medRxiv - Respiratory Medicine最新文献

{"title":"Building and validating a predictive model for stroke risk in Chinese community-dwelling patients with chronic obstructive pulmonary disease using machine learning methods","authors":"Yong Chen, Yonglin Yu, Dongmei Yang, Xiaoju Chen","doi":"10.1101/2024.09.12.24313533","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313533","url":null,"abstract":"Abstract\u0000Background: The occurrence of stroke in patients with chronic obstructive pulmonary disease (COPD) can have potentially devastating consequences; however, there is still a lack of predictive models that accurately predict the risk of stroke in community-based COPD patients in China. The aim of this study was to construct a novel predictive model that accurately predicts the predictive model for the risk of stroke in community-based COPD patients by applying a machine learning methodology within the Chinese community. Methods: The clinical data of 809 Community COPD patients were analyzed by using the 2020 China Health and Retirement Longitudinal Study (CHARLS) database. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze predictors. Multiple machine learning (ML) classification models are integrated to analyze and identify the optimal model, and Shapley Additive exPlanations (SHAP) interpretation was developed for personalized risk assessment.Results:The following six variables:Heart_disease,Hyperlipidemia,Hypertension,ADL_score, Cesd_score and Parkinson are predictors of stroke in community-based COPD patients. Logistic classification model was the optimal model, test set area under curve (AUC) (95% confidence interval, CI):0.913 (0.835-0.992), accuracy: 0.823, sensitivity: 0.818, and specificity: 0.823.\u0000Conclusions: The model constructed in this study has relatively reliable predictive performance, which helps clinical doctors identify high-risk populations of community COPD patients prone to stroke at an early stage.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CORELSA - Remote stethoscope system for fast and standardized auscultations of large numbers of patients with respiratory syndromes","authors":"Kris Ides, Arne Aerts, Rens baeyens, Niels Balemans, Tom Bosschaerts, Jonathan Cazaerck, David Ceulemans, Fons De Mey, Wouter Jansen, Robin Kerstens, Dennis Laurijssen, Eline Lauwers, Anthony Schenck, Girmi Schouten, Ralph Simon, Thomas Verellen, Erik Verreycken, Philippe Jorens, Stijn Verhulst, Walter Daems, Jan Steckel","doi":"10.1101/2024.09.10.24313299","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313299","url":null,"abstract":"One of the major impacts of the current COVID-19 pandemic is the immense strain that is being put on the intensive care units. As a typical SARS-CoV-2 infection often leads to severe acute respiratory syndromes, one of the most basic essential examinations is lung auscultation. There are different categories of lung sounds that can be assessed with a stethoscope like crackles, wheezes, rhonchi and coarse breath sounds. Each of these malicious lung sounds contribute to a clinical assessment and follow-up of the patient's airways and lungs and can indicate the development of pneumonia. Therefore, auscultation on a regular basis is essential, but it also takes a lot of time for the physicians. Moreover, because of the risk of infection for health care workers, it is becoming increasingly difficult or sometimes impossible to safely use a stethoscope. Here we introduce a remote stethoscope system that can help to reduce the workload of physicians and nurses, diminishes the risk of contamination and leads to more standardized auscultation, which can also be stored and reevaluated. We provide a detailed description of our system, which consists of parts that are low cost, easily available in most parts of the world, or can be 3D printed. We provide instructions and an open source software stack to run such a system for a large number of patients which can be remotely auscultated from a central computer. We believe that the system described in this paper can allow various institutes to replicate the system, and increase the safety and reduce the overall workload in the intensive care units around the world.