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Hwa-Yen Chiu,1– 4 Yung-Yang Liu,1,4 Tsu-Hui Shiao,1,4 Kang-Cheng Su,1,4 Kun-Ta Chou,1,4 Yuh-Min Chen1,4 1Chest Department, Taipei Veterans General Hospital, Taipei, 11217, Taiwan, Republic of China; 2Institute of Biophotonics, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, Republic of China; 3Division of Internal Medicine, Hsinchu Branch, Taipei Veterans General Hospital, Hsinchu, 31064, Taiwan, Republic of China; 4School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, Republic of ChinaCorrespondence: Yung-Yang Liu, Chest Department, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City, 11217, Taiwan, Republic of China, Tel +886-2-2871-2121 ext. 3071, Fax +886-2-2875-7858, Email yyliu1103@gmail.comPurpose: Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia and sleep fragmentation. While apnea is pronounced with severe desaturation during rapid eye movement (REM) sleep, REM-related OSA is a distinct phenotype of OSA associated with respiratory disturbances predominantly during REM sleep. In this study, we investigated the clinical features of REM-related OSA in Taiwan.Patients and Methods: All patients diagnosed with OSA in the Taipei Veterans General Hospital from 2015 to 2017 were analyzed retrospectively and classified into REM-related OSA (REM-OSA) group, non-REM related OSA (NREM-OSA) group, and non-stage specific-OSA group. The clinical demographics, OSA-related symptoms, polysomnography results, and medical comorbidities of the three groups were analyzed.Results: Among 1331 patients with OSA, 414 (31.1%) were classified as REM-OSA, 808 (60.7%) as NREM-OSA, and 109 (8.2%) as non-stage specific-OSA. After being adjusted for OSA severity, the REM-OSA group was associated with less portion of males, longer desaturation duration, and lower nadir oxygen saturation (SpO2) compared with the NREM-OSA group in mild and moderate OSA. In moderate OSA, the non-stage specific-OSA group featured more OSA severity and more desaturation compared with the other groups. The Epworth Sleepiness Scale scores and the prevalence of comorbidities did not vary among the REM-OSA, NREM-OSA, and non-stage specific-OSA groups. High REM-AHI/NREM-AHI ratio was associated with young age, female gender, high BMI, and low AHI.Conclusion: OSA patients with high REM-AHI/NREM-AHI ratio are related to young age, female gender, high BMI, and low AHI. Patients with REM-related OSA presented with longer desaturation duration and lower nadir SpO2 after being adjusted for OSA severity.Keywords: obstructive sleep apnea, OSA, rapid eye movement, REM, intermittent hypoxia, sleep-disordered breathing

Background and Objective: Correlations between the image analysis of CT scan, lung function and quality of life in patients with idiopathic pulmonary fibrosis (IPF) remain unclear. This study aimed to investigate the impacts of pulmonary blood-vessel distribution and the extent of fibrosis on the lung function and quality of life of patients with IPF., Methods: Patients were enrolled in an IPF registry and had completed pulmonary function tests, chest HRCT, St. George Respiratory Questionnaire (SGRQ) and echocardiography. Pulmonary blood-vessel distribution, specific image-derived airway volume (siVaw) and fibrosis extent (siVfib) were quantitatively calculated by functional respiratory imaging on HRCT., Results: The study subjects were categorized into DLco <40% pred. (n = 40) and DLco ≥40% pred. (n = 19) groups. Patients with DLco <40% pred. had significantly higher scores of SGRQ, composite physiologic index (CPI), exercise oxygen desaturation (∆SpO 2 ), siVaw, lower FVC% pred. and 6-minute walking distance% pred. The proportion of small blood vessels in the upper lobes (BV5PR-UL) was significantly correlated with CPI, DLco % Pred., FVC% pred., SGRQ and ∆SpO 2 . Only BV5PR-UL had a significant impact on all indices but not BV5PR in the lower lobes (BV5PR-LL). siVfib was significantly negatively correlated with BV5PR-UL, DLco% pred. and FVC% pred., as well as positively correlated with CPI, ∆SpO 2 and siVaw., Conclusion: BV5PR-UL and siVfib had significant correlations with lung function and may become important indicators to assess the severity of IPF and the impact on quality of life., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Objective: This study aimed to evaluate trends in polypharmacy prevalence among adults with asthma in the United States., Methods: Data from the 2001-2020 National Health and Nutrition Examination Survey were used to estimate the weighted prevalence of polypharmacy. Joinpoint regression analysis was conducted to evaluate trends in polypharmacy. Trends were first evaluated overall and then stratified by asthma severity and asthma control. A multivariable logistic regression model was used to identify factors associated with polypharmacy., Results: From 2001 to 2020, a stable trend in polypharmacy among U.S. adults with asthma was observed (average annual percent change [AAPC]=1.02, p =0.71). Trends across different asthma severity were stable (mild asthma: AAPC=2.93, p =0.20; moderate asthma: AAPC=-2.22, p =0.35; severe asthma: AAPC=0.45, p =0.82). Trends in adults with good asthma control and those with poor control stayed constant (good control: AAPC=0.82, p =0.68; poor control: AAPC=-1.22, p =0.82). Several factors, including older age, females, Non-Hispanic Black, health insurance coverage, family income, number of healthcare visits, former smokers, multi-morbidities, asthma severity, and asthma control, were associated with polypharmacy., Conclusions: Polypharmacy prevalence has remained constant among U.S. adults with asthma over the past two decades. Despite a stable overall trend, disparities in polypharmacy prevalence persist across different asthma severity and control status, underscoring the need for tailored medication management to improve asthma care.

Introduction: The English PUMA questionnaire emerges as an effective COPD case-finding tool. We aimed to use the PUMA questionnaire in combination with peak expiratory flow rate (PEFR) to improve case-finding efficacy in Chinese population., Methods: This cross-sectional, observational study included two stages: translating English to Chinese PUMA (C-PUMA) questionnaire with linguistic validation and psychometric evaluation, followed by clinical validation. Eligible participants (with age ≥40 years, respiratory symptoms, smoking history ≥10 pack-years) were enrolled and subjected to three questionnaires (C-PUMA, COPD assessment test [CAT], and generic health survey [SF-12V2]), PEFR measurement, and confirmatory spirometry. The C-PUMA score and PEFR were incorporated into a PUMA-PEFR prediction model applying binary logistic regression coefficients to estimate the probability of COPD (P COPD )., Results: C-PUMA was finalized through standard forward-backward translation processes and confirmation of good readability, comprehensibility, and reliability. In clinical validation, 240 participants completed the study. 78/240 (32.5%) were diagnosed with COPD. C-PUMA exhibited significant validity (correlated with CAT or physical component scores of SF-12V2, both P<0.05, respectively). PUMA-PEFR model had higher diagnostic accuracy than C-PUMA alone (area under ROC curve, 0.893 vs. 0.749, P<0.05). The best cutoff values of C-PUMA and PUMA-PEFR model (P COPD ) were ≥6 and ≥0.39, accounting for a sensitivity/specificity/numbers needed to screen of 77%/64%/3 and 79%/88%/2, respectively. C-PUMA ≥5 detected more underdiagnosed patients, up to 11.5% (vs. C-PUMA ≥6)., Conclusion: C-PUMA is well-validated. The PUMA-PEFR model provides more accurate and cost-effective case-finding efficacy than C-PUMA alone in at-risk, undiagnosed COPD patients. These tools can be useful to detect COPD early., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Background: Limited research has investigated the relationship between small airway dysfunction (SAD) and static lung hyperinflation (SLH) in patients with post-acute sequelae of COVID-19 (PASC) especially dyspnea and fatigue., Methods: 64 patients with PASC were enrolled between July 2020 and December 2022 in a prospective observational cohort. Pulmonary function tests, impulse oscillometry (IOS), and symptom questionnaires were performed two, five and eight months after acute infection. Multivariable logistic regression models were used to test the association between SLH and patient-reported outcomes., Results: SLH prevalence was 53.1% (34/64), irrespective of COVID-19 severity. IOS parameters and circulating CD4/CD8 T-cell ratio were significantly correlated with residual volume to total lung capacity ratio (RV/TLC). Serum CD8 + T cell count was negatively correlated with forced expiratory volume in the first second (FEV 1 ) and forced vital capacity (FVC) with statistical significance. Of the patients who had SLH at baseline, 57% continued to have persistent SLH after eight months of recovery, with these patients tending to be older and having dyspnea and fatigue. Post-COVID dyspnea was significantly associated with SLH and IOS parameters R5-R20, and AX with adjusted odds ratios 12.4, 12.8 and 7.6 respectively. SLH was also significantly associated with fatigue., Conclusion: SAD and a decreased serum CD4/CD8 ratio were associated with SLH in patients with PASC. SLH may persist after recovery from infection in a substantial proportion of patients. SAD and dysregulated T-cell immune response correlated with SLH may contribute to the development of dyspnea and fatigue in patients with PASC., (© 2024. The Author(s).)

