Lung Blood Research Articles

Utility of the Enhanced Liver Fibrosis score as a blood biomarker of pulmonary fibrosis secondary to SARS-CoV-2 pneumonia

IntroductionSARS-CoV-2 pneumonia can lead to several sequelae, among them, pulmonary fibrosis. The Enhanced Liver Fibrosis (ELF) score is a panel of serum markers of liver fibrosis. We aimed to describe the utility of the ELF score as a biomarker of pulmonary fibrosis secondary to COVID-19 pneumonia. MethodsChest computed tomography (CT) scan, lung function tests (LFT) and blood analysis were obtained at three months after discharge. Data were analysed according to ELF scores and posteriorly divided into ELF tertiles. ResultsOne hundred twenty-nine patients were recruited; of these, 85.7% presented bilateral pneumonia at diagnosis of SARS-CoV2 infection. At 3 months after discharge, CT scan was available in 123 patients, 73 (59.3%) of whom presented parenchymal lung abnormalities (PLA) and LFT showed impairment in 28 (22.7%) patients. Globally, the most frequent PLA was ground glass opacities (50%), followed by bronchial thickening (26.8%), reticular pattern (19.5%), consolidation (10.5%) and air bronchogram sign (7.3%). Radiological findings were only significant in the higher tertile of ELF, with a reticular pattern as the predominant PLA (p = 0.002). Moreover, patients with both PLA and LFT impairment, presented a trend towards higher levels of ELF compared with patients with only PLA or LFT impairment, or no impairment (9.9 (0.7) vs 9.6 (0.8), 9.1 (1.1) and 9.3 (0.7); p = 0.054). ConclusionPatients with both PLA and LFT alteration at 3 months after SARS-CoV-2 pneumonia had higher ELF scores. The ELF score may be useful to identify patients with risk of fibrotic changes after SARS-CoV-2 pneumonia.

De novo identification of complex traits associated with asthma.

Asthma is a heterogeneous inflammatory disease often associated with other complex phenotypes. Identifying asthma-associated diseases and uncovering the molecular mechanisms mediating their interaction can help detangle the heterogeneity of asthma. Network analysis is a powerful approach for untangling such inter-disease relationships. Here, we integrated information on physical contacts between common single nucleotide polymorphisms (SNPs) and gene expression with expression quantitative trait loci (eQTL) data from the lung and whole blood to construct two tissue-specific spatial gene regulatory networks (GRN). We then located the asthma GRN (level 0) within each tissue-specific GRN by identifying the genes that are functionally affected by asthma-associated spatial eQTLs. Curated protein interaction partners were subsequently identified up to four edges or levels away from the asthma GRN. The eQTLs spatially regulating genes on levels 0-4 were queried against the GWAS Catalog to identify the traits enriched (hypergeometric test; FDR ≤ 0.05) in each level. We identified 80 and 82 traits significantly enriched in the lung and blood GRNs, respectively. All identified traits were previously reported to be comorbid or associated (positively or negatively) with asthma (e.g., depressive symptoms and lung cancer), except 8 traits whose association with asthma is yet to be confirmed (e.g., reticulocyte count). Our analysis additionally pinpoints the variants and genes that link asthma to the identified asthma-associated traits, a subset of which was replicated in a comorbidity analysis using health records of 26,781 asthma patients in New Zealand. Our discovery approach identifies enriched traits in the regulatory space proximal to asthma, in the tissue of interest, without a priori selection of the interacting traits. The predictions it makes expand our understanding of possible shared molecular interactions and therapeutic targets for asthma, where no cure is currently available.

The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response

Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response. The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function. The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal. The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08–2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11–8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found. Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.

