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One promising approach to overcome drug resistance in asthma treatments involves dual-target therapy, specifically targeting the β2 adrenergic receptor (β2-AR) and muscarinic-3 acetylcholine receptor (M3R). This study investigated the anti-asthma effects and dual-target mechanisms of glycyrrhizic acid, hesperidin, and platycodin D (GHP) from Zhisou San. GHP administration effectively attenuated OVA-induced inflammatory infiltration and overproduction of mucus in asthmatic mice. Additionally, GHP treatment significantly suppressed M3R and promoted β2-AR activation, resulting in the relaxation of tracheal smooth muscle. These findings concluded that GHP mitigated asthma by targeting β2-AR and M3R to ameliorate airway inflammation and modulate airway smooth muscle relaxation. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐33 released from airway epithelial cells plays a vital role in shaping type 2 immune responses by binding to the ST2 receptor present in many immune cells, including mast cells (MCs). Intranasal administration of IL‐33 in mice induces type 2 lung inflammation, an increase in lung MC progenitors, and transepithelial migration of leukocytes to the bronchoalveolar space. The aim of this study was to determine the contribution of MCs in IL‐33‐induced lung pathology. Four daily intranasal administrations of IL‐33 reduced spirometry‐like lung function parameters, induced airway hyperresponsiveness, and increased leukocytes in bronchoalveolar lavage fluid (BAL) in an ST2‐dependent manner. MC‐deficient (Cpa3cre/+) mice, which lack MCs, had intact spirometry‐like lung function but slightly reduced airway hyperresponsiveness, possibly related to reduced IL‐33 or serotonin. Strikingly, Cpa3cre/+ mice exposed to IL‐33 had 50% reduction in BAL T‐cells, and CXCL1 and IL‐33 were reduced in the lung. Intranasal IL‐33 induced CXCR2 expression in T‐cells in a MC‐independent fashion. Furthermore, IL‐33‐induced lung MCs were immunopositive for CXCL1 and localized in the epithelium of wild‐type mice. These results suggest that MCs are required to sustain intact lung IL‐33 and CXCL1 levels in mice with IL‐33‐induced airway inflammation, thereby facilitating T‐cell accumulation in the bronchoalveolar space. [ABSTRACT FROM AUTHOR]

Summary: A 3‐year‐old Quarter Horse gelding originating from Texas presented for fever and inappetence. An encapsulated, mixed echogenic cranial mediastinal mass visible ultrasonographically in the left and right fourth intercostal space that displaced the heart caudally was identified. Histological evaluation of needle biopsies obtained under general anaesthesia revealed a severe pyogranulomatous inflammatory process associated with intralesional round, 15–25 μm in diameter, thick double‐contoured cell wall fungal structures. Sequencing of products obtained from DNA extracted from the paraffin‐embedded biopsy sample and a panfungal PCR assay targeting the large ribosomal unit region had a 99.1% identity to either Coccidioides immitis or C. posadessii. Bronchoscopy revealed purulent exudate in the right primary bronchus. Cytological evaluation of bronchial alveolar lavage fluid (BALF) contained 96% moderately degenerative neutrophils and 4% macrophages. Fungal structures were not appreciated in the BALF. However, the mediastinitis could have resulted from inhalation and dissemination of arthroconidia through lymphatics or directly from the lung parenchyma. Quantitative immunodiffusion of serum for the presence of coccidioidal IgG antibodies yielded a titre of 1:256 suggestive of disseminated coccidioidomycosis. After oral fluconazole for 24 months, the horse's general health and athletic performance had returned to normal and the mediastinal mass was not appreciated sonographically. [ABSTRACT FROM AUTHOR]