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"191 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The post-viral GPNMB+ immune niche persists in long-term Covid, asthma, and COPD","authors":"Kangyun Wu, Yong Zhang, Huiqing Yin-DeClue, Kelly Sun, Dailing Mao, Erika C. Crouch, Derek E. Byers, Michael J. Holtzman","doi":"10.1101/2024.08.27.24312640","DOIUrl":"https://doi.org/10.1101/2024.08.27.24312640","url":null,"abstract":"Epithelial injury calls for a regenerative response from a coordinated network of epithelial stem cells and immune cells. Defining this network is key to preserving the repair process for acute resolution, but also for preventing a remodeling process with chronic dysfunction. We recently identified an immune niche for basal-epithelial stem cells using mouse models of injury after respiratory viral infection. Niche function depended on an early sentinel population of monocyte-derived dendritic cells (moDCs) that provided ligand GPNMB to basal-ESC receptor CD44 for reprogramming towards chronic lung disease. These same cell and molecular control points worked directly in mouse and human basal-ESC organoids, but the findings were not yet validated in vivo in human disease. Further, persistence of GPNMB expression in moDCs and M2-macrophages in mouse models suggested utility as a long-term disease biomarker in humans. Here we show increased expression of GPNMB localized to moDC-macrophage populations in lung tissue samples from long-term Covid, asthma, and COPD. The findings thereby provide initial evidence of a persistent and correctable pathway from acute injury to chronic disease with implications for cellular reprogramming and inflammatory memory.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung functions among children and adolescents with sickle cell disease receiving care at Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu, Kenya","authors":"Fredrick O. Olewe, Constance N. Tenge, Irene K. Marete","doi":"10.1101/2024.08.22.24312427","DOIUrl":"https://doi.org/10.1101/2024.08.22.24312427","url":null,"abstract":"Background\u0000Sickle cell disease is a genetic disorder associated with lifelong symptoms of anemia, vaso-oclusive crisis and organ damage. Pulmonary complications and declining lung functions are contributors to morbidity and mortality. Determination of lung functions can enable early diagnosis and institution of appropriate intervention.\u0000Methods and findings A cross sectional study done at Jaramogi Oginga Odinga Teaching and Referral Hospital in Kisumu, Kenya, to determine the prevalence, patterns, and the factors associated with abnormal lung functions in children and adolescents aged 6-17 years with confirmed diagnosis Sickle Cell Disease. A total of 138 participants were recruited. A structured data collection tool was used to collect Socio-demographics and clinical characteristics. The spirometry was done using NDD Easy-On PC spirometer and results entered into database, cleaned and analyzed for proportions, frequency, mean, range and odds ratio at 95% confidence level.\u0000Females were 65(47%), males 73(53%), and the mean age was 10.99 years with SD of 3.15. A total of 79(57%) were from rural and fuel used was fired wood 41%. Hospital admission were 84(61%), vaso-oclusive crisis 104 (75%), acute chest syndrome 61(44%) and blood transfusions 56(40%) in the last 12 months. Prevalence of abnormal lung functions was 28 % (39), restrictive pattern 26(67%) and obstructive pattern 13(33%). Urban setting (OR 24.101 p value 0.163), being female (OR 18.911 p value 0.069), and blood transfusion (OR 11.683 p value 0.195) had high odds ratio while, stable hydroxyurea use (OR 0.525 p value 0.678) and hospital admission (OR 0.048 p value 0.121) had low odds ratio, but not statistically significant.\u0000Conclusion\u0000One third had abnormal lung function mostly restrictive followed by obstructive pattern. Residence in urban setting, being female and blood transfusion had high odds ratio, while stable hydroxyurea use and hospital admission had low odds ratio but no statistically significant","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMI-related Genetic Factors and COPD Imaging Phenotypes","authors":"Jingzhou Zhang, Matthew Moll, Catherine L. Debban, Brian D. Hobbs, Heena Rijhwani, George R. Washko, Bartolome Celli, Edwin K. Silverman, Per Bakke, Elizabeth C Oelsner, R Graham Barr, Alvar Agusti, Rosa Faner, Guy Brusselle, Stephen M Humphries, David A Lynch, Josee Dupuis, Ani W. Manichaikul, George T. O'Connor, Michael H. Cho","doi":"10.1101/2024.08.16.24312135","DOIUrl":"https://doi.org/10.1101/2024.08.16.24312135","url":null,"abstract":"Background: While low body mass index (BMI) is associated with emphysema and obesity is associated with airway disease in chronic obstructive pulmonary disease (COPD), the underlying mechanisms are unclear. Methods: We aggregated genetic variants from population-based genome-wide association studies to generate a polygenic score of BMI (PGSBMI). We calculated this score for participants from COPD-enriched and community-based cohorts and examined associations with automated quantification and visual interpretation of computed tomographic emphysema and airway wall thickness (AWT). We summarized the results using meta-analysis.