Pub Date : 2026-01-02DOI: 10.1016/j.rmed.2025.108632
Gerald S. Zavorsky
Robert A. Rigby, Mikis D. Stasinopoulous, Achim Zeilis, Sanja Stanojevic, Gillian Heller, Fernanda de Bastiani, Thomas Kneib, Andreas Mayr, Reto Stauffer, and Nikolaus Umlauf contend that segmented linear regression (SLR) is inadequate for spirometry reference equations and over-/underdiagnoses abnormality compared with Generalized Additive Models of Location, Scale, and Shape (GAMLSS). Using a refined NHANES 2007-2012 dataset (n=16,596), I reassessed calibration and the lower limit of normal (LLN) discordance with additional analyses. Out-of-sample root mean square error (RMSE) and correlations were essentially identical across approaches, and overall, the prevalence below the LLN differed by <1 percentage point. Ages 5-80 were resampled to the 2020-2024 U.S. Census age structure, and observed below-LLN counts (z<−1.645) were compared with exact 95% binomial bands; most age-sex strata for FEV1, FVC, and FEV1/FVC fell within expected sampling variability, with modest departures mainly in older men. Age-stratified concordance showed 93.5-93.8% normal by both methods and 4.0-4.8% abnormal by both; discordance was uncommon (GAMLSS-only 0.20-0.78%, SLR-only 1.23-1.65%). Estimated week-to-week measurement variability produced LLN flip rates of ∼3% (FEV1), ∼3.5% (FVC), and ∼6% (FEV1/FVC), exceeding model-driven differences. GAMLSS remains useful, but simpler, transparent regressions can often yield comparable practical interpretation.
Robert a: Rigby, Mikis D. Stasinopoulous, Achim Zeilis, Sanja Stanojevic, Gillian Heller, Fernanda de Bastiani, Thomas Kneib, Andreas Mayr， Reto Stauffer和Nikolaus Umlauf认为，与广义位置、尺度和形状加性模型（GAMLSS）相比，分段线性回归（SLR）不足以用于肺量测量参考方程和过度/不足诊断异常。使用精炼的NHANES 2007-2012数据集（n=16,596），我重新评估了校准和正常（LLN）不一致的下限，并进行了额外的分析。样本外均方根误差（RMSE）和相关性在两种方法之间基本相同，总体而言，低于lln的患病率差异为1，FVC和FEV1/FVC在预期的抽样变异性范围内，主要在老年男性中有适度的偏离。两种方法的年龄分层一致性均为93.5 ~ 93.8%正常，4.0 ~ 4.8%异常；差异不常见（gamlss仅为0.20-0.78%，slr仅为1.23-1.65%）。估计每周测量变异性产生的LLN翻转率为~ 3% （FEV1）、~ 3.5% （FVC）和~ 6% (FEV1/FVC)，超过了模型驱动的差异。GAMLSS仍然有用，但更简单的透明回归通常可以产生类似的实际解释。
{"title":"When the noise exceeds the signal: day-to-day variability in spirometry dominates LLN discordance","authors":"Gerald S. Zavorsky","doi":"10.1016/j.rmed.2025.108632","DOIUrl":"10.1016/j.rmed.2025.108632","url":null,"abstract":"<div><div>Robert A. Rigby, Mikis D. Stasinopoulous, Achim Zeilis, Sanja Stanojevic, Gillian Heller, Fernanda de Bastiani, Thomas Kneib, Andreas Mayr, Reto Stauffer, and Nikolaus Umlauf contend that segmented linear regression (SLR) is inadequate for spirometry reference equations and over-/underdiagnoses abnormality compared with Generalized Additive Models of Location, Scale, and Shape (GAMLSS). Using a refined NHANES 2007-2012 dataset (n=16,596), I reassessed calibration and the lower limit of normal (LLN) discordance with additional analyses. Out-of-sample root mean square error (RMSE) and correlations were essentially identical across approaches, and overall, the prevalence below the LLN differed by <1 percentage point. Ages 5-80 were resampled to the 2020-2024 U.S. Census age structure, and observed below-LLN counts (z<−1.645) were compared with exact 95% binomial bands; most age-sex strata for FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/FVC fell within expected sampling variability, with modest departures mainly in older men. Age-stratified concordance showed 93.5-93.8% normal by both methods and 4.0-4.8% abnormal by both; discordance was uncommon (GAMLSS-only 0.20-0.78%, SLR-only 1.23-1.65%). Estimated week-to-week measurement variability produced LLN flip rates of ∼3% (FEV<sub>1</sub>), ∼3.5% (FVC), and ∼6% (FEV<sub>1</sub>/FVC), exceeding model-driven differences. GAMLSS remains useful, but simpler, transparent regressions can often yield comparable practical interpretation.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108632"},"PeriodicalIF":3.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-02DOI: 10.1016/j.rmed.2026.108633
Mauro Maniscalco , Claudio Candia , Francesco Pennisi , Alfio Pennisi , Giuseppe De Simone , Pasquale Ambrosino
Chronic Obstructive Pulmonary Disease (COPD) remains a leading cause of morbidity and mortality worldwide. For patients with a high disease burden, triple therapy with fluticasone furoate/umeclidinium bromide/vilanterol trifenatate (FF/UMEC/VI) has demonstrated significant benefits in health-related quality of life (HRQoL), exacerbation reduction, and lung function improvement. Efforts have been made to define clinical stability (CS), yet real-world data on CS during FF/UMEC/VI therapy remain limited.