Background : Micrococcus antarcticus (M. antarcticus) is an aerobic Gram-positive spherical actinobacterium that was initially isolated from Chinese Great-Wall station in Antarctica in 2000. M. antarcticus was considered to be of low pathogenicity, no previous cases of human infection by this organism have been reported. Here we describe the first report with community-acquired pneumonia (CAP) caused by M. antarcticus. Case presentation: An 87-year-old female was presented to the Central Hospital of Wuhan in November 2023 with a chief complaint of cough, sputum production, and chest tightness for 2 weeks. Microbial culture of the patient's bronchoalveolar lavage fluid (BALF) and identification of the isolates using Matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing revealed M. antarcticus infection. Combined with clinical symptoms, laboratory and imaging examination, the patient was diagnosed with CAP. Then cefoperazone/sulbactam and levofloxacin was administrated, the patient's condition was improved and she was discharged after a week after admission, no abnormalities were detected during a 5-month follow-up. Conclusions: This case highlights that M. antarcticus, first identified from a patient with CAP, is an extremely rare pathogenic microorganism. Clinicians should be aware of its potential as a pathogen in the diagnosis and treatment of CAP. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsDiscussionAcute intranasal (IN) instillation of lupus-prone NZBWF1 mice with crystalline silica (cSiO2) triggers robust lung inflammation that drives autoimmunity. Prior studies in other preclinical models show that soluble epoxide hydrolase (sEH) inhibition upregulates pro-resolving lipid metabolites that are protective against pulmonary inflammation. Herein, we assessed in NZBWF1 mice how acute IN cSiO2 exposure with or without the selective sEH inhibitor TPPU influences lipidomic, transcriptomic, proteomic, and histopathological biomarkers of inflammation, fibrosis, and autoimmunity.Female 6-week-old NZBWF1 mice were fed control or TPPU-supplemented diets for 2 weeks then IN instilled with 2.5 mg cSiO2 or saline vehicle. Cohorts were terminated at 7 or 28 days post-cSiO2 instillation (PI) and lungs analyzed for prostaglandins, cytokines/chemokines, gene expression, differential cell counts, histopathology, and autoantibodies.cSiO2-treatment induced prostaglandins, cytokines/chemokine, proinflammatory gene expression, CD206+ monocytes, Ly6B.2+ neutrophils, CD3+ T cells, CD45R+ B cells, centriacinar inflammation, collagen deposition, ectopic lymphoid structure neogenesis, and autoantibodies. While TPPU effectively inhibited sEH as reflected by skewed lipidomic profile in lung and decreased cSiO2-induced monocytes, neutrophils, and lymphocytes in lung lavage fluid, it did not significantly impact other biomarkers.cSiO2 evoked robust pulmonary inflammation and fibrosis in NZBWF1 mice that was evident at 7 days PI and progressed to ELS development and autoimmunity by 28 days PI. sEH inhibition by TPPU modestly suppressed cSiO2-induced cellularity changes and pulmonary fibrosis. However, TPPU did not affect ELS formation or autoantibody responses, suggesting sEH minimally impacts cSiO2-triggered lung inflammation, fibrosis, and early autoimmunity in our model. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Methods Results Conclusions and Clinical Importance Respirable mineral particles can induce lower airway inflammation, but the role they play in asthma of horses is unknown.Respirable mineral particles, particularly respirable silica, are an overlooked determinant of chronic lung inflammation (asthma) in horses.Twenty‐three horses from an equine hospital population: 11 moderately affected (MEA), 7 severely asthmatic (SEA), and 5 control horses free from respiratory clinical signs.Prospective observational study. The quantity and quality of mineral particles found in bronchoalveolar lavage fluid (BALF) were characterized, with particular attention to silica content. Polarized light microscopy performed on cytospin slides identified intracellular birefringent particles as silica. Spectrometry‐based analysis performed on whole BALF determined total mineral and silica percentage and concentration. Group‐related differences in BALF mineral and silica load were investigated as well as associations with BALF cytology.Intracellular birefringent particles were increased in SEA vs MEA (median [interquartile range, IQR]), 12 [7] vs 4 [5] particles/30 high power fields [hpf], respectively; P = .01) and vs controls (4 [2] particles/30 hpf; P = .02). Total mineral concentration in BALF was similar between the groups studied, whereas silica concentration and percentage were increased in SEA vs MEA (1758 [887] particles/mL and 20 [10]% vs 867 [662] particles/mL and 8 [6]%; P = .009 and P = .001) and control group (355 [330] particles/mL and 6 [3]%; P = .0003 and P = .002). Silica load in BALF was associated with BALF neutrophilia in MEA and SEA.Respirable silica is associated with neutrophilic lower airway inflammation in horses and might contribute to asthma development. [ABSTRACT FROM AUTHOR]

