Bronchoalveolar Lavage Research Articles

COVID-19 Pneumonia Diagnosed by Bronchoalveolar Lavage Fluid, With CD4 T-cell Depletion Contributing to Prolonged Infection: Two Case Reports

COVID-19 Pneumonia Diagnosed by Bronchoalveolar Lavage Fluid, With CD4 T-cell Depletion Contributing to Prolonged Infection: Two Case Reports

Pulmonary infection with an unusual microorganism.

Pulmonary trichomoniasis is an underdiagnosed disease. In most cases, there is an underlying clinical condition related to immunosuppression. The results of molecular biology techniques indicate that trichomonad infections have been significantly underestimated. A 7-year-old girl with a medical history of suspected juvenile rheumatoid arthritis presented with a fever, chills, and a productive cough. Her chest computed tomography scan indicated a pericardial effusion and consolidation in the left lower lobe. In direct microscopy of the bronchoalveolar lavage fluid, we identified a motile and flagellated organism. Based on the morphology, size, and rolling motility, we identified this organism as Trichomonas hominis. The patient's fever stopped after 3 days of intravenous metronidazole administration. In immunocompromised patients with evidence of pneumonia, sputum or bronchial samples should be examined more carefully. The possibility of unusual pathogens should be considered if they do not respond to antibacterial treatments.

Whole transcriptome sequencing identifies key lncRNAs, circRNAs and miRNAs in sepsis-associated acute lung injury

Purpose: In this study, we identified differentially expressed genes (DEGs) and signaling pathways to gain insight into the pathogenesis of acute lung injury (ALI). Methods: C57BL/6 mice were intravenously injected with lipopolysaccharide (LPS) to establish a sepsis-induced ALI model. Hematoxylin-eosin (H&E) and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate the model. Whole transcriptome sequencing was performed to identify the expression changes in lncRNAs, circRNAs, miRNAs and mRNAs in lung tissues. The crucial RNAs and the biological function of the target genes were confirmed and annotated based on bioinformatics analysis. Real-time quantitative reverse transcription-polymerase chain reaction (qRT–PCR) was employed to verify the expression levels of key lncRNAs, circRNAs, miRNAs and mRNAs in the lung tissues and human bronchoalveolar lavage (BALF). Results: A total of 3304 (1632 upregulated and 1672 downregulated) differentially expressed mRNAs, 794 (397 up and 397 down) differentially expressed lncRNAs, 89 (58 up and 31 down) differentially expressed circRNAs, and 14 (11 up and 3 down) differentially expressed miRNAs were identified between the control and LPS lung tissues. The lncRNA ceRNA subnetwork and circRNA ceRNA subnetwork were constructed based on the observed interaction and co-expression among the differentially expressed RNAs. An analysis of the protein–protein interaction (PPI) network and hub genes revealed crucial mRNAs for circRNA-Tcf20. The lncRNA-Snhg12, Edn1, Stat1, miR-212-3p and miR-223-3p were upregulated in sepsis ARDS patients. CircRNA-Tcf20, Col1a1, Col1a2 and Flt3 were significantly downregulated in sepsis ARDS patients. The biological function analysis indicated that these genes were enriched in the TNF signaling pathway, Necroptosis signaling pathway and the PI3K-Akt signaling pathway. Conclusions: Our findings suggest that circRNA-Tcf20, miR-212-3p, miR-223-3p, Col1a1, Col1a2 and Flt3 may be new regulatory factors that participate in the pathogenesis of sepsis-related acute lung injury. CircRNA-Tcf20, lncRNA-Snhg12 and all the other RNAs may be potential biomarkers for septic ALI/ARDS.

Tuberculosis presenting with multiple osteolytic lesions in an adolescent boy with fanconi anemia

Tuberculosis (TB) is well known to present with varied clinical and radiological features. Multifocal bone involvement in tuberculosis is rare. Multiple lytic lesions raise the possibility of malignancy usually, especially, in children with predisposing conditions like Fanconi anemia. However, a thorough evaluation with repeated attempts at histopathological confirmation and microbiological evaluation is mandatory in children with unique presentations with inconclusive initial diagnostic tests. We report an adolescent boy with an underlying Fanconi anemia who presented with fever, cough and respiratory distress. On evaluation, he had pallor, wasting, features of right upper lobe consolidation and multiple lytic lesions. Initial diagnostic evaluation including bone marrow evaluation and a diagnostic biopsy from ribs and bronchoalveolar lavage failed to yield a conclusive diagnosis. After nearly 5 weeks of broad-spectrum antibiotics and antifungals, as the clinical signs were progressing, a complete re-evaluation including biopsy from the rib lesion was done and further, he was diagnosed to have skeletal tuberculosis based on the Mycobacterium Growth Indicator Tube (MGIT) culture for Acid Fast bacilli (AFB). Child was empirically started on anti-tuberculous therapy pending cultures, which have led to significant clinical improvement in 2 weeks of therapy. Low bacterial load in skeletal TB reduces the chance to diagnosis, hence making clinical judgment imperative in diagnosis; and repeated testing is mandatory when there is high index of suspicion.

