Respiratory Research

Respiratory monitoring in daily-life settings is important for health assessment, yet extracting physiologically interpretable information from breathing signals under natural conditions remains challenging, as breathing is inherently dynamic and strongly modulated by behavior. Here, a portable breathing monitoring device based on a flexible lead zirconate titanate sensor is developed to address this challenge. By exploiting polarity-opposed piezoelectric and pyroelectric responses through sensor orientation, the recorded breathing waveform exhibits a characteristic dual-component structure, consisting of a narrow transient spike followed by a broad quasi-steady peak within each breathing phase. This intrinsic waveform structure enables phase-resolved quantification of how breathing effort is distributed between transient and quasi-steady components during inhalation and exhalation. Pilot measurements in healthy subjects and patients with chronic obstructive pulmonary disease or asthma reveal systematic shifts toward transient-enhanced breathing in patients, providing clearer differentiation than conventional descriptors based on breathing duration or amplitude. By transforming complex breathing dynamics into stable and physiologically meaningful signal components under daily-life conditions, this dual-response sensing approach enables more robust access to function-related changes in natural breathing.

Background and AimsThe prognosis of interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) has not been studied as extensively as IPF. This study aimed to evaluate baseline factors associated with mortality in non-IPF ILD, including demographic characteristics, respiratory function test (RFT), comorbidities, and ILD subtypes. MethodsThis retrospective cohort study analysed prospectively collected data of patients with non-IPF ILD at a single tertiary centre in Malaysia (2010-2023). Patients without baseline RFT or HRCT were excluded. Survival was assessed using Kaplan-Meier analysis, and mortality predictors were identified using Cox regression. ResultsThe mean age was 60 {+/-} 15 years, with a male-to-female ratio of 1:3. Indian ethnicity constituted the largest group (n = 109, 47.6%). The mean baseline forced vital capacity (FVC) was 53.3 {+/-} 21% predicted. An FVC <50% predicted, age [&ge;]50 years at diagnosis, specific ILD subtypes, and ethnicity were independently associated with mortality. Compared with Malays, both Chinese (hazard ratio [HR] 9.86, 95% confidence interval [CI] 1.27-76.89, p = 0.037) and Indians (HR 8.59, 95% CI 1.14-64.69, p = 0.001) were associated with a higher risk of death. Kaplan-Meier analysis demonstrated significant differences in survival across non-IPF ILD subtypes (log-rank p = 0.048), with hypersensitivity pneumonitis showing the poorest prognosis (mean survival 6.1 years). ConclusionEthnicity emerged as an independent prognostic factor for mortality in non-IPF ILD. The underlying mechanisms remain unclear and may reflect differences in genetic variation, cultural factors, or environmental exposures. Larger prospective studies are required to validate these findings.

