Atherosclerotic cardiovascular disease shows a marked male predominance(1–3), yet the biological basis for this disparity remains unclear. Mosaic loss of chromosome Y (LOY) in blood – a common, acquired and age associated mutation(4,5)- has been linked to mortality and major causes of death, including myocardial infarction(6,7). Experimental studies indicate that LOY in leukocytes is causally related to mortality(8) and promotes pathology across organs by impairing immunosurveillance of senescent cells(9), providing a mechanistic explanation for systemic effects of leukocyte Y loss. Whether LOY in blood contributes to atherosclerosis, however, is unknown. Here we show that LOY in blood is associated with subclinical and clinical atherosclerotic disease by analyzing two large, population-based cohorts: the Swedish CArdioPulmonary bioImage Study (SCAPIS) and the UK Biobank. SNP array–derived estimates of LOY mosaicism in blood leukocytes revealed dose-dependent associations with prevalence of coronary atherosclerosis, more extensive segment involvement, greater coronary stenosis and calcified plaques in SCAPIS. In UK Biobank, LOY was associated with greater carotid intima–media thickness, atherosclerosis, and myocardial infarction. Together, these findings point to a potential association between LOY in blood and a spectrum of atherosclerotic outcomes, offering one possible explanation for the higher cardiovascular risk observed in men.

Background Heated tobacco products (HTPs) are increasingly popular alternative nicotine delivery systems. While marketed as lower-risk alternatives to combustible cigarettes, HTP aerosols still contain combustion byproducts. The acute systemic and pulmonary effects associated with these products have not yet been thoroughly examined. We aimed to evaluate the acute effects of HTP inhalation on the release of extracellular vesicles (EVs) bearing lung-specific and inflammatory biomarkers. Methods In a randomized, crossover study, 23 healthy occasional tobacco users underwent an active HTP exposure session (using an IQOS 3 Multi device) and a control session. Blood samples were collected at baseline and 4 hours post-exposure. Circulating EVs were isolated via ultracentrifugation and analyzed using flow cytometry. We quantified EVs expressing Angiotensin-Converting Enzyme (ACE), Aldehyde dehydrogenase 3B1 (ALDH3B1), Uteroglobin, Complement component 3 (C3), C-C motif chemokine ligand 3 (CCL3/MIP-1α), Palate lung and nasal epithelial clone protein (PLUNC), and Prolyl 4-hydroxylase beta (P4HB). Results Acute inhalation of HTP aerosols induced a statistically significant increase in circulating EVs expressing ACE, P4HB, C3, and CC16/Uteroglobin compared to the non-exposure control. A trend toward elevated ALDH3B1 expression was observed, while levels of CCL3 and PLUNC remained unchanged. Conclusion Acute exposure to HTPs triggers a rapid release of EVs associated with cellular stress, pulmonary injury, and pro-inflammatory responses. Increases in biomarkers such as ACE, C3, and the cancer-associated protein P4HB indicate that HTPs could impair lung health and initiate pro-thrombotic and pro-inflammatory cascades, supporting the need for more stringent regulatory controls.

Diffusing capacity for carbon monoxide (DLCO) is a measure of gas exchange in the lungs. Reduced DLCO with normal spirometry is a common finding that is incompletely understood. To assess determinants of isolated, reduced DLCO in an unselected population. The Swedish CArdioPulmonary bioImage Study (SCAPIS) is a multicentre population-based study of adults aged 50–64 years. The 5th percentile of DLCO in healthy never smokers was used as the lower limit of normal (LLN). Using multivariable analysis, we studied factors associated with DLCO < LLN in 24 261 subjects with normal spirometry, defined as FEV1, FVC and FEV1/FVC > LLN. Emphysema and interstitial lung abnormalities (ILA) were assessed through computed tomography, physical activity through accelerometry and other factors through questionnaires. Isolated DLCO < LLN (n = 1 472) was independently associated with emphysema (odds ratio and 95