Anti-Inflammatory Effects of Aptamin C in Pulmonary Fibrosis Induced by Bleomycin

Background/Objectives: Vitamin C is a well-known antioxidant with antiviral, anticancer, and anti-inflammatory properties. However, its therapeutic applications are limited by rapid oxidation due to heat and light sensitivity. Aptamin C, which employs aptamers to bind vitamin C, has demonstrated enhanced stability and efficacy. This study investigates the potential of Aptamin C to inhibit the progression of pulmonary fibrosis, a prominent inflammatory lung disease with no effective treatment. Methods: Mice bearing bleomycin-induced pulmonary fibrosis were administered vitamin C or Aptamin C, and their weight changes and survival rates were monitored. Inflammatory cell infiltration was assessed in the bronchoalveolar lavage fluid (BALF), and the degree of alveolar fibrosis was measured by H&E and Masson’s trichrome staining. To elucidate the mechanism of action of Aptamin C, Western blot analysis was performed in HaCaT and lung tissues from bleomycin-induced pulmonary fibrosis mice. Results: The Aptamin C-treated group showed a notably higher survival rate at 50%, whereas all subjects in the vitamin C-treated group died. Histological examination of lung tissue showed that inflammation was significantly suppressed in the Aptamin C-supplemented group compared to the vitamin C-supplemented group, with a 10% greater reduction in cell infiltrations, along with noticeably less tissue damage. Additionally, it was observed that Aptamin C increased SVCT-1 expression in the HaCaT cells and the lung tissues. Conclusions: Taken together, Aptamin C not only increases the stability of vitamin C but also induces an increase in SVCT-1 expression, facilitating greater vitamin C absorption into cells and tissues, thereby inhibiting the progression of symptoms and associated inflammatory responses in pulmonary fibrosis.

Artificial intelligence and microbiome research: Evolution of hotspots, research trends, and thematic-based narrative review.

Artificial intelligence (AI) and microbiome have emerged in recent years as transformative fields with far-reaching implications for various biomedical domains. This paper presents a comprehensive bibliometric analysis examining the intersection of AI and the microbiome (AIM). The study aims to provide information on this interdisciplinary field's research landscape, trends, and emerging topics. Using a systematic approach, data-driven studies were extracted from the Scopus database on 23 November 2023 and analyzed using the VOSviewer and Bibliometrix applications. The regression coefficient of 0.94 and the yearly growth rate of 7.46% in AIM production indicate a consistent increase over time. Identification of essential contributors, organizations, and nations illuminated cooperative networks and research hotspots. The trend themes are the gut microbiome, disease prediction, machine learning, transfer learning, categorization, big data, artificial neural networks, chronic rhinosinusitis, epidemiology, COPD, and bronchoalveolar lavage. These hot issues in AIM reflect the present emphasis on research and developments in our knowledge of the microbiome's function in health, sickness, and individualized treatment. The findings give researchers, policymakers, and industry experts a thorough picture of the research environment and guide future paths in AIM's fascinating and promising subject.

Pseudomonas aeruginosa sepsis in a neonate Franciscana dolphin (Pontoporia blainvillei): clinical approach and laboratory findings

A neonate (4,2 kg and 71 cm total body length) female Franciscana dolphin, Pontoporia blainvillei, was found stranded alive on a beach in Santa Catarina, Southern Brazil, with respiratory signs (dyspnea, crackles during thoracic auscultation and changes in buoyancy) suggestive of pneumonia. Hand-rearing and rehabilitation efforts were unsuccessful, and the neonate died three days after it was rescued. Postmortem investigation was conducted using diagnostic imaging techniques, such as endoscopy and computed tomography. A complete necropsy and histopathology were performed, revealing bronchopneumonia as well as neutrophilic and discrete otitis media. A pure Pseudomonas aeruginosa culture was obtained from the blowhole, bronchoalveolar lavage, and blood using the API NE System. Our results indicate the cause of death to be related to bacterial sepsis. Further understanding of the main causes of death of Franciscana dolphin calves is warranted for conserving this threatened and understudied species. Keywords: bacterial septicemia, cetacean, otitis, pneumonia, Pseudomonas aeruginosa, rehabilitation, stranding event