We aimed to develop and validate a machine learning model using impulse oscillometry system (IOS) profiles for accurately classifying patients into three assessment-based categories: no airflow obstruction, asthma, and chronic obstructive pulmonary disease (COPD). Our research questions were as follows: (1) Can machine learning methods accurately classify obstructive disease states based solely on multidimensional IOS data? (2) Which IOS parameters and modeling algorithms provide the best discrimination? We used data for 480 patients (240 with COPD and 240 with asthma) and 84 healthy individuals for training. Physiological and IOS parameters were combined into six feature combinations. The classification algorithms tested were logistic regression, random forest, neural network, k-nearest neighbor, and support vector machine. The optimal feature combination for identifying individuals without pulmonary obstruction, with asthma, or with COPD included 15 IOS and physiological features. The neural network classifier achieved the highest accuracy (0.786). For discriminating between healthy and unhealthy individuals, two combinations of twenty-three features performed best in the neural network algorithm (accuracy of 0.929). When distinguishing COPD from asthma, the best combination included 15 features and the neural network algorithm achieved an accuracy of 0.854. This study provides compelling technical evidence and clinical justifications for advancing IOS data-driven models to aid in COPD and asthma management.

Background: Mouth opening/breathing during sleep is common in patients with obstructive sleep apnea (OSA), which is probably associated with more water loss and higher risk for nocturnal ischemic heart attack. This study aimed to evaluate nocturnal changes in hematocrit/hemoglobin levels and estimated plasma volume loss in OSA patients and its relation to their OSA severity and mouth open/breathing., Methods: Sixty OSA patients and fifteen healthy controls were enrolled and underwent overnight polysomnography. Mouth status was evaluated via an infrared camera and nasal/mouth airflow. Hematocrit and hemoglobin levels in peripheral venous blood were measured before and after sleep to estimate the change of plasma volume., Results: Compared to controls, OSA patients had a greater nocturnal increase in hematocrit (1.35% vs. 1.0%, p = 0.013), hemoglobin (0.50% vs. 0.30%, p = 0.002) and more estimated water loss (5.5% vs 3.7% of plasma volume, p < 0.013). The extent of increase was correlated to apnea-hypopnea index (AHI)&#95;the marker of OSA severity (Spearman's ρ = 0.332, p = 0.004; ρ = 0.367, p = 0.001 for hematocrit, hemoglobin, respectively), which remained significant after serial multivariate adjustment. OSA patients had more sleep time with mouth open (96.7% vs 26.7% of total sleep time, p < 0.001) and time with complete mouth breathing (14.1% vs 2.7%, p < 0.001). The extent of mouth breathing was correlated to AHI (ρ=0.487, p < 0.001), nocturnal increase in hematocrit/hemoglobin levels (ρ = 0.236, p = 0.042; ρ = 0.304, p = 0.008, respectively) and estimated plasma volume loss (ρ = 0.262, p = 0.023)., Conclusion: OSA patients had a greater increase in hematocrit/hemoglobin levels after sleep, which is probably linked to more water loss and more sleep time with mouth open/breathing., Competing Interests: Conflicts of interests The authors declared no potential conflict of interests., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Just Transitions are gaining attention in environmental research, and most studies have focused on climate change; however, the insights from this work may be usefully applied to the rarely discussed area in just transition studies. This article uses traditional dimensions of environmental and social justice, such as distributive, procedural, recognition, and restorative justice, to understand why heavy-duty diesel truck drivers fought back against stricter air pollution regulations while demanding destigmatization. The protest resulted in policy failure, and Taiwan's transition to cleaner, newer diesel trucks were halted. This study finds that the key social contextual factor in Taiwan's transportation industry was the labor relations of license-leasing. The drivers' protest began with a lack of procedural justice, and communication occurred only after the law was passed. There was insufficient regard for procedural justice, and although the drivers were concerned, the new rule would significantly impact their right to work and life. Furthermore, the drivers felt disrespected and even carried the stigma of creating environmental pollution. The article assumes that the results should be different if the governance mechanism can handle the key factor in a social context and make appropriate arrangements for the four dimensions of Just Transition. This argument may be relevant for other countries looking to transition from older diesel vehicles to cleaner vehicles through Just Transition., (© The Author(s) 2023.)

Aims: Transforming growth factor-β2 (TGF-β2) plays an important role in pleiotropic functions and has been reported to be involved in the pathogenesis of chronic obstructive lung disease. The role of TGF-β2 in regulating cigarette smoke (CS)-induced lung inflammation and injury has not been investigated, and its underlying mechanism remains unclear., Main Methods: Primary bronchial epithelial cells (PBECs) were treated with cigarette smoke extract (CSE), and the signaling pathway of TGF-β2 regulating lung inflammation was investigated. Mice were exposed to CS and treated with TGF-β2 i.p. or bovine whey protein extract containing TGF-β2 p.o., and the role of TGF-β2 in alleviating lung inflammation/injury was studied., Key Findings: In vitro, we demonstrated that TGF-β2 attenuated CSE-induced IL-8 production from PBECs through the TGF-β receptor I (TGF-βRI), Smad3, and mitogen-activated protein kinase signaling pathways. Selective TGF-βRI inhibitor (LY364947) and antagonist of Smad3 (SIS3) abolished the effect of TGF-β2 on alleviating CSE-induced IL-8 production. In vivo, CS exposure for 4 weeks in mice increased the levels of total protein, inflammatory cell counts, and monocyte chemoattractant protein-1 in bronchoalveolar fluid and induced lung inflammation/injury, as revealed by immunohistochemistry. Administration of TGF-β2 through intraperitoneal injection or oral feeding with bovine whey protein extract containing TGF-β2 significantly reduced CS-induced lung inflammation and injury., Significance: We concluded that TGF-β2 reduced CSE-induced IL-8 production through the Smad3 signaling pathway in PBECs and alleviated lung inflammation/injury in CS-exposed mice. The anti-inflammatory effect of TGF-β2 on CS-induced lung inflammation in humans deserves further clinical study., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Obstructive sleep apnea (OSA)-induced endothelial cell (EC) dysfunction contributes to OSA-related cardiovascular sequelae. The mechanistic basis of endothelial impairment by OSA is unclear. Objectives: The goals of this study were to identify the mechanism of OSA-induced EC dysfunction and explore the potential therapies for OSA-accelerated cardiovascular disease. Methods: The experimental methods include data mining, bioinformatics, EC functional analyses, OSA mouse models, and assessment of OSA human subjects. Measurements and Main Results: Using mined microRNA sequencing data, we found that microRNA 210 (miR-210) conferred the greatest induction by intermittent hypoxia in ECs. Consistently, the serum concentration of miR-210 was higher in individuals with OSA from two independent cohorts. Importantly, miR-210 concentration was positively correlated with the apnea-hypopnea index. RNA sequencing data collected from ECs transfected with miR-210 or treated with OSA serum showed a set of genes commonly altered by miR-210 and OSA serum, which are largely involved in mitochondrion-related pathways. ECs transfected with miR-210 or treated with OSA serum showed reduced [Formula: see text]o 2 rate, mitochondrial membrane potential, and DNA abundance. Mechanistically, intermittent hypoxia-induced SREBP2 (sterol regulatory element-binding protein 2) bound to the promoter region of miR-210, which in turn inhibited the iron-sulfur cluster assembly enzyme and led to mitochondrial dysfunction. Moreover, the SREBP2 inhibitor betulin alleviated intermittent hypoxia-increased systolic blood pressure in the OSA mouse model. Conclusions: These results identify an axis involving SREBP2, miR-210, and mitochondrial dysfunction, representing a new mechanistic link between OSA and EC dysfunction that may have important implications for treating and preventing OSA-related cardiovascular sequelae.