This retrospective study aimed to assess the prevalence of CS after 12 months (T12) of FF/UMEC/VI treatment in COPD patients. CS was defined as the concurrent presence at T12 of: no acute exacerbations in the prior 12 months, a ≥ 2-point improvement in COPD Assessment Test (CAT) score from baseline, and a forced expiratory volume in 1 s (FEV1) decline <100 mL.
A total of 47 patients was included. Of them, 10 (21.3 %) achieved CS. These individuals had a lower baseline exacerbation rate (P = 0.020) and a trend toward better baseline lung function. They also demonstrated greater improvement in 6-min walking distance compared with non-CS patients (P = 0.048).
These findings suggest that CS is attainable in routine clinical practice, with prevalence comparable to that observed in clinical trials. Patients achieving CS tended to have milder disease, indicating potential benefits of earlier FF/UMEC/VI initiation. This might have a relevant impact in clinical practice, especially in the setting of pulmonary rehabilitation. Nonetheless, further multicenter prospective studies are warranted to validate our findings and to identify predictors of treatment success.
{"title":"Clinical stability under FF/UMEC/VI triple inhaled therapy: A 12-month real life retrospective observational study","authors":"Mauro Maniscalco , Claudio Candia , Francesco Pennisi , Alfio Pennisi , Giuseppe De Simone , Pasquale Ambrosino","doi":"10.1016/j.rmed.2026.108633","DOIUrl":"10.1016/j.rmed.2026.108633","url":null,"abstract":"<div><div>Chronic Obstructive Pulmonary Disease (COPD) remains a leading cause of morbidity and mortality worldwide. For patients with a high disease burden, triple therapy with fluticasone furoate/umeclidinium bromide/vilanterol trifenatate (FF/UMEC/VI) has demonstrated significant benefits in health-related quality of life (HRQoL), exacerbation reduction, and lung function improvement. Efforts have been made to define clinical stability (CS), yet real-world data on CS during FF/UMEC/VI therapy remain limited.</div><div>This retrospective study aimed to assess the prevalence of CS after 12 months (T12) of FF/UMEC/VI treatment in COPD patients. CS was defined as the concurrent presence at T12 of: no acute exacerbations in the prior 12 months, a ≥ 2-point improvement in COPD Assessment Test (CAT) score from baseline, and a forced expiratory volume in 1 s (FEV<sub>1</sub>) decline <100 mL.</div><div>A total of 47 patients was included. Of them, 10 (21.3 %) achieved CS. These individuals had a lower baseline exacerbation rate (P = 0.020) and a trend toward better baseline lung function. They also demonstrated greater improvement in 6-min walking distance compared with non-CS patients (P = 0.048).</div><div>These findings suggest that CS is attainable in routine clinical practice, with prevalence comparable to that observed in clinical trials. Patients achieving CS tended to have milder disease, indicating potential benefits of earlier FF/UMEC/VI initiation. This might have a relevant impact in clinical practice, especially in the setting of pulmonary rehabilitation. Nonetheless, further multicenter prospective studies are warranted to validate our findings and to identify predictors of treatment success.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108633"},"PeriodicalIF":3.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-31DOI: 10.1016/j.rmed.2025.108625
Gloria Maria Citton , Caterina Antonaglia , Antonio Fabozzi , Alessia Steffanina , Silvia Giannone , Mattia Manna , Giulia Prezioso , Chiara Torregiani , Paola Confalonieri , Francesco Salton , Barbara Ruaro , Paolo Palange , Marco Confalonieri
Background
Obstructive Sleep Apnea Syndrome (OSAS) is the most common sleep-related breathing disorder, considered more prevalent in males. Recent evidences suggest that prevalence of OSAS in females is underestimated, with a clinical phenotype marked by sleep fragmentation, poor sleep quality, and neurobehavioral symptoms. We hypothesized that a low arousal threshold (low AT) may be more common in females, which may underline these clinical and polysomnographic differences.
Methods
In this retrospective multicentric study, 84 females and 93 males with OSA underwent a Home Sleep Apnea Test (HSAT) reviewed by a sleep expert. Low AT was predicted using the Edwards score criteria.
Results
Out of 177 patients, low AT was identified in 60.7 % of females and 40.9 % of males (p = 0.008). Stratifying by OSA severity, low AT was more prevalent in patients with mild disease, both in females and males. Among obese patients (Body Mass Index, BMI ≥30 kg/m2), low AT was present in 60.9 % of females compared to 24.3 % of males (p = 0.001).
Conclusion
Our findings indicate that a low AT is significantly more prevalent in OSA females, remembering that our female population mainly corresponds to post-menopausal females. This may explain the more pronounced sleep fragmentation and neurobehavioral symptoms in women.