Vaşak (Lynx lynx)’ta Larynx Kıkırdakları, Trachea ve Akciğerler Üzerine Makroanatomik ve Histolojik Bir Çalışma

In this study the larynx, trachea, and lungs of one 1.5-year-old adult female lynx (Lynx lynx) were examined. The macro anatomical and histological structure of the larynx cartilages, trachea, and lungs were tried to be revealed by dissection and measurements. It was determined that the trachea had 48 cartilage rings (cartilago trachealis) up to the bifurcatio trachealis, the diameters of which narrow as they approach the lungs. The total tracheal length was 172.36 mm. It was seen that the cross-section of the lynx trachea resembled a circle. The hyaline cartilage structure surrounding the trachea was determined. A muscle structure called musculus transversus trachea, which closes the open ends of this cartilage and surrounds the cartilage from the outside, was detected. It was determined that the trachea consisted of tunica mucosa, submucosa, and tunica adventitia layers. The pulmo sinister in the lynx lung consisted of two main lobes, lobus cranialis, and lobus caudalis. Lobus cranialis was also divided among itself as pars cranialis and pars caudalis. Pulmo dexter was divided into four main lobes as lobus cranialis, lobus medius, lobus caudalis, and lobus accessorius. It was determined that there was connective tissue capsule surrounding the lung, respiratory bronchioles, alveoli, intraalveolar septum, and abundant blood vessels. In intraalveolar septum; capillaries, erythrocytes were determined. Type I and type II pneumocytes were seen covering the alveolar surface. In addition, it was determined that there were macrophages in the alveolar sacs.

Blood multiple heavy metals exposure and lung function in young adults: A prospective Cohort study in China

The content of single heavy metal in blood is associated with lung function decline, but there is little evidence on the joint effect of multiple heavy metals on lung function. To explore whether heavy metal mixture exposure is associated with lung function reduction among young adults. The study based on a cohort of 518 students recruited from a college in Shandong, China. We measured their lung function and blood heavy metal concentrations. The BKMR model was used to analyse the association between blood heavy metals mixture levels and lung function, and to identify the critical single heavy metal which contributes most to joint effects. As the sensitivity analysis, we used quantile g-computation model and GLM to explore the joint effect and independent effects of heavy metals. Our findings revealed a significant reduction of FVC and FEV1 levels after exposure to heavy metals mixture. An IQR increase in Cu was associated with a 0.079 L and 0.083 L decrease in FEV1 and FVC, respectively. And an IQR increase in Fe was associated with 0.036 L higher FEV1 and 0.033 L higher FVC. For adults, reducing blood heavy metals concentration might be an effective intervention to protect lung function.

Moderate hypoxia induces metabolic divergence in circulating monocytes and tissue resident macrophages from Berkeley sickle cell anemia mice.

Human and murine sickle cell disease (SCD) associated pulmonary hypertension (PH) is defined by hemolysis, nitric oxide depletion, inflammation, and thrombosis. Further, hemoglobin (Hb), heme, and iron accumulation are consistently observed in pulmonary adventitial macrophages at autopsy and in hypoxia driven rodent models of SCD, which show distribution of ferric and ferrous Hb as well as HO-1 and ferritin heavy chain. The anatomic localization of these macrophages is consistent with areas of significant vascular remodeling. However, their contributions toward progressive disease may include unique, but also common mechanisms, that overlap with idiopathic and other forms of pulmonary hypertension. These processes likely extend to the vasculature of other organs that are consistently impaired in advanced SCD. To date, limited information is available on the metabolism of macrophages or monocytes isolated from lung, spleen, and peripheral blood in humans or murine models of SCD. Here we hypothesize that metabolism of macrophages and monocytes isolated from this triad of tissue differs between Berkley SCD mice exposed for ten weeks to moderate hypobaric hypoxia (simulated 8,000 ft, 15.4% O2) or normoxia (Denver altitude, 5000 ft) with normoxia exposed wild type mice evaluated as controls. This study represents an initial set of data that describes the metabolism in monocytes and macrophages isolated from moderately hypoxic SCD mice peripheral lung, spleen, and blood mononuclear cells.