Transforming growth factor-β3/Smad2/Smad3 signaling pathway inhibition and autophagy by the Yunpi-Xiefei-Huatan decoction ameliorated airway inflammation and mucus hypersecretion in asthmatic rats

Ethnopharmacological relevanceThe Yunpi-Xiefei-Huatan decoction (YXHD) is a traditional Chinese medicine that can improve asthma-related symptoms, including cough, phlegm in the throat, and shortness of breath. However, the YXHD mechanism on asthma has not yet been elucidated. Study aimThe aim of this study is to investigate the effect of YXHD on airway inflammation, mucus hypersecretion, and autophagy modulation in asthma. Materials and methodsThe YXHD chemical constituents were observed and analyzed using high-performance liquid chromatography-mass spectrometry. Ovalbumin sensitization and stimulation were used to establish an asthma rat model. A total of 80 Sprague-Dawley (SD) rats were segmented into eight groups at random: a Normal (NC) group, a Model (Mod) group, a YXHD low-dose group (10 g/kg/d), a YXHD moderate-dose group (20 g/kg/d), a YXHD high-dose group (40 g/kg/d), a Rapamycin group (4 mg/kg/d), a 3-methyladenine (3-MA) group (15 mg/kg/d), and a Dexamethasone (DEX) group (0.5 mg/kg/d). Whole-body plethysmography (WBP) detection was used to evaluate airway hyperresponsiveness. An enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors in the peripheral blood. Inflammatory cells in the bronchoalveolar lavage fluid (BALF) were also counted. Pathological changes in the lung tissues were marked using hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. The localization of MUC5AC and the co-localization of LC3B + MUC5AC were observed using immunofluorescence. The expressions of autophagy and the TGF-β3/Smad2/Smad3 pathway in the lung tissues were detected using a Western blot assay (WB) and qPCR, and the autophagosomes in the lung tissues were detected using a transmission electron microscope (TEM). ResultsTwenty signal peaks were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) technology. The TGF-β3/Smad2/Smad3 signal pathway activation was induced using ovalbumin (OVA) exposure in the rats. The upregulated expression of autophagy, enhanced MUC5AC fluorescence and LC3B fluorescence, and their co-localized expression in the airway epithelium indicated inflammatory cell infiltration and excessive mucus secretion in the lungs. This resulted in airway hyper-responsiveness. The YXHD inhibited the activation of the TGF-β3/Smad2/Smad3 signaling pathway, and autophagy expression reduced inflammatory factors, abnormal mucus secretion, and airway hyperresponsiveness. ConclusionThe YXHD improved lung function, relieved lung inflammation, and inhibited airway mucus secretions in asthmatic rat models. Its mechanism may have been related to the blockage of the TGF-β3/Smad2/Smad3 signaling pathway and autophagy downregulation.

Qingke Pingchuan granules alleviate airway inflammation in COPD exacerbation by inhibiting neutrophil extracellular traps in mice