{"title":"Sex differences in low arousal threshold in obstructive sleep apnea","authors":"Gloria Maria Citton , Caterina Antonaglia , Antonio Fabozzi , Alessia Steffanina , Silvia Giannone , Mattia Manna , Giulia Prezioso , Chiara Torregiani , Paola Confalonieri , Francesco Salton , Barbara Ruaro , Paolo Palange , Marco Confalonieri","doi":"10.1016/j.rmed.2025.108625","DOIUrl":"10.1016/j.rmed.2025.108625","url":null,"abstract":"<div><h3>Background</h3><div>Obstructive Sleep Apnea Syndrome (OSAS) is the most common sleep-related breathing disorder, considered more prevalent in males. Recent evidences suggest that prevalence of OSAS in females is underestimated, with a clinical phenotype marked by sleep fragmentation, poor sleep quality, and neurobehavioral symptoms. We hypothesized that a low arousal threshold (low AT) may be more common in females, which may underline these clinical and polysomnographic differences.</div></div><div><h3>Methods</h3><div>In this retrospective multicentric study, 84 females and 93 males with OSA underwent a Home Sleep Apnea Test (HSAT) reviewed by a sleep expert. Low AT was predicted using the Edwards score criteria.</div></div><div><h3>Results</h3><div>Out of 177 patients, low AT was identified in 60.7 % of females and 40.9 % of males (p = 0.008). Stratifying by OSA severity, low AT was more prevalent in patients with mild disease, both in females and males. Among obese patients (Body Mass Index, BMI ≥30 kg/m<sup>2</sup>), low AT was present in 60.9 % of females compared to 24.3 % of males (p = 0.001).</div></div><div><h3>Conclusion</h3><div>Our findings indicate that a low AT is significantly more prevalent in OSA females, remembering that our female population mainly corresponds to post-menopausal females. This may explain the more pronounced sleep fragmentation and neurobehavioral symptoms in women.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108625"},"PeriodicalIF":3.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-31DOI: 10.1016/j.rmed.2025.108630
Feng Chen , Mingzhu Lu , Jia Ye , Lei Zhang , Lei Gu , Wei Liu
Objective
The association between FeNO and blood eosinophil count among children and adolescents with asthma in the United States was investigated using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2012.
Methods
A total of 934 children and adolescents with asthma aged 7–19 years were included in the analysis. Multivariate linear regression, smooth curve fitting, threshold effect analysis, and subgroup analyses were performed to evaluate the association between FeNO and blood eosinophil count.
Results
After adjustment for covariates, each one-unit increase in blood eosinophil count was associated with a 5.34 ppb increase in FeNO among children and adolescents with asthma (β = 5.34, 95 % CI: 4.16–6.52). Moreover, FeNO and blood eosinophil count demonstrated a nonlinear relationship pattern, with evidence suggesting a change in the slope at higher blood eosinophil counts. Subgroup analyses revealed significant interactions across age, sex, race/ethnicity, and body mass index (BMI).
Conclusions
This population-based study demonstrated a significant positive association between FeNO and blood eosinophil count among children and adolescents with asthma in the United States.
{"title":"Association between fractional exhaled nitric oxide (FeNO) and blood eosinophil count among children and adolescents with asthma in the United States: a population-based study","authors":"Feng Chen , Mingzhu Lu , Jia Ye , Lei Zhang , Lei Gu , Wei Liu","doi":"10.1016/j.rmed.2025.108630","DOIUrl":"10.1016/j.rmed.2025.108630","url":null,"abstract":"<div><h3>Objective</h3><div>The association between FeNO and blood eosinophil count among children and adolescents with asthma in the United States was investigated using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2012.</div></div><div><h3>Methods</h3><div>A total of 934 children and adolescents with asthma aged 7–19 years were included in the analysis. Multivariate linear regression, smooth curve fitting, threshold effect analysis, and subgroup analyses were performed to evaluate the association between FeNO and blood eosinophil count.</div></div><div><h3>Results</h3><div>After adjustment for covariates, each one-unit increase in blood eosinophil count was associated with a 5.34 ppb increase in FeNO among children and adolescents with asthma (β = 5.34, 95 % CI: 4.16–6.52). Moreover, FeNO and blood eosinophil count demonstrated a nonlinear relationship pattern, with evidence suggesting a change in the slope at higher blood eosinophil counts. Subgroup analyses revealed significant interactions across age, sex, race/ethnicity, and body mass index (BMI).</div></div><div><h3>Conclusions</h3><div>This population-based study demonstrated a significant positive association between FeNO and blood eosinophil count among children and adolescents with asthma in the United States.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108630"},"PeriodicalIF":3.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is associated with clinically amyopathic dermatomyositis (CADM) and life-threatening rapidly progressive interstitial lung disease (RP-ILD). Although ILD without skin or muscle involvement has been reported in anti-MDA5-positive patients, the clinical characteristics of this atypical presentation remain unclear.
Procedures
We conducted a multicenter retrospective study of anti-MDA5 antibody-positive ILD in 10 hospitals in Japan between January 2006 and December 2024. Patients were classified into three subgroups: classic dermatomyositis (DM), CADM, and hypocutaneous amyopathic DM (HADM), which is defined as ILD without skin or muscle involvement. The clinical features and outcomes among the groups were analyzed.
Results
Of the 89 patients, 19 (21.3 %) were classified as having classic DM, 59 (66.3 %) as having CADM, and 11 (12.4 %) as having HADM. Compared to classic DM and CADM, patients with HADM were older, more often smokers, and more likely to first present to pulmonologists. Chest HRCT patterns of ILD were similar across the three groups, and the frequency of RP-ILD was comparable; however, patients with HADM were less likely to receive triple combination therapy (glucocorticoids, calcineurin inhibitor, and intravenous cyclophosphamide). Notably, the HADM group had the poorest prognoses. Among patients with HADM, those with RP-ILD had significantly higher anti-MDA5 antibody titers than those without RP-ILD.
Conclusions
A subset of patients with anti-MDA5-positive ILD presents without prominent skin or muscle involvement and may be associated with an increased risk of RP-ILD and poor prognosis. Increased awareness and early recognition of this subtype, together with timely and appropriate immunosuppressive treatment, may improve outcomes.