Prospective Evaluation of the Correlation of Lung Ultrasonography Score and Blood Gas Parameters in Neonates With Respiratory Distress.

Introduction Lung ultrasonography (LUS) has become frequently used in neonatal intensive care units (NICU) because it is diagnostic, useful, harmless, radiation-free, and practical for bedside use due to its portability. Objective This study aimed to evaluate the association between lung ultrasound (LUS) scores and diagnoses of neonates hospitalized for respiratory distress and determine the value of the combined use of laboratory and imaging methods in patient evaluation by looking at the correlation between blood gas parameters and LUS score. Materials and methods Between March and July 2022, a total of 55 patients who were born term or premature and admitted due to respiratory distress in the NICU of Malatya Training and Research Hospital were included in the study. In this observational, prospective study, demographic information such as birth weights, gestational weeks, mode of delivery, Apgar scores, blood gas sample results, LUS results and scores, ventilation types, and discharge time were recorded during hospitalization in our unit. According to the newborns' clinical, laboratory, and radiologic evaluations, the diagnoses of respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), or congenital pneumonia were made, and the relationship between the diagnoses and LUS scores was evaluated. The pH value and PCO2 value in the venous blood gas obtained on the day of LUS were recorded. Correlation analysis was performed between the LUS score and pH value, LUS score and PCO2 value. Results Twenty-seven newborns were diagnosed with TTN, 18 with RDS, and 10 with congenital pneumonia. There was a statistical difference between LUS scores and diagnoses (p<0.001). According to Spearman correlation analysis, a significant negative moderate correlation was found between LUS scores and venous blood gas pH value (p<0.001, r:-0.49). There was also a significant positive low, moderate correlation with venous blood gas PCO2 value (p<0.001, r:0.36). Conclusion This study demonstrates that LUS scoring has a role in determining the severity of disease and making diagnoses in patients hospitalized for respiratory distress. When LUS is widely used, it will be informative about the severity and prognosis of the disease, together with laboratory evaluation.

Efficacy and Safety Evaluation of Different Maintenance Dose Regimens of Caffeine Citrate in the Treatment of Primary Apnea in Preterm Infants

We have investigated the efficacy and safety of different maintenance doses of caffeine citrate in the treatment of primary apnea in preterm infants. To this end, apneic premature infants were treated with 5 mg/kg (low dose) or 10 mg/kg (high dose) caffeine citrate, and the frequency of apnea at 48 h and 72 h, improvement of clinical symptoms, respiratory mechanics parameters related to lung function, and blood gas analysis indexes were compared between the two groups, and safety was evaluated. The frequency of apnea at 48 h and 72 h was significantly lower in the high-dose group than in the low-dose group, and the difference was statistically significant (P &lt; 0.05). The time to resolution of apnea, the time to mechanical ventilation, and the time to citrate use were significantly shorter in the high-dose group than in the low-dose group (P &lt; 0.05). The tidal volume and peak expiratory flow values were significantly higher in the high-dose group than in the low-dose group (P &lt; 0.05). The oxygen partial pressure and pulse oximetry levels in the blood gas analysis indexes of the high-dose group were significantly higher than those of the low-dose group, and the partial pressure of carbon dioxide level was significantly lower than that of the low-dose group, with statistically significant differences (P &lt; 0.05). The safety evaluation results showed no significant difference in the rate of adverse reactions and short-term complications between the high-dose group and the low-dose group (P &gt; 0.05). Caffeine citrate at a maintenance dose of 10 mg/kg can effectively reduce the frequency of apnea, shorten the improvement time of clinical symptoms, and improve the lung function and blood gas analysis level of children with a high safety profile.