ObjectiveMyositis-associated interstitial lung disease (myositis-ILD) consists of two predominant radiologic patterns of lung injury--nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP)--that oftentimes coexist. However, it remains unclear whether either is associated with clinical outcomes. We aimed to assess the therapeutic response in patients with NSIP-compared to those with OP-predominant myositis-ILD. MethodsThis retrospective, single-center cohort study recruited participants from the Northwestern University ILD Registry with a circulating myositis-associated antibody, ILD, and at least 6 months of follow-up while on immunomodulatory therapy during a 24-month observation period after diagnosis. Two thoracic radiologists determined the predominant radiologic pattern (NSIP or OP). The primary outcome was the absolute change in forced vital capacity (FVC) at 24 months post-diagnosis. Secondary outcomes included changes in the diffusing capacity of the lung for carbon monoxide (DLCO) and radiologic qualitative and quantitative measures of lung injury. ResultsForty-one participants were included in analyses. 71% had an OP-predominant while 29% had an NSIP-predominant radiologic pattern of lung injury. Both exposure cohorts had improvement in mean absolute FVC (OP cohort = +0.18L [p=0.005], NSIP cohort = +0.24L [p=0.07]) over the 24-month observation period. The OP (p<0.05) but not the NSIP cohort (p=0.20) had an increase in DLCO. The OP cohort demonstrated improvement in the qualitative assessment of follow-up imaging (p<0.05), driven by quantitative improvement in groundglass/consolidative opacities (p=0.006). A subset of participants demonstrated features of NSIP/OP overlap and had greater baseline radiologic severity of lung injury. ConclusionPatients with circulating myositis-associated antibodies and an OP-predominant pattern of lung injury may have a more favorable response to therapy than those with NSIP. Further studies are needed to validate our findings and delineate other features cognate with these associations. Significance and InnovationsO_LIRadiologic phenotyping may predict therapeutic response in myositis-ILD. This study demonstrates that an OP-predominant computed tomography (CT) pattern of lung injury is associated with greater improvement in lung function and radiologic signs of inflammation over 24 months on at least 6 months of immunomodulatory therapy compared with an NSIP-predominant pattern, suggesting that CT pattern may provide clinically meaningful prognostic information. C_LIO_LIFirst study to integrate blinded qualitative radiologic adjudication with quantitative CT scoring in myositis-ILD. By combining dual-radiologist review with Kazerooni quantitative scoring and longitudinal pulmonary function testing, this study offers a rigorous and multidimensional assessment of treatment response. C_LIO_LIExpands risk stratification beyond antibody-based toward imaging-based phenotyping strategies. In a heterogeneous population defined by diverse myositis-associated antibodies, this work introduces radiologic pattern as a practical and accessible framework for anticipating treatment responsiveness. C_LIO_LIProvides hypothesis-generating data for precision management in myositis-ILD. The findings support the concept that imaging-defined subgroups may exhibit differential therapeutic trajectories, laying groundwork for future multicenter studies integrating CT phenotype, antibody profile, and treatment strategy. C_LI

BackgroundReliable detection of latent Mycobacterium tuberculosis (Mtb) infection (LTBI) remains challenging, particularly in TB contacts and immunocompromised individuals, where interferon-{gamma} release assays (IGRAs) demonstrate variable sensitivity. IP-10, a chemokine produced at substantially higher concentrations than IFN-{gamma}, represents a promising immune marker. This study aimed to evaluate the diagnostic performance of two IP-10 based assays RIDA(R)QUICK TB (lateral flow) and RIDASCREEN(R) TB (ELISA), by comparison with QuantiFERON-TB Gold Plus (QFT-Plus) assay or a composite reference standard. MethodsA cross-sectional diagnostic accuracy study enrolled 99 adults: 49 with culture-confirmed active pulmonary TB, 30 close TB contacts and 20 individuals with autoimmune disease, in Bucharest, Romania. All participants underwent RIDA Quick, RIDA Screen and QFT-Plus testing. Indeterminate results for all assays were reclassified using a composite reference standard. ResultsAgainst culture in active TB cases, RIDA(R)QUICK TB demonstrated a sensitivity of 85.7% (95% CI: 72.8-94.1) and PPV of 97.7%, while RIDA(R)SCREEN TB achieved 91.8% sensitivity (95% CI: 80.4-97.7) and 97.8% PPV. Specificity and NPV could not be reliably estimated due to the near-absence of true-negative individuals. Agreement with QFT-Plus was moderate to good ({kappa}=0.47-0.93).ROC analysis performed against QFT-Plus as a comparator demonstrated good immunological discrimination for RIDA(R)QUICK TB (AUC = 0.828) and RIDA(R)SCREEN TB (AUC = 0.767), reflecting concordance with QFT-Plus rather than diagnostic accuracy against confirmed infection. ConclusionIP-10 based assays demonstrated higher sensitivity than QFT-Plus and excellent PPV across bacteriological standard, supporting their use as complementary tools for LTBI detection. Larger, more heterogeneous cohorts are needed to accurately define specificity and operational integration.