Background Early diagnosis of invasive fungal disease is essential for optimizing management. Although the clinical utility of fungal polymerase chain reaction (PCR) testing on plasma and bronchoalveolar lavage (BAL) has been established, the role of follow-up testing remains unclear. Methods This was a retrospective single-center study. The yield of follow-up PCR for Aspergillus species, Mucorales agents, Fusarium species, Scedosporium species, dimorphic fungi, Pneumocystis jirovecii , and Candida species on plasma and/or BAL was measured at intervals of 1, 2, 3, and 4 weeks following a negative result. Results A total of 1389 follow-up tests on 406 plasma specimens from 264 patients and 983 BAL specimens from 431 patients were evaluated. Overall, the positivity rate at 1, 2, 3, and 4 weeks was 2.7% (4/148), 3.3% (4/123), 5.1% (4/78), and 3.5% (2/57), respectively, on plasma, and 0% (0/333), 0.3% (1/288), 0.4% (1/228), and 0.7% (1/134), respectively, on BAL. Conversions occurred with Aspergillus species, Mucorales agents, and Fusarium species PCR on plasma and Aspergillus species and P jirovecii PCR on BAL. All patients who converted were immunocompromised. Within 1 week of a prior negative test, 2 Aspergillus and 2 Mucorales PCRs were positive on plasma, and zero tests were positive on BAL. In week 1, only 1 Aspergillus species that was positive on day 7 was classified as probable fungal disease. Conclusions Fungal PCR follow-up testing on plasma and BAL within 4 weeks of a prior negative result was of low yield and rarely generated a positive result considered clinically significant in the first week. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess the diagnostic values of bronchoalveolar lavage fluid (BALF) real-time polymerase chain reaction (PCR) and BALF metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PJP) in patients infected with human immunodeficiency virus (HIV). Methods: A total of 99 HIV-infected PJP patients and 61 HIV-infected patients diagnosed with non-PJP pneumonia between March 2019 and December 2022 were enrolled. P. jirovecii and multiple other co-pathogens detected in BALF by mNGS were analyzed. The clinical final diagnosis was employed as a benchmark. We compared the diagnostic performance of mNGS in PJP with serum BDG and BALF real-time PCR. The mixed infections detected by mNGS and modifications of antimicrobial treatment were also analyzed. Results: The sensitivity of mNGS test of BALF samples reached 85.86%, which was significantly higher than serum BDG (39.39%, P < 0.001). The sensitivity of BALF P. jirovecii PCR (84.85%) was similar with mNGS (P > 0.05). The specificity of mNGS (100%) was also same as PCR (100.0%), and superior to serum BDG (88.52%, P < 0.001). Besides, mNGS performs remarkably well in identifying co-pathogens of PJP patients infected with HIV. In addition to P. jirovecii, 82 cases (82.83%) of other co-pathogens were identified based on mNGS. Moreover, thirty-four patients (34.34%) increased therapeutic dose of trimethoprim-sulfamethoxazole (TMP-SMZ) based on BALF P. jirovecii PCR. Based on the mNGS results, initial antimicrobial treatment was modified in 86.87% (86/99) of PJP patients. Conclusion: BALF mNGS and real-time PCR are two powerful techniques for rapid diagnosis of PJP with high specificity and sensitivity. Moreover, the benefit of mNGS is that it may identify other organisms besides PJP and it may benefit proper and prompt treatment. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effect of molecular size on the pulmonary pharmacokinetics (PK) of proteins following systemic and local administration in wild-type mice. Methods: A non-cross-reactive antibody trastuzumab, and F(ab′)2, Fab, and scFv fragments of this antibody were used for the investigation. Proteins were injected intravenously or via intratracheal instillation, and PK was measured in plasma, lungs, trachea, bronchi, and bronchoalveolar lavage (BAL) using ELISA. Concentrations in BAL were urea normalized. Results: Following systemic administration, the biodistribution coefficient (BC) for lungs, trachea, bronchi, and BAL was 11%, 11%, 15%, and 2% for the antibody; 15%, 7%, 13%, and 8% for F(ab′)2; 25%, 17%, 28%, and 46% for Fab; and 14%, 1%, 2%, and 50% for scFv. The antibody exposure in BAL was ~50-fold lower than plasma and ~5–7-fold lower than lung tissues. A tissue-dependent BC vs. molecular size relationship was observed, where distribution in tissues was the highest for Fab (50 kDa), and scFv demonstrated the highest distribution in the BAL. PK data generated following local administration were quite variable; however, local dosing resulted in BAL exposures that were 10–100-fold higher than those achieved after systemic dosing for all proteins. The BAL antibody concentrations were 100–1000-fold higher than plasma concentrations initially, which normalized by day 14. For most proteins, local dosing resulted in higher lung concentrations than trachea and bronchi, opposite to what was observed after systemic dosing. Conclusions: The PK data presented here provide an unprecedented quantitative insight into the effect of molecular size on the pulmonary disposition of proteins following systemic and local administration. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the mediating role of the activation degree of arginine-proline metabolism in the association of coal dust and decreased lung function. Methods: Cumulative dust exposure (CDE) represented coal dust exposure, whereas the hydroxyproline-to-arginine concentration ratio (Hyp/Arg) in bronchoalveolar lavage fluid gauged arginine-proline metabolism activation. Pulmonary function indicators, including predicted value of forced vital capacity (FVC%pred), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC%), and the ratio of actual to predicted value of FEV1 (FEV1%pred), diffusing capacity of the lungs for carbon monoxide (DLCO%pred), difference value between alveolar air and arterial partial oxygen pressure (P(A-a) O2), and 6-minutewalking distance test (6MWT), were assessed. Results: Findings revealed a significant association between elevated CDE and increased Hyp/Arg, increased P(A-a) O2, decreased 6MWT, DLCO%pred, and decreased FVC%pred. However, no statistically significant association was found between CDE and FEV1%pred or FEV1/FVC%. The mediating effect of Hyp/Arg was significant for CDE's impact on P(A-a) O2 and DLCO%pred but not on 6MWT and FVC%pred. Conclusions: These results highlight the role of Hyp/Arg in mediating the association between CDE and lung function parameters, shedding light on potential therapeutic avenues for mitigating coal dust-induced lung function impairment. [ABSTRACT FROM AUTHOR]