Acute oral toxicity assessment of galbanic acid in albino rat according to OECD 425 TG

In spite of the broad biological and also anticarcinogenic effects which have been reported for galbanic acid in various studies, its toxic effects are not still well characterized. The study was accomplished to evaluate the acute oral toxicity of galbanic acid pursuant to Organisation for Economic Co-operation and Development (OECD) TG No. 425. Female rats were received asafoetida extract and galbanic acid in distilled water by oral gavage. According to the existing information, limit test was done for aqueous extract of asafoetida and main test was done for galbanic acid. The animals were monitored for 2 weeks. Then under general anesthesia, the blood samples were obtained from the heart for biochemical and hematological assessment and the vital organs of rats were isolated for pathological evaluation. The results showed that although the Median lethal dose (LD50) of asafoetida extract was above the 2000 mg/kg body weight, the galbanic acid estimated LD50 was 310.2 mg/kg. There was no considerable change in body weight of vehicle and extract treated animals but in galbanic acid treated animals, the body weights were not normally increased. A significant rise was observed in high-density lipoprotein (HDL), (aspartate aminotransferase) AST and (alanine aminotransferase) ALT levels as well as in white blood cells (WBC), platelet and lymphocytes counts in galbanic acid group compared to vehicle and extract groups. Based on the obtained results, we suggest that although the asafoetida aqueous extract could be categorized as group 5 (LD50 > 2000 mg/kg), but galbanic acid estimated LD50 is about 310.2 mg/kg and toxicity signs also appeared in lung, liver enzymes and complete blood count (CBC) of galbanic acid treated animals.

Integrated mRNA and microRNA profiling in lung tissue and blood from human silicosis.

The overwhelming majority of subjects in the current silicosis mRNA and microRNA (miRNA) expression profile are of human blood, lung cells or a rat model, which puts limits on the understanding of silicosis pathogenesis and therapy. To address the limitations, our investigation was focused on differentially expressed mRNA and miRNA profiles in lung tissue from silicosis patients to explore potential biomarker for early detection of silicosis. A transcriptome study was conducted based on lung tissue from 15 silicosis patients and eight normal people, and blood samples from 404 silicosis patients and 177 normal people. Three early stage silicosis, five advanced silicosis and four normal lung tissues were randomly selected for microarray processing and analyze. The differentially expressed mRNAs were further used to conduct Gene Ontology and pathway analyses. Series test of cluster was performed to explore possible changes in differentially expressed mRNA and miRNA expression patterns during the process of silicosis. The blood samples and remaining lung tissues were used in a quantitative real-time PCR (RT-qPCR) (RT-qPCR). In total, 1417 and 241 differentially expressed mRNAs and miRNAs were identified between lung tissue from silicosis patients and normal people (p < 0.05). However, there was no significant difference in most mRNA or miRNA expression between early stage and advanced stage silicosis lung tissues. RT-qPCR validation results in lung tissues showed expression of four mRNAs (HIF1A, SOCS3, GNAI3 and PTEN) and seven miRNAs was significantly down-regulated compared to those of control group. Nevertheless, PTEN and GNAI3 expression was significantly up-regulated (p < 0.001) in blood samples. The bisulfite sequencing PCR demonstrated that PTEN had significantly decreased the methylation rate in blood samples of silicosis patients. PTEN might be a potential biomarker for silicosis as a result of low methylation in the blood.

Dissecting shared genetic architecture between obesity and multiple sclerosis.