This study aimed to investigate the proportion of young OSA adults with sleep-related complaints in a sleep center, affiliated with a tertiary medical center for over a decade. This study presents a chronicle change in the numbers of young adults receiving polysomnography (PSG) and young patients with OSA from 2000 to 2017. We further analyzed 371 young patients with OSA among 2378 patients receiving PSG in our sleep center from 2016 to 2017 to capture their characteristics. Young adults constituted a substantial and relatively steady portion of examinees of PSG (25.1% ± 2.8%) and confirmed OSA cases (19.8 ± 2.4%) even though the total numbers increased with the years. Young adults with OSA tend to be sleepier, have a greater body mass index, and have a higher percentage of cigarette smoking and alcohol consumption. They also complained more about snoring and daytime sleepiness. They had a higher apnea-hypopnea index on average and experienced more hypoxemia during their sleep, both in terms of duration and the extent of desaturation. Even though the prevalence of comorbidities increased with age, hypertension in young male adults carried higher risks for OSA. Young adults with OSA have constituted a relatively constant portion of all confirmed OSA cases across time. The young adults with OSA were heavier, more symptomatic, and with more severe severity.Clinical trial: The Institutional Review Board of Taipei Veterans General Hospital approved the study (VGHIRB No. 2018-10-002CC). The study is registered with ClinicalTrials.gov, number NCT03885440., (© 2022. The Author(s).)

The risk of stroke in patients with gout is high. The effect of vaccines in lowering the stroke risk in patients with gout remains unclear. We retrospectively analyzed 23,949 patients with gout (age ≥ 55 years) from the National Health Insurance Research Database over a 12-year period. The patients were divided into vaccinated (n = 11,649) and unvaccinated groups (n = 12,300). Overall, the vaccinated group had significantly lower risks of all stroke, hemorrhagic stroke, and ischemic stroke than the unvaccinated group (adjusted hazard ratio [aHR], 0.59 and 95% confidence interval [CI], 0.55-0.63; aHR, 0.60 and 95% CI, 0.49-0.73; and aHR, 0.60 and 95% CI, 0.55-0.65, respectively). The association appeared to be dose-dependent for both hemorrhagic and ischemic stroke (hemorrhagic stroke: aHR, 0.81 and 95% CI, 0.61-1.08; aHR, 0.80 and 95% CI, 0.62-1.02; and aHR, 0.37 and 95% CI, 0.28-0.48; ischemic stroke: aHR, 0.83 and 95% CI, 0.74-0.94; aHR, 0.73 and 95% CI, 0.65-0.81; and aHR, 0.42 and 95% CI, 0.38-0.47 for patients vaccinated 1, 2 or 3, and ≥4 times, respectively, during the follow-up period). Patients with a history of atrial fibrillation did not have a lower risk of hemorrhagic stroke even after receiving four vaccinations (aHR, 0.59; 95% CI, 0.25-1.38). Influenza vaccination was associated with a lower risk of all stroke in people with gout, and the association appeared to be dose-dependent.

Introduction: Chronic obstructive pulmonary disease (COPD) with eosinophilic airway inflammation represents a distinct phenotype that might respond to treatment with inhaled corticosteroids. Fractional exhaled nitric oxide (FENO) might predict eosinophilic inflammation and guide treatment option. We hypothesized that COPD patients with different baseline levels of FENO might have differentiated response to treatment with salmeterol/fluticasone (SFC) or tiotropium (TIO)., Methods: This open-label, randomized-controlled trial enrolled treatment-naïve COPD patients who were stratified into high- (≥23.5ppb) and low-FENO group, followed by 12-week treatment with SFC or TIO. A linear mixed model with repeated measures was applied to analyze the changes in FENO (primary outcome), COPD assessment test (CAT) score, FEV 1 , and parameters in induced sputum and blood after treatment., Results: 134 patients were divided into 4 subgroups: low-FENO/SFC (n=30), low-FENO/TIO (n=29), high-FENO/SFC (n=37), and high-FENO/TIO (n=38). At baseline, FENO 23.5ppb clearly differentiated between eosinophilic and non-eosinophilic inflammation groups based on the eosinophils in induced sputum and blood. FENO significantly correlated with sputum and blood eosinophils at baseline. High-FENO/SFC (vs. high-FENO/TIO) subgroup had significant reduction in FENO and sputum inflammation profiles (including eosinophils, macrophages, matrix metalloproteinase-9, and interlukin-8) after treatment. These differences were not replicated between low-FENO/SFC and low-FENO/TIO subgroups. The improvement in CAT and FEV 1 after treatment was indiscriminate between SFC and TIO in the low- and high-FENO groups., Conclusion: High baseline FENO can serve as an indicator of eosinophilic airway inflammation in COPD patients who may respond favorably to treatment with inhaled corticosteroids/long-acting β 2 -agonists., Trial Registration Number: ClinicalTrials.gov Identifier: NCT02546349., (Copyright © 2021 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Human cytomegalovirus (CMV) is associated with aspergillosis, but the simultaneous presence of CMV viral interleukin-10 (cmvIL-10) and aspergillosis has never been investigated. CmvIL-10 is produced by CMV-infected cells and acts as an immune modulator during CMV infection. The aim of this study was to evaluate cmvIL-10 levels in peripheral blood and its influence on the clinical outcomes of Aspergillus infection., Methods: Patients who visited or were admitted to the hospital with suspected Aspergillus infection, including invasive aspergillosis (IA) and chronic pulmonary aspergillosis (CPA), were prospectively enrolled. The cmvIL-10, human IL-10 (hIL-10), IL-1B, IL-6, IL-8, IFN-γ, and TNF-α levels in peripheral blood were measured., Results: Patients with Aspergillus infection had a higher level of cmvIL-10 than the control group (158 ± 305 vs 27.9 ± 30.4 pg/ml, p < .05). The level of cmvIL-10 was not correlated with CMV viremia or end-organ disease. The cmvIL-10 but not hIL-10 level was positively correlated with the IFN-γ level (p < .05) and marginally negatively correlated with IL-1B and IL-8 levels (p < .1). In patients with CPA, a high level of cmvIL-10 (≥100 pg/ml) was a poor prognostic factor for long-term survival (p < .05). In contrast, CMV viremia or end-organ disease was associated with poor survival in patients with IA (p = .05)., Conclusions: Aspergillus infection was associated with CMV coinfection with cmvIL-10 in blood. A cmvIL-10 concentration ≥100 pg/ml was a predictor for unfavourable outcome in CPA patients., (© 2022 Wiley-VCH GmbH.)