{"title":"Anti-MDA5 antibody-positive interstitial lung disease without prominent skin or muscle manifestations: A high-risk and potentially overlooked subgroup","authors":"Atsushi Muto , Satoshi Watanabe , Yuko Waseda , Seisuke Okazawa , Toshiki Kido , Keigo Saeki , Toshiyuki Kita , Hazuki Takato , Hiroki Shirasaki , Yukio Kawagishi , Kenta Yamamura , Kazumasa Kase , Kazuhiko Iwasaki , Satoshi Tanaka , Yasunori Iwata , Yasuhito Hamaguchi , Takashi Matsushita , Seiji Yano","doi":"10.1016/j.rmed.2025.108629","DOIUrl":"10.1016/j.rmed.2025.108629","url":null,"abstract":"<div><h3>Purpose</h3><div>Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is associated with clinically amyopathic dermatomyositis (CADM) and life-threatening rapidly progressive interstitial lung disease (RP-ILD). Although ILD without skin or muscle involvement has been reported in anti-MDA5-positive patients, the clinical characteristics of this atypical presentation remain unclear.</div></div><div><h3>Procedures</h3><div>We conducted a multicenter retrospective study of anti-MDA5 antibody-positive ILD in 10 hospitals in Japan between January 2006 and December 2024. Patients were classified into three subgroups: classic dermatomyositis (DM), CADM, and hypocutaneous amyopathic DM (HADM), which is defined as ILD without skin or muscle involvement. The clinical features and outcomes among the groups were analyzed.</div></div><div><h3>Results</h3><div>Of the 89 patients, 19 (21.3 %) were classified as having classic DM, 59 (66.3 %) as having CADM, and 11 (12.4 %) as having HADM. Compared to classic DM and CADM, patients with HADM were older, more often smokers, and more likely to first present to pulmonologists. Chest HRCT patterns of ILD were similar across the three groups, and the frequency of RP-ILD was comparable; however, patients with HADM were less likely to receive triple combination therapy (glucocorticoids, calcineurin inhibitor, and intravenous cyclophosphamide). Notably, the HADM group had the poorest prognoses. Among patients with HADM, those with RP-ILD had significantly higher anti-MDA5 antibody titers than those without RP-ILD.</div></div><div><h3>Conclusions</h3><div>A subset of patients with anti-MDA5-positive ILD presents without prominent skin or muscle involvement and may be associated with an increased risk of RP-ILD and poor prognosis. Increased awareness and early recognition of this subtype, together with timely and appropriate immunosuppressive treatment, may improve outcomes.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108629"},"PeriodicalIF":3.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.rmed.2025.108627
Anuraag Sah , Matthew I. Derakhshesh , Hannah D. Bozell , Minahil Wasim , Fatima Javed , Peter Kirkpatrick , Emilio J. Fabian , Boris Shkolnik , Paul J. Feustel , Kurt Hu , Marc A. Judson , Radmila Lyubarova , Mikhail Torosoff , Amit Chopra
Rationale
Differentiating between congestive heart failure-related pleural effusion (CHF-PE) and non-CHF-PE is clinically important. However, this distinction can be challenging and often requires thoracentesis. Role of transthoracic echocardiography in the diagnosis of CHF-PE has never been evaluated.
Objective
Assess the diagnostic performance of echocardiography in differentiating CHF-PE from non-CHF-PE.
Methods
This is a single-center retrospective case-control study of patients with pleural effusions classified as either CHF-PE or non-CHF-PE based on a comprehensive clinical data analysis. Traditional indicators of CHF (reduced left ventricular ejection fraction) and contemporary echocardiographic parameters of elevated left atrial pressures (enlarged indexed left atrial volume - LAVI, increased E/A and E/e’ ratios) were investigated. Echocardiographic evaluations were blinded to the clinical classification of pleural effusions.
Results
The study cohort included 167 patients; most patients (112/167) were diagnosed with non-CHF-PE. Echocardiographic parameters of E/e’ > 14, E/A > 2, LAVI ≥34 ml/m2, and LVEF <40 % had high specificity (89 %, 98 %, 80 %, and 94 %, respectively) but low to modest individual sensitivity (45 %, 12 %, 72 %, and 27 %, respectively) in diagnosing CHF-PE. In a univariate logistic regression, both E/e’ and LAVI performed well in identifying CHF-PE (AUC = 0.832 and 0.835, respectively), however, the best results were seen when E/e’ and LAVI were combined (AUC = 0.903). Whereas reduced LVEF was not helpful in identifying CHF-PE (AUC = 0.635).
Conclusion
Echocardiographic parameters indicative of elevated left atrial pressure can be helpful in diagnosis of pleural effusions associated with CHF and may reduce the need for invasive thoracentesis in selected patients with pleural effusion.