Observational studies have associated obesity with an increased risk of multiple sclerosis (MS). However, the role of genetic factors in their comorbidity remains largely unknown. Our study aimed to investigate the shared genetic architecture underlying obesity and MS. By leveraging data from genome-wide association studies, we investigated the genetic correlation of body mass index (BMI) and MS by linkage disequilibrium score regression and genetic covariance analyser. The casualty was identified by bidirectional Mendelian randomisation. Linkage disequilibrium score regression in specifically expressed genes and multimarker analysis of GenoMic annotation was utilised to explore single-nucleotide polymorphism (SNP) enrichment at the tissue and cell-type levels. Shared risk SNPs were derived using cross-trait meta-analyses and Heritability Estimation from Summary Statistics. We explored the potential functional genes using summary-data-based Mendelian randomization (SMR). The expression profiles of the risk gene in tissues were further examined. We found a significantly positive genetic correlation between BMI and MS, and the causal association of BMI with MS was supported (β=0.22, P=8.03E-05). Cross-trait analysis yielded 39 shared risk SNPs, and the risk gene GGNBP2 was consistently identified in SMR. We observed tissue-specific level SNP heritability enrichment for BMI mainly in brain tissues for MS in immune-related tissues, and cell-type-specific level SNP heritability enrichment in 12 different immune cell types in brain, spleen, lung, and whole blood. The expressions of GGNBP2 were significantly altered in the tissues of patients with obesity or MS compared to those of control subjects. Our study indicates the genetic correlation and shared risk genes between obesity and MS. These findings provide insights into the potential mechanisms behind their comorbidity and the future development of therapeutics. This work was funded by the National Natural Science Foundation of China (82171698, 82170561, 81300279, and 81741067), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), Natural Science Foundation of Guangdong Province (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Programme of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201803, KJ012019099, KJ012021143, and KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial

Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding. We aimed to compare recombinant VWF with tranexamic acid for reducing heavy menstrual bleeding in patients with von Willebrand disease. VWDMin, a phase 3, open-label, randomised crossover trial, was done in 13 haemophilia treatment centres in the USA. Female patients aged 13-45 years with mild or moderate von Willebrand disease, defined as VWF ristocetin cofactor less than 0·50 IU/mL, and heavy menstrual bleeding, defined as a pictorial blood assessment chart (PBAC) score more than 100 in one of the past two cycles were eligible for enrolment. Participants were randomly assigned (1:1) to two consecutive cycles each of intravenous recombinant VWF, 40 IU/kg over 5-10 min on day 1, and oral tranexamic acid 1300 mg three times daily on days 1-5, the order determined by randomisation. The primary outcome was a 40-point reduction in PBAC score by day 5 after two cycles of treatment. Efficacy and safety were analysed in all patients with any post-baseline PBAC scores. The trial was stopped early due to slow recruitment on Feb 15, 2022, by a data safety monitoring board request, and was registered at ClinicalTrials.gov, NCT02606045. Between Feb 12, 2019, and Nov 16, 2021, 39 patients were enrolled, 36 of whom completed the trial (17 received recombinant VWF then tranexamic acid and 19 received tranexamic acid then recombinant VWF). At the time of this unplanned interim analysis (data cutoff Jan 27, 2022), median follow-up was 23·97 weeks (IQR 21·81-28·14). The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146 [95% CI 117-199] vs 213 [152-298]; adjusted mean treatment difference 46 [95% CI 2-90]; p=0·039). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs zero during recombinant VWF treatment) and other bleeding (four [6%] vs two [3%]). These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience. National Heart Lung Blood Institute (National Institutes of Health).

Diagnosis of COVID-19 Using Chest X-ray Images and Disease Symptoms Based on Stacking Ensemble Deep Learning.

The COVID-19 virus is one of the most devastating illnesses humanity has ever faced. COVID-19 is an infection that is hard to diagnose until it has caused lung damage or blood clots. As a result, it is one of the most insidious diseases due to the lack of knowledge of its symptoms. Artificial intelligence (AI) technologies are being investigated for the early detection of COVID-19 using symptoms and chest X-ray images. Therefore, this work proposes stacking ensemble models using two types of COVID-19 datasets, symptoms and chest X-ray scans, to identify COVID-19. The first proposed model is a stacking ensemble model that is merged from the outputs of pre-trained models in the stacking: multi-layer perceptron (MLP), recurrent neural network (RNN), long short-term memory (LSTM), and gated recurrent unit (GRU). Stacking trains and evaluates the meta-learner as a support vector machine (SVM) to predict the final decision. Two datasets of COVID-19 symptoms are used to compare the first proposed model with MLP, RNN, LSTM, and GRU models. The second proposed model is a stacking ensemble model that is merged from the outputs of pre-trained DL models in the stacking: VGG16, InceptionV3, Resnet50, and DenseNet121; it uses stacking to train and evaluate the meta-learner (SVM) to identify the final prediction. Two datasets of COVID-19 chest X-ray images are used to compare the second proposed model with other DL models. The result has shown that the proposed models achieve the highest performance compared to other models for each dataset.