Purpose: Current clinical guidelines are unclear regarding the association of cardiovascular medication with the risk of acute exacerbation (AE) in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO)., Methods: We conducted a retrospective cohort study by interrogating the claims database of Taipei Veterans General Hospital. Patients with coexistent fixed airflow limitation and asthma were enrolled as an ACO cohort between 2009 and 2017. Exposure to cardiovascular medications, including angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), non-selective beta-blockers, cardioselective beta-blockers, dihydropyridine (DHP) calcium channel blockers (CCBs), and non-DHP CCBs, in 3-month period each served as time-dependent covariates. Patients receiving a cardiovascular medication ≥ 28 cumulative daily doses were defined as respective cardiovascular medication users. Patients were followed up until December 31, 2018. The primary endpoint was severe AE, defined as hospitalization or emergency department visit for either asthma, COPD, or respiratory failure. The secondary outcome was moderate AE., Results: The final study cohort consisted of 582 ACO subjects, with a mean follow-up period of 2.98 years. After adjustment, ARB (hazard ratio [HR], 0.64, 95% confidence interval [CI], 0.44-0.93, P = 0.019), cardioselective beta-blocker (HR, 0.29, 95% CI, 0.11-0.72, P = 0.008) and DHP CCB (HR, 0.66, 95% CI, 0.45-0.97, P = 0.035) therapies were associated with lower risks of severe AE. ARB (HR, 0.42, 95% CI, 0.30-0.62, P < 0.001) and DHP CCB (HR, 0.55, 95% CI, 0.38-0.80, P = 0.002) therapies were associated with lower risks of moderate AE. Cardioselective beta-blockers, ARBs, and DHP CCBs were associated with lower risks of severe AE in frequent exacerbators. ACEI, non-selective beta-blocker, or non-DHP CCB use did not change the risk of severe AE., Conclusions: ARB, cardioselective beta-blocker, and DHP CCB therapies may lower the risk of AE in patients with ACO., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: The aim of study is to investigate the influence of pulmonary function on the prognosis in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI)., Patients and Methods: Data were collected retrospectively from 151 patients with stage IV NSCLC who received ICI and completed spirometry before ICI therapy in Taipei Veterans General Hospital between January 2016 and December 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS) between groups divided by 80% predicted FEV 1 since ICI therapy started; the secondary outcomes were objective response rate., Results: Among 151 patients enrolled to this study, 67.5% of patients were men, 75.5% were adenocarcinoma, 24.5% had known targetable driver mutation, 33.8% received first-line ICI, and 62.8% received ICI monotherapy. The objective response rate was 24.5% and disease control rate was 54.3%. In multivariable analysis, patient with reduced FEV 1 had inferior PFS (FEV 1 < 80% vs. FEV 1 ≥ 80%, adjusted HR = 1.80, P = 0.006) and OS (FEV 1 < 80% vs. FEV 1 ≥ 80%, adjusted HR = 2.50, P < 0.001). Median PFS and OS in the preserved FEV 1 group (≥80% predicted FEV 1 ) compared to the reduced FEV 1 group (<80% predicted FEV 1 ) were 5.4 vs. 2.9 months (HR = 1.76, P = 0.003) and 34.9 vs. 11.1 months (HR = 2.44, P < 0.001), respectively. The other independent prognostic factors of OS include stage IVA disease (adjusted HR = 0.57, P = 0.037), initial liver metastasis (adjusted HR = 2.00, P = 0.049), ICI monotherapy (adjusted HR = 1.73, P = 0.042) and ICI related pneumonitis (adjusted HR = 3 .44, P = 0.025)., Conclusions: Reduced FEV 1 is strongly associated with inferior clinical outcomes in patients with advanced NSCLC treated with ICI., Competing Interests: C-HC has received honoraria from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, and Takeda. C-LC has received speaking honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. C-IS has received support for attending meetings from Merck Sharp & Dohme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Shen, Chiang, Huang, Chou, Chiu, Chen and Luo.)

The objective of this study is to elucidate the relationship between obstructive sleep apnea (OSA) and the risk of work-related injuries (WRIs), synthesize the latest clinical evidence and conduct a systematic review and meta-analysis adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA 2020). Observational studies published before April 2020 in PubMed, Cochrane library, PsycINFO, Scopus, Google Scholar and Web of Science were included. Random-effects Mantel-Haenszel meta-analysis was performed. A total of 15 studies with 21,507 participants were included. Prespecified subgroup analyses based on study design and the characteristics of the enrollees were conducted. Overall, workers with OSA had 1.64-fold increased odds of being involved in WRIs compared to their counterparts (OR = 1.64, 95% CI = 1.24-2.16, p = 0.0005). In addition to the professional drivers that have been studied in the past, such a trend also existed in the general working population (OR = 1.68, 95% CI = 1.14-2.49, p = 0.01). We also found that workers with excessive daytime sleepiness (Epworth Sleepiness Scale score >10) had a 1.68-fold increased risk of WRIs compared to those with lower ESS scores (OR = 1.68, 95% CI = 1.22-2.30, p = 0.002). This study verified that OSA workers had a higher risk of WRIs, and such correlations do not show obvious differences in subgroups with different sample sizes, OSA diagnosis methods, job types or definitions of WRI. Based on the association between OSA and WRIs identified in our study, further studies investigating the protective effects of early identification and management of OSA on WRIs are warranted., (© 2021 European Sleep Research Society.)

Contrary to multicellular organisms that display segmentation during development, communities of unicellular organisms are believed to be devoid of such sophisticated patterning. Unexpectedly, we find that the gene expression underlying the nitrogen stress response of a developing Bacillus subtilis biofilm becomes organized into a ring-like pattern. Mathematical modeling and genetic probing of the underlying circuit indicate that this patterning is generated by a clock and wavefront mechanism, similar to that driving vertebrate somitogenesis. We experimentally validated this hypothesis by showing that predicted nutrient conditions can even lead to multiple concentric rings, resembling segments. We additionally confirmed that this patterning mechanism is driven by cell-autonomous oscillations. Importantly, we show that the clock and wavefront process also spatially patterns sporulation within the biofilm. Together, these findings reveal a biofilm segmentation clock that organizes cellular differentiation in space and time, thereby challenging the paradigm that such patterning mechanisms are exclusive to plant and animal development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

(1) Background: The presentation of chronic pulmonary aspergillosis (CPA) ranges from single granuloma to fibrosis in the affected lung. CPA can be divided into five categories according to European Respirology Society (ERS) guidance but is usually assessed by clinical physicians. Computer-based quantitative lung parenchyma analysis in CPA and its correlation with clinical manifestations, systemic inflammation, and angiogenesis have never been investigated. (2) Method: Forty-nine patients with CPA and 36 controls were prospectively enrolled. Pulmonary function tests (forced vital capacity (FVC), forced expiratory volume in one second (FEV 1 ), and FEV 1 /FCV) and biomarkers in the peripheral blood (the chemokines interleukin (IL)-1B, IL-6, IL-10, IL-8, CRP, ESR, MMP1, MMP7, MMP8, TNF-α, calprotectin, SDF-1α, and VEGFA) were measured before antifungal treatment. The disease severity was categorized into mild, moderate, and severe based on chest computed tomography (CT) images. The oxygen demand and overall mortality until the end of the study were recorded. Quantitative parenchyma analysis was performed using the free software 3Dslicer. (3) Results: The results of quantitative parenchyma analysis concorded with the visual severity from the chest CT, oxygen demand, FVC, and FEV 1 in the study subjects. The decrease in kurtosis and skewness of the lung density histograms on CT, increase in high attenuation area (HAA), and reduced lung volume were significantly correlated with increases in the PMN %, CRP, IL-1B, SDF-1α, MMP1, and Calprotectin in peripheral blood in the multivariable regression analysis. TNF-α and IL-1B at study entry and the CPA severity from either a visual method or computer-based evaluation were predictors of long-term mortality. (4) Conclusion: The computer-based parenchyma analysis in CPA agreed with the categorization on a visual basis and was associated with the clinical outcomes, chemokines, and systemic proinflammation profiles.

