Annals of the American Thoracic Society
● American Thoracic Society
Preprints posted in the last 90 days, ranked by how well they match Annals of the American Thoracic Society's content profile, based on 11 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.
Trap, L.; Buyukcelik, R.; Antonissen, N.; Sidorenkov, G. A.; Ruiter, R.; Van Heemst, J.; Sedaghati-Khayat, B.; Stikker, B. S.; Dumoulin, D. W.; Gietema, H. A.; Heuvelmans, M. A.; Mohamed Hoesein, F. A. A.; De Jong, P. A.; Uitterlinden, A. G.; Brusselle, G.; Jacobs, C.; Aerts, J. G. J. V.; Vermeulen, R. C. H.; De Bock, G. H.; Groen, H. J. M.; Vliegenthart, R.; Downward, G. S.; Stadhouders, R.; Van Rooij, J.; NELSON-POP consortium,
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Background: Randomized controlled trials have shown that computed tomographic (CT) screening reduces lung cancer mortality. Improved identification of at-risk groups, by leveraging non-smoking risk factors, could help refine screening selection. Aim: To evaluate polygenic risk scores (PRSs) and ambient air pollution (AAP) exposure for risk stratification in the NELSON lung cancer screening cohort. Methods: Two PRSs (PRS-McKay/PRS-Byun) and several AAPs (including nitrogen dioxide, ozone, and particulate matter [PM]) were assessed in the NELSON lung cancer screening trial (N=7,364). PRSs were validated in the Rotterdam Study (N=11,493). Associations with lung cancer, mortality, screening results, and discriminative ability to distinguish lung cancer were evaluated. Results: PRS-McKay and PRS-Byun were associated with lung cancer (odds ratio [OR] per SD [95%CI]: 1.22 [1.08-1.37] and 1.28 [1.13-1.44], respectively) and lung cancer-specific mortality (OR [95%CI]: 1.24 [1.05-1.47], for both), but not with non-lung cancer mortality (OR [95%CI]: 1.01 [0.94-1.10] and 1.03 [0.95-1.12], respectively). Exposure to PM2.5 was associated with lung cancer (OR [95%CI]: 1.11 [1.01-1.22]). PM constituents were associated with adenocarcinoma, particularly PM10 (OR [95%CI]: 1.16 [1.01-1.32]) and ultra-fine particles (OR [95%CI]: 1.16 [1.04-1.30]). PRS and AAP added modestly to the discriminative ability for lung cancer on top of pack-years, age, and sex (area under the curve [95%CI]: 0.659 [0.624-0.695] vs. 0.643 [0.608-0.679]). Conclusions: PRSs and exposure to PM were associated with lung cancer in a high-risk screening population. The primary potential of PRSs may reside in refining lung cancer screening selection toward individuals at higher risk of dying from lung cancer specifically.
Onishchenko, D.; Martinez, F.; Gerber, A. N.; Cantu, E.; Nair, G.; Chattopadhyay, I.
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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.
Flores, A.; Bin Jamil, S.; Gudleski, G.; Monegro, A.
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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.
Aleligne, Y.; Romero, E.; Santana, C.; Bidwell, J. T.; Lopez, J.; Nuno, M.; Ebong, I.; Izu, L.; Liem, D.; Chiamvimonvat, N.; Cadeiras, M.