Background: Interstitial lung abnormalities (ILA) are radiologic findings of increased lung density or fibrosis in individuals without clinical interstitial lung disease (ILD) and are associated with increased mortality and progression to ILD. Understanding physiologic trajectories of lung function preceding ILA diagnosis may illuminate early mechanisms of lung injury. Methods: We recruited participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Lung Study, a prospective cohort of adults enrolled at ages 18 to 30 years and followed longitudinally for 25 years. Percent predicted forced vital capacity (ppFVC) was measured at five study visits over 20 years. Individual ppFVC trajectories were estimated using random coefficient models. Person specific slopes were incorporated into logistic regression models to examine associations with visually detected ILA on chest CT at exam year 25. Models were adjusted for age, sex, race, body mass index, pack years of smoking, and study center. Results: Among 3,136 participants with complete data, 57 (1.8%) had ILA at mean age 51 years. In univariable and multivariable models, individuals with ILA had greater cumulative decline in ppFVC over the 20 years preceding diagnosis. Each 10% absolute decline in ppFVC was associated with more than twice the odds of ILA (adjusted OR 2.21; 95% confidence interval 1.47, 3.31; p = 0.0001). Conclusions: Greater longitudinal decline in FVC from early adulthood was strongly associated with the presence of ILA at midlife. These findings suggest that physiologic impairments precede radiologic evidence of subclinical parenchymal lung abnormalities, underscoring the potential of life course lung function trajectories to identify individuals at risk for developing ILD.

The genetic relationship between asthma and lung function may be dependent on age-at-onset (AAO) of asthma. We investigated whether the shared genetics between asthma AAO and lung function is dependent on AAO. Asthma cases from UK Biobank were subset according to their AAO and genetic correlation was used to obtain genetically homogeneous groups, i.e., [&le;]20 (LT20), 20-40, and >40 (GT40) years. Association analysis and fine-mapping were performed to identify shared genetics between AAO groups and lung function. Mediation and quantitative trait locus (QTL) analyses were performed to identify mechanisms underlying shared genetic associations. Chr5, chr6, chr12, and chr17 each had one region that displayed a cross-phenotype replicated association with at least one AAO group and lung function. Overlapping credible sets obtained from fine-mapping were observed on chr5 and chr6. Mediation analyses demonstrated that for each region the proportion mediated through asthma on lung function was larger for asthma LT20 compared to 20-40 and GT40 suggesting that their effects on lung function were more strongly driven by this association. Tissue-specific QTL analysis revealed shared etiology on chr5 may be acting through SLC22A5 and C5orf56 which might play an important role in decreased lung function among individuals with earlier-onset asthma.

Rapid prediction of the severity of acute coronary syndrome (ACS) is crucial for appropriate intervention in emergency department. Neutrophils (Neu), lymphocytes (Lym) and monocytes (Mon) and their ratios (Neu/Lym, NLR; Mon/Lym, MLR NeuxMon/Lym, SIRI) are acknowledged to be associated with the prediction of the severity and adverse outcome of ACS patients. Here, we analysed retrospectively eosinophils (Eos) and Eos-derived novel ratios (Neu/Eos, NER; Mon/Eos, MER; Neu x Mon/Eos, SIII; Neu/Eos x Lym, NEL; Mon/Eos x Lym, MEL; Neu x Mon/Eos x Lym, SV) of first admitted 1053 ACS patients within 24 hours of symptom onset to predict ST-segment elevation of myocardial infarction (STEMI), high Gensini score (H) and cardiac dysfunction (Killip Classification l to III grades). Results showed that Eos was significantly decreased in ST (n=227), Gensini (H) (n=311) and Killip I group (n=237) (P<0.05). All Eos-derived ratios (NER, MER, SIII, NEL, MEL, SV) were significantly higher with diagnostic severity (ST, Gensini (H), and Killip I group (P<0.05). ROC analysis revealed that SIII and SV predicted ST and Gensini (H) with high specificity and sensitivity, which were similar to that of NLR, MLR and SIRI. Conclusion: Eos and Eos-derived ratios, SIII and SV in particular, are strongly linked to the prediction of the severity of ACS, along with those of well-established leukocyte ratios. The new ratios of Eos hold significant importance in emergency department for quick evaluation of ACS patients.