Identifying the direction of signal flows in neural networks is important for understanding the intricate information dynamics of a living brain. Using a dataset of 213 projection neurons distributed in more than 15 neuropils of a Drosophila brain, we develop a powerful machine learning algorithm: node-based polarity identifier of neurons (NPIN). The proposed model is trained only by information specific to nodes, the branch points on the skeleton, and includes both Soma Features (which contain spatial information from a given node to a soma) and Local Features (which contain morphological information of a given node). After including the spatial correlations between nodal polarities, our NPIN provided extremely high accuracy (>96.0%) for the classification of neuronal polarity, even for complex neurons with more than two dendrite/axon clusters. Finally, we further apply NPIN to classify the neuronal polarity of neurons in other species (Blowfly and Moth), which have much less neuronal data available. Our results demonstrate the potential of NPIN as a powerful tool to identify the neuronal polarity of insects and to map out the signal flows in the brain's neural networks if more training data become available in the future., (© 2021. The Author(s).)

Study Objectives: Polysomnography is the gold standard in identifying sleep stages; however, there are discrepancies in how technicians use the standards. Because organizing meetings to evaluate this discrepancy and/or reach a consensus among multiple sleep centers is time-consuming, we developed an artificial intelligence system to efficiently evaluate the reliability and consistency of sleep scoring and hence the sleep center quality., Methods: An interpretable machine learning algorithm was used to evaluate the interrater reliability (IRR) of sleep stage annotation among sleep centers. The artificial intelligence system was trained to learn raters from 1 hospital and was applied to patients from the same or other hospitals. The results were compared with the experts' annotation to determine IRR. Intracenter and intercenter assessments were conducted on 679 patients without sleep apnea from 6 sleep centers in Taiwan. Centers with potential quality issues were identified by the estimated IRR., Results: In the intracenter assessment, the median accuracy ranged from 80.3%-83.3%, with the exception of 1 hospital, which had an accuracy of 72.3%. In the intercenter assessment, the median accuracy ranged from 75.7%-83.3% when the 1 hospital was excluded from testing and training. The performance of the proposed method was higher for the N2, awake, and REM sleep stages than for the N1 and N3 stages. The significant IRR discrepancy of the 1 hospital suggested a quality issue. This quality issue was confirmed by the physicians in charge of the 1 hospital., Conclusions: The proposed artificial intelligence system proved effective in assessing IRR and hence the sleep center quality., (© 2021 American Academy of Sleep Medicine.)

The independent risk factors for death in patients admitted for asthma exacerbation have not been thoroughly investigated. This study aimed to investigate these independent risk factors and the relationship between mortality and the prescription patterns of anti-asthmatic medications in patients admitted for asthma exacerbation. Using a nested case-control design, we identified 267 cases (death after asthma admission) and 1035 controls (survival after asthma admission) from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2010. Conditional logistic regressions were used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs). We identified the independent risk factors for death as the comorbidities of pneumonia (aOR 3.82, 95% CI 2.41-6.05), genitourinary disease (aOR 1.75, 95% CI 1.17-2.62), septicemia (aOR 4.26, 95% CI 2.61-6.94), diabetes mellitus (aOR 2.10, 95% CI 1.30-3.38), arrhythmia (aOR 2.00, 95% CI 1.14-3.50), and a history of asthmatic hospitalization (aOR 4.48, 95% CI 2.77-7.25). Moreover, the use of short-acting β 2 -agonist (SABA) and the dosage of oral corticosteroids (OCSs) >70 mg prednisolone during previous hospitalization (all p < 0.05) and the dosage of OCSs ≥110 mg prednisolone/month (aOR 2.21, 95% CI 1.08-4.50) during outpatient treatment independently increased the risk of death. The inhaled corticosteroids (ICSs) ≥4 canisters/year (aOR 0.39, 95% CI 0.19-0.78) independently reduced the risk of death. Specific comorbidities, asthma severity, and prescription patterns of SABA, OCSs, and ICSs were independently associated with mortality in patients admitted for asthma exacerbation. These results can be utilized to help physicians identify asthmatic patients who are at a higher mortality risk and to refine the management of the condition.

Tumor progression with chemoresistance and local recurrence is commonly happened during treatment of esophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSC) may respond for tumor progression. However, there are few reports regarding metabolism of esophageal CSCs with clinical correlation. In this work, we demonstrated that ESCC cell lines in spheroid culture display CSC phenotypes, including increased ALDH activity, chemoresistance and tumor initiation, which are dependent on Hsp27 activation. Esophageal CSCs also exhibit reprogrammed metabolic features particularly higher glycolysis and oxidative phosphorylation, which are regulated via the Hsp27-AKT-HK2 pathway. Moreover, HK2 is required for maintenance of CSC phenotypes. Inhibition of CSC metabolism reduces cell growth and tumor formation. Clinically, patients who underwent surgical resection for esophageal cancer, and displayed overexpression of both Hsp27 and HK2, had the worst prognosis of all expression types. In conclusion, stem cells features and aberrant metabolic reprogramming of esophageal CSCs depend on the Hsp27-AKT-HK2 pathway. Targeting Hsp27 and HK2 could be novel therapeutic strategy for treating esophageal cancer and warrants further investigation., (© 2019 UICC.)

Sleep apnea has been associated with a variety of diseases, but its impact on sepsis outcome remains unclear. This study investigated the effect of intermittent hypoxia [IH]-the principal feature of sleep apnea-on murine sepsis. 5-week-old male C57BL6 mice were assigned to groups receiving severe IH (O2 fluctuating from room air to an O2 nadir of 5.7% with a cycle length of 90 seconds), mild IH (room air to 12%, 4 minutes/cycle), or room air for 3 weeks. Sepsis was induced by cecal ligation and puncture and survival was monitored. Sepsis severity was evaluated by murine sepsis scores, blood bacterial load, plasma tumor necrosis factor-α [TNF-α]/interleukin-6 [IL-6] levels and histopathology of vital organs. Compared with normoxic controls, mice subjected to severe IH had earlier mortality, a lower leukocyte count, higher blood bacterial load, higher plasma TNF-α and IL-6 levels, more severe inflammatory changes in the lung, spleen and small intestine. Mice subjected to mild IH did not differ from normoxic controls, except a higher IL-6 level after sepsis induced. The adverse impact of severe IH was reversed following a 10-day normoxic recovery. In conclusion, severe IH, not mild IH, contributed to poorer outcomes in a murine sepsis model.

This retrospective, observational cohort study aimed to determine the independent risk factors and impact of prolonged non-invasive positive pressure ventilation (NIPPV) after extubation among patients in the intensive care unit following cardiac surgery. Patients who received prophylactic NIPPV after extubation were categorized into prolonged (NIPPV duration >3 days, n = 83) and non-prolonged groups (NIPPV duration ≤3 days, n = 105). The perioperative characteristics and hospital outcomes were recorded. The multivariate analyses identified the preoperative residual volume/total lung capacity (RV/TLC) ratio (adjusted odds ratio [AOR]: 1.10; 95% CI:1.01-1.19, p = 0.022) and postoperative acute kidney injury (AKI) with Kidney Disease Improving Global Outcomes (KDIGO) stage 2-3, 48 h after surgery (AOR: 3.87; 95% CI:1.21-12.37, p = 0.023) as independent predictors of prolonged NIPPV. Patients with both RV/TLC ratio > 46.5% and KDIGO stage 2-3 showed a highly increased risk of prolonged NIPPV (HR 27.17, p = 0.010), which was in turn associated with higher risk of postoperative complications and prolonged ICU and hospital stays. Preoperative RV/TLC ratio and postoperative AKI could identify patients at higher risk for prolonged NIPPV associated with poor outcomes. These findings may allow early recognition of patients who are at a higher risk for prolonged NIPPV, and help refine the perioperative management and critical care.