{"title":"Diagnostic accuracy of echocardiography in identifying heart failure related pleural effusions","authors":"Anuraag Sah , Matthew I. Derakhshesh , Hannah D. Bozell , Minahil Wasim , Fatima Javed , Peter Kirkpatrick , Emilio J. Fabian , Boris Shkolnik , Paul J. Feustel , Kurt Hu , Marc A. Judson , Radmila Lyubarova , Mikhail Torosoff , Amit Chopra","doi":"10.1016/j.rmed.2025.108627","DOIUrl":"10.1016/j.rmed.2025.108627","url":null,"abstract":"<div><h3>Rationale</h3><div>Differentiating between congestive heart failure-related pleural effusion (CHF-PE) and non-CHF-PE is clinically important. However, this distinction can be challenging and often requires thoracentesis. Role of transthoracic echocardiography in the diagnosis of CHF-PE has never been evaluated.</div></div><div><h3>Objective</h3><div>Assess the diagnostic performance of echocardiography in differentiating CHF-PE from non-CHF-PE.</div></div><div><h3>Methods</h3><div>This is a single-center retrospective case-control study of patients with pleural effusions classified as either CHF-PE or non-CHF-PE based on a comprehensive clinical data analysis. Traditional indicators of CHF (reduced left ventricular ejection fraction) and contemporary echocardiographic parameters of elevated left atrial pressures (enlarged indexed left atrial volume - LAVI, increased E/A and E/e’ ratios) were investigated. Echocardiographic evaluations were blinded to the clinical classification of pleural effusions.</div></div><div><h3>Results</h3><div>The study cohort included 167 patients; most patients (112/167) were diagnosed with non-CHF-PE. Echocardiographic parameters of E/e’ > 14, E/A > 2, LAVI ≥34 ml/m2, and LVEF <40 % had high specificity (89 %, 98 %, 80 %, and 94 %, respectively) but low to modest individual sensitivity (45 %, 12 %, 72 %, and 27 %, respectively) in diagnosing CHF-PE. In a univariate logistic regression, both E/e’ and LAVI performed well in identifying CHF-PE (AUC = 0.832 and 0.835, respectively), however, the best results were seen when E/e’ and LAVI were combined (AUC = 0.903). Whereas reduced LVEF was not helpful in identifying CHF-PE (AUC = 0.635).</div></div><div><h3>Conclusion</h3><div>Echocardiographic parameters indicative of elevated left atrial pressure can be helpful in diagnosis of pleural effusions associated with CHF and may reduce the need for invasive thoracentesis in selected patients with pleural effusion.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108627"},"PeriodicalIF":3.1,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.rmed.2025.108622
Yiqin Yan , Jialong Jiang , Lihan Xiang , Jinmei Zhang , Dandan Hu , Liming Lou , Yue Sun
Background
Current therapeutic strategies for chronic obstructive pulmonary disease (COPD) remain insufficient to halt disease progression or prevent acute exacerbations. This study aimed to investigate vascular endothelial glycocalyx components (Syndecan-1, Heparan Sulfate, and Hyaluronic Acid) as biomarkers for detecting disease severity and predicting acute exacerbations (AECOPD).
Methods
100 patients with COPD and 50 healthy volunteers from the Third Affiliated Hospital of Zhejiang Chinese Medical University. The serum glycocalyx (SDC-1, HS, and HA) levels of the subjects were detected, and the differences were compared.
Results
The level of SDC-1, HS, and HA were higher in the exacerbation group than in the stable group and the control group (P < 0.05), and in the stable group than in the control group (P < 0.05). SDC-1, HS, and HA were negatively correlated with PaO2, FVC % pred, FEV1 % pred, and FEV1/FVC (P < 0.05) while positively correlating with PaCO2 (P < 0.05). The logistic regression analysis showed that SDC-1, HS, and HA were influential factors in the acute exacerbation of COPD (AECOPD). The receiver operating characteristics analysis showed that SDC-1, HS, and HA had good predictive efficacy in the AECOPD. Strong correlations between hospital stay and levels of glycocalyx were evident, especially for SDC-1, HS, signifying robust associations with prolonged hospitalization.
Conclusion
The circulating levels of glycocalyx degradation products (SDC-1, HS, and HA) were markedly elevated in AECOPD patients and demonstrated significant correlations with the severity of impaired lung function and gas exchange. Analysis revealed that these biomarkers were independent predictors of acute exacerbations and strongly associated with prolonged hospitalization. Therefore, our study provides clinical evidence that quantifying these components offers a promising, non-invasive approach for assessing disease severity and predicting outcomes in COPD.
{"title":"Clinical value of vascular endothelial glycocalyx in acute exacerbation of chronic obstructive pulmonary disease","authors":"Yiqin Yan , Jialong Jiang , Lihan Xiang , Jinmei Zhang , Dandan Hu , Liming Lou , Yue Sun","doi":"10.1016/j.rmed.2025.108622","DOIUrl":"10.1016/j.rmed.2025.108622","url":null,"abstract":"<div><h3>Background</h3><div>Current therapeutic strategies for chronic obstructive pulmonary disease (COPD) remain insufficient to halt disease progression or prevent acute exacerbations. This study aimed to investigate vascular endothelial glycocalyx components (Syndecan-1, Heparan Sulfate, and Hyaluronic Acid) as biomarkers for detecting disease severity and predicting acute exacerbations (AECOPD).</div></div><div><h3>Methods</h3><div>100 patients with COPD and 50 healthy volunteers from the Third Affiliated Hospital of Zhejiang Chinese Medical University. The serum glycocalyx (SDC-1, HS, and HA) levels of the subjects were detected, and the differences were compared.</div></div><div><h3>Results</h3><div>The level of SDC-1, HS, and HA were higher in the exacerbation group than in the stable group and the control group (P < 0.05), and in the stable group than in the control group (P < 0.05). SDC-1, HS, and HA were negatively correlated with PaO<sub>2</sub>, FVC % pred, FEV1 % pred, and FEV1/FVC (P < 0.05) while positively correlating with PaCO<sub>2</sub> (P < 0.05). The logistic regression analysis showed that SDC-1, HS, and HA were influential factors in the acute exacerbation of COPD (AECOPD). The receiver operating characteristics analysis showed that SDC-1, HS, and HA had good predictive efficacy in the AECOPD. Strong correlations between hospital stay and levels of glycocalyx were evident, especially for SDC-1, HS, signifying robust associations with prolonged hospitalization.</div></div><div><h3>Conclusion</h3><div>The circulating levels of glycocalyx degradation products (SDC-1, HS, and HA) were markedly elevated in AECOPD patients and demonstrated significant correlations with the severity of impaired lung function and gas exchange. Analysis revealed that these biomarkers were independent predictors of acute exacerbations and strongly associated with prolonged hospitalization. Therefore, our study provides clinical evidence that quantifying these components offers a promising, non-invasive approach for assessing disease severity and predicting outcomes in COPD.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108622"},"PeriodicalIF":3.1,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.rmed.2025.108628
Mira Abou-Rjeili , Raquel Farias , Yousof Mostafavi , Benjamin Smith , Nadia Giannetti , Jean Bourbeau
Chronic Obstructive Pulmonary Disease (COPD) and Heart failure (HF) are often concomitant, they are overlooked in practice. The objectives of this study were to determine the prevalence of HF in diagnosed COPD and COPD in diagnosed HF from a specialized clinics and determine patients’ characteristics which could be used to in clinical practice for active screening.