Background Proteomic profiling might add to the understanding of mechanisms of respiratory symptoms and help identify novel candidate biomarkers for disease. We aimed to study associations between respiratory symptoms and cardiovascular and inflammatory protein markers, in a general population sample. Methods A cross-sectional analysis in the Swedish CArdioPulmonary bioImage Study (SCAPIS) (n=5016) as discovery cohort and SCAPIS Pilot study (n=1068) as replication cohort. Associations between respiratory symptoms and plasma protein expression (184 proteins: Olink CVDII and CVDIII panels) were analysed in adjusted regression models and stratified by presence or absence of respiratory disease. Results Respiratory symptoms were significantly associated with altered levels of 22 proteins. Wheeze, reported by 3.6%, was associated with four proteins, breathlessness, reported by 4.0%, with 16 proteins and chronic bronchitis, reported by 4.4%, with ten proteins. Increased levels of Urokinase plasminogen activator surface receptor (U-PAR) and Fatty acid-binding protein, adipocyte (FABP4) were associated with all three symptoms. In the group without respiratory disease, U-PAR was still associated with breathlessness and chronic bronchitis, Angiotensin-converting enzyme 2 (ACE2) with wheeze and chronic bronchitis, and Cystatin-B with chronic bronchitis. Conclusions We identified several proteins associated with respiratory symptoms. In the group without respiratory disease, symptoms were significantly associated with increased levels of the inflammatory marker U-PAR as well as with ACE2 and Cystatin-B. The results highlight the role of inflammation and, possibly, also infection in respiratory symptoms and suggest these proteins as potential markers of early subclinical respiratory disease.

Background Chronic obstructive pulmonary disease (COPD) in never-smokers may have other clinical characteristics than tobacco smoking-related COPD.Research question What are the risk factors, biomarkers, respiratory symptoms and health status in never-smoking individuals with COPD?Study design and methods We investigated never-smokers with COPD (n=154, mean age 60 years) from the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS), and compared them with four control groups: never-smokers with normal lung function (n=281), current smokers with normal lung function (n=97), ex-smokers with COPD (n=103) and current smokers with COPD (n=55). COPD was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than the lower limit of normal (LNN) after bronchodilation. We examined fractional exhaled nitric oxide (FeNO), blood biomarkers, respiratory symptoms, health status, medical history and living conditions.Results The never-smoker COPD group reported more respiratory symptoms and worse health status than never-smokers with normal lung function, but fewer symptoms, milder airflow limitation and better health status compared with ex-smokers and smokers with COPD. Never-smokers with COPD had more self-reported asthma. Moreover, never-smokers with COPD had higher Immunoglobulin E sensitisations to a mix of aeroallergens, higher geometrical mean FeNO levels and blood eosinophil counts than never-smokers with normal lung function. When participants with self-reported asthma were excluded, never-smokers with COPD still had more wheeze, cough and higher FeNO.Conclusion Never-smokers with COPD had more respiratory symptoms and elevated markers of type-2 inflammation, suggesting they might represent a distinct clinical phenotype which may differ from smoking-related COPD. They may therefore need to be treated and followed differently.Trial registration number NCT03049202.

Abstract Background Despite the high prevalence and clinical significance of emphysema, few genetic risk loci have been consistently replicated. We conducted a genome-wide association study (GWAS) of CT-based emphysema, with a particular focus on non-smoking-related genetic determinants. Methods We analyzed 25,639 individuals of European ancestry from the SCAPIS national cohort, aged 50–65 years, of which 51% were never-smokers. Emphysema was assessed through semi-quantitative visual scoring of CT scans. GWAS was performed in the whole sample and stratified on smoking status. We also examined the association of previously reported emphysema- and lung function-related variants with emphysema in our dataset. Results Emphysema criteria were fulfilled for 1,479 participants (5.6%), with higher prevalence among current ( N = 576, 18.2%) and former smokers ( N = 612, 6.5%) compared to never-smokers ( N = 263, 2.0%). We identified three independent genetic loci for emphysema in smokers and no signals in never-smokers. The strongest signal was observed in the well-established nicotinic acetylcholine receptor cluster (CHRNA5-A3-B4) locus on chromosome 15. Additionally, we discovered novel associations near the dysferlin (DYSF) gene on chromosome 2 and in an intergenic region on chromosome 3. By assessing previously lung phenotype-associated variants we also found evidence supporting association with emphysema in smokers for variants in the EFEMP1/MIR217HG/PNPT1 locus on chromosome 2, previously linked to reduced FEV 1 /FVC ratio. Conclusion This study, based on the largest unselected population sample to date, provides novel insights into the genetic architecture of emphysema. However, no signals were detected in never-smokers despite the large sample-size, likely due to the low prevalence of emphysema in that group. The proposed genetic risk loci require external replication.

