Severe Pulmonary Damage Research Articles

Mitigating Oxidative Stress and Lung Fibrosis with Low Dose Radiation Therapy in Paraquat Poisoning: A Case Series

Paraquat poisoning, a frequent cause of fatalities in India, has become a significant public health issue, particularly among farmers. This herbicide, known for its high toxicity, results in severe pulmonary damage, with no specific antidote available. Ingestion of even small amounts of paraquat can lead to rapid multiorgan failure and death, largely due to its accumulation in the lungs, triggering oxidative stress and alveolar fibrosis. The toxicological mechanism involves the generation of free radicals that damage cellular membranes, eventually causing extensive lung fibrosis and alveolitis. Mortality rates remain high, with no definitive treatment. Recent advancements in low-dose radiotherapy (LDRT) have shown promise in treating lung injury caused by paraquat. LDRT’s anti-inflammatory properties have been previously explored in non-cancerous conditions like musculoskeletal disorders. Its ability to modulate inflammatory responses in lung tissue suggests potential benefits in mitigating paraquat-induced lung fibrosis. While preliminary evidence from small-scale studies has shown some improvement in patients treated with LDRT, the efficacy remains uncertain. At our center, we have treated five patients using LDRT, with mixed outcomes. Some patients showed improvement, while others succumbed to early pulmonary fibrosis. Further research is needed to establish the role of LDRT in managing paraquat poisoning. Larger studies are required to assess its ability to prevent lung fibrosis and improve long-term survival in patients with severe poisoning.

Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy

Acute lung injury (ALI), a critical complication of COVID-19, is characterized by widespread inflammation and severe pulmonary damage, necessitating intensive care for those affected. Although glucocorticoids (GCs), such as dexamethasone (Dex), have been employed clinically to lower mortality, their nonspecific systemic distribution has led to significant side effects, limiting their use in ALI treatment. In this study, we explored the conjugation of Dex to hyaluronic acid (HA) to achieve targeted delivery to inflamed lung tissues. We achieved a conjugation efficiency exceeding 98 % using a cosolvent system, with subsequent ester bond cleavage releasing the active Dex, as verified by liquid chromatography. Biodistribution and cellular uptake studies indicated the potential of the HA conjugate for cluster of differentiation 44 (CD44)-mediated targeting and accumulation. In a lipopolysaccharide-induced ALI mouse model, intravenous (IV) HA-Dex administration showed superior anti-inflammatory effects compared to free Dex administration. Flow cytometry analysis suggested that the HA conjugate preferentially accumulated in lung macrophages, suggesting the possibility of reducing clinical Dex dosages through this targeted delivery approach.

The angiotensin-(1-7)/MasR axis improves pneumonia caused by Pseudomonas aeruginosa: Extending the therapeutic window for antibiotic therapy.

Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia.

Curcumin as a Potential Candidate for Patients with COVID-19 Infection and Diabetes: A Review

Abstract: COVID-19 causes a range of illnesses, from mild symptoms resembling the common cold to severe pulmonary damage leading to Acute Respiratory Distress Syndrome (ARDS). Researchers worldwide are actively searching for the most effective medications with minimal side effects for treating COVID-19. This review aimed to discuss the therapeutic potential of Curcumin (CUR) in managing COVID-19 infection in patients with comorbidities, such as Diabetes Mellitus (DM), as well as the underlying mechanisms of action responsible for CUR's anti-inflammatory and immunomodulatory effects. Given the natural origin and fewer adverse effects of herbal and medicinal plants, many researchers have turned their attention to exploring their therapeutic properties. Turmeric, the main source of polyphenol CUR, has long been recognized for its beneficial pharmacological effects in traditional Ayurveda medicine in China and has recently gained attention from scientists. The study reviewed various types of studies investigating the antiviral activity of CUR. Among the 16 studies reviewed, 4 were computational studies, 2 were in vitro studies, and the remaining 10 were clinical trials. Among the 10 recent studies, 4 studies focused on patients with COVID-19 who had diabetes as an underlying condition. The findings from these studies suggested that CUR is a safe and pleiotropic molecule with multiple effects on intracellular signaling pathways, including alterations in cell growth, apoptosis, inflammation, and oxidation.