We conducted a prospective cohort study in a specialized COPD clinic and HF clinic. Patients underwent detailed cardiopulmonary evaluation to establish diagnosis and were followed for 12 months.
The prevalence of unrecognized COPD and HF were respectively 26.1 % and 26.8 %, and these patients were older, more likely to be male and heavy smokers. COPD patients with abnormal vs those with normal echocardiography had an increased rate of mod-severe exacerbation like events (1.3 vs 0.6). They also had a higher prevalence of self-reported heart disease, diabetes, abnormal ECG, cardiovascular medication use, higher blood eosinophil and troponin but no difference on lung function, computed tomography-assessed emphysema and gas trapping, symptom burden and health status.
HF patients with abnormal vs those with normal spirometry had increased exacerbation like-events (16.7 % vs 6.3 % but reach statistical significance). They also had more heart disease, worse lung function by definition and gas trapping, higher blood eosinophil but no difference in symptom burden and health status.
In two specialized clinics the prevalence of concomitant disease -undiagnosed HF in COPD patients and undiagnosed COPD in HF patients was common. Distinctive features were limited to clinical characteristics, but specific biomarkers cannot be recommended.
慢性阻塞性肺疾病（COPD）和心力衰竭（HF）往往是合并症，在实践中被忽视。本研究的目的是确定在专门诊所诊断为慢性阻塞性肺病的心衰患病率和慢性阻塞性肺病在诊断为心衰的患者中的患病率，并确定患者的特征，这些特征可用于临床实践中的主动筛查。我们在一家专门的COPD诊所和心衰诊所进行了一项前瞻性队列研究。患者接受详细的心肺评估以确定诊断，并随访12个月。未被识别的COPD和HF患病率分别为26.1%和26.8%，这些患者年龄较大，多为男性和重度吸烟者。与超声心动图正常的COPD患者相比，超声心动图异常的COPD患者发生中度-重度加重样事件的比率增加（1.3 vs 0.6）。他们自我报告的心脏病、糖尿病、心电图异常、心血管药物使用、较高的嗜酸性粒细胞和肌钙蛋白的患病率也较高，但在肺功能、计算机断层扫描评估的肺气肿和气体潴留、症状负担和健康状况方面没有差异。肺活量异常与正常的HF患者加重样事件增加（16.7% vs 6.3%，但有统计学意义）。他们也有更多的心脏病，更差的肺功能和气体捕获，更高的血嗜酸性粒细胞，但症状负担和健康状况没有差异。在两个专科诊所中，伴发疾病——COPD患者中未确诊的HF和HF患者中未确诊的COPD的患病率很普遍。独特的特征仅限于临床特征，但不能推荐特定的生物标志物。
{"title":"Personalizing the approach for the diagnosis of patients with concomitant Chronic Obstructive Pulmonary Disease and Heart failure","authors":"Mira Abou-Rjeili , Raquel Farias , Yousof Mostafavi , Benjamin Smith , Nadia Giannetti , Jean Bourbeau","doi":"10.1016/j.rmed.2025.108628","DOIUrl":"10.1016/j.rmed.2025.108628","url":null,"abstract":"<div><div>Chronic Obstructive Pulmonary Disease (COPD) and Heart failure (HF) are often concomitant, they are overlooked in practice. The objectives of this study were to determine the prevalence of HF in diagnosed COPD and COPD in diagnosed HF from a specialized clinics and determine patients’ characteristics which could be used to in clinical practice for active screening.</div><div>We conducted a prospective cohort study in a specialized COPD clinic and HF clinic. Patients underwent detailed cardiopulmonary evaluation to establish diagnosis and were followed for 12 months.</div><div>The prevalence of unrecognized COPD and HF were respectively 26.1 % and 26.8 %, and these patients were older, more likely to be male and heavy smokers. COPD patients with abnormal vs those with normal echocardiography had an increased rate of mod-severe exacerbation like events (1.3 vs 0.6). They also had a higher prevalence of self-reported heart disease, diabetes, abnormal ECG, cardiovascular medication use, higher blood eosinophil and troponin but no difference on lung function, computed tomography-assessed emphysema and gas trapping, symptom burden and health status.</div><div>HF patients with abnormal vs those with normal spirometry had increased exacerbation like-events (16.7 % vs 6.3 % but reach statistical significance). They also had more heart disease, worse lung function by definition and gas trapping, higher blood eosinophil but no difference in symptom burden and health status.</div><div>In two specialized clinics the prevalence of concomitant disease -undiagnosed HF in COPD patients and undiagnosed COPD in HF patients was common. Distinctive features were limited to clinical characteristics, but specific biomarkers cannot be recommended.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108628"},"PeriodicalIF":3.1,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.rmed.2025.108626
Yingqi Yang , Xia Tang , Tianchi Zhuang , Chang You , Hongkai Yu , Lu Hu , Haokun Mei , Ting Xu , Haili Ren , Hairong Yu , Yibo Gu , Xiaoying Duan , Ning Li , Minghui Ji
Background
Sleep apnea syndrome (SAS) affects one billion people worldwide and is a potential risk factor for a range of diseases. However, its association with respiratory infections is currently unknown.