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Background: Neighborhood-level social determinants of health influence cardiovascular outcomes; however, their association with post-discharge healthcare utilization in heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. Methods: We conducted a retrospective cohort study of 6,702 adults hospitalized for HFpEF (2014 to 2022). Patients were assigned to one of four neighborhood environments (NEnv-1 to NEnv-4) using a validated clustering framework based on ZIP code-level socioeconomic variables. The primary outcome was time to first HF readmission, evaluated within prespecified post-discharge intervals (0-30 days, >30-90 days, and >90-365 days). Secondary outcomes included HF-related healthcare re-encounters and HF hospitalization burden (0, 1, or [≥]2 admissions). Cox proportional hazards and multinomial logistic regression models were used. Results: Neighborhood environment was independently associated with post-discharge outcomes with distinct temporal patterns. Early (0-30 days) HF readmission risk was higher in NEnv-3 (aHR, 1.63) and NEnv-4 (aHR, 1.76), with similar increases in HF-related re-encounters (aHR, 1.72 and 1.84) persisting through the >30-90-day interval. In contrast, NEnv-2 demonstrated a delayed-risk pattern, with the highest risk occurring in the >90-365-day interval (readmission aHR, 3.42; re-encounter aHR, 3.45). All non-reference environments were associated with a higher likelihood of at least one post-index HF admission (aOR range, 1.84-2.24). NEnv-4 uniquely demonstrated higher odds of recurrent hospitalization ([≥]2 vs. 1 admission; aOR, 1.64). Conclusions: Neighborhood environment is associated with distinct, time-dependent patterns of HF utilization in HFpEF, including early, delayed, and recurrent risks. Incorporating neighborhood context may help identify when patients with HFpEF are most vulnerable after discharge and guide the timing of post-discharge interventions.
Edakalavan, S.; Bon, J.; Nouraie, S. M.
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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.
Martin, E. A.; Lee, S.; Walker, R.; Pitka, E.; Soroush, M. Z.; Ezekowitz, J.; Howlett, J. G.; Fine, N. M.; Bakal, J. A.; Quan, H.; Eastwood, C. A.
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Importance: Heart failure readmissions remain common following hospitalization, but accurately identifying which patients will be readmitted after discharge remains challenging. Improved prediction could support targeted transitional care interventions and more efficient allocation of clinical resources. Objective: In this study we attempted to improve readmission prediction after heart failure hospitalization by using variables chosen through a modified Delphi process, and using inpatient Electronic Medical Record (EMR) data, focusing on clinical notes. Design: This prognostic study developed competing risk survival models to predict readmission after heart failure hospitalization. Variables were chosen using a modified Delphi process, and extracted from EMR notes using various natural language processing techniques or from other EMR elements where appropriate. Patients were admitted between 2011 through 2019, and at least one year of follow-up was available for all patients. Models were evaluated using C-statistics, as well as sensitivity, specificity, positive and negative predictive values. Setting: During the study period, all acute-care facilities in Calgary, Alberta used the same EMR system, from which patients were selected. Participants: Patients were 18 years or older, resided in Alberta, and were admitted to a Calgary hospital. All corresponding admissions with a most responsible diagnosis of heart failure were included (n=15,160). Main Outcomes and Measures: The main outcome of interest was readmission within 30 days, though 90- and 365-day time frames were also analyzed. Death was treated as a competing risk and analysed at those time frames as well.
Merdad, R. H.; Ramirez, M.; Christenson, M.; Pettine, W. W.; Locke, B. W.
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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.
Mutic, A. D.; McCauley, L.; Andrew, A.; Fitzpatrick, A.
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Background: Children spend more than 90% of their time indoors, and early childhood education settings (ECEs) are an understudied, high-occupant-density indoor microenvironment where exposure to volatile organic compounds, particulate matter, and other toxicants has been documented. Limited knowledge exists on ECE-specific exposures affecting young children and how they compare to exposures in the home. Methods: This prospective, repeated-measures pilot study targeted enrollment of 44 preschool-aged children and 8 ECE staff across two geographically and sociodemographically distinct ECEs in metropolitan Atlanta, Georgia. Paired silicone wristbands, one home-designated and one ECE-designated, were exchanged between settings across three consecutive days and nights beginning at enrollment to characterize microenvironment-specific exposure. A single spot urine sample was also collected from each child. Continuous indoor air quality monitoring was conducted in two classrooms per site. Caregivers and ECE staff completed structured questionnaires assessing home and ECE environmental characteristics, child respiratory risk, and protocol feasibility and acceptability. Feasibility was evaluated using eight pre-specified indicators spanning recruitment and enrollment, wristband wear duration and loss by microenvironment, urine sample collection completeness, and survey completion by instrument and respondent group. Conclusion: This pilot will establish feasibility and acceptability parameters for a paired, multi-matrix silicone wristband protocol across home and ECE microenvironments. Findings will inform the design, sample size, and power calculations for a subsequent study testing indoor air interventions and pediatric respiratory outcomes in ECEs. Feasibility outcomes are reported in a companion manuscript.