BackgroundChronic obstructive pulmonary disease (COPD) imposes a significant global health and socioeconomic burden. Exacerbations of COPD (ECOPD), characterized by heightened airway inflammation and mucus hypersecretion, adversely affect patient health and accelerate disease progression. Qingke Pingchuan (QKPC) granules, a formulation from Traditional Chinese Medicine initially prescribed for acute bronchitis, have shown unexplored potential in ECOPD management, with mechanisms of action yet to be clarified. PurposeThis study investigates the therapeutic effects of QKPC in a mouse model of ECOPD, focusing on underlying molecular mechanisms. MethodsCOPD was induced in mice through chronic cigarette smoke (CS) exposure, followed by intratracheal administration of Pseudomonas aeruginosa lipopolysaccharide (LPS) to trigger exacerbation, after which mice were treated with QKPC granules. Major compounds in QKPC were identified via UHPLC-QE-MS, and high-throughput RNA sequencing of lung tissue samples identified differentially expressed genes. Transcriptomic data were integrated with network pharmacology analysis to pinpoint potential pathways, bioactive compounds, and target genes through which QKPC might attenuate ECOPD. Molecular docking, protein-small molecule binding assays, and in vitro analyses further validated interactions between key compounds and target genes, shedding light on plausible signaling pathways. ResultsQKPC treatment led to significant reductions in airway leukocyte infiltration and goblet cell metaplasia in CS- and LPS-exposed mice, accompanied by decreased levels of inflammatory cytokines (IL-6, IL-1β, CXCL1, and TNF-α) and mucin MUC5AC in bronchoalveolar lavage fluid. The integrative transcriptomic and network pharmacology analysis identified the neutrophil extracellular trap (NET) formation pathway as a key mechanism underlying QKPC's protective effect against ECOPD. In vitro assays demonstrated that epigallocatechin-3-gallate (EGCG) and quercetin, two important bioactive compounds in QKPC, significantly inhibited NETosis induced by cigarette smoke extract (CSE) plus LPS in human neutrophils. The two compounds were found to interact directly with the reactive oxidative species (ROS)-generating enzyme NOX2 and its regulatory subunit p47phox. Subsequent in vitro studies further confirmed EGCG and quercetin's capacity to reduce ROS production and downregulate NOX2 and p47phox protein levels in neutrophils stimulated with CSE and LPS. Additionally, in vivo studies confirmed QKPC's efficacy in reducing NET formation, oxidative stress, and NOX2/p47phox protein expression in the lung tissue of ECOPD mice. ConclusionThese findings suggest that QKPC granules alleviate airway inflammation in ECOPD, potentially through inhibition of pulmonary NET formation via the NOX2/p47phox-ROS pathway, underscoring their potential therapeutic application for ECOPD management in clinical settings.

Leptin augments IL-13-induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma

BackgroundAirway tissue eosinophilia can be an observed feature of obesity associated T2 asthma, but the processes mediating this inflammation are unknown. ObjectiveWe investigated a process whereby leptin, an adipokine elevated in obesity, potentiates pulmonary eosinophilia and eotaxin production by airway fibroblasts in T2 asthma. MethodsWe assessed associations between body mass index and airway eosinophilia, leptin and eotaxin production in 78 asthma participants, 36 of which exhibited obesity. Cultured human airway fibroblasts and mouse models of chronic allergic airway disease were used to evaluate leptin’s effect on eotaxin production and lung eosinophilia. The role of interleukin-13 receptor alpha 2 (IL-13Rα2) in mediating these processes was examined using specific neutralizing antibodies in vitro. ResultsIn T2 asthma participants with obesity, we observed that airway tissue eosinophilia did not associate with traditional T2 inflammation metrics such as peripheral and/or bronchoalveolar lavage fluid (BALF) eosinophil counts or with fractional concentration of exhaled nitric oxide (FeNO). Alternatively, we observed elevated BALF leptin and eotaxin-1 levels. In airway fibroblasts from asthma participants, leptin augmented IL-13-induced eotaxin-1 and -3 production and IL13RA2 expression. In mice, elevated leptin promoted airway IL-13Rα2 and eotaxin production by lung fibroblasts and lung tissue eosinophilia following chronic house dust mite allergen exposure. Inhibition of IL-13Rα2 reduced combined leptin and IL-13-stimulated eotaxin secretion by human airway fibroblasts. ConclusionWe identified a potential association explaining airway tissue eosinophil retention in obesity-associated T2 asthma through leptin-mediated enhancement of IL-13-induced eosinophil chemokine production by airway fibroblasts, a process requiring IL-13Rα2.

Analysis of clinical characteristics and laboratory examination data of 112 cases of Mycoplasma pneumoniae pneumonia in children

