring its association with risk factors of lung health. The prognostic validity was measured using a survival analysis. Sampling weights were applied to all analyses. Results: In 14,123 adult participants, the mean (SD) of accelerated lung age (PARS) was 0 (8.2) years. Participants with a history of asthma and emphysema had 4- and 10-year higher PARS. Cigarette smoking, lower socioeconomic status, black race, higher serum cadmium, and lower serum selenium and magnesium were associated with higher PARS. During 116 months of follow-up, PARS was associated with a higher mortality (HR = 1.06, 95%CI: 1.05-1.07 per year). Females with higher PARS had a higher risk of death (P for interaction < 0.001). Results were consistent across different subgroups and sensitivity analyses. Conclusion: PARS is a noninvasive lung aging marker and can be applied as a single measure of lung accelerated aging in the adult population. Its strong construct and predictive validity support its future application among different populations with and without lung disease.

Background and Objective: Diabetes mellitus (DM) causes autonomic neuropathy, which may alter nocturnal respiratory rate (NRR). To test the association between DM and NRR, we analyzed elective polysomnograms of four large observational cohorts. Research Design and Methods: We performed cross-sectional analysis of over 25,000 individuals with polysomnograms (PSGs) from the Sleep Heart Health Study (SHHS), Hispanic Community Health Study/Study of Latinos (HCHS/SOL), Osteoporotic Fractures in Men Study (MrOS), and Wisconsin Sleep Cohort (WSC). Patient-level NRRs were derived from inductance plethysmography waveforms. DM status was determined by self-report, physician diagnosis, medication use, or laboratory values, depending on the cohort. We related DM and NRR (continuous and dichotomized) using logistic regression models and adjusted for potential confounders. Cohort-specific results were combined using random-effects meta-analysis. Results: Meta-analysis of unadjusted models showed a pooled odds ratio (OR) of 1.10 (95% CI:1.04-1.17) for each breath-per-minute (brpm) increase in NRR. This association remained significant after multivariable adjustment (OR:1.06, 95% CI:1.02-1.11). Dichotomized analyses similarly showed higher odds of DM across dichotomization thresholds ranging from 15 to 21 brpm. At a threshold of 18 brpm, the unadjusted pooled OR was 1.77 (95% CI:1.23-2.55, P=0.0022), and the adjusted OR was 1.49 (95% CI:1.10-2.02, P=0.0098). Conclusions: Clinically stable outpatients with elevated NRR have an increased prevalence of DM. Additional studies are needed to investigate whether the mechanism is autonomic neuropathy and whether monitoring NRR can detect early complications of DM.

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.

Rationale: Fibrosing interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF), have heterogeneous postdiagnosis courses. Existing prognostic tools often rely on pulmonary function testing, imaging, or laboratory data that may not be uniformly available and rarely provide individualized, time-updated forecasts of multiple clinically relevant trajectory events. Objectives: To determine whether longitudinal healthcare claims can generate test-free, time-updated forecasts of clinically actionable postdiagnosis trajectory events in patients with fibrosing ILD and IPF. Methods: Using de-identified longitudinal administrative claims from the Merative MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases, we constructed code-based digital twins (ZeBRA) encoding each patient's evolving diagnosis, pharmacy, and procedure history. Horizon-specific models forecast seven claims-observable events: supplemental oxygen escalation, pulmonary hypertension, acute respiratory failure/ARDS composite, nausea, diarrhea, liver injury, and gastrointestinal bleeding. The analytic cohort included 345,918 patients with fibrosing ILD, including 17,284 with IPF. Predictions were evaluated in a time-updated follow-up setting at 1-month, 6-month, and 1-year horizons. Results: Predictive discrimination was consistent across events and horizons. In fibrosing ILD, AUC ranged from 0.691 for liver injury at 1 year to 0.912 for oxygen dependence at 1 month, with PPV ranging from 0.189 to 0.714. At 1 month, oxygen dependence achieved an AUC of 0.912 +/- 0.005 with PPV of 0.473 +/- 0.005, and pulmonary hypertension achieved an AUC of 0.881 +/- 0.005 with PPV of 0.539 +/- 0.005. The IPF subcohort showed analogous horizon-dependent performance, with AUC ranging from 0.687 to 0.855 and PPV from 0.245 to 0.817. At 1 month in IPF, PPV was 0.753 +/- 0.015 for oxygen dependence and 0.817 +/- 0.011 for pulmonary hypertension. Conclusions: A test-free digital-twin framework derived from routine longitudinal claims can provide individualized, time-updated forecasts of actionable fibrosing ILD and IPF trajectory events without imaging, pulmonary function tests, laboratory data, clinical notes, or patient-facing data collection. These forecasts may support low-burden reassessment, anticipatory care planning, and earlier recognition of elevated near-term risk for respiratory deterioration or management-altering complications.