BackgroundAsthma is a frequent comorbidity in children with sickle cell disease and has been associated with an increased risk of acute complications, particularly vaso-occlusive crises and acute chest syndrome. However, determinants of clinical severity among children with sickle cell disease and confirmed asthma remain poorly characterized, especially in tropical settings. This study aimed to identify factors associated with clinical severity in this population. MethodsWe conducted an observational study among children with sickle cell disease followed in French Guiana. The analysis was restricted to children with confirmed asthma. Clinical severity was defined as the occurrence of at least two hospitalizations during the 12 months preceding evaluation for vaso-occlusive crises and/or acute chest syndrome. Factors associated with severity were assessed using univariate and multivariate logistic regression analyses. ResultsA total of 138 children with sickle cell disease and confirmed asthma were included, of whom 49 (35.5%) presented a severe clinical form. In multivariate analysis, no variable was independently associated with clinical severity. However, a trend toward an increased risk of severe disease was observed among children living in rural areas (adjusted OR = 1.94; 95% CI: 0.77-4.86), while a trend toward a protective effect was observed for Strongyloides stercoralis infection (adjusted OR = 0.18; 95% CI: 0.02-1.51). Allergic sensitization, although frequent (64.5%), was not associated with clinical severity after adjustment (adjusted OR = 0.66; 95% CI: 0.31-1.44). ConclusionAmong children with sickle cell disease and confirmed asthma, more than one third experience severe clinical disease. Severity does not appear to be driven by allergy but may be influenced by environmental and contextual factors specific to tropical settings. These findings support a stratified approach to sickle cell-associated asthma to identify high-risk children and prevent avoidable acute complications.

Smoking Cessation Efforts for Patients with Asthma and COPD IntroductionSmoking cessation can alter the natural history of both COPD and asthma by reducing the frequency and severity of exacerbations and slowing disease progression. Accordingly, the Global Initiative for Asthma and the Global Initiative for Chronic Obstructive Lung Disease recommend that clinicians address smoking cessation at every visit using counseling and pharmacotherapy. MethodsThe Mount Sinai Health System includes seven hospitals and more than 400 outpatient locations in the New York metropolitan area, all using a unified electronic medical record (Epic). De-identified data from calendar year 2024 were extracted for individuals identified as current smokers via the EMR smoking status tool. Patients with asthma and/or COPD were identified using ICD-10 codes. Tobacco treatment was defined as receipt of counseling or pharmacotherapy, including varenicline, bupropion, or nicotine replacement therapy. ResultsAmong 961,997 patients, 58,566 (6.1%) were identified as current cigarette smokers. Across all health system encounters, 32.6% of smokers with both asthma and COPD were given any treatment, followed by 26.7% of smokers with COPD, 13.0% of smokers with asthma, and 9.9% of cigarette smokers without these conditions. Smokers seen in pulmonary clinics were the most likely to be given treatment (17.4%), followed next by primary care (6.6%).The most commonly used treatment for all cohorts and all treatment settings was nicotine with the exception of the pulmonary clinic where varenicline predominated. DiscussionDespite higher treatment rates among smokers with asthma and COPD, only one-third of those with either condition received cessation treatment over a full year, underscoring the need for sustained system-wide quality improvement efforts.

Functional capacity, muscle strength, and patient-reported outcome measures are important indicators of health. In chronic obstructive pulmonary disease (COPD), these traits are often impaired beyond normal age-related decline. Substantial variability exists in both COPD and healthy populations, the biological basis of which remains poorly understood. Given the known contribution of genetics to complex traits, genetic factors may partly explain this variability. This study aimed to identify genetic variants associated with measures used to characterise extrapulmonary traits in COPD. Genome-wide association studies were conducted on the Lab3R-ESSUA cohort for the 6-minute walk test (6MWT), the 1-minute sit-to-stand test (1-min STS), the quadriceps maximal voluntary contraction (QMVC), the handgrip muscle strength, and the chronic airways assessment test (CAAT), adjusting for age, sex, body mass index, pack-years and ancestry. Variants with P<1E-05 were selected for replication in the EARLYCOPD cohort, and effects compared between COPD and healthy populations (two-way ANOVA). A total of 639 participants (364 people with COPD, 275 healthy; 75% male, median age 67 years; BMI of 27 Kg/m2; 10 pack-years) were included. Significant variants were identified for the 6MWT (rs1108983:G, {beta}=-186.5m, P=4.8E-08), the 1-min STS (rs5889103:GTT, {beta}=4.2reps, P=4.8E-08), the Handgrip (rs67352743:A, {beta}=-4.4Kg, P=2.8E-08), and for the CAAT (rs11747040:C, {beta}=4.4points, P=4.0E-09; rs11041680:A, {beta}=-2.6points, P=2.5E-08). Effects were independent of COPD diagnosis. Replication in EARLYCOPD (n=282) confirmed one SNP for 6MWT and three for CAAT. These findings highlight genetic contributions to functional capacity, muscle strength, and disease burden. COPD-related impairments appear to build on pre-existing genetic predisposition, contributing to disease heterogeneity.

