-
Biochimica Et Biophysica Acta.... Jun 2024Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a...
Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a study in which 2-3-month-old K18-hACE2 (K18) mice were fed a western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with a sublethal dose of SARS-CoV2 WA1 (a strain ancestral to the Wuhan variant). After infection, the WD-fed K18 mice lost significantly more body weight and had more severe lung inflammation than normal chow (NC)-fed mice. Bulk RNA-seq analysis of lungs and adipose tissue revealed a diverse landscape of various immune cells, inflammatory markers, and pathways upregulated in the infected WD-fed K18 mice when compared with the infected NC-fed control mice. The transcript levels of IL-6, an important marker of COVID-19 disease severity, were upregulated in the lung at 6-9 days post-infection in the WD-fed mice when compared to NC-fed mice. Transcriptome analysis of the lung and adipose tissue obtained from deceased COVID-19 patients found that the obese patients had an increase in the expression of genes and the activation of pathways associated with inflammation as compared to normal-weight patients (n = 2). The K18 mouse model and human COVID-19 patient data support a link between inflammation and an obesity-accelerated COVID-19 disease phenotype. These results also indicate that obesity-accelerated severe COVID-19 caused by SARS-CoV-2 WA1 infection in the K18 mouse model would be a suitable model for dissecting the cellular and molecular mechanisms underlying pathogenesis.
PubMed: 38942338
DOI: 10.1016/j.bbadis.2024.167322 -
Ecotoxicology and Environmental Safety Jun 2024Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults....
Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV and FVC by 35.26 mL (95 % CI: -60.75, -9.78) and 38.56 mL (95 % CI: -66.60, -10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.
PubMed: 38941662
DOI: 10.1016/j.ecoenv.2024.116594 -
Medicine Jun 2024The aim of this study is to delineate the distinctive high-resolution computed tomography features of pulmonary cryptococcosis in non-HIV-infected patients. This...
The aim of this study is to delineate the distinctive high-resolution computed tomography features of pulmonary cryptococcosis in non-HIV-infected patients. This retrospective analysis encompasses high-resolution computed tomography scans from 58 patients with histologically confirmed pulmonary cryptococcosis, focusing on the diagnostic challenges and the factors that lead to misdiagnosis. Analysis of computed tomography scans from these patients indicated that nodular or mass-like presentations were evident in 32 cases (55.2%), consolidation presentations in 7 cases (12.1%), and mixed presentations in 19 cases (32.8%). Lesions were predominantly located in the lower lobes of the lungs (40 cases, 69.0%) and in peripheral zones (55 cases, 94.8%). Notable radiographic signs included the presence of the burr sign in 55 cases (94.8%), lobulation sign in 53 cases (91.4%), halo sign in 53 cases (91.4%), and air bronchogram in 46 cases (79.0%). Moreover, 24 cases (41.4%) exhibited necrosis or cavitation, mediastinal lymphadenopathy was noted in 6 cases (10.3%), and pleural effusion was present in 5 cases (8.6%). Lesions were devoid of calcification. Pulmonary cryptococcosis ought to be contemplated in the differential diagnosis when computed tomography imaging exhibits patterns including, but not limited to, lower lobe and peripheral distribution, a broad base abutting the pleura, clustered growth with a propensity for fusion, air bronchogram within lesions, and peripheral halo sign.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Cryptococcosis; Tomography, X-Ray Computed; Lung Diseases, Fungal; Adult; Aged; Lung; Young Adult
PubMed: 38941424
DOI: 10.1097/MD.0000000000038671 -
Medicine Jun 2024Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic... (Observational Study)
Observational Study
Elevated neutrophil-to-lymphocyte ratio combined with decreased lymphocyte-to-monocyte ratio is associated with increased peripheral airway resistance in patients with hepatic steatosis.
Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Neutrophils; Lymphocytes; Monocytes; Airway Resistance; Fatty Liver; Adult; Aged; Leukocyte Count; Lymphocyte Count
PubMed: 38941417
DOI: 10.1097/MD.0000000000038530 -
Medeniyet Medical Journal Jun 2024While the coronavirus disease-2019 (COVID-19) pandemic has generally resulted in milder illness among children than adults, persistent respiratory symptoms have been...
OBJECTIVE
While the coronavirus disease-2019 (COVID-19) pandemic has generally resulted in milder illness among children than adults, persistent respiratory symptoms have been increasingly reported in this population.
METHODS
We conducted a prospective, single-center cohort study focusing on children experiencing prolonged respiratory symptoms after contracting COVID-19. Spirometry, 6- minute walk tests (6MWTs), and tests of lung volume, the diffusing capacity of the lungs for carbon monoxide (DLCO), and fractional exhaled nitric oxide (FeNO) were performed on COVID-19 survivors at least 4 weeks after infection and a group of healthy control subjects.