\u0000Results: In the random-effects meta-analyses combining results of all cohorts (n=16,349), a standard deviation increase of the PGSBMI was associated with less emphysema as quantified by log-transformed percent of low attenuation areas ≤ 950 Hounsfield units (β= -0.062, p<0.0001) and 15th percentile value of lung density histogram (β=2.27, p<0.0001), and increased AWT as quantified by the square root of wall area of a 10-mm lumen perimeter airway (β=0.016, p=0.0006) and mean segmental bronchial wall area percent (β=0.26, p=0.0013). For imaging characteristics assessed by visual interpretation, a higher PGSBMI was associated with reduced emphysema in both COPD-enriched cohorts (OR for a higher severity grade=0.89, p=0.0080) and in the community-based Framingham Heart Study (OR for the presence of emphysema=0.82, p=0.0034), and a higher risk of airway wall thickening in the COPDGene study (OR=1.17, p=0.0023). Conclusions: In individuals with and without COPD, a higher body mass index polygenic risk is associated with both quantitative and visual decreased emphysema and increased AWT, suggesting genetic determinants of BMI affect both emphysema and airway wall thickening.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"322 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common and rare variant analyses reveal novel genetic factors underlying Idiopathic Pulmonary Fibrosis and shared aetiology with COVID-19","authors":"Athanasios Kousathanas, Christopher A Odhams, James Cook, Yao Hu, Stephan Klee, A Mesut Erzurumluoglu, Fidel Ramirez, Christoph Mayr, Dennis Schafer, Lara Beck, Ingrid Christ, Taekyu Lee, James Christopher Tarr, Steven W. Fesik, Boehringer Ingelheim - Global Computational Biology and Digital Sciences, James Duboff, Frederik Wirtz-Peitz, Loukas Moutsianas, Matthew A Brown, Jan Kriegl, Goerge Okafo, Jan N Jensen, Matthew J Thomas, Zhihao Ding","doi":"10.1101/2024.08.16.24312138","DOIUrl":"https://doi.org/10.1101/2024.08.16.24312138","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating respiratory disease with limited therapeutic options. We carried out genome-wide association (GWAS), post-GWAS and rare variant analyses utilising the whole genome sequencing data (WGS) from the 100,000 Genomes Project (100kGP) of a cohort of IPF participants (n=586) to identify novel associations and potential drug targets. Meta-analysis combining 100kGP and published GWASs of IPF (total 11,746 cases and 1,416,493 controls) identified a novel association signal at the 1q21.2 locus (rs16837903, OR[95%CI]=0.88[0.85, 0.92], P=9.54x10-9) which was also successfully replicated with independent data and linked to the probable effector gene MCL1. MCL1 showed increased expression levels in IPF patients versus controls in alveolar epithelial type I cells. Despite its known antiapoptotic role, inhibition of MCL1 in vitro did not selectively deplete senescent cells, hinting at the complexity involved in targeting MCL1. Rare variant burden analysis identified ANGPTL7, a secreted glycoprotein involved in the regulation of angiogenesis, as a novel IPF candidate gene (OR[95%CI]=28.79 [8.51-97.43], P=6.73x10-8). Transcriptome-wide association analysis (TWAS) revealed that overexpression of cell cycle regulator SERTAD2 and nuclear importer TPNO3 were associated with increased IPF risk. We also investigated shared genetic mechanisms between IPF with severe COVID-19 and expanded the list of shared genetic loci with three novel colocalised signals at 1q21.2, 6p24.3 and 16p13.3 with probable effector genes MCL1, DSP and RHBDF1, implicating regulation of apoptosis, cell adhesion and epidermal growth factor signalling, respectively. By leveraging the genetic correlation between IPF and severe COVID-19 (rg[95% CI]) = 0.39 [0.25-0.53]) through multi-trait meta-analysis, we further identified and replicated an additional novel candidate IPF signal at 2p16.1 with probable effector gene BCL11A, a regulator of haematopoiesis and lymphocyte development. Based on prioritized genes across analyses, we propose mechanisms mediating IPF disease risk and shared mechanisms between IPF and severe COVID-19, thereby expanding the potential for developing common treatments.