Examining fermented mustard brine in terms of traditional Chinese medicine

Fermented mustard brine was a unique liquid fermented with mustard long used in traditional Chinese medicine. It was previously known as Ji Shui, which refered to the yellow salty water after vegetables were fermented. Fermented mustard brine was not established in TCM until the Ming Dynasty. It was found that the original plant of ancient mustard was Brassica juncea (L.) Czern et Coss. var. juncea, and the origin of the mustard used in mustard brine mainly refereed to the cultivated species of Brassica (Brassica juncea var. multiceps Tsen et Lee) in the Brassica branch of the Cruciferae family, which belonged to the mustard leaf class in tillering mustard. Fermented mustard brine tasted spicy and salty and was considered as a feature of cold, and went to the lung meridian. Its effects were of clearing heat and reducing phlegm, calming coughing and expelling pus. It was mainly used for the treatment of lung carbuncle, and also for diseases such as lung impotence, laryngeal tinea, wheezing, coughing, vomiting pus and blood, and facial swelling. The ways to use it involved taking it directly (or taking it warm), taking it with hot soybean milk, having it with food, mixing it with decoction, and mixing it with houttuynia cordata juice. It was mainly produced in the Jiaxing area of Zhejiang province, especially famous for the collection by the Tianning Temple in Tianning in Jiashan, not the Tianning Temple in Changzhou.

Hydrogen inhalation attenuates lung contusion after blunt chest trauma in mice

BackgroundLung contusion caused by blunt chest trauma evokes a severe inflammatory reaction in the pulmonary parenchyma that may be associated with acute respiratory distress syndrome. Although hydrogen gas has antioxidant and anti-inflammatory effects and is protective against multiple types of lung injury at safe concentrations, the effects of inhaled hydrogen gas on blunt lung injury have not been previously investigated. Therefore, using a mouse model, we tested the hypothesis that hydrogen inhalation after chest trauma would reduce pulmonary inflammation and acute lung injury associated with lung contusion. MethodsInbred male C57BL/6 mice were randomly divided into 3 groups: sham with air inhalation, lung contusion with air inhalation, and lung contusion with 1.3% hydrogen inhalation. Experimental lung contusion was induced using a highly reproducible and standardized apparatus. Immediately after induction of lung contusion, mice were placed in a chamber exposed to 1.3% hydrogen gas in the air. Histopathological analysis and real-time polymerase chain reaction in lung tissue and blood gas analysis were performed 6 hours after contusion. ResultsHistopathological examination of the lung tissue after contusion revealed perivascular/intra-alveolar hemorrhage, perivascular/interstitial leukocyte infiltration, and interstitial/intra-alveolar edema. These histological changes and the extent of lung contusion, as determined by computed tomography, were significantly mitigated by hydrogen inhalation. Hydrogen inhalation also significantly reduced inflammatory cytokine and chemokine mRNA levels and improved oxygenation. ConclusionHydrogen inhalation therapy significantly mitigated inflammatory responses associated with lung contusion in mice. Hydrogen inhalation therapy may be a supplemental therapeutic strategy for treating lung contusion.

Integrative proteomic profiling of lung tissues and blood in acute respiratory distress syndrome.