Background: Invasive aspergillosis affects solid organ transplant (SOT) recipients, carrying a high risk of mortality and morbidity in this population. Rapid and accurate diagnosis is essential to ensure the initiation of correct antifungal therapy. We aimed to evaluate the performance of the bronchoalveolar lavage (BAL) Eurofins Viracor Aspergillus PCR (AspPCR) in diagnosing invasive pulmonary aspergillosis (IPA) in SOT recipients. Methods: We conducted a multicenter retrospective study of SOT recipients in Arizona from February 2019 to December 2022 who had AspPCR done at the time of the clinical encounter. Probable IPA was defined as a positive BAL culture with Aspergillus spp. with clinical and imaging findings of IPA per EORTC/MSGERC criteria. Results: Ninety‐nine SOT recipients with 131 encounters with BAL AspPCR testing were included. The median age was 66, the majority were White, non‐Hispanics (60%), and males (66%). Among the participants, 93 lung transplant recipients with 87 of the encounters received antifungal prophylaxis active against Aspergillus spp. Sixty‐four encounters had BAL galactomannan (GM), all of which had BAL GM <1 OD, and one case had a serum GM of 10 OD. Nine cases met the definition of IPA. The sensitivity of the BAL AspPCR was 67% (95% CI 30%–93%), and the specificity was 98% (95% CI 93%–99%). Conclusion: BAL AspPCR had moderate sensitivity and high specificity in identifying IPA in our cohort of SOT recipients. Further studies in populations with a higher prevalence of IPA are needed to evaluate the performance of this test. [ABSTRACT FROM AUTHOR]

Background: Clinical biomarkers, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker identification of putative biomarkers, validation of biomarkers is necessary for translation of discoveries into clinical application. Objective: Accordingly, in this study, we emphasize the potential of in silico approaches and have proposed and applied 3 novel sequential in silico pre-clinical validation steps to better identify the biomarkers that are truly desirable for clinical investment. Design: As protein biomarkers are becoming increasingly important in the clinic alongside other molecular biomarkers and lung cancer is the most common cause of cancer-related deaths, we used protein biomarkers for lung cancer as an illustrative example to apply our in silico pre-clinical validation approach. Methods: We collected the reported protein biomarkers for 3 cases (lung adenocarcinoma-LUAD, squamous cell carcinoma-LUSC, and unspecified lung cancer) and evaluated whether the protein biomarkers have cancer altering properties (i.e., act as tumor suppressors or oncoproteins and represent cancer hallmarks), are expressed in body fluids, and can be targeted by FDA-approved drugs. Results: We collected 3008 protein biomarkers for lung cancer, 1189 for LUAD, and 182 for LUSC. Of these protein biomarkers for lung cancer, LUAD, and LUSC, only 28, 25, and 6 protein biomarkers passed the 3 in silico pre-clinical validation steps examined, and of these, only 5 and 2 biomarkers were specific for lung cancer and LUAD, respectively. Conclusion: In this study, we applied our in silico pre-clinical validation approach the protein biomarkers for lung cancer cases. However, this approach can be applied and adapted to all cancer biomarkers. We believe that this approach will greatly facilitate the transition of cancer biomarkers into the clinical phase and offers great potential for future biomarker research. Plain Language Summary: Biomarkers, which are routinely used in clinics, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker identification of putative biomarkers, validation of biomarkers is necessary for translation of discoveries into clinical application. This research article highlights the challenges of translating cancer biomarkers into clinical practice and summarizes feasible step toward "in silico pre-clinical validation" using the example of lung cancer types. Accordingly, protein biomarkers proposed for lung cancer are being investigated using the "in silico pre-clinical validation" approach to determine whether they have cancer altering properties (i.e., oncoprotein, tumor suppressor, and cancer hallmark), are expressed in body fluids (i.e., plasma/serum, saliva, urine, and bronchoalveolar lavage) and can be targeted with FDA-approved drugs. We believe that the step of in silico pre-clinical validation is the future of biomarker research for all professionals involved in clinical, biological, epidemiological, biostatistical and health research, and that it will greatly facilitate the transition of biomarkers to the clinical phase. [ABSTRACT FROM AUTHOR]