Pulmonary Thrombotic Complication of Mycoplasma pneumoniae Pneumonia in Chinese Children: Clinical Feature and Risk Factor Analysis.

Thrombotic disease is a rare but severe complication of Mycoplasma pneumoniae pneumonia in children, with pulmonary thrombosis (PT) being the most frequent type. This study aims to describe the clinical features of pediatric severe Mycoplasma pneumoniae pneumonia (SMPP) patients with PT, and to identify risk factors predictive of PT development in this population. We retrospectively enrolled 60 children with SMPP complicated by PT who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2019 to October 2023. We reviewed their demographic data, laboratory tests and imaging examinations to describe their clinical features. We used multivariate logistic regression analysis to identify significant risk factors for PT in SMPP. The PT group exhibited higher incidences of chest pain, hemoptysis, inflammation and elevated D-dimer levels, as well as more severe pulmonary damage and transaminitis complication, compared to the non-PT group. The left pulmonary artery was the predominant location of PT in SMPP children. A multivariate analysis revealed that C-reactive protein (CRP) and D-dimer were significant predictors of PT in SMPP patients, with odds ratios of 1.10 and 3.37, respectively. The optimal cutoff values of CRP and D-dimer for predicting PT in SMPP were 76.73 mg/L and 3.98 µg/mL, respectively. In SMPP, CRP >76.73 mg/L and D-dimer >3.98 µg/mL are independent predictors of PT. These findings suggest that SMPP-induced excessive inflammation may contribute to PT pathogenesis. Early and intensive anticoagulant, anti-inflammatory and antimycoplasma therapy may improve the disease course and prognosis.

Chronic lymphocytic leukemia in combination with COVID-19: clinical features and unfavorable prognosis factors

Background. At the end of 2019, a new coronavirus infection caused by the SARS-CoV-2 virus was registered. In March 2020, the first cases of COVID-19 were detected in Moscow. Patients with chronic lymphocytic leukemia, characterized by profound immune dysfunction, have risk factors for severe viral disease.Aim. To identify risk factors for hospital mortality and severe course of COVID-19, as well as to optimize therapeutic and preventive measures.Materials and methods. The analysis included 238 patients (142 (59 %) men and 96 (41 %) women) with chronic lymphocytic leukemia and COVID-19 with a median age of 66 (37-90) years, who were hospitalized at City Clinical Hospital No. 52 (Moscow) between April 2020 and April 2023. To compare hospital mortality and severity of COVID-19, patients were divided into 2 groups depending on the hospitalization period: 2020-2021 and 2022-2023, which correlates with the prevalence of some SARS-CoV-2 variants from December 2021 and changes in Moscow epidemiological situation.Results. Overall hospital mortality rate in 2020-2021 was 25 % (n = 45). Age over 73 years was a significant unfavorable factor in men. Cardiovascular diseases increase the risk of death by 2.3 times. Patients with a Charlson Comorbidity Index of 6 or more have a 2.2 times greater risk of death. A history of 1 or more lines of immunochemotherapy increased the risk of hospital mortality by 1.5 times. Relapse/progression of the disease were factors of unfavorable prognosis for patient survival. Binet stage C also showed a significant unfavorable prognosis. When studying all cases of death (n = 51), complications such as myelotoxic agranulocytosis, secondary bacterial complications and severe interstitial pulmonary damage >75 % were identified.Conclusion. Coronavirus infection caused by SARS-CoV-2 represents an infectious threat among patients with chronic lymphocytic leukemia and may affect the regimen and tactics of antitumor therapy. The use of a full range of preventive measures, vaccination and pre-exposure prophylaxis in this cohort of patients is of great importance.