The appropriate treatment for patients with coexistent chronic obstructive pulmonary disease (COPD) and heart failure (HF) remains unclear. Data from the Taiwan National Health Insurance Research Database was used for this retrospective cohort study. Patients diagnosed with both diseases between 1997 and 2012 were enrolled as the COPD-heart failure overlap cohort. Patients were categorized as non-users and users of specific COPD and HF medications. Medication prescriptions in each 3-month and 1-year period served as time-dependent covariates. The primary endpoint was cumulative survival. The validation study confirmed the accuracy of definitions of COPD (94.0% sensitivity) and HF (96.3% sensitivity).The study included 275,436 patients with COPD-heart failure overlap, with a mean follow-up period of 9.32 years. The COPD-heart failure overlap cohort had more medical service use and higher mortality than did the COPD alone cohort. Use of inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations, long-acting muscarinic antagonist (LAMA), angiotensin receptor blockers (ARBs), β blockers, aldosterone antagonists, and statins reduced mortality risk compared with non-use. Sensitivity and subgroup analyses confirmed the consistency and robustness of results.ICS/LABA combinations, LAMA, ARBs, β blockers, aldosterone antagonists, and statins use was associated with a lower mortality risk in patients with COPD-heart failure overlap.

Underuse or unavailability of spirometry is one of the most important factors causing underdiagnosis of COPD. We reported the development of a COPD prediction model to identify at-risk, undiagnosed COPD patients when spirometry was unavailable. This cross-sectional study enrolled subjects aged ≥40 years with respiratory symptoms and a smoking history (≥20 pack-years) in a medical center in two separate periods (development and validation cohorts). All subjects completed COPD assessment test (CAT), peak expiratory flow rate (PEFR) measurement, and confirmatory spirometry. A binary logistic model with calibration (Hosmer-Lemeshow test) and discrimination (area under receiver operating characteristic curve [AUROC]) was implemented. Three hundred and one subjects (development cohort) completed the study, including non-COPD (154, 51.2%) and COPD cases (147; stage I, 27.2%; II, 55.8%; III-IV, 17%). Compared with non-COPD and GOLD I cases, GOLD II-IV patients exhibited significantly higher CAT scores and lower lung function, and were considered clinically significant for COPD. Four independent variables (age, smoking pack-years, CAT score, and percent predicted PEFR) were incorporated developing the prediction model, which estimated the COPD probability (P COPD ). This model demonstrated favorable discrimination (AUROC: 0.866/0.828; 95% CI 0.825-0.906/0.751-0.904) and calibration (Hosmer-Lemeshow P = 0.332/0.668) for the development and validation cohorts, respectively. Bootstrap validation with 1000 replicates yielded an AUROC of 0.866 (95% CI 0.821-0.905). A P COPD of ≥0.65 identified COPD patients with high specificity (90%) and a large proportion (91.4%) of patients with clinically significant COPD (development cohort). Our prediction model can help physicians effectively identify at-risk, undiagnosed COPD patients for further diagnostic evaluation and timely treatment when spirometry is unavailable.

Background: The dysbiosis of gut microbiome and interaction with host immunity after Mycobacterium tuberculosis (MTB) infection are under investigation. We had found fatigue symptom concurrent with dysbiosis by decreasing the ratio of Firmicutes to Bacteroidetes (F/B ratio) in active tuberculosis (TB). The study aims to assess the inflammatory biomarkers and their interaction with gut microbiome in active TB and latent TB infection before starting anti-TB regimens., Materials and Method: Interleukin-1 beta (IL-1B), IL-4, IL-6, IL-10, CD3+, CD4+, CD8+ T cells and interferon-gamma (IFN-γ) releasing assay (IGRA) were measured in 25 active TB patients, 32 LTBI subjects and 23 healthy controls (HC). Gut microbiome profiles were obtained using 16S rRNA MiSeq sequencing method., Results: The leucocytosis (7032 ± 387 cell/cum, P < 0.05), increase in IL-6 (229.7 ± 104 µg/dL, P < 0.05), and decrease in IL-4 (0.27 µg/dL ± 0.1, P < 0.05) were presented in active TB. The proportion of polymorphic neutrophil (PMN) in peripheral blood was positively related to the relative abundance of Bacteroidetes in LTBI and active TB (R 2  = 0.23, P < 0.05). The F/B ratio was positively related to the detectable IL-1B in TB (R 2  = 0.97, P < 0.01) and to the IL-4 in LTBI (R 2  = 0.27, P < 0.05). In LTBI, the relative abundances of Coriobacteriaceae were positively related to the secretion of IFN-gamma against MTB-antigens more likely associated with of CD4+ T cell (R 2  = 0.42, P < 0.05)., Conclusion: In active TB, dysbiosis with higher relative abundances of Bacteroidetes in stool and low F/B ratio was related to systemic proinflammation. In LTBI, dose-response relationship between peripheral PMN and relative abundances of Bacteroidetes was remained but not leads to systemic inflammation., (© 2019 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Based on current guidelines, more research is urgently needed to guide appropriate treatment for patients with asthma-chronic obstructive pulmonary disease (COPD) overlap., Objective: The objective of this study was to investigate medication effects on acute exacerbation in patients with coexistent COPD and asthma., Methods: Using Taiwan's National Health Insurance Research Database, we conducted a nationwide population-based study to evaluate medication effects in patients with COPD and asthma. Patients diagnosed with both asthma and COPD between 1997 and 2012 were enrolled as the COPD + asthma cohort. The primary endpoint was acute exacerbation. The definitions of COPD and asthma were validated. The validation study confirmed the accuracy of definitions of COPD (86.2% sensitivity) and asthma (92.0% sensitivity)., Results: The study included 251,398 patients with COPD + asthma and 514,522 patients with COPD alone, with a mean follow-up period of 9.85 years. After adjustment, hazard ratios (HRs) for long-acting muscarinic antagonist (LAMA) and inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA) combinations were lower (time-dependent model, 1 year: LAMA, HR 0.51, 95% confidence interval [CI] 0.49-0.54; ICS/LABA combinations, HR 0.61, 95% CI 0.60-0.62; all P < .0001) than were those for LABAs or ICSs in patients with COPD and asthma., Conclusions: The use of LAMA or ICS/LABA combinations was associated with a lower risk of acute exacerbation in patients with COPD and asthma in this study., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: Radiomics, which extract large amount of quantification image features from diagnostic medical images had been widely used for prognostication, treatment response prediction and cancer detection. The treatment options for lung nodules depend on their diagnosis, benign or malignant. Conventionally, lung nodule diagnosis is based on invasive biopsy. Recently, radiomics features, a non-invasive method based on clinical images, have shown high potential in lesion classification, treatment outcome prediction., Methods: Lung nodule classification using radiomics based on Computed Tomography (CT) image data was investigated and a 4-feature signature was introduced for lung nodule classification. Retrospectively, 72 patients with 75 pulmonary nodules were collected. Radiomics feature extraction was performed on non-enhanced CT images with contours which were delineated by an experienced radiation oncologist., Result: Among the 750 image features in each case, 76 features were found to have significant differences between benign and malignant lesions. A radiomics signature was composed of the best 4 features which included Laws&#95;LSL&#95;min, Laws&#95;SLL&#95;energy, Laws&#95;SSL&#95;skewness and Laws&#95;EEL&#95;uniformity. The accuracy using the signature in benign or malignant classification was 84% with the sensitivity of 92.85% and the specificity of 72.73%., Conclusion: The classification signature based on radiomics features demonstrated very good accuracy and high potential in clinical application.