The aim of this study was to analyze the clinical characteristics of Mycoplasma pneumoniae (MP) infection in children and provide a basis for the diagnosis and treatment of MP and refractory Mycoplasma pneumoniae pneumonia (MPP) in children. A total of 112 children with MPP admitted to Luoyang Maternal and Child Health Hospital between January 31, 2023 and December 31, 2023 were studied, and their clinical characteristics were retrospectively analyzed, including children’s general data, clinical symptoms, imaging changes, bronchoscopy, and laboratory data, including inflammatory factors such as C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), bacterial culture results of bronchoalveolar lavage or sputum, and results of MP culture and detection of MP drug resistance gene loci 23sRNA A2063G and A2064G. Among the 112 children with MPP included in the analysis, 48 were males (42.86%), 64 were females (57.14%), with an average age of 5.74 ± 2.62 years old, 55 cases were older than 6 years old (49.11%), 35 cases were 3 to 6 years old (31.25%), and 22 cases were <3 years old (19.64%), with the older children being the most; 103 cases were fever (91.96%), 94 cases were cough (83.93%), and 46 cases were dyspnea (41.07%). Fiber bronchoscopy showed that 112 cases were mucosal congestion and edema (100.00%), 69 cases were sputum embolism (61.61%), and 19 cases were mucosal erosion (16.96%); the incidence of CRP, PCT, IL-6, and bacterial infection in the MPP group were lower than those in the RMPP group (P < .05), and there was no significant difference in the mutation rate of 23sRNA A2063G and A2064G between the 2 groups (P > .05); logistic regression analysis showed that CRP, PCT, IL-6, alanine aminotransferase, lactate dehydrogenase, immunoglobulin A, IgG, and immunoglobulin M were the main influencing factors of RMPP (P < .05); the length of hospital stay, biochemical treatment of alanine aminotransferase, lactate dehydrogenase, cardiac troponin I, and inflammatory factors of CRP, PCT, and IL-6 in the bronchoalveolar lavage treatment group were lower than those in the general treatment group (P < .05). Children with MPP have more fever, cough, and dyspnea as the starting point, and mucosal congestion, edema, sputum embolism are the most common in bronchoscopy. Children with RMPP may be accompanied by decreased immune function and increased inflammation.

Whole lung and sequential bronchoscopic lavage for pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that results from the accumulation of lipoproteinaceous material in the alveoli due to abnormal surfactant homeostasis. Since its introduction in the 1960s, whole lung lavage (WLL) has been the primary treatment for PAP. This review focuses on WLL, including its technique modifications, and sequential bronchoscopic lavage. Autoimmune PAP, which accounts for the majority of cases, occurs when antigranulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies lead to the deficiency of bioavailable GM-CSF. At present, there are no international guidelines or consensus statements for PAP treatment. Traditionally, therapeutic decisions are made based on the severity and type of PAP. Despite emerging data on GM-CSF-based therapies, WLL remains a central component in the therapeutic strategy for PAP. Although the technique of WLL has evolved over time, there is still no universally adopted, standardized protocol. However, key periprocedural aspects - such as preprocedural planning, patient evaluation, anesthetic technique, lavage protocol, and postprocedural care - remain essential to ensuring the safety and success of WLL.

Metrnl/IL-41 Alleviates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Inflammatory Responses through the AMPK/SIRT1 Signaling Pathway

Introduction: Interleukin-41 (IL-41), also known as Metrnl, is a multifunctional adipokine recognized for its neurotrophic and anti-inflammatory properties that play a significant role in diseases such as sepsis and chronic obstructive pulmonary disease. Despite its crucial biological functions, the mechanisms by which IL-41 mitigates lipopolysaccharide (LPS)-induced acute lung injury (ALI) are not well understood. This study aimed to elucidate the protective effects of IL-41 against LPS-induced inflammation and apoptosis in a murine model and in vitro using bronchial epithelial cells (Beas-2b). Methods: We administered recombinant IL-41 to mice subjected to LPS-induced ALI and observed changes in lung histopathology, inflammation, and apoptosis. Concurrently, Beas-2b cells were transfected with IL-41 constructs, and the role of the AMPK/SIRT1 pathway was investigated using specific inhibitors and agonists. Results: Our results demonstrated that LPS-induced ALI is characterized by increased inflammatory cell chemotaxis in lung lavage fluid, enhanced phosphorylation of NFκB p65, and elevated Bax protein expression, coupled with a decrease in IL-41 protein levels. Treatment with recombinant IL-41 effectively mitigated these pathological changes by upregulating AMPK phosphorylation and SIRT1 expression and inhibiting IκB/NFκB p65 phosphorylation. In cellular assays, overexpression of IL-41 reversed LPS-induced oxidative stress, apoptosis, and the secretion of inflammatory cytokines, whereas suppression of IL-41 or inhibition of AMPK reversed these protective effects. Conclusions: In conclusion, IL-41 exerts significant protective effects against ALI by activating the AMPK/SIRT1 signaling pathway and reducing excessive inflammation and apoptosis. These findings suggest that IL-41 holds promise as a therapeutic target for ALI, potentially allowing for personalized treatments based on serum IL-41 levels.