BackgroundInterleukin-6 (IL-6) is a cytokine that plays a key role in systemic hyperinflammation and may mediate the relationship between acute COVID-19 and severe long-term outcomes such as Long COVID or death. IL-6 modulating drugs may reduce patients risk of severe post-COVID-19 outcomes. MethodsWe conducted an emulated target trial in a retrospective cohort of patients with moderate-to-severe rheumatoid arthritis who were prescribed IL-6 receptor antagonists (sarilumab or tocilizumab, pooled treatment) or other biologic agents (anakinra or baricitinib, pooled comparator) in 2022. We compared the 12-month cumulative incidence of mortality and Long COVID (diagnosed and probable) between groups using Super Learner and targeted maximum likelihood estimation, adjusting for covariates of interest. ResultsIn our cohort of 3,553 patients, we found that prescription of IL-6 receptor antagonists was associated with a lower 12-month cumulative mortality (adjusted relative risk (aRR) 0.40, 95% CI 0.27, 0.59), diagnosed Long COVID aRR 0.42, 95% CI 0.23, 0.78), and probable Long COVID (aRR 0.71, 95% CI 0.61, 0.83), compared to prescription of other biologic agents, among rheumatoid arthritis patients. ConclusionsIL-6 receptor antagonists may prevent the incidence of severe post-COVID-19 outcomes, such as Long COVID or mortality. This supports the hypothesis that IL-6 may be a mechanistic biomarker of COVID-19 sequelae and that acute COVID-19 severity may mediate this relationship.

BackgroundLow mitochondrial DNA (mtDNA) abundance in blood cells has been associated with various diseases and major causes of mortality. However, the causal link and molecular mechanisms involved remain unclear, and previous studies have had limited follow-up durations. To address these gaps, we examined the relationship of blood mtDNA abundance with all-cause and cause-specific mortality over three decades, and integrated blood transcriptomic profiling to explore underlying molecular mechanisms. Our goal was to improve the understanding of blood mtDNA abundance as a potential early biomarker for major clinical conditions. Methods and findingsWe utilized the clinical and epidemiological data from the prospective OPERA cohort (Oulu Project Elucidating Risk of Atherosclerosis), comprising 1045 individuals initially assessed in the 1990s and followed for over three decades, with a second visit in the 2010s. Blood mtDNA was quantified using real-time quantitative polymerase chain reaction at both time points, and RNA-sequencing was performed on 450 follow-up blood samples. Lower blood mtDNA levels in the 1990s samples were significantly associated with increased overall morbidity and all-cause mortality, assessed up to the end of 2022. Similar trends were observed in a subset of 597 participants from the 2010s. When causes of death were categorized as "cardiovascular", "cancer", or "other", lower blood mtDNA levels predicted higher mortality across all categories. Transcriptomic analysis of the follow-up samples suggested that blood mtDNA variation may be linked to subclinical inflammation involving innate immunity. ConclusionsBlood cell mtDNA abundance shows promise as an early biomarker for general morbidity and mortality in the middle-aged population, although it is not specific to distinct causes of death. The underlying pathomechanism of lower blood mtDNA levels may involve inflammatory processes. These findings, combined with the three-decade follow-up, support the potential use of blood mtDNA in the primary prevention of morbidity and mortality of various etiology.