The quantitative and reproducible analysis of the standard body movement in Tai Chi Chuan (TCC) was performed in this study. We aimed to provide a reference of the upper extremities for standardizing TCC practice. Microsoft Kinect was used to record the motion during the practice of TCC. The preparation form and eight essential forms of TCC performed by an instructor and 101 practitioners were analyzed in this study. The instructor completed an entire TCC practice cycle and performed the cycle 12 times. An entire cycle of TCC was performed by practitioners and images were recorded for statistics analysis. The performance of the instructor showed high similarity (Pearson correlation coefficient ( r ) = 0.71 ~ 0.84) to the first practice cycle. Among the 9 forms, lay form had the highest similarity ( r mean = 0.90) and push form had the lowest similarity ( r mean = 0.52). For the practitioners, ward off form ( r mean = 0.51) and roll back form ( r mean = 0.45) had the highest similarity with moderate correlation. We used Microsoft Kinect to record the spatial coordinates of the upper extremity joints during the practice of TCC and the data to perform quantitative and qualitative analysis of the joint positions and elbow joint angle.

Sleep disorders are common non-motor symptoms in patients with Parkinson's disease. Our study aims to explore the relationship between non-apnea sleep disorders and future Parkinson's disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91 273 adult patients who had non-apnea sleep disorders without pre-existing Parkinson's disease were enrolled. An age-, gender-, income-, urbanization- and Charlson comorbidity index score-matched control cohort consisting of 91 273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinson's disease, death or until the end of 2010, whichever came first. The Kaplan-Meier analyses revealed patients with non-apnea sleep disorders tended to develop Parkinson's disease (log-rank test, P < 0.001). After a multivariate adjustment in a Cox regression model, non-apnea sleep disorders was an independent risk factor for the development of Parkinson's disease [crude hazard ratio: 1.63, 95% confidence interval (CI): 1.54-1.73, P < 0.001; adjusted hazard ratio: 1.18, 95% CI: 1.11-1.26, P < 0.001]. In the subgroup analysis, patients with chronic insomnia (lasting more than 3 months) had the greatest risk (crude hazard ratio: 2.91, 95% CI: 2.59-3.26, P < 0.001; adjusted hazard ratio: 1.37, 95% CI: 1.21-1.55, P < 0.001). In conclusion, this study revealed that non-apnea sleep disorders, especially chronic insomnia, are associated with a higher risk for future Parkinson's disease., (© 2017 European Sleep Research Society.)

Introduction: The relationship between bronchodilator responsiveness and eosinophilic airway inflammation has not been well documented in COPD. It has been investigated in this retrospective study. This issue has grown in importance due to increasing interest in the asthma-COPD overlap syndrome., Methods: 264 stable COPD patients with no past history of asthma were retrospectively analyzed. Correlation analyses between FEV 1 reversibility and sputum eosinophil levels were conducted. Sputum eosinophil levels were dichotomized using FEV 1 reversibility cut-off points (>0.4L and >15% vs. >0.2L and >12%) and compared. The effectiveness of FEV 1 reversibility to predict sputum eosinophilia (>3%) was analyzed with a logistic regression and a ROC analysis., Results: 82 (31.1%) patients with higher FEV 1 reversibility values (0.14 vs. 0.11L, P=.01) presented sputum eosinophilia. FEV 1 reversibility was weakly correlated with the sputum eosinophil level (r=0.162, P=.008). Patients with FEV 1 >0.4L and >15% increment had higher sputum eosinophil levels (6.11 vs. 1.02%, P=.049) whereas the level did not differ when dichotomized by FEV 1 increment >0.2L and >12%. Very positive FEV 1 reversibility (>0.4L and >15%) predicted sputum eosinophilia after adjustment forage, baseline FEV 1 and FVC (OR: 4.262, P=.029). In the ROC analysis, the AUC was 0.58 (P=.034), and FEV 1 increment>0.4L and >15% had a positive predictive value of 63.6% and an overall accuracy of 70.1%., Conclusions: FEV 1 reversibility was weakly correlated with sputum eosinophil levels in COPD. Positive FEV 1 reversibility (>0.4L and >15%) is moderately successful in predicting sputum eosinophilia (>3%)., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

The major problem with ventilation distribution calculations using DIR and 4DCT is the motion artifacts in 4DCT. Quite often not all phases would exhibit mushroom motion artifacts. If the ventilation series similarity is sufficiently robust, the ventilation distribution can be calculated using only the artifact-free phases. This study investigated the ventilation similarity among the data derived from different respiration phases. Fifteen lung cancer cases were analyzed. In each case, DIR was performed between the end-expiration phase and all other phases. Ventilation distributions were then calculated using the deformation matrices. The similarity was compared between the series ventilation distributions. The correlation between the majority phases was reasonably good, with average SCC values between 0.28 and 0.70 for the original data and 0.30 and 0.75 after smoothing. The better correlation between the neighboring phases, with average SCC values between 0.55 and 0.70 for the original data, revealed the nonlinear property of the dynamic ventilation. DSC analysis showed the same trend. To reduce the errors if motion artifacts are present, the phases without serious mushroom artifacts may be used. To minimize the effect of the nonlinearity in dynamic ventilation, the calculation phase should be chosen as close to the end-inspiration as possible.

Background: Statins are widely used to lower cholesterol levels and cardiovascular risk. Further, studies have shown that statins may decrease the risks of infectious diseases and infection-related mortality; however, the association between statin use and active TB disease remains unclear., Methods: Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population-based study. Patients taking statins between 2000 and 2013, without antecedent TB disease, were included. Data from 102,424 statin users and 202,718 age-, sex-, and enrollment date-matched subjects were analyzed. The two cohorts were monitored until December 31, 2013, for incident TB disease. The definition of TB disease was validated using the claims database of Taipei Veterans General Hospital., Results: The statin and matched cohorts were observed for 571,568 and 1,027,385 person-years, respectively. Of the total 305,142 subjects, 1,264 (0.41%) developed subsequent TB disease. Validation study confirmed the accuracy of the definition of TB disease (sensitivity, 96.3%), with excellent interobserver agreement (κ = 1.00). Multivariate analysis revealed a reduced risk of TB disease among the statin cohort (hazard ratio [HR], 0.53; 95% CI, 0.47-0.61; P < .001). Compared with the matched group, statin use showed a dose-response relationship with the incident TB disease risk (<180 cumulative defined daily doses [cDDDs]: HR, 1.06; 95% CI, 0.91-1.24; P = .477; 180 to 365 cDDDs: HR, 0.57; 95% CI, 0.45-0.72; P < .001; >365 cDDDs: HR, 0.27; 95% CI, 0.22-0.33; P < .001)., Conclusions: Statin use associates with a lower risk of incident TB disease., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: A variety of disorders, most notably cardiovascular diseases, was linked to sleep apnea (SA), but their impact on mortality of SA patients had not been systematically investigated. We aimed to develop a composite index based on the comorbidity burden to predict mortality risk., Methods: Using Taiwan National Health Insurance Research Database, 9853 adult SA patients were enrolled and their comorbidity profile at baseline was recorded. The subjects were followed from 1995 till death or the end of 2011. A Cox regression model was used for multivariable adjustment to identify independent predictors for mortality., Results: During an average follow-up period of 5.3 ± 3.1 years, 311 (3.2%) subjects died. SA patients with any comorbidity had a higher risk for death compared to those without comorbidity (HR: 11.01, 95% CI 4.00-30.33, p < 0.001). Age and 10 comorbidities related to increased overall mortality were identified, from which the CoSA (Comorbidities of Sleep Apnea) index was devised. The corresponding hazard ratios for patients with CoSA index scores of 0, 1-3, 4-6, and >6 were 1 (reference), 3.29 (95% CI, 2.04-5.28, p < 0.001), 13.56 (95% CI, 8.63-21.33, p < 0.001), and 38.47 (95% CI, 24.92-59.38, p < 0.001), respectively., Conclusions: Based on the comorbidity burden, we developed an easy-to-use tool to evaluate mortality risk in SA. Key messages: Sleep apnea (SA) is linked to a variety of disorders, particularly cardiovascular diseases. SA patients with any comorbidity may experience a higher risk of death in comparison to those without comorbidity. Comorbidities related to increased mortality are identified and converted into a simple risk indicator, the CoSA (Comorbidities of Sleep Apnea) index scores, which may help to stratify risk of death in daily practice.