The use of electronic nicotine delivery systems, such as e-cigarettes and heated tobacco products (HTPs), is increasing, but knowledge of their short and long-term toxicological effects remains limited. Here, aerosols generated from an e-cigarette using a flavour-free e-liquid base, both with and without nicotine, an HTP, and a conventional cigarette were characterised for the production of polycyclic aromatic hydrocarbons (PAHs), carbonyls and volatile organic compounds (VOCs). Furthermore, extracts from vapour and smoke were generated, and their acute toxicity was assessed in human lung epithelial cells and fibroblasts. Cigarette smoke contained significantly more toxic compounds and induced the highest degree of toxicity in all the tested cell lines, followed by the HTP, and then the nicotine containing e-cigarette. Notably, the nicotine containing e-cigarette produced similar levels of formaldehyde as the HTP and cigarette smoke, and caused a greater decrease in cell viability in primary lung fibroblasts compared to the nicotine-free e-cigarette. Although the HTP aerosol contained lower levels of toxicants than cigarette smoke, some VOCs specific to HTPs were detected. More independent research is needed to identify toxicant-specific production in emerging nicotine delivery systems and their potential health impacts to better inform policy makers, health care providers and the general public.

OBJECTIVES:To describe the rationale, design and data collection procedures of the Swedish CArdioPulmonary bioImage Study (SCAPIS) re-examination, which, in its further scope, aims to quantify and explain the development of atherosclerosis, pathological cardiovascular ageing, longitudinal decline in lung function and the malignant transformation of pulmonary nodules among middle-aged Swedes in the longitudinal SCAPIS. METHODS:SCAPIS re-examination is a prospective observational study reassessing approximately 15,000 participants (50% of the original SCAPIS cohort) from six university hospitals. Participants were aged 55-75 years at follow-up, occurring a median of 8.1 years after the baseline investigation. Standardized protocols replicated baseline imaging and functional assessments, including questionnaires, clinical assessments and extensive computer tomography imaging. RESULTS:Interim analyses of the first 5000 participants (50% women; median age 65.5 [61.8-69.1] years) indicated an expected age-related increase in the prevalence and treatment of hypertension (from 22% to 37%) and diabetes (from 4% to 8%), together with a modest rise in central adiposity. Body mass index (median 26.6 kg/m2) and the proportion of obesity (22%) remained largely stable, whereas current smoking decreased from 7.5% to 3.4%. The observed patterns were consistent in men and women. CONCLUSION:Here we present the rationale, design, methods and management of incidental findings in the SCAPIS re-examination. By integrating serial imaging, functional testing and biomarker profiling, the re-examination will furnish unprecedented insight into cardiopulmonary disease dynamics in an ageing population. These data will underpin personalized risk prediction and inform preventive strategies, while serving as a benchmark for future population-based imaging cohorts.

Background Tobacco smoking remains a leading global cause of premature death and disability, and the tobacco industry has increasingly promoted electronic cigarettes (e-cigarettes) as alternatives. Despite their growing popularity, particularly among adolescents, the long-term health effects of e-cigarettes are not fully understood. Nicotine, a primary component of e-cigarettes, has been implicated in adverse cardiovascular outcomes; however, its acute effects on endothelial function remain poorly characterized. Objective This study aimed to investigate the acute effects of inhaled nicotine on endothelial function using venous occlusion plethysmography (VOP), a well-established method for assessing vascular responses. Methods Nineteen healthy male sporadic-tobacco-using volunteers participated in a double-blind, randomized, crossover study. Participants were exposed to nicotine-containing or nicotine-free e-cigarette aerosol in two sessions separated by a 7-day washout period. Forearm blood flow (FBF) was measured following intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP). Results Acute exposure to nicotine-containing e-cigarette aerosol significantly enhanced ACh-mediated vasodilation compared to nicotine-free aerosol (p = 0.04), whereas no significant corresponding changes in FBF were observed following SNP exposure. Conclusions This study demonstrates that acute nicotine exposure enhances endothelium-dependent vasodilation, likely mediated through activation of nicotinic acetylcholine receptors (nAChRs). This response may represent an early pathological adaptation rather than a protective effect, as chronic nAChR stimulation is linked to adverse cardiovascular outcomes, including endothelial dysfunction and atherosclerosis.