BackgroundThe never-ending emergence of superbugs casts a shadow over the victorious age of antibiotics. In fact, the triumph of antibiotics was previously viewed in retrospection as our final victory over bacteria. Bacteria like Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli are now raising an alarming number of infections across hospitals and communities around the globe. The objective was to evaluate the implications for antimicrobial stewardship based on identifying the antibiotic resistance profiles, genotype mechanisms, and trends in common pathogenic bacteria found in various hospitals across Iraq. MethodsWe used a two-fold approach that was comprehensive in scope and involved both efficient multicenter surveillance as well as cutting edge genetic analysis to unravel the complex topography of antibiotic resistance. We provided a geographically heterogeneous but diverse set of clinically obtained isolates to participate in hospitals for a period of 24 months and concentrated our efforts on prioritized pathogens K. pneumoniae, A. baumannii, E. coli, P. aeruginosa, and S. aureus that are well known to pose serious threats. Beginning with clinically obtained isolates sourced across the entire globe, we used standardized techniques such as broth microdilution to first undertake phenotyping in a central reference lab to establish microbial identity based on resistance phenotypes to a set of prioritized antibiotics that include carbapenems, third generation cephalosporins, or fluoroquinolones. Finally, we derived data concerning the emergence patterns and geographic distribution of resistant microbes such as MRSA or CRE. We used genome-wide sequencing to unlock information concerning the genetic blueprints for a set of specifically chosen isolates based on their representational diversity across geographic locales, resistance phenotypes, and specific times. ResultsThe sample was made up of Escherichia coli (n = 225), Klebsiella pneumoniae (n = 185), Staphylococcus aureus (n = 135), Pseudomonas aeruginosa (n= 90), and Acinetobacter baumannii (n = 125). Ceftriaxone resistance was found in 80.4% of E. Coli, ciprofloxacin resistance in 45.6%, and meropenem resistance in 15.1%. K. pneumoniae exhibited 38.9% resistance to aminoglycosides and 70.2% resistance to carbapenems. The percentage of MRSA in S. aureus was 55.5%. P. aeruginosa showed 22.2% resistance to colistin, 37.8% resistance to piperacillin tazobactam, and 50.0% resistance to ceftazidime. Imipenem resistance was found in 85.6% of A. baumannii isolates, whereas colistin resistance was found in 28.8% of isolates. In all, 3.4% of isolates are pan-drug-resistant (PDR), 14.6% are extensively drug-resistant (XDR), and 52.1% are multidrug-resistant (MDR). WGS identified common genes such bla_NDM-1, bla_OXA-48, mcr-1, aac (6)-Ib, and plasmid replicons IncF, IncL/M, and IncI2. Carbapenem resistance in Gram-negative bacteria rose by around 18% over the course of five years. ConclusionsThis study shows that the rapid spread of complex genetic information in bacteria causes antibiotic resistance problems. High-level resistance represents an expected consequence of the spread of resistance genes and successful bacteria within healthcare systems. We demonstrate in our results that our expertise in overcoming resistance at a molecular level will play a crucial role in combating infectious diseases in the coming years.

IntroductionSporadic colorectal cancer (CRC) remains a significant driver of worldwide morbidity and mortality. Environmental factors associated with CRC are increasingly well-described and now include generalized colonic dysbiosis and individual enteric bacteria. Clostridioides difficile is one such species, with recent mouse model work suggesting prolonged exposure to C. difficile toxin B is conducive to colonic tumorigenesis. However, there is a dearth of real-world human evidence linking C. difficile infection and CRC. MethodsHerein, we analyzed a multicenter, longitudinal, Electronic Health Record (EHR)-based dataset to test the association between C. difficile test positivity and the risk for incident CRC utilizing unadjusted and multivariable (controlled for clinical conditions independently associated with CRC development) Cox proportional hazard modeling to compare C. difficile exposed and non-exposed cohorts ResultsWe found that individuals who tested recurrently positive for C. difficile had a significantly increased risk for incident CRC (aHR 2.05 [95% CI 1.27-3.29]) compared with those who tested positive only once (aHR 0.70 [0.45-1.10]) or never. Furthermore, we found potential trends that the effect of C. difficile test positivity on the risk for incident CRC was stronger amongst females compared with males. ImportanceThese findings help translate emerging mouse model work on C. difficile-influenced colorectal tumorigenesis and lay groundwork for more substantial human investigations into this connection. These findings also may begin to help guide the personalized deployment of novel fecal microbiota-based therapies designed to interrupt the life cycle of C. difficile within the gut of human hosts and, potentially, prevent long-term health sequelae of chronic C. difficile infection.