Methods
We first employed a multi-model logistic regression approach to control confounding factors and explore the association between SAS and respiratory infections with data from NHANES. Subsequently, a Mendelian randomization (MR) analysis was employed to investigate the causal relationship between SAS and 15 respiratory infections outcomes. Heterogeneity tests were conducted and MR-Egger and MR-PRESSO were used to test for horizontal pleiotropy. Leave-one-out analysis was performed to identify influential SNPs. The study adhered to STROBE-MR guidelines for reporting MR results.
Results
In data from NHANES, we observed that SAS was an independent risk factor for respiratory infections (Model 2: P = 0.031, OR = 1.147, 95 % CI = 1.012–1.299). MR analysis showed that SAS was a risk factor for acute upper respiratory infections (P = 0.014, OR = 1.049, 95 % CI = 1.010–1.090) and other acute lower respiratory infections (P = 0.001, OR = 1.128, 95 % CI = 1.052–1.210). In the reverse MR analysis, COVID-19 (very severe respiratory confirmed vs. population) (P = 0.013, OR = 0.969, 95 % CI = 0.945–0.993), anti-influenza virus subtype H3N2 IgG levels (P = 0.028, OR = 0.974, 95 % CI = 0.952–0.997) and respiratory tuberculosis (P = 0.047, OR = 0.972, 95 % CI = 0.946–1.000) were protective factors for SAS.
Conclusion
SAS is a causal risk factor for respiratory infections and certain infections or specific immune responses may in turn reduce the risk of SAS, revealing a complex bidirectional relationship between them. Future studies are needed to validate the underlying mechanisms.
背景：睡眠呼吸暂停综合征（SAS）影响全球10亿人，是多种疾病的潜在危险因素。然而，它与呼吸道感染的关系目前尚不清楚。方法：我们首先采用多模型逻辑回归方法控制混杂因素，并利用NHANES的数据探讨SAS与呼吸道感染之间的关系。随后，采用孟德尔随机化（MR）分析来调查SAS与15种呼吸道感染结局之间的因果关系。进行异质性检验，采用MR-Egger和MR-PRESSO进行水平多效性检验。进行留一分析以确定有影响的snp。本研究遵循STROBE-MR报告MR结果的指南。结果：在NHANES的数据中，我们观察到SAS是呼吸道感染的独立危险因素（模型2:P = 0.031, OR = 1.147, 95% CI = 1.012-1.299）。MR分析显示SAS是急性上呼吸道感染（P = 0.014, OR = 1.049, 95% CI = 1.010 ~ 1.090）和其他急性下呼吸道感染（P = 0.001, OR = 1.128, 95% CI = 1.052 ~ 1.210）的危险因素。在反向MR分析中，COVID-19（非常严重呼吸道确诊vs.人群）（P = 0.013, OR = 0.969, 95% CI = 0.945-0.993）、抗流感病毒亚型H3N2 IgG水平（P = 0.028, OR = 0.974, 95% CI = 0.952-0.997）和呼吸道结核（P = 0.047, OR = 0.972, 95% CI = 0.946-1.000）是SAS的保护因素。结论：SAS是呼吸道感染的一个因果危险因素，某些感染或特定免疫反应可反过来降低SAS的风险，两者之间存在复杂的双向关系。需要进一步的研究来验证潜在的机制。
{"title":"Association of sleep apnea syndrome with respiratory infections: insights from NHANES and Mendelian randomization","authors":"Yingqi Yang , Xia Tang , Tianchi Zhuang , Chang You , Hongkai Yu , Lu Hu , Haokun Mei , Ting Xu , Haili Ren , Hairong Yu , Yibo Gu , Xiaoying Duan , Ning Li , Minghui Ji","doi":"10.1016/j.rmed.2025.108626","DOIUrl":"10.1016/j.rmed.2025.108626","url":null,"abstract":"<div><h3>Background</h3><div>Sleep apnea syndrome (SAS) affects one billion people worldwide and is a potential risk factor for a range of diseases. However, its association with respiratory infections is currently unknown.</div></div><div><h3>Methods</h3><div>We first employed a multi-model logistic regression approach to control confounding factors and explore the association between SAS and respiratory infections with data from NHANES. Subsequently, a Mendelian randomization (MR) analysis was employed to investigate the causal relationship between SAS and 15 respiratory infections outcomes. Heterogeneity tests were conducted and MR-Egger and MR-PRESSO were used to test for horizontal pleiotropy. Leave-one-out analysis was performed to identify influential SNPs. The study adhered to STROBE-MR guidelines for reporting MR results.</div></div><div><h3>Results</h3><div>In data from NHANES, we observed that SAS was an independent risk factor for respiratory infections (Model 2: P = 0.031, OR = 1.147, 95 % CI = 1.012–1.299). MR analysis showed that SAS was a risk factor for acute upper respiratory infections (<em>P</em> = 0.014, OR = 1.049, 95 % CI = 1.010–1.090) and other acute lower respiratory infections (<em>P</em> = 0.001, OR = 1.128, 95 % CI = 1.052–1.210). In the reverse MR analysis, COVID-19 (very severe respiratory confirmed vs. population) (<em>P</em> = 0.013, OR = 0.969, 95 % CI = 0.945–0.993), anti-influenza virus subtype H3N2 IgG levels (<em>P</em> = 0.028, OR = 0.974, 95 % CI = 0.952–0.997) and respiratory tuberculosis (<em>P</em> = 0.047, OR = 0.972, 95 % CI = 0.946–1.000) were protective factors for SAS.</div></div><div><h3>Conclusion</h3><div>SAS is a causal risk factor for respiratory infections and certain infections or specific immune responses may in turn reduce the risk of SAS, revealing a complex bidirectional relationship between them. Future studies are needed to validate the underlying mechanisms.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108626"},"PeriodicalIF":3.1,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1016/j.rmed.2025.108623