Abstract Background Exposure to wood smoke is associated with negative respiratory health outcomes such as airway infections and development of chronic obstructive pulmonary disease (COPD). Previous controlled exposure studies in humans with bronchoscopy sampling have shown wood smoke-induced bronchial cytotoxicity and impaired macrophage phagocytosis. The present study investigated whether an early and transient acute inflammatory response, as reflected in bronchial mucosal biopsies and lavage fluids, could be detected 6 h after wood smoke exposure. Methods On two separate occasions, fourteen healthy participants were exposed, in a double-blind, randomised crossover design, for 2 h to filtered air and diluted wood smoke generated from incomplete wood log combustion with a mean particulate matter concentration of 409 ± 43 µg/m3. Bronchoscopy with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 6 h post-exposure. Biopsies were immunohistochemically stained, and lavage fluids analysed for soluble mediators. Results In bronchial mucosal biopsies, nuclear translocation of the transcription factors aryl hydrocarbon receptor (AhR) and phosphorylated c-jun (p-c-jun) was significantly reduced within the bronchial epithelium after wood smoke exposure compared to filtered air. There was no endothelial adhesion molecule-mediated recruitment of neutrophils or other inflammatory cells into the bronchial mucosa. Conclusions Exposure to wood smoke from incomplete wood log combustion suppressed nuclear translocation of transcription factors and the expected inflammatory response in endobronchial mucosal biopsies at 6 h post-exposure. This contrasts to the strong proinflammatory effects of other air pollutants such as ozone and diesel exhaust. Together with previous findings of increased cytotoxicity and impaired airway macrophage phagocytosis in humans, this response may be in line with compromised immune defence and increased susceptibility to airway infections, chronic bronchitis and COPD observed in populations exposed to high levels of indoor air pollution from wood smoke.

Background Pulmonary nodules (PNs) are clinically challenging because differentiation between benign and malignant PNs is not possible at CT detection; recurring CT examinations and invasive procedures are often required in PN follow-up. Purpose To investigate PN prevalence in a middle-aged population and the risk factors associated with these nodules. Materials and Methods In this secondary analysis of the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (known as SCAPIS, from November 2013 to November 2018), participants aged 50-64 years with chest CT data were analyzed. Risk factors such as smoking history, occupational exposure (vapor, dust, gas, and fumes), and lung diseases were derived from comprehensive questionnaires. Robust Poisson regression was used to evaluate associations, adjusted for age and sex, between potential risk factors and the binary outcome of nodule presence or absence. Prevalence ratios (PRs), adjusted for age and sex, and 95% CIs were estimated. Results Among 29 574 participants (median age, 57.4 years; IQR, 53.7-61.2 years; 15 168 women), solid nodules sized 100-300 mm3, part-solid, and ground-glass nodules were found in 1420 (4.8%), 199 (0.7%), and 430 (1.5%), respectively. The prevalence of solid nodules among participants who never, formerly, and currently smoked was 32.5% (4713 of 14 515), 34.5% (3602 of 10 437), and 37.9% (1381 of 3644), respectively. Solid nodules sized 100-300 mm3 were associated with current smoking (PR, 1.38; 95% CI: 1.19, 1.60), chronic obstructive pulmonary disease (PR, 1.72; 95% CI: 1.17, 2.53), occupational exposure (PR, 1.31; 95% CI: 1.11, 1.54), emphysema (PR, 1.56; 95% CI: 1.31, 1.86), reticulation (PR, 1.96; 95% CI: 1.47, 2.61), and bronchiectasis (PR, 2.03; 95% CI: 1.64, 2.50). In participants who had never smoked, associations were found between solid nodules at least 100 mm3 and reticulation (PR, 2.28; 95% CI: 1.55, 3.36), reported lung disease other than asthma or chronic obstructive pulmonary disease (PR, 2.26; 95% CI: 1.49, 3.43), and bronchiectasis (PR, 2.17; 95% CI: 1.60, 2.94). Conclusion PN prevalence was approximately the same in a middle-aged population regardless of smoking history. In participants who had never smoked, nodules were linked to reported lung disease, reticulation, and bronchiectasis. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article.