BackgroundWhile multi-omics approaches, incorporating polygenic risk scores (PRS), metabolomics, and proteomics have shown promise in predicting major adverse cardiovascular events (MACE), their added value beyond cardiovascular disease (CVD) risk factors remains underexplored. We aimed to assess whether integrating multi-omics biomarkers into the SCORE2 model improves the prediction of MACE in apparently healthy individuals. MethodsThis study included 24,042 UK Biobank participants without CVD or diabetes mellitus, aged 40-69 years. Multi-omics biomarkers were fitted in sex-specific models including the variables of SCORE2 and 9 metabolites, 12 proteins, and a PRS for CVD in males, as well as 7 metabolites, 11 proteins, and a PRS for CVD in females. The performance of the SCORE2 model and its multi-omics extensions was compared using Harrells C-index and the net reclassification index (NRI) in a training and test set (70% and 30% of study population). ResultsIn 10-year follow-up, 1,204 MACE events occurred. Integrating multi-omics biomarkers into SCORE2 significantly improved the predictive performance (C-index: 0.708 to 0.769, P<0.001; NRI=26.2%). In males, the C-index improved from 0.682 to 0.752 ({Delta}C-index=+0.070, P<0.001; NRI=12.4%), while in females, it increased from 0.724 to 0.782 ({Delta}C-index=+0.058, P<0.001; NRI=30.4%). However, full multi-omics measurements may not be needed because the combination of proteomics and PRS yielded comparable performance in males (C-index=0.749) and females (C-index=0.782). ConclusionsIntegrating a protein panel and a PRS significantly improves MACE risk prediction by the SCORE2 model, which includes HDL and total cholesterol. Adding further metabolites has limited additional predictive value.

Advances in our understanding of the biology of skeletal muscle ageing are being made at pace, with great potential for these findings to inform the identification of novel treatments for sarcopenia. However, translation of findings from animal models to humans has been hampered by limitations of existing human muscle biopsy studies. Devised to directly address this challenge, the Muscle Ageing and Sarcopenia Study (MASS) Lifecourse is a unique resource for the study of human muscle ageing across adulthood. This deep-phenotyped observational study of 260 community-dwelling men and women aged 18 to 85 years living in North East England includes muscle biopsy samples and detailed characterisation of physical function, health status and sociodemographic and behavioural risk factors. Underpinned by broad interdisciplinary research and clinical expertise this study is catalysing cutting-edge translational research on human muscle ageing across the adult life course.

ObjectiveTo examine whether the association between smoking status and cardiovascular (CV) mortality differs by arterial stiffness, assessed by pulse pressure index (PPI), among U.S. adults without baseline cardiovascular disease (CVD). MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) 2005-2016, we analyzed 16,605 adults aged 40-79 years without baseline CVD, with mortality follow-up through December 31, 2019. PPI was calculated as (systolic blood pressure [SBP] - diastolic blood pressure [DBP])/SBP and split at the cohort median (0.415) as low versus high. Smoking status was classified as never, former, or current, yielding six joint PPI-smoking groups. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CV mortality, adjusting for demographics and cardiometabolic risk factors. ResultsOver a median follow-up of 8.4 years, 518 CV deaths (3.1%) occurred. Among individuals with low PPI, former smokers had CV mortality comparable to never smokers (HR 0.86, 95% CI 0.56-1.33), whereas current smokers remained at elevated risk (HR 2.51, 95% CI 1.65-3.81). This pattern was not observed in the high PPI stratum, where both former and current smokers had significantly higher CV mortality than never smokers. ConclusionFormer smokers with low PPI had CV mortality similar to never smokers, whereas former smokers with high PPI remained at elevated risk. These findings suggest that the CV benefit of smoking cessation may be greatest when arterial stiffness is minimal, supporting early cessation before substantial vascular aging occurs.