Benedetta Bondi , Fulvio Braido , Ilaria Baiardini , Federico Di Marco , Carola Montagnino , Martina Buscema , Cesare de Tommaso , Filippo Tarchino , Marcello Mincarini , Anna Maria Riccio , Diego Bagnasco
Background
The relationship between environmental pollution and human health is well-documented, and exposure has been linked to an increased risk of respiratory and psychological diseases. In our clinical practice, a trend of self-medication and self-diagnosis has emerged, defined as independent web searches for self-reported symptoms aimed at obtaining a diagnosis and related treatment in the absence of medical advice.
Objective
This study aims to investigate the relationship between air pollution and public health, focusing on the impact of particulate matter (PM 2.5, PM 10), nitrogen dioxide (NO2), ozone (O3), and other pollutants on respiratory and mental health, and their relationship with web searches for health-related topics.
Methods
The study compares search trends for specific terms (e.g., cough, dyspnea, asthma, etc.), obtained using Google Trends, a tool for assessing public interest in health-related issues, with air main pollutants concentrations collected over the same period in 2024 in Genoa, Liguria region.
Results
Correlation between searches for cough and levels of PM 2.5, O3, benzene, and NO2 was established, while depression also showed a connection to PM 2.5 and benzene.
Discussion
These findings underscore the potential of Google Trends as a valuable resource for epidemiological surveillance. The study highlights the necessity for healthcare systems to adapt to the implications of air quality on health outcomes. It emphasizes the need for innovative approaches, including real-time tracking of air pollution and its health impacts, to enhance patient care and inform clinical practice. The integration of technology and data analytics in healthcare is proposed as a forward-looking strategy to improve therapeutic adherence and patient management in the context of environmental health challenges.
{"title":"Google Trends as a health sentinel. ALERT study: Analyzing Symptoms Perceptions Related To Environmental pollution","authors":"Benedetta Bondi , Fulvio Braido , Ilaria Baiardini , Federico Di Marco , Carola Montagnino , Martina Buscema , Cesare de Tommaso , Filippo Tarchino , Marcello Mincarini , Anna Maria Riccio , Diego Bagnasco","doi":"10.1016/j.rmed.2025.108623","DOIUrl":"10.1016/j.rmed.2025.108623","url":null,"abstract":"<div><h3>Background</h3><div>The relationship between environmental pollution and human health is well-documented, and exposure has been linked to an increased risk of respiratory and psychological diseases. In our clinical practice, a trend of self-medication and self-diagnosis has emerged, defined as independent web searches for self-reported symptoms aimed at obtaining a diagnosis and related treatment in the absence of medical advice.</div></div><div><h3>Objective</h3><div>This study aims to investigate the relationship between air pollution and public health, focusing on the impact of particulate matter (PM 2.5, PM 10), nitrogen dioxide (NO2), ozone (O3), and other pollutants on respiratory and mental health, and their relationship with web searches for health-related topics.</div></div><div><h3>Methods</h3><div>The study compares search trends for specific terms (e.g., cough, dyspnea, asthma, etc.), obtained using Google Trends, a tool for assessing public interest in health-related issues, with air main pollutants concentrations collected over the same period in 2024 in Genoa, Liguria region.</div></div><div><h3>Results</h3><div>Correlation between searches for cough and levels of PM 2.5, O3, benzene, and NO2 was established, while depression also showed a connection to PM 2.5 and benzene.</div></div><div><h3>Discussion</h3><div>These findings underscore the potential of Google Trends as a valuable resource for epidemiological surveillance. The study highlights the necessity for healthcare systems to adapt to the implications of air quality on health outcomes. It emphasizes the need for innovative approaches, including real-time tracking of air pollution and its health impacts, to enhance patient care and inform clinical practice. The integration of technology and data analytics in healthcare is proposed as a forward-looking strategy to improve therapeutic adherence and patient management in the context of environmental health challenges.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"252 ","pages":"Article 108623"},"PeriodicalIF":3.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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