BACKGROUND:Beta-blockers may improve outcomes in patients with chronic obstructive pulmonary disease (COPD) without cardiovascular disease, but randomized trials have been inconclusive. METHODS:This was a multicenter, open-label, pragmatic, phase 4 randomized trial. Patients 40 years of age or older with COPD, sinus rhythm, and no cardiovascular disease were randomly assigned in a 1:1 ratio to receive metoprolol, at a target dose of 100 mg daily, in addition to standard care or to receive standard care alone. The primary end point was the time to the first occurrence of a COPD exacerbation, cardiovascular event, or death during 1 year of follow-up. RESULTS:A total of 1695 patients underwent random assignment; their mean age was 70 years, and 62% were female. The primary end point occurred in 27% of patients assigned to receive metoprolol and in 30% assigned to receive standard care (hazard ratio, 0.87; 95% confidence interval [CI], 0.73 to 1.05; P=0.14). The corresponding hazard ratios were 0.88 (95% CI, 0.72 to 1.06) for COPD exacerbations, 0.73 (95% CI, 0.48 to 1.11) for cardiovascular events, 0.92 (95% CI, 0.48 to 1.77) for death, and 0.87 (95% CI, 0.58 to 1.28) for exacerbations requiring hospitalization. Serious adverse events occurred in 80 (9.4%) of 848 participants in the metoprolol group and 66 (7.8%) of 847 participants in the standard care group. Nonserious adverse events occurred in 293 (34.6%) of 848 patients in the metoprolol group and 247 (29.2%) of 847 in the standard care group. CONCLUSIONS:Among patients with COPD and no cardiovascular disease, metoprolol did not significantly improve the time to a composite of exacerbations, cardiovascular events, or death. (Funded by research grants from the Swedish Research Council and others; ClinicalTrials.gov number, NCT03566667.).

BACKGROUND:Aortic valve calcification (AVC) is a disease process driven by inflammation and lipid infiltration, serving as a precursor to aortic stenosis. While male sex has been implicated as a risk factor for AVC, sex-specific differences, particularly among younger individuals in the general population, are not well characterised. METHODS:The Swedish CArdioPulmonary BioImage Study was used, comprising 30 154 individuals between 50 and 64 years, randomly selected from the general population. Study participants were part of a prospective cohort and underwent laboratory tests, clinical examinations, comprehensive questionnaires and cardiac CT. Cardiac CT was used for determining presence of AVC. Logistic regression analysis was performed to assess associations between traditional cardiovascular risk factors and AVC. RESULTS:In total, 29 160 participants were included and AVC was found in 1291 men (9%) and 730 women (5%). Male sex was an independent predictor of AVC (OR 1.91; 95% CI 1.71 to 2.13). Characteristics associated with AVC were similar between the sexes. In the adjusted analyses, lipoprotein(a), hyperlipidaemia, hypertension and smoking were strongly associated with AVC, whereas low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes, glycated haemoglobin and estimated glomerular filtration rate showed no significant associations with AVC. Higher body mass index (BMI) was associated with AVC in men but not women. CONCLUSIONS:Male sex was independently associated with AVC, and the prevalence of AVC was nearly twice as high in men as in women. Traditional cardiovascular risk factors, including lipoprotein(a), hyperlipidaemia, hypertension and smoking, were associated with AVC, with similar associations between sexes, except for BMI, which was associated with AVC in men but not in women.

BACKGROUND AND AIMS:Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally, but its prevalence and severity remain poorly characterized in the general population. Our aim was to estimate the prevalence of MASLD and the risk of advanced fibrosis in a large Swedish general population cohort. METHODS:From the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort, we analyzed 27,763 participants aged 50-64 years who underwent extensive clinical characterization. MASLD was defined as <48 HU on non-contrast liver computed tomography (CT) imaging. The risk for advanced fibrosis was assessed using the dynamic aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio. RESULTS:MASLD was present in 18.1% of participants and was more common in men than women (25.5% vs. 11.2%). Prevalence increased with cardiometabolic burden: from 7.0% among those without obesity, hypertension, or Type 2 diabetes mellitus (T2DM) to 70.2% among those with all three conditions. MASLD risk was elevated in individuals with obesity alone (adjusted odds ratio [aOR] 5.56; 95% CI = 4.89-6.31), T2DM alone (aOR = 2.66; 95% CI = 2.13-3.33), or hypertension alone (aOR = 1.78; 95% CI = 1.59-1.99). The combination of all three conferred the highest risk (aOR = 17.1; 95% CI = 14.0-20.9). Among persons with MASLD, 24.8% were classified as at risk for advanced fibrosis. Fibrosis risk was independently associated with hypertension (aOR = 1.44; 95% CI = 1.24-1.66), T2DM (aOR = 1.24; 95% CI = 1.06-1.46), male sex (aOR = 1.20; 95% CI = 1.02-1.42), and alcohol consumption (aOR per gram/day = 1.02; 95% CI = 1.01-1.03). CONCLUSIONS:In Sweden, almost one in five middle-aged adults is affected by MASLD, with a quarter of cases at risk of advanced fibrosis. Male sex, obesity, T2DM, and hypertension are important predictors of the prevalence and severity of MASLD.