Cystic fibrosis (CF) is characterized by defective CFTR-mediated chloride transport, resulting in elevated sweat chloride concentrations. As people with CF (PwCF) now live longer due to highly effective CFTR modulators, exercise has become integral to maintaining health, yet it introduces additional physiological demands on salt and fluid balance. In this study, we used a wearable microfluidic biosensor (CF Patch) to quantify sweat rate and chloride loss during exercise performed both in the supervised laboratory and remote free-living in PwCF and healthy volunteers (HV). Participants completed exercise sessions under both conditions, with continuous heart rate monitoring and sweat collection with real-time measurement of sweat characteristics. Sweat volume and chloride concentration were assessed by colorimetric image analysis, enabling estimation of total fluid and chloride loss at the end of each exercise session. PwCF exercised for a longer duration at a lower average heart rate during remote exercise compared to laboratory exercise though exercise volume (average heart rate x duration) was greater during remote exercise. There was a positive association between exercise volume and both fluid and chloride loss for both PwCF and HV. PwCF exhibited greater chloride loss for a given exercise volume compared to HV, though fluid loss was similar. Further, compared to HV, PwCF demonstrated significantly greater intra- and interindividual variability in sweat chloride loss across the remote exercise sessions. Collectively, these findings provide evidence for the feasibility and physiological validity of remote exercise assessment and establish the feasibility and physiological validity of wearable sweat sensing for remote monitoring of fluid and electrolyte dynamics during real-world exercise. In addition, the variability of chloride loss in response to exercise suggests utility of the CF Patch in providing personalized fluid and salt repletion data for PwCF and advances the translational potential of digital sweat diagnostics for personalized CF care.

Background Elexacaftor-tezacaftor-ivacaftor (ETI) has been demonstrated to improve lung function in clinical trials; however, evidence describing effects on trajectories and whether long-term improvements are sustained (>1-year) is lacking. We estimated within-person lung clearance index (LCI) trajectories before and after ETI initiation, assessing changes in level and rate of change, alongside acute LCI change, up to three years after ETI initiation. Methods Prospective observational study of children at a tertiary hospital. Children aged 3-17 years with [&ge;]2 LCI testing occasions (i) before and (ii) after starting ETI were used to describe lung function trajectories. Children with [&ge;]1 pre-ETI and [&ge;]1 post-ETI LCI occasion(s) were used to describe acute LCI change after ETI initiation. Age-adjusted LCI trajectories for time periods (i) before and (ii) after ETI initiation were estimated using linear mixed-effects models, and pre- and post-ETI LCIs were compared using paired Wilcoxon tests. Results Mean pre-ETI and post-ETI longitudinal changes in LCI were -0.007 (95% CI: -0.28, 0.27; n=35) and 0.12 (95% CI: -0.17, 0.41; n=20) turnovers per year, respectively. Before ETI initiation, 57% (30/53) of patients had an LCI[&ge;]7.1 turnovers (indicating impaired lung function), compared to 26% (14/53) post-ETI, with a median LCI difference of -0.70 (95% CI -0.84, -0.46; p<0.001) turnovers. Within-individual variability in LCI decreased post-ETI. Conclusions Our real-world data within a unique longitudinal study provide a comprehensive picture of ETI benefit by outlining not only acute improvement in LCI but maintained stability in LCI trajectories and improved LCI stability sustained up to three years post-initiation.