Pedros-Valls, R.; Gupta, K. S.; Harrington, N.; Yu, J. D.; Orr, J.; Owens, R. L.; Torres Barba, D.; King, K. R.
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Background: Respiratory rate (RR) predicts short-term mortality in acute care settings, yet its prognostic significance in clinically stable outpatients remains poorly defined. Objectives: To determine whether the median and variability of nocturnal respiratory rate (NRR) are independently associated with long-term cardiovascular and all-cause mortality in outpatients with cardiovascular disease. Methods: We analyzed overnight chest belt waveforms from elective polysomnography in 5,679 older adults with cardiovascular disease enrolled in the Sleep Heart Health Study (SHHS). NRR was quantified at 30-second resolution, and per-subject median NRR and within-night variability (standard deviation) were derived. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate associations with cardiovascular and all-cause mortality over 3-year and 15-year follow-up periods, adjusting for demographic characteristics, cardiopulmonary comorbidities, and sleep apnea severity. Results: Higher median NRR and greater NRR variability were each associated with increased cardiovascular and all-cause mortality. Combining these metrics identified a high-risk group characterized by elevated median and high variability of NRR, with approximately five-fold higher 3-year all-cause mortality compared with a low-risk group; this association remained significant in Cox models (unadjusted HR: 2.61; 95% CI: 1.65, 4.14; p<0.001; adjusted HR: 2.15; 95% CI: 1.30, 3.55; p=0.003). Conclusions: Both the baseline level and variability of NRR independently predict mortality in clinically stable outpatients with cardiovascular disease. Densely profiled NRR represents a promising, underutilized biomarker for long-term risk stratification.
Chesley, C.; Yakusheva, O.; Lu, Y.; Kohn, R.; Belk, A.; Scott, S.; Halpern, S.; Kerlin, M.
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Rationale. Racial disparities in outcomes among patients with acute respiratory failure are well-described, but the contributions of clinicians to these disparities have not been evaluated. Objectives. Among mechanically ventilated patients, we evaluated racial disparities in severity of illness trajectories and adapted value-added modeling to quantify nurse and physician relationships with these disparities. Methods. In a retrospective cohort of mechanically ventilated patients across five hospitals between 2018 and 2022, we used generalized estimating equations to model the change in Laboratory-based Acute Physiology Score version 2 (LAPS) from the start to end of intensive care unit admission ({Delta}LAPS). Consistent with value-added modeling, we randomly allocated the cohort into development and testing partitions, and fit separate multiple linear regression models of {Delta}LAPS using concurrent nurse and physician assignments (determined at 4-hour intervals), patient race, and clinician-race interaction terms as fixed effects. Clinician-specific and clinician-race interaction coefficients were extracted to determine race-specific value-add for each clinician. We defined the race-contextual value-add difference (RCVAD) as a clinician-level measurement of the difference in that clinician's value-add between Black and White patients in their care; a positive RCVAD indicates a more favorable severity of illness trajectory for Black relative to White patients and vice versa. Measurement and Main Results. Among 6,555 distinct patients, 7,247 clinical encounters, 405 nurses, and 70 physicians, Black patients accounted for 2,926 (40%) encounters. Overall, Black patients had significantly less improvement in {Delta}LAPS than White patients (difference in LAPS decline = 2.26 [0.23, 4.29], p=0.029). In the development partition, median nurse RCVAD was -0.10 (interquartile range [IQR]: -1.17, 1.14) with 191 (47%) nurses having a positive RCVAD; median physician RCVAD was -0.18 (IQR: -1.34, 0.56) with 29 (41%) having a positive RCVAD. Conclusions. Black mechanically ventilated patients experience less improvement in severity of illness during intensive care unit admission than White patients. While the majority of physicians and nurses were associated with disparities-exacerbating illness trajectories, many other clinicians were associated with disparities-mitigating trajectories. Future work to understand practices associated with disparities-exacerbating and disparities-mitigating care profiles could inform interventions to reduce disparities overall.
Fujita, Y.; Saito, S.; Yagishita, S.; Araya, J.; Nakagawa, R.