Breathlessness is a common symptom in clinical practice, yet evidence for cost-effective strategies to diagnose the underlying health conditions causing breathlessness remains limited. Using Swedish population data with individuals with moderate to severe breathlessness, we developed an artificial intelligence (AI) reinforcement learning model to identify optimal, low-cost diagnostic pathways for breathlessness tailored to subgroups based on sex and smoking exposure. Sixteen clinically relevant conditions were defined, along with their diagnostic tests and standard healthcare costs. The AI-based approach successfully produced efficient and low-cost diagnostic pathways for breathlessness with high diagnostic yield. The optimal sequences were overall similar between the subgroups. For all participant subgroups, the AI-derived pathways initially identified (or order of effectiveness in relation to costs) clinical evaluations of body mass index, anxiety and depression, physical activity levels, and spirometry. Subsequent steps included diffusing capacity measurements, chest computer tomography, and hemoglobin assessment. Overall, investigations of the lungs were prioritized ahead of investigations of the heart. This strategy has the potential to streamline the evaluation of breathlessness, reduce unnecessary testing, lead to an earlier diagnosis at lower cost, and support more targeted clinical management.

To describe the rationale, design and data collection procedures of the Swedish CArdioPulmonary bioImage Study (SCAPIS) re-examination, which, in its further scope, aims to quantify and explain the development of atherosclerosis, pathological cardiovascular ageing, longitudinal decline in lung function and the malignant transformation of pulmonary nodules among middle-aged Swedes in the longitudinal SCAPIS. SCAPIS re-examination is a prospective observational study reassessing approximately 15,000 participants (50% of the original SCAPIS cohort) from six university hospitals. Participants were aged 55–75 years at follow-up, occurring a median of 8.1 years after the baseline investigation. Standardized protocols replicated baseline imaging and functional assessments, including questionnaires, clinical assessments and extensive computer tomography imaging. Interim analyses of the first 5000 participants (50% women; median age 65.5 [61.8–69.1] years) indicated an expected age-related increase in the prevalence and treatment of hypertension (from 22% to 37%) and diabetes (from 4% to 8%), together with a modest rise in central adiposity. Body mass index (median 26.6 kg/m 2 ) and the proportion of obesity (22%) remained largely stable, whereas current smoking decreased from 7.5% to 3.4%. The observed patterns were consistent in men and women. Here we present the rationale, design, methods and management of incidental findings in the SCAPIS re-examination. By integrating serial imaging, functional testing and biomarker profiling, the re-examination will furnish unprecedented insight into cardiopulmonary disease dynamics in an ageing population. These data will underpin personalized risk prediction and inform preventive strategies, while serving as a benchmark for future population-based imaging cohorts.

RATIONALE:Long-term oxygen therapy (LTOT) given for at least 15 hours/day improves survival in patients with severe chronic hypoxemia. However, the recent REDOX trial showed that LTOT prescribed for 24 hours/day was not superior to 15 hours/day in terms of death, hospitalizations, or self-reported outcomes. OBJECTIVES:We aimed to examine the cost effectiveness of prescribing LTOT for 24 versus 15 hours/day. METHODS:A cost minimization analysis of the REDOX trial data on 241 patients with severe hypoxemic respiratory failure randomized 1:1 to either LTOT 24 hours/day (n = 117) or 15 hours/day (n = 124) and followed up to 12 months. Data on medical care consumption including prescribed medication costs, specialized outpatient care, and inpatient care were retrieved from national registries. Mean differences in healthcare consumption costs (United States dollars [$], 2024 prices) between groups were analyzed using generalized linear models. The cost analysis took a healthcare payer perspective and oxygen therapy costs are presented separately as out-of-pocket payments. RESULTS:During the 12 months of follow-up, patients prescribed LTOT for 24 hours/day had significantly lower mean costs for respiratory-specific medications (-$175 [95% CI, -$329 to -$29]) but higher oxygen therapy costs ($173 [95% CI, $80 to $268]), compared to patients prescribed LTOT 15 hours/day. There were no significant differences between the groups in mean specialized outpatient and inpatient care costs, total medication costs, or in overall total costs (-$4951 [95% CI, -$10 667 to $443]) but numerically favoring usage of LTOT 24 hours/day. A population-level projection shows substantial potential cumulative cost savings of $7.64 million if LTOT 24 hours/day is adopted. CONCLUSIONS:In addition to previously shown similar treatment efficacy, overall healthcare costs did not significantly differ between LTOT prescribed 15 hours/day and LTOT 24 hours/day. However, there is an observable numerical difference in favor of usage of LTOT 24 hours/day.