RESULTS
Fifty-five children with long-term COVID and 55 healthy control subjects were recruited. The weight, height, and body mass index Z-scores were similar in the groups. Within a median duration of 85 days (minimummaximum: 35-194) following COVID-19 infection, a restrictive pattern was observed to be more common in the study group (p=0.021). In children with long COVID, 6MWT distances, DLCO Z-scores, and the predicted values of spirometry and lung volume tests were found to be significantly lower but in the normal range. The average predicted values for DLCO, FeNO, and 6MWT were similar in the two groups.
CONCLUSIONS
Prolonged respiratory symptoms often persist long after COVID-19 infection, necessitating comprehensive evaluation of affected children. Close monitoring, including spirometry and lung volume assessments, is crucial for children with abnormalities in lung imaging. However, FeNO measurements were found to be ineffective in monitoring long COVID.
PubMed: 38940402
DOI: 10.4274/MMJ.galenos.2024.15853 -
Journal of Global Health Jun 2024Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that...
Analysis of clinical characteristics, prognosis and influencing factors in patients with bronchiectasis-chronic obstructive pulmonary disease overlap syndrome: A prospective study for more than five years.
BACKGROUND
Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that investigates the clinical characteristics and prognosis of bronchiectasis-COPD overlap syndrome (BCOS). Further, we aimed to explore factors associated with acute exacerbation and death in BCOS, which may be of value in its early diagnosis and intervention.
METHODS
We recruited inpatients with COPD from the second Xiangya Hospital of Central South University in China in August 2016, with follow-up until March 2022. Patients in the BCOS group had to meet the criteria for diagnosing bronchiectasis. We used self-completion questionnaires, clinical records, and self-reported data as primary data collection methods. We used Kaplan-Meier survival analyses and Cox proportional hazard models to assess the risk of severe acute exacerbation and death for BCOS during the follow-up period.
RESULTS
A total of 875 patients were included and followed up. Patients in the BCOS group had more females, fewer smokers, lower discharge COPD assessment test (CAT) scores, lower forced vital capacity (FVC), a higher likelihood of co-occurring active tuberculosis, higher levels of eosinophils and inflammatory markers, and a higher rate of positive sputum cultures for Pseudomonas aeruginosa than patients in the COPD-only group. Patients in the acute exacerbation group (AE+) were found to have lower body mass index (BMI), more frequent acute exacerbations, higher modified Medical Research Council (mMRC) dyspnoea grade on admission, higher inflammatory markers, lower FVC, higher rates of using inhaled bronchodilators, and higher rates of both positive and Pseudomonas aeruginosa positive sputum cultures. Patients in the 'death' group were older, had a lower BMI, had spent longer time in the hospital, had higher mMRC dyspnoea grade and CAT scores upon admission and discharge, had higher levels of inflammatory markers, lower rates of using inhaled bronchodilators, were more likely to have a combination of pulmonary heart disease and obsolete pulmonary tuberculosis, as well as a higher rate of fungus-positive sputum cultures. Both erythrocyte sedimentation rate at baseline and Pseudomonas aeruginosa culture positivity were confirmed as independent predictors of severe acute exacerbation in multivariate analysis during the years of follow-up. Fungus culture positivity baseline blood urea nitrogen, baseline lymphocyte count, comorbidities with obsolete pulmonary tuberculosis and comorbidities with pulmonary heart disease were verified as independent predictors of death in multivariate analysis during the years of follow-up. Kaplan-Meier curves under survival analysis demonstrated no statistically significant difference in mortality between the COPD and the BCOS groups at the full one, two, and three years of follow-up.
CONCLUSIONS
Patients with BCOS present with reduced lung function, increased susceptibility to different complications, elevated blood eosinophils and inflammatory markers, and elevated rates of positive Pseudomonas aeruginosa cultures. These distinctive markers are linked to a greater risk of severe acute exacerbations and mortality.
Topics: Humans; Female; Pulmonary Disease, Chronic Obstructive; Male; Bronchiectasis; Middle Aged; Prospective Studies; Aged; Prognosis; China; Risk Factors; Syndrome; Disease Progression
PubMed: 38940273
DOI: 10.7189/jogh.14.04129 -
JACC. Advances Jan 2024Hypertensive disorders of pregnancy (HDP) can be classified into gestational hypertension, preeclampsia (PRE), and chronic hypertension with superimposed preeclampsia...
BACKGROUND
Hypertensive disorders of pregnancy (HDP) can be classified into gestational hypertension, preeclampsia (PRE), and chronic hypertension with superimposed preeclampsia (SPE).