Pulmonary inflammation is a condition that can result from different diseases such as asthma, chronic obstructive pulmonary disease, and influenza as well as other antigenic substances including a high-fat diet. The potency of syringic acid (SYR), a bioactive substance with therapeutic properties, was evaluated on high-fat (HF) diet–induced pulmonary inflammation in male Wistar rats. Thirty male rats were randomly grouped into five: control, SYR (50 mg/kg), HF only, HF + SYR (25 mg/kg), and HF + SYR (50 mg/kg). Animals were sacrificed after 7 weeks of SYR treatments. Blood, bronchoalveolar lavage fluid (BALF), and lungs were collected for biochemical and histopathological analyses. SYR at 50 mg/kg significantly reversed the HFD-induced dyslipidemia. Furthermore, the observed alterations in both the enzymic and non-enzymic oxidative indicators (MDA, SOD, CAT, and GST) due to intake of HF were ameliorated by SYR. A further dose-dependent increase in GSH was observed following treatments. The increased levels of inflammatory cytokines (NF-κB, IL6, TNF-α, and COX-2) quantified in the BALF and lung tissue were significantly lowered when treated with SYR. Furthermore, exposure to HF lowered the inflammatory indices (albumin) quantified in the BALF, while the levels of LDH and globulin were significantly increased. Also, inflammatory indices including platelet/lymphocytes and (neutrophils × platelets)/lymphocytes quantified in the BALF were significantly lowered with SYR treatments, while over twofold increase in albumin/globulin ratio was recorded by 50 mg/kg SYR. SYR demonstrated antioxidative and anti-inflammatory effects via inhibition of HF-induced activation of pro-inflammatory cytokines in rats. Summary of the findings in this study [ABSTRACT FROM AUTHOR]

Severe SARS-CoV-2 infections may still be observed in people bearing risk factors, such as the use of anti-CD20 monoclonal antibodies (mAbs), which are adopted in several autoimmune disorders including multiple sclerosis (MS). COVID-19 diagnosis is routinely based on nasopharyngeal swab testing, but suboptimal sensitivity for SARS-CoV-2 detection compared to bronchoalveolar lavage (BAL) may lead to misdiagnosis in some cases. Such diagnostic issues were described in a few MS patients receiving anti-CD20 mAbs, including middle-aged people and lacking information on subsequent MS therapeutic management, a debated topic as no evidence-based guidance on de-risking strategies is currently available. Here, we report the case of a young MS patient who developed severe COVID-19 pneumonia under treatment with the anti-CD20 mAb ocrelizumab, and who was finally diagnosed with SARS-CoV-2 by BAL despite repeatedly negative nasopharyngeal swabs. Ocrelizumab was then discontinued, and treatment with a sphingosine-1 phosphate receptor modulator was started, followed by maintenance of clinical and radiological MS stability. Challenges in diagnosing COVID-19 pneumonia in people without risk factors other than immunomodulatory treatment are hence discussed, as well as potential strategies for de-risking MS therapies. The latter topic is increasingly debated based on raising concerns for potential long-term safety issues of high-efficacy treatments, including anti-CD20 mAbs. [ABSTRACT FROM AUTHOR]