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A time-multiplexing approach to shared ventilation","authors":"Jacob Q Yarinsky, Abby Blocker, Carolyna Yamamoto Alves Pinto, Christopher L Passaglia, Stefano Pasetto, Aaron R Muncey, Heiko Enderling","doi":"10.1101/2024.08.06.24311558","DOIUrl":"https://doi.org/10.1101/2024.08.06.24311558","url":null,"abstract":"Ventilator shortages during the COVID-19 pandemic forced some hospitals to practice and many to consider shared ventilation, where a single ventilator is used to ventilate multiple patients simultaneously. However, the high risk of harm to co-ventilated patients secondary to the inability to treat anatomically different patients or safely adapt to dynamic ventilation requirements has prevented full adoption of multi-patient coventilation. Here, a time-multiplexing approach to shared ventilation is introduced to overcome these safety concerns. A proof-of-concept device consisting of electromechanically coupled ball valves to induce customized resistances and facilitate the delivery of alternating breaths from the ventilator to each patient is presented. The approach successfully ventilated two test lungs, and individualized tidal volume combinations of various magnitudes were produced. Over five hours of co-ventilation, consistency in tidal volume delivery was comparable to independent ventilation. Time-multiplexing was able to facilitate delivery of statistically unique tidal volumes to two test lungs and maintain the consistency of tidal volumes within each test lung while independently ventilated with identical parameters. The ability to adjust each test lung's inspiratory pressures dynamically and independently was also demonstrated. The time-multiplexing approach has the potential to increase the viability of co-ventilation for ongoing and future ventilator shortages.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of a Post-Bronchodilator FEV1/FVC < 0.7 on COPD Diagnosis and Treatment: A Regression Discontinuity Design","authors":"Alexander T Moffett, Scott D Halpern, Gary Eric Weissman","doi":"10.1101/2024.08.05.24311519","DOIUrl":"https://doi.org/10.1101/2024.08.05.24311519","url":null,"abstract":"Background\u0000Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend the diagnosis of chronic obstructive pulmonary disease (COPD) only in patients with a post-bronchodilator forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) less than 0.7. However the impact of this recommendation on clinical practice is unknown. Research Question\u0000What is the effect of a documented post-bronchodilator FEV1/FVC &lt; 0.7 on the diagnosis and treatment of COPD? Study Design and Methods\u0000We used a national electronic health record database to identify clinical encounters be- tween 2007 to 2022 with patients 18 years of age and older in which a post-bronchodilator FEV₁/FVC value was documented. An encounter was associated with a COPD diagnosis if a diagnostic code for COPD was assigned, and was associated with COPD treatment if a prescription for a medication commonly used to treat COPD was filled within 90 days. We used a regression discontinuity design to measure the effect of a post-bronchodilator FEV₁/FVC &lt; 0.7 on COPD diagnosis and treatment. Results\u0000Among 27 817 clinical encounters, involving 18 991 patients, a post-bronchodilator FEV₁/FVC &lt; 0.7 was present in 14 876 (53.4%). The presence of a documented post-bronchodilator FEV₁/FVC &lt; 0.7 had a small effect on the probability of a COPD diagnosis, increasing by\u000026.0% (95% confidence interval [CI] 1.1% to 10.9%) from 38.0% just above the 0.7 cutoff to 44.0% just below this cutoff. The presence of a documented post-bronchodilator FEV₁/FVC had no effect on the probability of COPD treatment (−2.1%, 95% CI −7.2% to 3.0%). Interpretation\u0000The presence of a documented post-bronchodilator FEV₁/FVC &lt; 0.7 has only a small effect on the probability that a clinician will make a guideline-concordant diagnosis of COPD and has no effect on corresponding treatment decisions.