This study was to investigate the clinical outcomes between radiation dose and pretreatment metabolic tumor volume (MTV) in patients with head and neck cancer treated with definitive chemoradiotherapy.Thirty-four patients received pretreatment F-fluorodeoxyglucose (F-FDG) positron emission tomography-computed tomography (PET/CT) were recruited for this study. The CT-based volume (gross tumor volume of the primary [GTVp]) and 4 types of MTVs were measured on the basis of either a maximal standardized uptake value (SUVmax) of 2.5 (MTV2.5), 3.0 (MTV3.0), or a fixed threshold of 40% (MTV40%), 50% (MTV50%). F-FDG PET-CT images before treatment, and data including response to treatment, local recurrence, death due to the cancer, disease-free survival (DFS) and primary relapse-free survival (PRFS), were collected for analysis.The Wilcoxon rank test showed that all values determined by the different delineation techniques were significantly different from the GTVp (P < .05). Tumor volume and the homogeneity of target dose of MTV2.5, MTV3.0, MTV40%, and MTV50% were significantly different between the 2 groups of patients through treatment outcomes (P < .05).The survival curves for DFS and PRFS demonstrated that the homogeneity of the target dose in MTVs was a good indicator. The homogeneity of target dose in the tumor is a potential indicator of DSF and PRFS in patients with head and neck cancer who underwent radiotherapy.

Epidemiological studies have identified a trend in the development of depressive and anxiety disorders following a diagnosis of chronic obstructive pulmonary disease (COPD). However, the relationship between COPD and subsequent bipolar disorder remains unclear. From January 1, 2000, we identified adult patients with COPD from the Taiwan National Health Insurance Research Database. A nationwide population-based study was conducted; 46,778 COPD patients and 46,778 age-, sex-, and comorbidity-matched subjects between 2000 and 2011 were enrolled. The two cohorts were followed up till December 31, 2011 and observed for occurrence of bipolar disorder. We observed the COPD and comparison cohorts for 263,020 and 267,895 person-years, respectively, from 2000 to 2011. The incidence rate for bipolar disorder was 1.6/1000 person-years in the COPD cohort and 1.2/1000 person-years in the comparison cohort ( p < 0.001). After multivariate adjustment, the hazard ratio (HR) for subsequent bipolar disorder among the COPD patients was 1.42 (95% confidence interval [CI], 1.22-1.64; p < 0.001). In the COPD patients, short-acting beta-agonists (SABAs) was associated with a significantly increased risk of bipolar disorder development (HR = 1.83, 95% CI = 1.25-2.69, p = 0.002). Other COPD medications were not associated with the risk of bipolar disorder development. The study results indicate that COPD may be an independent risk factor for the development of bipolar disorder. The regular use of SABAs might increase the risk of bipolar disorder in COPD patients.

Background: While Candida pneumonia is life-threatening, biomarker measurements to early detect suspected Candida pneumonia are lacking. This study compared the diagnostic values of measuring levels of (1, 3)-β-D-glucan in endotracheal aspirate, bronchoalveolar lavage fluid, and serum to detect suspected Candida pneumonia in immunocompromised and critically ill patients., Methods: This prospective, observational study enrolled immunocompromised, critically ill, and ventilated patients with suspected fungal pneumonia in mixed intensive care units from November 2010 to October 2011. Patients with D-glucan confounding factors or other fungal infection were excluded. Endotracheal aspirate, bronchoalveolar lavage fluid and serum were collected from each patient to perform a fungal smear, culture, and D-glucan assay., Results: After screening 166 patients, 31 patients completed the study and were categorized into non-Candida pneumonia/non-candidemia (n = 18), suspected Candida pneumonia (n = 9), and non-Candida pneumonia/candidemia groups (n = 4). D-glucan levels in endotracheal aspirate or bronchoalveolar lavage were highest in suspected Candida pneumonia, while the serum D-glucan level was highest in non-Candida pneumonia/candidemia. In all patients, the D-glucan value in endotracheal aspirate was positively correlated with that in bronchoalveolar lavage fluid. For the detection of suspected Candida pneumonia, the predictive performance (sensitivity/specificity/D-glucan cutoff [pg/ml]) of D-glucan in endotracheal aspirate and bronchoalveolar lavage fluid was 67%/82%/120 and 89%/86%/130, respectively, accounting for areas under the receiver operating characteristic curve of 0.833 and 0.939 (both P < 0.05), respectively. Measuring serum D-glucan was of no diagnostic value (area under curve =0.510, P = 0.931) for the detection of suspected Candida pneumonia in the absence of concurrent candidemia., Conclusions: D-glucan levels in both endotracheal aspirate and bronchoalveolar lavage, but not in serum, provide good diagnostic values to detect suspected Candida pneumonia and to serve as potential biomarkers for early detection in this patient population.

Background: Patients with chronic obstructive pulmonary disease (COPD) are liable to develop significant comorbidities, including lung cancer. Whether they are at a higher risk for cancer of other types remains debatable, especially for Asians. We studied the risk of incident cancer in COPD patients using a nationwide representative database, the Taiwan National Health Insurance Research Database., Methods: From 1995 to 2008, 50,875 COPD patients who were free of antecedent malignancy were identified and followed up to development of malignancy, death or end of 2008, whichever came first. The risk of cancer was determined with the standardized incidence ratio (SIR), which is based on comparison to the national cancer incidence among the general population., Results: During a median follow-up period of 5.61 years, 3623 (7.02 %) patients developed cancer and the SIR was 1.2 [95 % confidence interval (CI) 1.16-1.24, p < 0.001]. The risk remained higher at <1, 1-5, and even ≥5 years after the diagnosis of COPD (SIR 1.83, 1.07, and 1.11, respectively). Furthermore, the risk was significantly higher for some specific types of cancer, including head and neck cancer (SIR 1.23, 95 % CI 1.08-1.39, p = 0.002), esophageal cancer (SIR 1.35, 95 % CI 1.08-1.67, p = 0.010), lung and mediastinal cancer (SIR 1.86, 95 % CI 1.74-1.99, p < 0.001), breast cancer (SIR 1.19, 95 % CI 1.01-1.4, p = 0.041), prostate cancer (SIR 1.20, 95 % CI 1.06-1.35, p < 0.001), cancer of the central nervous system (SIR 1.58, 95 % CI 1.05-2.28, p = 0.030), lymphoma (SIR 1.53, 95 % CI 1.22-1.90, p < 0.001), and multiple myeloma (SIR 1.95, 95 % CI 1.31-2.80, p = 0.001)., Conclusion: COPD patients had increased risk for incident cancers, including lung cancer and several extrapulmonary cancers.