Exploring Mycoplasma ovipneumoniae NXNK2203 infection in sheep: insights from histopathology and whole genome sequencing

BackgroundMycoplasma ovipneumoniae (M. ovipneumoniae) is a significant pathogen causing respiratory infections in goats and sheep. This study focuses on investigating vulnerability of Hu sheep to M. ovipneumoniae infection in the context of late spring’s cold weather conditions through detailed autopsy of a severely affected Hu sheep and whole genome sequencing of M. ovipneumoniae.ResultsThe autopsy findings of the deceased sheep revealed severe pulmonary damage with concentrated tracheal and lung lesions. Histopathological analysis showed tissue degeneration, mucus accumulation, alveolar septum thickening, and cellular necrosis. Immunohistochemistry analysis indicated that M. ovipneumoniae was more in the bronchi compared to the trachea. Genome analysis of M. ovipneumoniae identified a 1,014,835 bp with 686 coding sequences, 3 rRNAs, 30 tRNAs, 6 CRISPRs, 11 genomic islands, 4 prophages, 73 virulence factors, and 20 secreted proteins.ConclusionThis study investigates the vulnerability of Hu sheep to M. ovipneumoniae infection during late spring’s cold weather conditions. Autopsy findings showed severe pulmonary injury in affected sheep, and whole genome sequencing identified genetic elements associated with pathogenicity and virulence factors of M. ovipneumoniae.

Differential Toxicity of Electronic Cigarette Aerosols Generated from Different Generations of Devices In Vitro and In Vivo.

Electronic cigarettes (e-cigs) have become increasingly popular, especially among youth, raising concerns about their potential health risks. JUUL and Tank devices are two common types of e-cigs that deliver aerosols with varying nicotine levels and flavors. However, the differences in the aerosols generated from different devices and their corresponding cytotoxicity and pulmonary injury effects remain poorly understood. This study addresses these knowledge gaps by characterizing the aerosols of JUUL and Tank e-cig devices and testing their toxic effects on THP-1 and BEAS-2B human cell lines as well as the C57BL/6J mouse model. In our study, the lower-voltage device, the 3.7 V JUUL generates 2.72 mg/puff aerosols by using e-liquid containing 3% nicotine salt (i.e., nicotine benzoate), which is less than the 11.06 mg/puff aerosols generated by the 7.5 V Tank using e-liquid containing 2.4% freebase nicotine. Yet, the cytotoxicity results reveal that JUUL aerosols induced higher toxicity and increased production of pro-inflammation cytokines compared to Tank aerosols per puff. Additionally, we observed that JUUL induced more severe pulmonary inflammation and DNA damage compared to Tank after normalizing for cotinine, a nicotine metabolite, in vivo. Our findings suggest that the device design plays a more important role in e-cig aerosol-induced toxicity than the composition of the e-liquid or voltage. These results provide valuable insights into the health risks associated with various electronic-cig devices and offer an approach for evaluating them.

Potential Therapeutic Uses of Thalidomide for Pulmonary Fibrosis

Thalidomide was widely used to avoid morning sickness in pregnant women, but was recalled due to its teratogenic effects and malformations in thousands of children. However, potential beneficial effects such as anti-inflammatory, system regulatory activities and the anti-angiogenic effect of thalidomide have been reported. As the studies about thalidomide continued, its new effects and applications made researchers more interested in it and became a promising agent in the treatment of a variety of clinical situations where standard treatments have failed. To make this purpose more achievable, Scopus, Science Direct, Google Scholar, and PubMed were searched. After obtaining and reviewing articles related to thalidomide and its indications, different therapeutic uses of thalidomide for pulmonary diseases are classified on mechanisms. In recent years, thalidomide has been an effective agent in treating cough associated with pulmonary fibrosis and the main suggested mechanism refers to regulation production of inflammatory mediators, including cytokines and chemokines, which trigger Epithelial-Mesenchymal Transition (EMT). The mechanism of EMT is related to the inhibition of Transforming growth factor-beta (TGF-β1)-mediated signaling pathways, Smad2 (Suppressor of Mothers against decapentaplegic homolog 2) / 3, Akt / Glycogen synthase kinase 3 beta (GSK-3β), and Mitogen-activated protein kinase (MAPK). Thalidomide is also involved in paraquat-induced and bleomycin-induced pulmonary fibrosis. Also, Thalidomide gained attention as a suitable agent for the treatment of cough associated with idiopathic pulmonary fibrosis (IPF) and for severe pulmonary damage cause by severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), responsible for the global pandemic in 2020, due to its anti-inflammatory-anti-angiogenesis and pro-apoptotic properties.