Effect of metagenomic next-generation sequencing on clinical outcomes in adults with severe pneumonia post-cardiac surgery: a single-center retrospective study

Reports on the application of metagenomic next-generation sequencing (mNGS) in adult patients with severe pneumonia after cardiac surgery remain limited. This study aimed to evaluate the clinical outcomes of mNGS analysis of bronchoalveolar lavage fluid (BALF) in such patients.A retrospective cohort study was conducted on adult patients with severe pneumonia after cardiac surgery. Samples were collected from patients in the surgical intensive care unit (SICU) of Sichuan Provincial People’s Hospital between January 2019 and March 2024. Upon diagnosis of severe pneumonia, bronchoalveolar lavage fluid was obtained via bronchoscopy within 24 h. The mNGS group was composed of patients tested using mNGS and conventional microbiological tests. BALF was detected only by the conventional microbiological test (CMT) method in the CMT group, which involved examining bacterial and fungal smears and cultures at least. We reviewed a total of 4,064 cardiac surgeries, and based on the inclusion criteria, a total of 113 adult patients with severe pneumonia after cardiac surgery were included in this study. The overall positive rate detected by mNGS was significantly higher than that of the culture method (98% vs. 58%, P<0.0001). After receipt of the microbiological results, the mNGS group exhibited a higher incidence of antibiotic adjustments in comparison to the CMT group (P = 0.0021). After adjusting the treatment plan based on microbial testing results, the mNGS group showed an improvement in ventilator-free days within 28 days (P = 0.0475), with a shorter duration of invasive ventilation compared to the CMT group (P = 0.0208). The detection of mNGS can significantly improve the Acute Physiology and Chronic Health Evaluation-II (APACHE II) score (P = 0.0161) and Sequential Organ Failure Assessment (SOFA) score (P = 0.0076) on the 7th day after admission to the SICU. In this study, the mNGS group showed signs of having a positive impact on the length of stay in ICU (median: 9 days, IQR: 7–10 days vs. median: 10 days, IQR: 8-13.75 days, P = 0.0538), length of stay in Hospital (median: 20 days, IQR: 17–28 days vs. median: 25 days, IQR: 18–29 days, P = 0.1558), mortality in 28 days (19% vs. 20%, P = 0.8794), in-hospital mortality (19% vs. 22%, P = 0.7123); however, statistical analysis did not confirm these differences to be significant. mNGS could serve as a valuable complement to conventional diagnostic approaches in adult patients with severe pneumonia after cardiac surgery, potentially improving diagnostic accuracy and leading to more precise and timely interventions, with significant potential to inform clinical decision-making and enhance patient outcomes.

Liuwei Buqi Formula delays progression of chronic obstructive pulmonary disease in rats by regulating the NLRP3/caspase-1/GSDMD pyroptosis pathway

To explore the therapeutic mechanism of Liuwei Buqi (LWBQ) Formula for chronic obstructive pulmonary disease (COPD) in rat models. SD rat models of COPD established by cigarette smoking combined with intratracheal lipopolysaccharide (LPS) instillation and hormone injection were treated with LWBQ Formula by gavage with or without intraperitoneal injection of MCC950 for 3 weeks, starting at the 5th week of modeling. After the treatments, the rats were examined for lung pathologies, lung function, total cell count and white blood cell count in bronchoalveolar lavage fluid (BALF), and serum levels of IL-6, TNF-α, IL-18 and NO. The mRNA expressions of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in the lung tissue were detected with qRT-PCR. Compared with the normal control rats, the COPD rat models had severe lung pathologies and showed significantly decreased lung function, increased total cell and leukocyte subset counts in BALF, and increased serum levels of IL-6, TNF-α, IL-18 and NO and mRNA expressions of pyroptosis-related proteins in the lung tissue. Treatment of the rat models with LWBQ Formula significantly improved lung pathology and lung function, reduced total cell and leukocyte counts in BALF, and decreased serum levels of the inflammatory factors and expressions of pyroptosis-related proteins in the lung tissue. The combined treatment with MCC950 further improved lung pathology and function in spite of a significant difference, but BALF cell counts, serum inflammatory factor levels and pulmonary expressions of pyroptosis-related proteins were all significantly reduced following the treatment. LWBQ Formula can delay the progression of COPD in rats possibly by inhibiting lung tissue pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway to reduce inflammatory response and lung damage.

Network Pharmacology and Molecular Docking Reveal Anti-Asthmatic Potential of Zephyranthes rosea Lindl. in an Ovalbumin-Induced Asthma Model.