Double primary malignancy though uncommon, we often encounter in our clinical practice. The lung malignancy is known to cause left vocal cord paralysis. Bilateral abductor paralysis secondary to adenocarcinoma of the lung with concurrent basal cell carcinoma of the face is not common. Proper counseling and timely management are needed in these cases of multiple primary malignancies. Early evaluation in all cases of hoarseness can help in early diagnosis and management. [ABSTRACT FROM AUTHOR]

Objective: To explore the protective effect and the underlying mechanism of silibinin (SIB), one of the active compounds from Silybum marianum (L.) Gaertn in endotoxemia. Methods: Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin (IL)-1 α, IL-1 β, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide (LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB (100 mg/kg), and low-dose-SIB (100 mg/kg) groups (n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB (200 εmol/L), and low-dose-SIB (100 εmol/L) groups (n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D (GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1 β were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay. Results: SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1 α, IL-1 β, and IL-18 induced by LPS (P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS (P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models (P<0.05). Conclusions: SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model, at least in part, by inhibiting the caspase-11-mediated cleavage of GSDMD. Additionally, SIB inhibits the interaction of LPS and caspase-11 and inhibits the LPS-mediated up-regulation of caspase-11 expression, which relieves caspase-11-dependent cell pyroptosis and consequently attenuates LPS-mediated lethality. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to investigate the effect of mixed probiotics on the diversity of the pulmonary flora in critically ill patients requiring mechanical ventilation by analysing the changes in lung microbes. Methods: 24 adult critically ill patients who needed mechanical ventilation in our hospital were randomly divided into a probiotic group and a control group. Then, the probiotic group was given Live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules, Oral (Bifico) by nasal feeding within 24 h after mechanical ventilation. Bronchoalveolar lavage fluid (BALF) and venous blood were collected within 24 h after mechanical ventilation and on the 5th day after mechanical ventilation, and the treatment status of patients (mechanical ventilation time, 28-day survival), measured cytokine levels (IL-1 β, IL-6, IL-8, IL-17A) and changes in pulmonary microorganisms were observed. Results: The microbial diversity of BALF samples decreased in the control group, and there was no significant difference in the probiotic group. Species difference analysis showed that among the three probiotics (Bifidobacterium, Lactobacillus, Enterococcus) used for intervention, Lactobacillus caused significant differences in BALF in the control group. Clinical factor association analysis displayed significant associations with IL-17A levels in both blood and BALF. Conclusion: Mechanical ventilation can cause a decline in pulmonary microbial diversity, which can be improved by administering mixed probiotics. [ABSTRACT FROM AUTHOR]

Background: Chlamydia abortus, as a pathogen of atypical pneumonia, is rare in humans, especially in HIV infection patients. Case presentation: We present the case of a 48-year-old man with a history of HIV infection who started high fever and developed pneumonia. The pathogen-targeted next-generation sequencing (ptNGS) results of bronchial lavage fluid showed Chlamydia abortus infection. Conclusion: This is the first report of Chlamydia abortus infection presented as atypical pneumonia in an AIDS patient. [ABSTRACT FROM AUTHOR]

Background: Respiratory disease is a predominantly observed problem in neonates. Moreover, the application of flexible bronchoscopy in newborns is gradually increasing. This study aimed to investigate the value of bronchoscopy in neonates respiratory abnormalities and evaluate the safety of bronchoscopy application. Methods: Clinical data and outcomes of 56 neonates who underwent flexible bronchoscopy were retrospectively analyzed. Correlations among indications for bronchoscopy, findings, and clinical diseases were assessed. Results: A total of 56 neonates had a minimum weight of 1200 g at the time of bronchoscopy, while the minimum gestational age at birth was 26 + 1 weeks. A total of 22 cases (39.3%) had two or more clinical indications; the five most common indications were respiratory distress in 24 (42.9%), stridor in 22 (39.3%), pulmonary atelectasis in 10 (17.6%), feeding difficulty in 10 (17.6%), and difficult weaning from mechanical ventilation in 6 (10.7%) cases. A total of 13 types of abnormalities were detected in the respiratory tract. The most common abnormalities were laryngomalacia in 29 (59.2%), tracheobroncomalacia in 8 (16.3%), and vocal cord paralysis in 6 (12.2%) cases. Bronchoalveolar lavage was performed in 39 cases. Eight cases were diagnosed by bronchoscopy and then treated with surgery in the Thoracic Surgery/Otolaryngology Department; all of them were cured and discharged from the hospital after surgery. No serious complications, such as pneumothorax or shock, occurred in any of the children, of whom none died. Conclusions: Flexible bronchoscopy could play an important role in diagnosing and identifying respiratory disorders in neonates and be safely used with few serious complications. [ABSTRACT FROM AUTHOR]