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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.
You, Y.; Hu, H.; Yin, L.; Sang, J.; Yu, R.; Hong, X.; Liu, Y.; Liu, F.; Su, W.; Jiang, S.; Tang, Y.; Zhang, Y.; Pan, H.; Cao, Y.; Liu, Z.
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Abstract Background Non-cardiac chest pain (NCCP) is commonly regarded as a low-risk condition. However, long-term mortality, cause-specific death, and high-risk subgroup characteristics remain poorly defined. Methods In this multicentre registry-linked cohort study, we linked the Chest Pain Center Registry from 101 hospitals in Hunan, China, with the Mortality and Cause of Death Registry. Adults diagnosed with NCCP from Jan 1, 2017, to Dec 31, 2021, were included. We assessed 3-year all-cause, cardiovascular, and non-cardiovascular mortality using Cox, restricted cubic spline, and Fine-Gray models. Findings Among 160,245 patients, 4674 deaths occurred within 3 years (2.9%). Mortality increased sharply after 60.5 years. Age [≥] 60.5 years (adjusted hazard ratio [aHR] 7.49 [95% CI 6.89-8.14]), rural residence (time-varying aHR 1.46 [1.35-1.57] in year 1 and 1.66 [1.46-1.89] in years 1-3), and male sex (aHR 1.47 [1.38-1.57]) independently predicted death. Three-year mortality ranged from 0.3% in younger urban women to 8.4% in older rural men. Cardiovascular diseases accounted for 56.4% of deaths among older patients, whereas other non-cardiovascular causes (22.8%) and malignancy (20.8%) were the largest categories among younger decedents. Interpretation NCCP is not uniformly benign. Age, rural residence, and sex identify patients who could benefit from risk-stratified follow-up, with cardiovascular prevention prioritised for older rural men and broader non-cardiovascular assessment considered for younger patients.
Cyrille-Superville, N.; Gaggin, H. K.; Rosen, A.; Udall, M.; Hennum, L.; Zeldow, B.; Gao, X.; Nagelhout, E.; Keshishian, A.; Davis, M. K.
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BACKGROUND Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease. Sociodemographic factors may influence time to treatment initiation and resulting clinical outcomes, yet these relationships are poorly characterized. OBJECTIVE Assess the effects of sex and race on tafamidis initiation and subsequent outcomes and their interaction with factors such as ATTR-CM type and social deprivation measures. METHODS A retrospective cohort analysis was conducted using the US Komodo Healthcare Map (01/2016-06/2024) among patients with amyloidosis, identified by ICD-10-CM diagnosis codes. Cumulative incidence of treatment initiation and survival probabilities for cardiovascular-related hospitalization (CVH) or death were estimated by Kaplan-Meier, stratified by sex and race. Cox proportional hazards models were fitted for both endpoints to estimate hazard ratios, adjusting for demographics and clinical characteristics. RESULTS Of 11,311 patients identified, White and Black patients (n=9,223) were included in subsequent analyses. Within 12 months of diagnosis, White women had the lowest cumulative incidence of tafamidis initiation (11.4%), followed by Black women (22.0%), Black men (26.7%), and White men (31.0%). Event-free survival at 12 months was lowest in Black women (42.9%), followed by Black men (46.8%), White women (48.6%), and White men (54.4%). Median (95% CI) time to CVH or death was shortest for Black women (8.0 months [6.8-10.0]) followed by Black men (9.9 months [8.8-12.0]), White women (11.0 months [9.6-13.0]), and White men (15.0 months [14.0-16.0]). CONCLUSIONS In this large, real-world cohort of US patients with ATTR-CM, sex and race contributed to disparities in tafamidis initiation and survival, underscoring compounded disparities in both access and outcomes.
Duckworth, A.; Prague, J. K.; Knight, B.; Norris, K.; Emms, H.; Goodrum, S.; Crook, C. S.; Sayers, R.; Steward, M.; Thould, H.; Savill, A.; Mandizha, J.; Lines, S.; Barnes, A.; Kirkwood, J.; Almond, H.; Lunnon, K.; Lindsay, M. A.; Tyrrell, J.; Stanel, S.; Baird, D. M.; Russell, a.-m.; Rivera Ortega, P.; Gibbons, M. A.; Scotton, C. J.