Background Hypercapnia may indicate a primary ventilatory syndrome, a complication of another illness, or an epiphenomenon of severe disease. The presenting context of hypercapnia is poorly quantified, limiting clinical interpretation and synthesis of epidemiologic studies. Methods We performed a retrospective cross-sectional study of Medical Information Mart for Intensive Care IV (MIMIC-IV) hospital admissions linked to an emergency department (ED) presentation from 2011 through 2019. Admissions were included if the triage chief complaint was not missing and at least one prespecified criterion for hypercapnia was met: an International Classification of Diseases (ICD) code for hypercapnic respiratory failure or obesity hypoventilation syndrome, arterial blood gas (ABG) PCO2 45 mmHg, venous blood gas (VBG) PCO2 50 mmHg, or indeterminate-source blood gas PCO2 50 mmHg. Triage chief-complaint text was classified by natural language processing (NLP) into 17 National Hospital Ambulatory Medical Care Survey reason-for-visit (RFV) categories using a multi-label framework. Primary analyses estimated admission-level RFV category prevalences; secondary analyses compared distributions by overlapping ascertainment indicator, age, and acidemia. Results The total cohort included 11,941 admissions: 1,542 (12.9%) met both blood-gas and ICD-code criteria, 9,958 (83.4%) met blood-gas criteria only, and 441 (3.7%) met ICD-code criteria only. Median age at admission was 68 years (IQR 56-78), and 6,423 admissions (53.8%) were for male patients. Respiratory RFV categories were most prevalent (30.2%), followed by administrative reasons (17.5%), digestive symptoms (14.0%), injuries and adverse effects (14.0%), and nervous-system symptoms (13.8%); categories were not mutually exclusive. Respiratory categories were more common in ICD-positive admissions (50.2%) than in VBG-defined (36.3%) or ABG-defined admissions (27.3%). Injuries and adverse effects were most prevalent among admissions for patients aged 18-39 years (34.4%), whereas respiratory categories increased from 13.7% among admissions for patients aged 18-39 years to 36.5% among admissions for patients aged 80 years. NLP-derived classifications showed mean set-F1 of 0.84 against adjudicated clinician labels in the full annotated benchmark sample. Conclusions Among ED-linked admissions with hypercapnia by diagnosis code, blood gas, or both, respiratory complaints were the most common chief-complaint category but represented fewer than one-third of admissions. Presentation context should be incorporated when defining, comparing, and interpreting hypercapnia cohorts, particularly those ascertained by blood-gas criteria.

Introduction: Respiratory syncytial virus (RSV) causes significant disease in older and comorbid adults. Current UK vaccination recommendations restrict eligibility to adults [&ge;]75-years, 65-74-years with chronic respiratory disease or immunosuppression, and those in care homes, but evidence on clinical burden in adults <75-years with comorbidities is limited. This study assessed patient characteristics, healthcare resource utilisation (HCRU), and mortality in adults hospitalised with RSV in England. Methods: Population-based retrospective cohort study using linked Clinical Practice Research Datalink Aurum and Hospital Episode Statistics. Adults [&ge;]60-years hospitalised with RSV between October 2014-March 2019 were included. RSV episodes defined as 90-days post diagnosis. Case definitions were created using diagnosis codes related to confirmed RSV (RSV-specific) or acute lower respiratory tract infection where other causative pathogens were excluded (RSV-possible). All-cause HCRU (hospitalisations, critical care admissions, outpatient attendance, primary care consultations, and prescriptions) and case fatality rates were assessed. Results were stratified by age (60-74 and [&ge;]75-years), case definitions (RSV-specific, RSV-possible) and comorbidity profiles (chronic respiratory disease, immunocompromised, cardiovascular disease). Results: A total of 97,712 hospitalised episodes in those aged [&ge;]60-years were included in the analysis, where 785 (0.8%) were RSV-specific cases (n=338 aged 60-74-years, n=447 aged [&ge;]75-years). In RSV-specific cases, median (IQR) cumulative length of stay (LoS) for those [&ge;]75-years was 10.00 (6.00-22.00) days which was equivalent to or lower than each comorbidity sub-group in those aged 60-74-years, with longest LoS in those immunocompromised (11.50 [7.00-26.00] days). Critical care admissions were more often observed across comorbidity stratifications (13.85%-22.34%) compared to those [&ge;]75-years (5.03%). All-cause and RSV-related case fatality rates for RSV-specific cases were highest among those [&ge;]75-years (all-cause: 19.3%; RSV-related: 10.3%). Conclusion: HCRU within RSV episodes in those aged 60-74-years across comorbidity profiles was equal to or greater compared to those aged [&ge;]75-years. These findings highlight the need to prioritise consideration of comorbidity groups that could benefit from RSV vaccination. Key words: Respiratory syncytial virus; vaccine; chronic obstructive pulmonary disease; diabetes mellitus; immunocompromised; asthma; chronic kidney disease; cardiovascular disease; healthcare resource utilisation.