OBJECTIVES
The purpose of this study was to retrospectively examine the echocardiographic differences in biventricular structure and function in 3 HDP groups of women in comparison to normotensive pregnant controls.
METHODS
Women with an echocardiogram during or within the first year of pregnancy were identified within our integrated health network. Exclusion criteria included age <18 years, diagnosis of pulmonary embolism, malignancy, autoimmune disease, and structural heart disease.
RESULTS
We identified a total of 706 subjects (cases: n = 427, normotensive controls: n = 279). Cases were divided into 3 groups: gestational hypertension (n = 57), PRE (n = 291), and SPE (n = 79). In adjusted analyses, echocardiographic parameters demonstrated a graded difference in left ventricular (LV) mass index, relative wall thickness, mitral inflow E, mitral inflow A, septal e', lateral e', E/e', left atrial volume index, tricuspid velocity, and lateral e' velocities with the most profound findings noted in the SPE group. Specifically, adjusted LV mass index (adjusted β = 14.45, 95% CI: 9.00-19.90) and E/e' (adjusted β = 2.97, 95% CI: 2.27-3.68) was highest in the SPE group in comparison to controls ( < 0.001).
CONCLUSIONS
LV remodeling and diastolic filling abnormalities are more common in HDP and are most evident in SPE and PRE. Echocardiography during or immediately after pregnancy may be useful in these high-risk women to identify these abnormalities. The long-term implications of these echocardiographic abnormalities require further study.
PubMed: 38939814
DOI: 10.1016/j.jacadv.2023.100725 -
Journal of Arrhythmia Jun 2024Periesophageal vagal nerve injury (PNI) is an unpredictable and serious complication of atrial fibrillation (AF) ablation. We aimed to identify the factors associated...
BACKGROUND
Periesophageal vagal nerve injury (PNI) is an unpredictable and serious complication of atrial fibrillation (AF) ablation. We aimed to identify the factors associated with symptomatic PNI.
METHODS
This study included 1391 patients who underwent ablation index-guided pulmonary vein isolation (PVI) using the CARTO system. The target ablation index was set at 550, except for the left atrial (LA) posterior wall near the esophagus, where radiofrequency (RF) power and duration were limited. Ten patients (0.72%) were diagnosed with symptomatic PNI. We randomly selected 40 patients without PNI (1:4 ratio) matched based on age, sex, body mass index, LA diameter, type of AF, and esophageal location. We measured the shortest distance from the RF lesions to the esophagus (LED) and classified the RF lesions according to the LED into four groups: 0-5, 5-10, 10-15, and 15-20 mm. We conducted a comparative analysis of classified RF lesions between patients with PNI ( = 10) and those without ( = 40).
RESULTS
The contact force at LED 0-5 mm was significantly higher in patients with PNI than in those without (14.6 ± 1.7 vs. 12.0 ± 2.9 g; = .01). Multivariate logistic analysis revealed that the independent factor for PNI was contact force at an LED of 0-5 mm (odds ratio: 1.506; 95% confidence interval: 1.053-2.153; = .025).
CONCLUSIONS
The symptomatic PNI was significantly associated with a higher contact force near the esophagus. Strategies for regulating contact force near the esophagus may aid in the prevention of PNI.
PubMed: 38939771
DOI: 10.1002/joa3.13036 -
JACC. Advances May 2024Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after...
BACKGROUND
Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known.
OBJECTIVES
This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation.
METHODS
The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours within the first 24 hours postoperatively, cardiac index ≥2.2 L/min/m and systemic vascular resistance <800 dyne/s/cm, and vasodilatory shock not attributable to other causes. Prolonged vasoplegia was defined as that lasting 12 to 24 hours; transient vasoplegia was that lasting 6 to <12 hours. Patient characteristics, outcomes, and risk factors were analyzed.
RESULTS
Of the 600 patients who underwent CF-LVAD implantation during the study period, 182 (30.3%) developed vasoplegia. Mean patient age was similar between the vasoplegia and no-vasoplegia groups. Prolonged vasoplegia (n = 78; 13.0%), compared with transient vasoplegia (n = 104; 17.3%), was associated with greater 30-day mortality (16.7% vs 5.8%; = 0.02). Risk factors for prolonged vasoplegia included preoperative dialysis and elevated body mass index.
CONCLUSIONS
Compared with vasoplegia overall, prolonged vasoplegia was associated with worse survival after CF-LVAD implantation. Treatment to avoid or minimize progression to prolonged vasoplegia may be warranted.
PubMed: 38939630
DOI: 10.1016/j.jacadv.2024.100916 -
Journal of Extracellular Biology Jul 2023High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung...
High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility.
PubMed: 38939072
DOI: 10.1002/jex2.98