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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.
Acheampong, C.; Bowe, A.; Hames, A.; Diaz, M.; Hayes, M.; Poonawalla, I.
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Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are indicated for weight reduction and offer cardiometabolic health benefits, yet there is little real-world evidence regarding their association with healthcare resource utilization (HCRU) and costs for Medicare Advantage (MA) beneficiaries with heart failure and obesity. Methods: We used a prevalent new-user study design and the Humana Healthcare Research database to identify MA beneficiaries with heart failure (HF) and obesity receiving standard HF therapy or HF therapy + newly initiating GLP-1 RA between January 1, 2022, and December 31, 2023. We observed adjusted, one-year mean difference in all-cause and heart failure-related HCRU. Results: In our cohort of 4,677 matched pairs (mean age 72 years, male: 41%), one-year, adjusted risk ratio (RR) for HF therapy + GLP-1 RA vs HF therapy was 0.89 (95% CI: 0.84 ? 0.93) for all-cause inpatient utilization, 0.88 (95% CI: 0.82 ? 0.94) for avoidable hospitalizations, and 0.99 (95% CI: 0.95 ? 1.03) for emergency department visits. For individuals receiving HF therapy + GLP-1 RA vs HF therapy, the mean difference was 30.6% (95% CI: 26.7% ?34.7%) for all-cause total costs, 105.9% (95% CI: 99.1% ?112.9%) for pharmacy costs, and ?4.7% (95% CI: ?8.7% to ?0.6%) for medical costs. HF-related HCRU measures were lower among beneficiaries augmenting HF therapy with GLP 1 RA vs individuals receiving HF therapy alone. Conclusions: Among MA beneficiaries with heart failure and obesity, the addition of GLP-1 RA to standard heart failure therapy reduced the likelihood of inpatient admissions or avoidable hospitalizations compared with HF therapy alone.
Mathew, Z.; Mehta, R.; Kim, S.; Jeyaraj, J.; Asif, T.
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Background: Primary malignant cardiac tumors (PMCTs) are rare and histologically heterogeneous. Objective: To compare demographics, specific ICD-O-3 morphologies, first-course treatment patterns, annual registered case counts, and unadjusted overall survival between soft-tissue and hematologic PMCTs. Methods: We identified 730 PMCT cases diagnosed from 2000 to 2021 in SEER 18 (ICD-O-3 topography C38.0). Histologic lineage was assigned from ICD-O-3 morphology. Comparative analyses included soft-tissue (n=458) and hematologic (n=212) tumors. First-course variables were primary-site surgery, chemotherapy (yes versus no/unknown), and radiotherapy (radiation versus none/unknown). Groups were compared with chi-square tests. Overall survival was estimated with Kaplan-Meier methods; follow-up was truncated at 120 months. Results: Soft-tissue PMCTs occurred predominantly at ages 45-64 years (67.9%), whereas hematologic PMCTs occurred predominantly at age [≥]65 years (63.2%; p<0.001). Men comprised 59.9% of hematologic and 49.3% of soft-tissue cases (p=0.014). The leading soft-tissue morphology was hemangiosarcoma/angiosarcoma (ICD-O-3 9120/3; 201/458, 43.9%); synovial sarcoma accounted for 20/458 cases (4.4%). Diffuse large B-cell lymphoma, NOS, accounted for 131/212 hematologic tumors (61.8%). Any primary-site surgery was recorded in 66.6% of soft-tissue versus 15.6% of hematologic cases (p<0.001). Chemotherapy was recorded in 67.5% versus 51.1% (p<0.001), and radiotherapy in 9.0% versus 20.5% (p<0.001). In exploratory Kaplan-Meier analyses, hematologic patients with recorded chemotherapy had higher unadjusted 120-month overall survival than those without recorded chemotherapy (42.0% versus 12.2%; log-rank p=7.5x10-). Radiation-associated survival differences were not statistically significant in either lineage. Conclusions: Soft-tissue and hematologic PMCTs have distinct age distributions, named histologies, and first-course treatment patterns in SEER. These findings describe registry coding and do not establish treatment effectiveness or population incidence.