Acute respiratory distress syndrome and acute lung injury (ARDS/ALI) still lack a recognized diagnostic test and pharmacologic treatments that target the underlying pathology. To explore the sensitive non-invasive biomarkers associated with pathological changes in the lung of direct ARDS/ALI, we performed an integrative proteomic analysis of lung and blood samples from lipopolysaccharide (LPS)-induced ARDS mice and COVID-19-related ARDS patients. The common differentially expressed proteins (DEPs) were identified based on combined proteomic analysis of serum and lung samples in direct ARDS mice model. The clinical value of the common DEPs was validated in lung and plasma proteomics in cases of COVID-19-related ARDS. We identified 368 DEPs in serum and 504 in lung samples from LPS-induced ARDS mice. Gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEPs in lung tissues were primarily enriched in pathways, including IL-17 and B cell receptor signaling pathways, and the response to stimuli. In contrast, DEPs in the serum were mostly involved in metabolic pathways and cellular processes. Through network analysis of protein-protein interactions (PPI), we identified diverse clusters of DEPs in the lung and serum samples. We further identified 50 commonly upregulated and 10 commonly downregulated DEPs in the lung and serum samples. Internal validation with a parallel-reacted monitor (PRM) and external validation in the Gene Expression Omnibus (GEO) datasets further showed these confirmed DEPs. We then validated these proteins in the proteomics of patients with ARDS and identified six proteins (HP, LTA4H, S100A9, SAA1, SAA2, and SERPINA3) with good clinical diagnostic and prognostic value. These proteins can be viewed as sensitive and non-invasive biomarkers associated with lung pathological changes in the blood and could potentially serve as targets for the early detection and treatment of direct ARDS especially in hyperinflammatory subphenotype.

Identification of novel candidate genes in East Asian COPD patients by the functional summary-based imputation and the unified test for molecular signatures: a transcriptome-wide association study

Identification of novel candidate genes in East Asian COPD patients by the functional summary-based imputation and the unified test for molecular signatures: a transcriptome-wide association study

Levels of Clara cell secretory protein and surfactant protein A in municipal solid waste management workers in Ibadan, Southwest Nigeria

Toxic pneumonitis and related respiratory symptoms are common among waste management workers (WMWs). Products of different cellular responses following exposure to toxic components of wastes can lead to the production of a variety of biomolecules. There is a growing recognition of the importance of biomarkers in risk assessment and a strong advocacy for their determination and use as indicators of health and safety. This study assessed the prevalence of respiratory symptoms and the relevance of pulmonary surfactant protein A (SP-A) and Clara cell 16 protein (CC16) as indicators of occupational inhalation exposure to toxic substances and irritants in WMW. A total of 172 subjects consisting of 112 WMWs and 60 Non-WMWs were recruited by purposive sampling. Data on socio-economic and work-related symptoms were collected using structured questionnaire. CC16 and SP-A were determined by ELISA in serum samples. Clinical history reveals a slightly higher prevalence of respiratory symptoms in WMWs relative to control subjects. Increased permeability of the lung-blood barrier, characterized by significant elevation of serum SP-A and serum CC16, was associated with respiratory symptoms in WMWs. Steady increases in SP-A and CC16, respectively, in relation to occupational duration were observed in WMWs relative to control. Receiver operating characteristic curve and multivariate analyses revealed SP-A and CC16 as important lung biomarkers for assessing sub-clinical effects of occupational exposure. Our data suggest SP-A and CC16 may be relevant indicators for assessing occupational inhalation exposure to toxic substances and irritants among WMWs.

Estimating individual treatment effects on COPD exacerbations by causal machine learning on randomised controlled trials

RationaleEstimating the causal effect of an intervention at individual level, also called individual treatment effect (ITE), may help in identifying response prior to the intervention.ObjectivesWe aimed to develop machine learning...

Risk Indicators of Sarcoidosis Evolution-Unified Protocol (RISE-UP): protocol for a multi-centre, longitudinal, observational study to identify clinical features that are predictive of sarcoidosis progression

IntroductionSarcoidosis is a pulmonary and systemic granulomatous disease with a wide range of potential outcomes, from spontaneous resolution to end-stage organ damage and death. Currently, clinicians have no easy-to-use risk...