Differences in Clinical and Imaging Features between Asymptomatic and Symptomatic COVID-19 Patients.

The clinical and imaging features of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 and symptomatic COVID-19 patients. The clinical and chest computed tomography imaging data of 47 asymptomatic carriers and 36 symptomatic COVID-19 patients were derived. All patients underwent 4-6 CT scans over a period of 2-5 days. The bulk of asymptomatic carriers who developed symptoms and most of the COVID-19 patients were older than 18 years of age with a decreased lymphocyte count, abnormal hepatic and renal function, and increased D-dimer and C-reactive protein. In the early stage, the pulmonary lesion involved mostly 1-2 lobes at the peripheral area in asymptomatic carriers but more than three lobes at both the central and peripheral areas in COVID-19 patients. In the progression stage, the lesion of asymptomatic carriers extended from the peripheral to the central area, and no significant difference was found in the lesion range compared with the symptomatic control group. In early improvement stage, the lesion was rapidly absorbed, and lesions were located primarily at the peripheral area in asymptomatic carriers; contrastingly, lesions were primarily located at both the central and peripheral areas in symptomatic patients. Asymptomatic carriers reflected a significantly shorter duration from disease onset to peak progression stage compared with the symptomatic. Asymptomatic carriers are a potential source of transmission and may become symptomatic COVID-19 patients despite indicating less severe pulmonary damage, earlier improvement, and better prognosis. Early isolation and intervention can eliminate such carriers as potential sources of transmission and improve their prognosis.

Metformin mitigates gas explosion‑induced blast lung injuries through AMPK‑mediated energy metabolism and NOX2‑related oxidation pathway in rats

Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation.

How the Innate Immune System of the Blood Contributes to Systemic Pathology in COVID-19-Induced ARDS and Provides Potential Targets for Treatment.

Most SARS-CoV-2 infected patients experience influenza-like symptoms of low or moderate severity. But, already in 2020 early during the pandemic it became obvious that many patients had a high incidence of thrombotic complications, which prompted treatment with high doses of low-molecular-weight heparin (LMWH; typically 150-300IU/kg) to prevent thrombosis. In some patients, the disease aggravated after approximately 10 days and turned into a full-blown acute respiratory distress syndrome (ARDS)-like pulmonary inflammation with endothelialitis, thrombosis and vascular angiogenesis, which often lead to intensive care treatment with ventilator support. This stage of the disease is characterized by dysregulation of cytokines and chemokines, in particular with high IL-6 levels, and also by reduced oxygen saturation, high risk of thrombosis, and signs of severe pulmonary damage with ground glass opacities. The direct link between SARS-CoV-2 and the COVID-19-associated lung injury is not clear. Indirect evidence speaks in favor of a thromboinflammatory reaction, which may be initiated by the virus itself and by infected damaged and/or apoptotic cells. We and others have demonstrated that life-threatening COVID-19 ARDS is associated with a strong activation of the intravascular innate immune system (IIIS). In support of this notion is that activation of the complement and kallikrein/kinin (KK) systems predict survival, the necessity for usage of mechanical ventilation, acute kidney injury and, in the case of MBL, also coagulation system activation with thromboembolism. The general properties of the IIIS can easily be translated into mechanisms of COVID-19 pathophysiology. The prognostic value of complement and KKsystem biomarkers demonstrate that pharmaceuticals, which are licensed or have passed the phase I trial stage are promising candidate drugs for treatment of COVID-19. Examples of such compounds include complement inhibitors AMY-101 and eculizumab (targeting C3 and C5, respectively) as well as kallikrein inhibitors ecallantide and lanadelumab and the bradykinin receptor (BKR) 2 antagonist icatibant. In this conceptual review we discuss the activation, crosstalk and the therapeutic options that are available for regulation of the IIIS.

RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice.

Seasonal influenza epidemics represent a significant global health threat. The exacerbated immune response triggered by respiratory influenza virus infection causes severe pulmonary damage and contributes to substantial morbidity and mortality. Regulator of G-protein signaling 10 (RGS10) belongs to the RGS protein family that act as GTPase activating proteins for heterotrimeric G proteins to terminate signaling pathways downstream of G protein-coupled receptors. While RGS10 is highly expressed in immune cells, in particular monocytes and macrophages, where it has strong anti-inflammatory effects, its physiological role in the respiratory immune system has not been explored yet. Here, we show that Rgs10 negatively modulates lung immune and inflammatory responses associated with severe influenza H1N1 virus respiratory infection in a mouse model. In response to influenza A virus challenge, mice lacking RGS10 experience enhanced weight loss and lung viral titers, higher mortality and significantly faster disease onset. Deficiency of Rgs10 upregulates the levels of several proinflammatory cytokines and chemokines and increases myeloid leukocyte accumulation in the infected lung, markedly neutrophils, monocytes, and inflammatory monocytes, which is associated with more pronounced lung damage. Consistent with this, influenza-infected Rgs10-deficent lungs contain more neutrophil extracellular traps and exhibit higher neutrophil elastase activities than wild-type lungs. Overall, these findings propose a novel, in vivo role for RGS10 in the respiratory immune system controlling myeloid leukocyte infiltration, viral clearance and associated clinical symptoms following lethal influenza challenge. RGS10 also holds promise as a new, potential therapeutic target for respiratory infections.

Pulmonary hypertension associated with busulfan.

Busulfan is widely used to treat malignant diseases, particularly for therapeutic intensification prior to an autologous stem cell graft. Numerous side effects consecutive to busulfan are described, but few descriptions of pulmonary hypertension exist, while bronchiolitis obliterans remains a rare complication. We report the clinical observations of four patients from the French Pulmonary Hypertension Registry who experienced subacute pulmonary hypertension after receiving busulfan as preparation regimen before an autologous stem cell graft for malignancies (Hodgkin’s disease, Ewing’s sarcoma and primary large B cell lymphoma of the brain). Patients experienced severe pulmonary arterial hypertension 2 to 4.5 months after busulfan administration. Pulmonary hypertension improved after treatment with approved drugs for pulmonary arterial hypertension and/or corticosteroids. During the follow-up period, two patients developed chronic respiratory insufficiency due to interstitial lung disease, leading to double lung transplantation. The pathological assessment of explanted lungs revealed interstitial lung fibrosis with advanced bronchiolar lesions and severe pulmonary vascular damage. Three of the four patients were still alive after 36 to 80 months and the fourth died unexpectedly and suddenly after 5 months. In conclusion, PAH is a rare but severe complication associated with busulfan chemotherapy in adults. Histological examinations provide evidence for diffuse pulmonary vascular damage combined with interstitial lung injury in most cases.

Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study

IntroductionSARS-CoV-2 replication in cell cultures has been shown to be inhibited by ivermectin. However, ivermectin's low aqueous solubility and bioavailabilityhinders its application in COVID-19 treatment. Also, it has been suggested that best outcomes for this medication can be achieved via direct administration to the lung. ObjectivesThis study aimed at evaluating the safety of a novel ivermectin inhalable formulation in rats as a pre-clinical step. MethodsHydroxy propyl-β-cyclodextrin(HP-β-CD) was used to formulate readily soluble ivermectin lyophilized powder. Adult male rats were used to test lung toxicity for ivermectin-HP-β-CD formulations in doses of 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg for 3 successive days. ResultsThe X-ray diffraction for lyophilized ivermectin-HP-β-CD revealed its amorphous structure that increased drug aqueous solubility 127-fold and was rapidly dissolved within 5 s in saline.Pulmonary administration of ivermectin-HP-β-CD in dosesof 0.2, 0.4 and 0.8 mg/kgshowed dose-dependent increase in levels of TNF-α, IL-6, IL-13 and ICAM-1 as well as gene expression of MCP-1, protein expression of PIII-NP and serum levels of SP-D paralleled by reduction in IL-10. Moreover, lungs treated with ivermectin (0.2 mg/kg) revealed mild histopathological alterations, while severe pulmonary damage was seen in rats treated with ivermectin at doses of 0.4 and 0.8 mg/kg. However, ivermectin-HP-β-CD formulation administered in doses of 0.05 and 0.1 mg/kg revealed safety profiles. ConclusionThe safety of inhaledivermectin-HP-β-CD formulation is dose-dependent. Nevertheless, use of low doses(0.05 and 0.1 mg/kg) could be considered as a possible therapeutic regimen in COVID-19 cases.

Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis.

COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01–30.26]; p = 0.048) and mortality (OR 5.21 [1.06–25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.

Effect of obstructive sleep apnea on cardiopulmonary function in patients with chronic obstructive pulmonary disease

Objective: To study the characteristics of cardiopulmonary function in patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlapping syndrome (OS). Methods: A total of 149 COPD patients, who were on stable treatment, were enrolled from the Second Affiliated Hospital of Soochow University from December 2017 to December 2019. The patients were divided into the OS group (n=56) and the COPD only group (n=93) according to their apnea hypopnea index (AHI) measured by the Apnealink device. Data were gathered from polysomnograph (PSG), spirometry, arterial blood gas and N-terminal pro-brain natriuretic peptide (NT-proBNP) assay to assess the cardiopulmonary function of patients. Partial correlation analysis was used to analyze the correlation between AHI and various factors, to study the characteristic changes in the cardiopulmonary function of these OS patients. Results: There were no significant cross-group differences in age and gender (all P>0.05). In the OS group, the forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC), the forced expiratory volume in the first second expressed as percent predicted (FEV1%pred), pH[M (Q1, Q3)], partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were lower than those in the COPD group [(49.46±12.98)% vs (54.38±11.72)%, (47.86±14.78)% vs (57.78±15.81)%, 7.37(7.34, 7.39) vs 7.40(7.39, 7.41), (80.75±10.20) vs (84.28±8.43) mmHg (1 mmHg=0.133 kPa), (94.46±2.52)% vs (95.74±2.28)%], whereas partial pressure of carbon dioxide (PaCO2) [M (Q1, Q3)] was higher than that in the COPD group [55.00 (45.50, 60.00) vs 44.00(40.00, 48.00)mmHg] (all P<0.05). Pulmonary arterial pressure and plasma NT-proBNP levels [M (Q1, Q3)] in the OS group were significantly higher than those in the COPD group [38.90 (28.60, 49.05) vs 28.60 (24.95, 32.60) mmHg, 434.00 (273.75, 631.00) vs 136.00 (86.00, 205.00) pg/ml] (P<0.05). Partial correlation analysis showed that AHI was positively correlated with PaCO2, pulmonary artery pressure, NT-proBNP, and acute exacerbation events (r values: 0.496, 0.544, 0.628, 0.446), and negatively correlated with FEV1/FVC, FEV1%pred, pH, PaO2, and SaO2 (r values:-0.309, -0.346, -0.410, -0.289, -0.267) (all P<0.05). Conclusion: Patients with OS suffer from more severe hypoxemia, hypercapnia and pulmonary function damage, and their pulmonary arterial pressure and NT-proBNP are significantly higher than those with COPD only.