Background: Predictive risk stratification tools are widely used to support proactive care for older adults, yet head-to-head external validation within local English health systems remains limited. Eclipse-PRISM implemented in UK primary care settings, while the Johns Hopkins Adjusted Clinical Groups (ACG) system provides risk scores derived from diagnosis groupings and healthcare utilisation data. Aim: To externally validate and compare PRISM and Johns Hopkins ACG scores for predicting emergency hospital admission among older adults in an English integrated care system. Methods: We conducted a retrospective cohort study in the Norfolk and Waveney Integrated Care System. Individuals aged 75 years and over at the index date with valid PRISM and ACG emergency admission risk scores and linkage to hospital activity data were included. The primary outcome was 1 or more emergency hospital admission within 1 month. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC), with paired AUCs compared using DeLongs test. Calibration was evaluated using calibration plots and quantified using calibration intercept and slope from logistic recalibration models. Overall accuracy was summarised using the Brier score. Clinical utility was assessed using decision curve analysis (DCA). Results: The cohort included 114,407 patients aged 75 years and over; 2,136 (1.87%) had 1 or more emergency admission within 1 month. ePRISM showed higher discrimination than Johns Hopkins ACG (AUC 0.860 [95% CI 0.852 to 0.867] vs 0.739 [95% CI 0.728 to 0.749]; difference-in-AUC 0.121 [95% CI 0.111 to 0.130]; DeLong p<0.0001), with consistent differences across age and sex subgroups. Calibration differed materially: ePRISM showed closer agreement between predicted and observed risks, whereas Johns Hopkins ACG systematically overpredicted risk across much of the range. Brier scores favoured ePRISM (0.017 [95% CI 0.017 to 0.018] vs 0.051 [95% CI 0.050 to 0.051]). In DCA, ePRISM provided higher net benefit across clinically plausible thresholds, while Johns Hopkins ACG showed lower or negative net benefit across much of the threshold range. Conclusions: In this English older population, ePRISM demonstrated higher discrimination and more favourable apparent calibration, overall accuracy and decision-analytic performance for predicting 1-month emergency admission than Johns Hopkins ACG. Model selection for short-term risk stratification should therefore consider calibration and clinical utility alongside discrimination, with local validation and recalibration where appropriate before implementation.

Inadequate autophagy promotes smoking-induced cellular senescence involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome axis. For the first time, we investigated the therapeutic potential of pemafibrate, a putative TFEB inducer. COPD lung epithelial cells showed reduced TFEB expression. Pemafibrate enhanced autophagy/mitophagy flux and restored lysosomal acidification observed during cigarette smoke (CS) extract exposure in human bronchial epithelial cells, resulting in reduced cellular senescence. TFEB knockdown demonstrated involvement of pemafibrate-induced TFEB in these effects. Pemafibrate induced TFEB expression, mitigated alveolar enlargement and airflow obstruction, and attenuated the CS-induced increase in static lung compliance in a long-term CS-exposed mouse model. It reduced the CS exposure-induced cellular senescence, possibly through autophagy/mitophagy, as suggested by bulk RNA sequencing of mouse lungs. A retrospective cohort study showed that patients given pemafibrate displayed attenuated FEV1.0 decline compared with those given bezafibrate or fenofibrate. In conclusion, pemafibrate is a promising therapeutic agent for COPD, potentially exerting its effects through the regulation of the TFEB-autophagy/mitophagy-lysosome axis.