Background: Equine asthma is a common, non-infectious, chronic lung disease that affects up to 80% of the horse population. Strict phenotyping and identification of subclinically asthmatic horses can be challenging. The aim of this study was to describe equine asthma phenotypes (mild, moderate, and severe asthma) defined by BALF cytology and occurrence of clinical signs in a population of privately owned horses and to identify the variables and examination steps with best discriminative potential. The standardised examination protocol included clinical examinations, blood work, airway endoscopy with bronchoalveolar lavage fluid analysis, arterial blood gas analysis and radiography under clinical conditions performed by one veterinarian. Results: Out of 26 horses, four were diagnosed with mild (subclinical), seven with moderate, and seven with severe asthma based on clinical examination and BALF cytology. Eight horses served as controls. Cough with history of coughing was the strongest variable in phenotype differentiation. Factor analysis revealed an increasing clinical variability with disease severity and an overlapping of clinical presentations between phenotypes. Elevated mast cell (4/4 horses) and neutrophil counts (3/4 horses) in bronchoalveolar lavage cytology differentiated mild asthmatic horses from healthy horses. Moderate and severe asthmatic horses were characterised by clinical signs and neutrophil counts. Conclusions: The results indicate that medical history, clinical examination and bronchoalveolar lavage cytology are minimum indispensable steps to diagnose equine asthma and that phenotypes are clinically overlapping. A differentiation of three phenotypes without neutrophil and mast cell counts in bronchoalveolar lavage cytology is not sufficient for clinical diagnostics. A comparably exact diagnosis cannot be achieved by relying on alternative examinations used in this study. Screenings of inconspicuous horses with bronchoalveolar lavage can aid in diagnosing subclinically affected animals, however, group size was small, the procedure is invasive and clinical relevance of slightly elevated cells in bronchoalveolar lavage remains unclear. Clinical relevance could not be clarified in this study, since follow-up examinations or lung function testing were not performed. [ABSTRACT FROM AUTHOR]

Background In burn patients, skin barrier disruption and immune dysfunctions increase susceptibility to invasive fungal diseases (IFDs) like invasive candidiasis (IC) and invasive mold infections (IMI). We provide an in-depth analysis of IFD-related factors and outcomes in a 10-year cohort of severe burn patients. Methods This retrospective cohort study includes adult patients admitted to the burn intensive care unit (BICU) between April 2014 and May 2023 with total burn surface area (TBSA) ≥15%. Patients were classified as proven IFD according to EORTC/MSGERC criteria applicable for IC. Putative IMIs were defined with: ≥2 positive cultures from a skin biopsy/bronchoalveolar lavage or ≥2 positive blood specific-quantitative polymerase chain reactions (qPCRs) or a combination of both. Results Among 1381 patients admitted, 276 consecutive patients with TBSA ≥15% were included. Eighty-seven (31.5%; IC n = 30; IMI n = 43; both n = 14) patients fulfilled the criteria for probable/putative IFD. At Day 30 after the burn injury, the estimated cumulative incidence proven/putative (pr/pu) IFD was 26.4% (95% confidence interval [CI], 21.4%–31.8%). Factors independently associated with IFDs were TBSA, severity scores and indoor burn injury (ie, from confined space fire). Overall mortality was 15.3% and 36.8% in the no IFD, pr/pu IFD groups respectively (P <.0001). IFD was independently associated with a risk of death (hazard ratio [HR]: 1.94 for pr/pu IFD; 95% CI, 1.12–3.36; P =.019). Conclusions This study describes twenty-first-century characteristics of IFDs in severe burn patients confirming known risk factors with thresholds and identifying the indoor injury as an independent factor associated to IFDs. This suggests a link to contamination caused by fire damage, which is highly susceptible to aerosolizing spores. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare targeted next-generation sequencing (tNGS) with metagenomic next-generation sequencing (mNGS) for pathogen detection in infants with severe postoperative pneumonia after congenital heart surgery. Methods: We conducted a retrospective observational study using data from the electronic medical record system of infants who developed severe pneumonia after surgery for congenital heart disease from August 2021 to August 2022. Infants were divided into tNGS and mNGS groups based on the pathogen detection methods. The primary outcome was the efficiency of pathogen detection, and the secondary outcomes were the timeliness and cost of each method. Results: In the study, 91 infants were included, with tNGS detecting pathogens in 84.6% (77/91) and mNGS in 81.3% (74/91) of cases (P = 0.55). No significant differences were found in sensitivity, specificity, PPA, and NPA between the two methods (P > 0.05). tNGS identified five strains with resistance genes, while mNGS detected one strain. Furthermore, tNGS had a faster detection time (12 vs. 24 h) and lower cost ($150 vs. $500) compared to mNGS. Conclusion: tNGS offers similar sensitivity to mNGS but with greater efficiency and cost-effectiveness, making it a promising approach for respiratory pathogen detection. [ABSTRACT FROM AUTHOR]