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Lipids as Biomarkers for Diagnosis of Tuberculosis: A Multi-cohort, Multi-omics Data Integration Analysis","authors":"Nguyen Tran Nam Tien, Nguyen Thi Hai Yen, Nguyen Ky Phat, Nguyen Ky Anh, Nguyen Quang Thu, Eunsu Cho, Ho-Sook Kim, Dinh Hoa Vu, Duc Ninh Nguyen, Dong Hyun Kim, Jee Youn Oh, Nguyen Phuoc Long","doi":"10.1101/2024.08.06.24311536","DOIUrl":"https://doi.org/10.1101/2024.08.06.24311536","url":null,"abstract":"ABSTRACT\u0000Background: Circulating immunometabolic biomarkers show promise for the diagnosis and treatment monitoring of tuberculosis (TB). However, biomarkers that can distinguish TB from nontuberculous mycobacteria (NTM) infections, latent tuberculosis infection (LTBI), and other lung diseases (ODx) have not been elucidated. This study utilized a multi-cohort, multi-omics approach combined with predictive modeling to identify, validate, and prioritize biomarkers for the diagnosis of active TB. Methods: Functional omics data were collected from two discovery cohorts (76 patients in the TB-NTM cohort and 72 patients in the TB-LTBI-ODx cohort) and one validation cohort (68 TB patients and 30 LTBI patients). An integrative multi-omics analysis was performed to identify the plasma multi-ome biosignatures. Machine learning-based predictive modeling was then applied to assess the performance of these biosignatures and prioritize the most promising candidates. Results: Conventional statistical analyses of immune profiling and metabolomics indicated minor differences between active TB and non-TB groups, whereas the lipidome showed significant alteration. Muti-omics integrative analysis identified three multi-ome biosignatures that could distinguish active TB from non-TB with promising performance, achieving area under the ROC curve (AUC) values of 0.7-0.9 across groups in both the discovery and validation cohorts. The lipid PC(14:0_22:6) emerged as the most important predictor for differentiating active TB from non-TB controls, consistently presenting at lower levels in the active TB group compared with counterparts. Further validation using two independent external datasets demonstrated AUCs of 0.77-1.00, confirming the biomarkers' efficacy in distinguishing TB from other non-TB groups.\u0000Conclusion: Our integrative multi-omics reveals significant immunometabolic alteration in TB. Predictive modeling suggests lipids as promising biomarkers for TB-NTM differential diagnosis and TB-LTBI-ODx diagnosis. External validation further indicates PC(14:0_22:6) as a potential diagnostic marker candidate for TB.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary 129Xe Magnetic Resonance Gas-exchange Abnormalities in Moderate-Severe Asthma","authors":"Grace Parraga, Sam Tcherner, Ali Mozaffaripour, Alexander M Matheson, Alexander Biancaniello, Cory Yamashita","doi":"10.1101/2024.08.01.24311378","DOIUrl":"https://doi.org/10.1101/2024.08.01.24311378","url":null,"abstract":"BACKGROUND: Asthma is recognized as an inflammatory disease of the airways, but inflammation may also affect the parenchyma and pulmonary vasculature. Hyperpolarized ¹²⁹Xe MRI and MR spectroscopy (MRS) provide a way to quantify the transfer of gas from the airways through the alveolar membrane and its binding to hemoglobin in the red blood cells (RBC) of the pulmonary microvasculature. The vast majority of ¹²⁹Xe MRS studies have investigated interstitial lung disease and the ratio of ¹²⁹Xe binding to the RBC and ¹²⁹Xe present in the alveolar membrane, (RBC:membrane) which is a surrogate of oxygen gas-transfer to the blood. We wondered if ¹²⁹Xe RBC:membrane would differ in asthma patients as compared to healthy volunteers because of recent work showing abnormally diminished pulmonary vascular small-vessel structure in severe- asthma.\u0000RESEARCH QUESTION: Do ¹²⁹Xe MRI gas-transfer measurements differ significantly in patients with moderate-severe asthma? STUDY DESIGN AND METHODS: In this retrospective study, healthy (NCT02484885) and asthma (NCT04651777; NCT02351141) participants were evaluated who provided written informed consent.\u0000RESULTS: Thirty-one participants with asthma (mean age=55 years ± 18; 22 females) and 32 healthy volunteers (mean age=31 years ± 14; 12 females) with ¹²⁹Xe MRS were evaluated. FEV1, VDP and DLCO/KCO were significantly different in asthma compared to healthy participants. Age-corrected 1RBC:membrane was significantly different in moderate-severe asthma (0.32±0.09) as compared to healthy participants (0.47±0.12, P=.01). RBC:membrane was significantly related to pulse-oximetry hemoglobin estimates (ρ=.29; P=.04) and DLCO (ρ=.71; P&lt;.001). Significant relationships between ¹²⁹Xe RBC:membrane and age were observed in healthy (ρ=-.55; P=.002) and asthma participants (ρ=-0.49; P=.006), adjusted for sex. A significant ANCOVA model also revealed the influence of age (P=.002), sex (P&lt;.001), hemoglobin (P=.003) and asthma status (P=.02) on RBC:membrane. INTERPRETATION: ¹²⁹Xe RBC:membrane values were significantly different in moderate-severe asthma compared to healthy volunteers and were explained by age, sex, hemoglobin, and asthma status.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}