Introduction Individuals with Gastroesophageal Reflux Disease (GERD) often experience airway inflammation and bronchoconstriction as a result of reflux aspiration and/or vagally mediated reflexes. The Impulse Oscillometry System (IOS) is a sensitive, non-invasive tool that can detect subtle changes in airway resistance. While there are few studies exploring airway resistance in GERD globally, no studies have been conducted in Sri Lanka. Therefore, we aim to compare the airway resistance using IOS in medical undergraduates with and without symptomatic GERD. Methods A cross-sectional study was conducted among 811 medical undergraduates (31.1% male; mean age 22.9 years) at the Faculty of Medicine, Rajarata University of Sri Lanka. Symptomatic GERD was screened using the validated GerdQ, and a cutoff of[&ge;]8 was used to diagnose those with GERD symptoms. Of the 242 (29.8%) with GERD symptoms, 188 with chronic respiratory diseases or recent respiratory symptoms were excluded, and 50 with GERD symptoms and 50 healthy, age- and sex-matched controls were recruited. Lung function was assessed using IOS and spirometry, according to American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines. Results Prevalence of symptomatic GERD among medical undergraduates was 29.8% (242/811). The common symptoms among GERD were heartburn (89.6%, 217/242) and regurgitation (85.5%, 207/242). Oscillometry parameters including, R5-R20 Hz (15.29% vs 9.69%, p=0.002), Fres (14.95 1/s vs 13.37 1/s, p = 0.04), and AX (0.66 vs 0.48, p = 0.02) were significantly higher in students with symptomatic GERD (mean = 15.29%) than in healthy controls (mean = 9.69%; p = 0.002). However, spirometry parameters including FEV1, FVC, and PERF did not differ between the GERD-positive and control groups. Conclusion Individuals with symptomatic GERD demonstrated a higher peripheral airway resistance compared to controls, whereas no significant difference was observed in upper airway resistance. This could be due to the gastric acid stimulation of vagal nerve terminations in the lower part of the esophageal wall, leading to increased resistance in the peripheral airways through vagally mediated bronchoconstriction.

Background: Mortality analysis traditionally focuses on the single underlying cause of death (UCD), which obscures the wider morbidity process at the end of life. Multiple causes of death (MCoD) data, recording all conditions on the death certificate, are increasingly used as a proxy for end-of-life multimorbidity, yet how accurately they represent it remains underinvestigated. We assessed whether recorded causes reflect end-of-life health conditions or rather the chain of events leading to death. Methods: Using linked Danish registers (Population, Cause of Death, Chronic Diseases, and Cancer), we studied residents aged 50+ diagnosed with COPD, dementia, diabetes, or cancer who died in 2010-2022 (ranging from 38779 to 224330 per disease cohort). We examined how often each diagnosed disease appeared on the certificate, its location and selection as the UCD, factors associated with its appearance (logistic regression), disease-specific mortality (multiple decrement life tables), and disease associations (Cause of Death Association Indicator, CDAI). Results: Cancers appeared on the death certificate far more often than chronic diseases (around 75% versus 19-58%) and were usually recorded in Part 1 and selected as the UCD, whereas chronic diseases were rarely the UCD. The odds of a disease appearing depended on factors such as age at and time since diagnosis. When a diagnosed disease was recorded, the certificate traced a coherent path to death; when it was absent, ill-defined causes became more common. The CDAI highlighted specific association pathways between diseases. Conclusions: MCoD data capture only part of the chronic disease burden present at death and should be interpreted cautiously as a proxy for end-of-life multimorbidity. They are, however, well suited to describing the pathways leading to death.

Excessive daytime sleepiness (EDS) is a common but inconsistently predicted symptom of obstructive sleep apnea (OSA). OSA is typically diagnosed with polysomnography (PSG), and the current standard for severity assessment is the apnea-hypopnea index (AHI). AHI has many limitations, including its inability to explain physiological mechanisms or reflect variability in patient symptoms, such as EDS. This retrospective study aims to find physiological and demographic parameters that better predict EDS in patients with OSA and to evaluate whether these parameters outperform AHI using PSG data from the Mount Sinai Integrative Sleep Center. Clinical variables used to predict EDS included arousal index (AI), average oxygen desaturation during sleep, average heart rate during sleep, and AHI, along with demographic variables including age, sex, and BMI. Hypothesis tests, logistic regression models, and decision tree classifier models were performed on the data to discriminate sleepy from nonsleepy patients as determined by an Epworth Sleepiness Scale (ESS) score [&ge;] 10. AI and oxygen desaturation were found to be the most predictive physiological variables, and sex and BMI were found to be the most predictive demographic variables. The final decision tree model with these four variables outperformed the AHI in predicting EDS. These findings suggest that daytime sleepiness in OSA can be better explained by measures of apnea burden, oxygenation impairment, and patient demographics than by AHI alone, although these remain only modestly predictive. Future studies should focus on investigating more comprehensive physiological markers, multi-night sleep data, and more objective assessments of sleepiness.