Absence of Cardiac Immune Pathology in a Rat Model of Fat Embolism Syndrome

Introduction Cardiopulmonary insufficiency is a common pathology associated with Fat Embolism Syndrome. We have previously demonstrated that fat embolism induced by intravenous injection of triolein (T) in rats induces severe histopathological pulmonary damage and significant mast cell and macrophage infiltration at 48 hours (hrs) that persists up to at least 10 weeks, but that hearts did not exhibit vasculitis of the coronary artery branches or myocardial inflammation. In light of the distinct pathological and clinical findings in heart and lung, we hypothesized that mast cell and macrophage infiltration would be associated with more severe injury in the lungs but not in the heart and examined this at 48 hrs and 10 weeks. Methodology 24 Sprague-Dawley rats were divided into four groups and treated with 0.2 ml saline or T for 48 hrs or 10 weeks. Hearts were collected and bisected coronally and the caudal portion was fixed in formaldehyde, embedded in paraffin and sectioned. Every fifth section was stained with Hematoxylin & Eosin, or trichrome to evaluate collagen. CD117 or CD68 immunostains were performed to identify mast cells or macrophages, respectively. Random photographed sections of the heart and lung at 100x and 400x were evaluated by two pathologists for mast cells and macrophage counts and histopathology. Statistical significance was calculated using a T-Test in GraphPad Software. Results Significant pulmonary damage was observed at 48 hrs and 10-weeks. In contrast, the heart did not show any histological damage. No statistically significant differences were found in mast cell (p=0.9651) or macrophage (p=0.7626) numbers in the myocardium of T-injected rats when compared to those in the saline controls. Mast cells and macrophages were found significantly elevated in the lungs of T-injected rats. Two distinct pulmonary macrophage morphologies were observed (very large cells with small fat droplets in the cytoplasm and the more numerous normal sized macrophages with few fat droplets). Such histopathological changes were not observed in the hearts of the T-injected animals. Conclusion The study confirms a significant difference between the presence and the severity of the histopathological damage in the lungs versus the heart in this model of fat embolization. These findings highlight the different cellular responses of different organs to a fat embolism insult. We are investigating the mechanisms that lead to pulmonary susceptibility and at the same time cardiac protection to better design a therapeutic intervention for Fat Embolism Syndrome.

Bronchiectasis is one of the indicators of severe coronavirus disease 2019 pneumonia.

Bronchiectasis is one of the indicators of severe coronavirus disease 2019 pneumonia.

Posterior urethral valves (PUVs): prenatal ultrasound diagnosis and management difficulties: a review of three cases

Abstract Objectives Lower urinary tract obstruction (LUTO) has different etiologies. The most common form is posterior urethral valve (PUVs). It is a condition that can lead to end stage renal disease (ESRD) in later life and severe renal and pulmonary damage in utero. Those born alive may end up with residual kidney disease leading to life long morbidity or death. This condition can be diagnosed through prenatal ultrasound but because diagnosis is done late when kidney injury has already happened it does not guarantee healthy survival after birth. There are various treatments in utero and after birth but they all have their complications. In developing countries diagnosis is possible but in most cases pregnant women with fetuses with PUVs present very late in pregnancy. In utero interventions are in most cases not possible and the only way out is expectant management with serial ultrasound assessment until the fetus has achieved level of maturity at which time it is delivered and further postnatal evaluations and treatment given. This series is aimed at highlighting the prenatal ultrasound features of PUVs and the management challenges faced by physicians in developing countries. Case presentation The three cases were managed in three different hospitals. All the cases presented at different gestational ages and different levels of fetal affectation. Because of these, outcomes of management and prognosis of each case differ. Conclusions Fetal PUVs pose specific challenges in management because of late presentation and lack of resource for intervention even where cases present early with minimal renal damage.