Walker, E. D.; Mandalapu, S. V.; Lefebvre, S.
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Background: Environmental noise and air pollution are both shaped by road traffic and the built environment, and exposure assessment increasingly folds them into composite indices or proxies both by traffic exposure. Whether the two share a social distribution has rarely been tested against direct measurement of several exposures in the same communities, and community noise is almost always characterized by A-weighted levels alone, which discount low-frequency energy. Methods: At 176 sites across Rhode Island, spanning the contiguous urban area of Providence, Central Falls, and Pawtucket together with four rural municipalities, we measured the acoustic environment under A- and C-weighting (LAeq, LCeq), fine particulate matter (PM2.5), night-time illuminance, and relative humidity across four session types over roughly one year (704 site-sessions). Exposures were linked to census-tract composition (American Community Survey), and mixed-effects models were fitted for each of eight area-level markers of disadvantage, adjusting for campaign and session. Relative humidity was carried through the identical model as a negative control. Results: A-weighted noise was consistently higher in more disadvantaged tracts, rising with non-White, poverty, renter, and no-vehicle shares and falling with income and older-resident share (six of eight markers significant; 1.3 to 1.8 dBA per standard deviation; 6.6 dBA between the least and most racially diverse neighborhoods). C-weighted levels followed the same gradient on every marker and exceeded their A-weighted counterparts at block-group scale for renter occupancy and vehicle absence. Night-time illuminance was also socially patterned, whereas short-term PM2.5 was roughly an order of magnitude weaker and relative humidity showed no gradient. The acoustic gradient persisted within the urban core alone. Conclusions: Measured burden was carried by the acoustic environment, including its low-frequency component, and by night-time light, not by short-term particulates. The exposure metric and the averaging time determine which disparities are visible at all.
Pajot, A.; Dje, S. A.; Tanoh, F. D. A.; Liousse, C.; Thivillon, T.; Doumbia, M.; Gnamien, S.; Marie, Y.; Fayon, M.; Yoboue, V.; Marcy, O.
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ABTRACT Background Children from low- and middle-income countries are particularly vulnerable to air pollution, a major environmental health risk, due to the immaturity of their lungs and their proximity to sources of household pollution. This study aimed to investigated the effect of exposure to biomass combustion through domestic and maternal occupational activities on respiratory health of children living in disadvantaged urban areas of Abidjan, Cote dIvoire. Methods Between February and December 2023, we conducted a cross-sectional observational study among children <16 years from households of women using biomass fuel for cooking (Group (G) 1), engaged in occupational fish smoking activities (G2), or primarily using gas for domestic cooking (G3). We assessed reported respiratory symptoms through standardized questionnaires and the presence of lung function impairments (LFI) though pulmonary function tests (spirometry and Rint). We assessed the association between study groups and key covariates with respiratory symptoms and LFI using mixed-effects regression models. Results Of 210 children enrolled - 119 (56.8%) female, median age 9 (6-12) years, 82 (39.0%) in G1, 47 (22.4%) in G2, and 81 (38.6%) in G3 - 15 (7.1%) reported wheezing in the last 12 months, 82 (39.0%) reported dry cough at night, 9 (4.9%) presented with dyspnea and 5 (2.7%) had chest pain on clinical examination, for an overall proportion of children with reported respiratory symptoms of 43.8% (92/210). Of 176 children who underwent pulmonary function testing, 59 (33.5%) had LFI detected, including 34 (45.9%) in G1, 8 (22.2%) in G2, and 17 (25.8%) in G3 (p = 0.011). Study group was associated with respiratory symptoms (G1 vs G3; aOR 3.82, 95% CI 1.68-8.68; p < 0.001), as well as with LFI (p = 0.042). Girls were at greater risk of LFI than boys (aOR 2.69, 95% CI 1.24-5.80; p = 0.012). Children whose mothers used charcoal or wood as cooking fuel had higher odds of respiratory symptoms (OR 2.61, 95% CI 1.22-5.58; p = 0.013) but no association was found with LFI (p = 0.459) compared with unexposed children. Conclusion Respiratory symptoms and lung function impairments were highly prevalent among children living disadvantaged, especially when mothers cook with wood or charcoal. Targeted maternal awareness and broader interventions to reduce household air pollution in disadvantaged urban areas are urgently needed to protect long-term respiratory health.