Background: This study aimed to evaluate the anti-inflammatory effects of a Zephyranthes rosea in an ovalbumin-induced asthma model. Methods: Allergic asthma was induced in mice via intraperitoneal injection, followed by intranasal ovalbumin challenge. Methanolic extract of Z. rosea bulb was orally administered to asthmatic mice for 14 days. Hematological parameters for bronchoalveolar lavage fluid (BALF) and blood were analyzed. The mRNA expression levels of interleukins and transforming growth factor beta (TGF-β1) in lung tissues were determined using reverse transcriptase-polymerase chain reaction (RT-PCR). Network pharmacology analysis was used to find possible Z. rosea targets. After building a protein-protein interaction network to find hub genes, GO and KEGG enrichment analyses were carried out to determine the potential mechanism. In silico analysis was performed by Molecular Operating Environment. Results: GC-MS analysis of Z. rosea extract detected major classes of phytochemicals. Hematological parameters in blood and BALF from Z. rosea extract-treated animals were significantly reduced in a dose-dependent fashion. Histopathology revealed that Z. rosea bulb had an ameliorative effect on lung tissues. Moreover, treatment with Z. rosea bulb extract significantly restored the normal levels of IL-4, IL-6, IL-1β, IL-10, IL-13, and TGF-β1 in allergic asthmatic mice compared to the diseased group. In silico analysis, particularly of the binding affinities of Z. rosea bulb phytoconstituents for IL6, AKT1, and Src, supported in vivo results. Conclusions: These findings indicated that Z. rosea bulb extract significantly ameliorates cellular and molecular biomarkers of bronchial inflammation and could be a potential candidate for treating allergic asthma.

Diagnostic test accuracy of cellular analysis of bronchoalveolar lavage fluid in distinguishing pulmonary infectious and non-infectious diseases in patients with pulmonary shadow.

This study aims to assess the diagnostic accuracy of cellular analysis of bronchoalveolar lavage fluid (BALF) in distinguishing between pulmonary infectious and non-infectious diseases in patients with pulmonary shadows. Additionally, it will develop and validate a novel scoring system based on a nomogram for the purpose of differential diagnosis. A retrospective analysis was conducted involving data from 222 patients with pulmonary shadows, whose etiological factors were determined at our institution. The cohort was randomly allocated into a training set comprising 155 patients and a validation set of 67 patients, (ratio of 7:3), the least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the model. Multivariable logistic regression analysis was applied to construct a predictive model. The receiver operating characteristic curve (ROC) and calibration curve were utilized to assess the prediction accuracy of the model. Decision curve analysis (DCA) and clinical impact curve (CIC) were employed to evaluate the clinical applicability of the model. Moreover, model comparison was set to evaluate the discrimination and clinical usefulness between the nomogram and the risk factors. Among the relevant predictors, the percentage of neutrophils in BALF (BALF NP) exhibited the most substantial differentiation, as evidenced by the largest area under the ROC curve (AUC = 0.783, 95% CI: 0.713-0.854). A BALF NP threshold of ≥16% yielded a sensitivity of 72%, specificity of 70%, a positive likelihood ratio of 2.07, and a negative likelihood ratio of 0.38. LASSO and multivariate regression analyses indicated that BALF NP (p < 0.001, OR = 1.04, 95% CI: 1.02-1.06) and procalcitonin (p < 0.021, OR = 52.60, 95% CI: 1.83-1510.06) serve as independent predictors of pulmonary infection. The AUCs for the training and validation sets were determined to be 0.853 (95% CI: 0.806-0.918) and 0.801 (95% CI: 0.697-0.904), respectively, with calibration curves demonstrating strong concordance. The DCA and CIC analyses indicated that the nomogram model possesses commendable clinical applicability. In models comparison, ROC analyses revealed that the nomogram exhibited superior discriminatory accuracy compared to alternative models, with DCA further identifying the nomogram as offering the highest net benefits across a broad spectrum of threshold probabilities. BALF NP ≥16% serves as an effective discriminator between pulmonary infectious and non-infectious diseases in patients with pulmonary shadows. We have developed a nomogram model incorporating BALF NP and procalcitonin (PCT), which has proven to be a valuable tool for predicting the risk of pulmonary infections. This model holds significant potential to assist clinicians in making informed treatment decisions.

Distinct Molecular Profiles Underpin Mild-To-Moderate Equine Asthma Cytological Profiles.