ObjectiveTo characterize associations between tattooing and health status. MethodsWe used data from [~]27,000 respondents to the 2020-2022 Utah Behavioral Risk Factor Surveillance System (BRFSS). Multivariable Poisson regression was used to calculate prevalence ratios (PR) and 95% confidence intervals (CI) associating ever receiving a tattoo with physical/mental health status. ResultsIn this cross-sectional study, ever receiving a tattoo was associated with self-reported "poorer" vs. "excellent" overall health, particularly among women (PR=3.08 [95% CI: 2.26- 4.21]). Tattooing was also associated with obesity (women, PR=1.40 [95% CI: 1.22-1.61]; men, PR=1.21 [95% CI: 1.04-1.40]) and chronic pain (women, PR=1.59 [95% CI: 1.43-1.77]; men, PR=1.55 [95% CI: 1.37-1.76]). Tattooed individuals were more likely to have been diagnosed with a depressive disorder (women, PR=1.64 [95% CI: 1.53-1.75]; men, PR=1.55 [95% CI: 1.39-1.73]) and to have had six or more teeth removed, vs. none (women, PR=2.18 [95% CI: 1.61-2.96]; men, PR=2.88 [95% CI: 2.10-3.95]). ConclusionsPublic health entities may consider partnering with tattoo studios and conventions to provide information about nutrition, exercise, dental care, mental health resources, and health screenings.

PurposeTo develop and validate a prediction model for sleep apnea syndrome (SAS) treated with continuous positive airway pressure (CPAP) in the general population. MethodsUsing claims and health checkup data held by JMDC Inc., linked to personal health records (Pep Up), we developed and internally validated a prediction model for SAS treated with CPAP, defined as a diagnosis of SAS and reimbursement records of CPAP. Every three months from January 1, 2022 to July 1, 2024 (i.e., 11 timepoints), we identified eligible individuals with available data both 1 year before and 1 year after that timepoint to define the presence/absence of SAS treated with CPAP, as well as 279 predictor variables. We developed a LightGBM model for the training and tuning datasets and evaluated its performance on the validation dataset. ResultsAmong 18,692,873 observations (mean age 44.8{+/-}11.3 years, women 37.5%) obtained from 1,858,566 people, 300,868 (1.6%) had SAS treated with CPAP. The area under the receiver operating characteristic curve was 0.898 (95% confidence interval 0.895-0.901). The positive predictive values among people with the top 1% and 10% prediction scores were 28.3% and 10.3%, respectively. According to the SHapley Additive exPlanations plot, male sex was the most important predictor, followed by age, body mass index, and waist circumference. We also demonstrated that personal health records significantly improved the predictive performance. ConclusionWe developed a prediction model to identify people at high risk of SAS and encourage them to undergo polysomnography or related tests.

Introduction: Neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and non-AD dementias share chronic neuroinflammatory mechanisms that contribute to neuronal injury and disease progression. While anti-inflammatory therapies (AITs) are associated with reduced neurodegenerative disease risk, knowledge regarding the impact of biological sex and treatment duration across multiple NDDs remains limited. Methods: We conducted a retrospective cohort analysis using a large propensity-score-matched population (n = 190,308; 95,154 treated vs 95,154 untreated) to evaluate associations between long-term AIT exposure and incidence of major NDDs. Disease-specific and combined outcomes were assessed across drug classes (NSAIDs, corticosteroids, immunomodulators), sex, age, and therapy duration. Results: AIT exposure was associated with a significantly lower risk of developing any NDD (RR = 0.47, 95% CI 0.43-0.48, p < .0001) and was equally effective in both sexes. Risk reduction was observed for each individual disease: AD (RR = 0.40), non-AD dementia (RR = 0.51), PD (RR = 0.43), MS (RR = 0.25), and ALS (RR = 0.48). Among drug classes, immunomodulators conferred the largest reduction (RR = 0.19), followed by corticosteroids (RR = 0.41) and NSAIDs (RR = 0.42). Duration analyses revealed a graded benefit, with RR declining from 0.94 (<1 year) to 0.25 (>6 years). Risk reduction was strongest in older participants (75-79 years). Discussion: Chronic use of anti-inflammatory or immunomodulatory therapies was associated with substantially reduced incidence of multiple neurodegenerative diseases in both sexes. The strongest effects were observed with immunomodulator use and prolonged therapy duration, suggesting that sustained modulation of systemic inflammation confers broad neuroprotective effects in both sexes. These findings highlight the potential of targeting immune-inflammatory pathways for neurodegenerative disease prevention and can inform prospective mechanistic and interventional studies.