Xi, D.; De la Cruz Libardi, A.; Pinho-Gomes, A. C.; Davies, B.; Gasparrini, A.; Blangiardo, M.; Konstantinoudis, G.
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Background: Heat exposure has been linked to chronic obstructive pulmonary disease (COPD) outcomes, but evidence on relative humidity and humidity-temperature interaction remains limited and inconsistent. Methods: We conducted a nationwide time-stratified case-crossover study of 473,494 COPD hospital admissions in England during the summer months (June-August) from 2003 to 2021. Case-control pairs were linked to high-resolution daily maximum temperature and relative humidity data derived from HadUK-Grid and ERA5-Land, respectively. Exposure-response relationships were modelled using distributed lag non-linear models. Joint effects were examined using interaction models, including linear interaction, temperature spline by humidity category, and fully categorical specifications. Analyses were stratified by age group, sex, and socioeconomic deprivation. Results: COPD admission risk increases steeply at higher temperatures following a J-shaped curve. The exposure-response for relative humidity is U-shaped with a relative risk of 1.08 (95% Confidence Intervals: 1.00 - 1.15) at the 99th relative humidity percentile. We find limited evidence of effect modification by socioeconomic deprivation for both exposures. An estimated 1,040 (95%CI: 820 - 1,270) summer COPD admissions per year are attributable to non-optimal temperatures and 910 (95%CI: 680 - 1,160) to relative humidity. Higher relative risks are observed with concurrent high temperature and high humidity, but the evidence is weak. Conclusion: High temperature and high relative humidity are associated with increased risk of COPD admission, with limited evidence of an interaction. Relative humidity should be considered alongside temperature in environmental risk assessment and targeted adaptation strategies, such as proactive heat-health advice for people living with COPD.
Aissami, N.; Steinack, C.; Engeli, R.; Baumgartner, P.; Amstitz, A.; Tanner, J.; Clarenbach, C.; Ulrich, S.; Kohler, M.; Gaisl, T.
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Background. Robotic-assisted bronchoscopy combined with integrated cone-beam computed tomography (RAB+CBCT) enables accurate sampling of peripheral pulmonary lesions (PPLs), but the acquisition of diagnostic proficiency and program-level efficiency remains incompletely characterized. Methods. We conducted a single-center cohort study of consecutive RAB+CBCT (Ion endoluminal system, Cios Spin) procedures performed by two experienced interventional pulmonologists. Strict lesion-level diagnostic yield was the primary outcome. Learning curve cumulative sum (LC-CUSUM) analysis determined operator-specific proficiency, followed by conventional CUSUM monitoring of post-proficiency performance. Secondary outcomes included procedure and intubation times, temporal changes in case complexity, and adverse events. Results. Overall, 427 procedures comprising 680 PPLs were analyzed. Median lesion long-axis diameter was 11 mm, 14.4% had a bronchus sign, and 36.5% of procedures involved multiple lesions. Strict lesion-level diagnostic yield was 85.4% (581/680). LC-CUSUM demonstrated proficiency after 48 and 86 PPLs, respectively; thereafter, both operators maintained acceptable performance without crossing the predefined CUSUM decision limit. Median procedure time decreased from 65 minutes during the first 10 procedures to 38 minutes during the last 10. The median intubation time was 70 minutes and declined significantly with increasing experience. Most indicators of lesion complexity remained stable, while short-axis diameter and bronchus-sign prevalence decreased modestly. Adverse-event frequency declined significantly over time. Conclusion. RAB+CBCT achieved high strict diagnostic yield, with heterogeneous operator-specific learning trajectories within a maturing multidisciplinary program. Diagnostic performance, procedural efficiency, and safety improved despite stable or modestly increasing case complexity. These findings support individualized, outcome-based proficiency assessment and longitudinal monitoring, rather than comparative operator ranking or reliance on fixed procedural-volume thresholds.