A state-of-the-art multi-omics approach was applied to improve our understanding of the aetio-pathogenesis of a highly prevalent, performance-limiting disorder of racehorses: mild-to-moderate equine asthma (MMEA). This is a prerequisite to improving prophylactic, management, and therapeutic options for this condition. Although a number of risk factors have been identified, options for intervention are limited. This study applied a multi-omic approach to reveal key inflammatory pathways involved in inflammatory cell recruitment to the lower airways and highlight distinct MMEA inflammatory profiles. We compared bronchoalveolar lavage fluid (BALF) cell gene and protein expression data from horses with non-inflammatory BALF cytology with those isolated from horses with neutrophilic, mastocytic, mixed neutrophilic/mastocytic, and eosinophilic/mastocytic inflammation. The analyses on transcriptomic/proteomic data derived from BALF from horses with neutrophilic cytology showed enrichment in classical inflammatory pathways, and horses with mastocytic inflammation showed enrichment in pathways involved in hypersensitivity reactions related to nonclassical inflammation potentially mimicking a Th2-immune response. The mixed eosinophilic/mastocytic group also presented with a nonclassical inflammatory profile, whereas the mixed neutrophilic/mastocytic group revealed profiles consistent with both neutrophilic inflammation and hypersensitivity. Our adopted multi-omics approach provided a holistic assessment of the immunological status of the lower airways associated with the different cytological profiles of equine asthma.

Clinical characteristics and outcomes of invasive pulmonary aspergillosis in renal transplant recipients: A single-center experience

ObjectiveThis study aimed to explore the clinical features, early diagnostic methods, and therapeutic approaches for invasive pulmonary aspergillosis (IPA) in patients after renal transplantation (RT). MethodsWe retrospectively examined 22 patients who were diagnosed with IPA post-RT and treated at our institution between 2005 and 2024. ResultsPatients had an average age of 46.4 ± 9.4 years, with a predominance of men (72.7 %). The incidence of IPA after RT was 1.29 %. The median time of IPA onset after transplantation was 12 months. Fever was the predominant symptom (72.7 %), followed by cough and expectoration (31.8 %) and hemoptysis (13.6 %). Frequent computed tomography findings included consolidations (68.2 %) and cavities (45.5 %) with halo signs, multiple nodules, and air crescent signs. Neutropenia was noted in five patients, including one case of agranulocytosis. Impaired renal function was observed in 59.1 % of the cases. Serum 1,3-β-D-glucan and galactomannan (GM) assays were positive in 45.5 % of patients, with bronchoalveolar lavage fluid GM tests confirming IPA in 83.3 % of those tested. Next-generation sequencing confirmed Aspergillus infection in 11 patients. Ultimately, 68.2 % of the patients recovered, whereas 31.8 % succumbed to the infection, with the deceased demonstrating a significantly high rate of complications. ConclusionsPatients with IPA had high mortality rates. The symptoms of IPA after RT are usually nonspecific, making diagnosis very difficult. Bronchoalveolar lavage fluid GM testing and next-generation sequencing proved relatively helpful as detection methods for IPA. Antifungal treatments should be initiated as soon as possible to avoid complications.

Endogenous Glucagon-Like Peptide-1 Receptor and Glucose-Dependent Insulinotropic Polypeptide Receptor Signaling Inhibits Aeroallergen-Induced Innate Airway Inflammation.

Anti-inflammatory effects of incretin signaling through the glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR) in mice have been reported. Therefore, we hypothesized that signaling through the endogenous GLP-1R and the GIPR individually decreases allergic airway inflammation and that the combination of GLP-1R and GIPR signaling together additively inhibits allergen-induced lung and airway inflammation. WT (C57BL/6J), GLP-1R knockout (KO), GIPR KO, and GLP-1R/GIPR double KO (DKO) mice were challenged intranasally with Alternaria alternata extract (Alt-Ext) or vehicle to evaluate the impact of signaling through these receptors on the innate allergen-induced inflammatory response that is primarily driven by group 2 innate lymphoid cells (ILC2). Alt-Ext-induced IL-33 release in the bronchoalveolar lavage fluid (BALF) was not different between the mouse strains, but thymic stromal lymphopoietin (TSLP) was significantly increased in GLP-1R/GIPR DKO mice challenged with Alt-Ext compared to the other strains. Furthermore, Alt-Ext-induced protein expression of IL-5, IL-13, CCL11, and CCL24 in the lung homogenates, the number of eosinophils, lymphocytes, and neutrophils in the BALF, and the number of lung GATA3+ ILC2 were significantly increased in GLP-1R/GIPR DKO mice compared to the other 3 strains. Furthermore, ICAM-1 expression on lung epithelial cells was increased in GLP-1R/GIPR DKO mice challenged with Alt-Ext compared to the other 3 strains. Deficiency of both GLP-1R and GIPR signaling together increased TSLP release, ILC2 activation, and early type 2 innate immune responses to aeroallergen exposure. Combined GLP-1R and GIPR signaling should be explored for the treatment of asthma.