Introduction: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. Methods: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. Results: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. Conclusion: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI. [ABSTRACT FROM AUTHOR]

Background: Although the emerging NGS-based assays, metagenomic nextgeneration sequencing (mNGS) and targeted next-generation sequencing (tNGS), have been extensively utilized for the identification of pathogens in pulmonary infections, there have been limited studies systematically evaluating differences in the efficacy of mNGS and multiplex PCR-based tNGS in bronchoalveolar lavage fluid (BALF) specimens. Methods: In this study, 85 suspected infectious BALF specimens were collected. Parallel mNGS and tNGS workflows to each sample were performed; then, we comparatively compared their consistency in detecting pathogens. The differential results for clinically key pathogens were confirmed using PCR. Results: The microbial detection rates of BALF specimens by the mNGS and tNGS workflows were 95.18% (79/83) and 92.77% (77/83), respectively, with no significant difference. mNGS identified 55 different microorganisms, whereas tNGS detected 49 pathogens. The comparative analysis of mNGS and tNGS revealed that 86.75% (72/83) of the specimens were complete or partial concordance. Particularly, mNGS and tNGS differed significantly in detection rates for some of the human herpesviruses only, including Human gammaherpesvirus 4 (P<0.001), Human betaherpesvirus 7 (P<0.001), Human betaherpesvirus 5 (P<0.05) and Human betaherpesvirus 6 (P<0.01), in which tNGS always had higher detection rates. Orthogonal testing of clinically critical pathogens showed a total coincidence rate of 50% for mNGS and PCR, as well as for tNGS and PCR. Conclusions: Overall, the performance of mNGS and multiplex PCR-based tNGS assays was similar for bacteria and fungi, and tNGS may be superior to mNGS for the detection of DNA viruses. No significant differences were seen between the two NGS assays compared to PCR. [ABSTRACT FROM AUTHOR]

Rationale: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. Objective: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. Methods: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). Results: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen's Kappa = 0.47 ± 0.07; P < 0.001). Nevertheless, self-reported and EHR-identified m/s-AECOPD events were both associated with higher BAL neutrophils (ß ± SEM: 3.0 ± 1.1 and 1.3 ± 0.5 per 10% neutrophil increase; P ≤ 0.018) and lymphocytes (0.9 ± 0.4 and 0.7 ± 0.3 per 10% lymphocyte increase; P ≤ 0.041). Exacerbation by either measure combined was associated with a larger estimated effect (3.7 ± 1.2 and 1.0 ± 0.5 per 10% increase in neutrophils and lymphocytes, respectively) but was not statistically significantly different compared to the self-report only approach. Among the 184 TEPS participants, there were fewer moderate to very severe respiratory exacerbations by self-report (n = 15 or 8%) or EHR-documentation (n = 9 or 5%), but a similar level of agreement as those with COPD was observed (Cohen's Kappa = 0.38 ± 0.07; P < 0.001). Discussion: While there is modest agreement between self-reported and EHR-identified m/s-AECOPD, events are missed by relying on either method alone. However, m/s-AECOPD quantified by self-report or health records is associated with BAL neutrophilia and lymphocytosis. [ABSTRACT FROM AUTHOR]

Introduction: Ventilator-associated pneumonia (VAP) causes increased time of mechanical ventilation (MV), prolonged intensive care unit (ICU) stay, and a higher mortality risk. The systematic review and meta-analysis aimed to compare the efficacies between fiberoptic bronchoscopy (FOB) and general sputum suction for the prevention of VAP in patients with invasive MV. Methodology: Relevant randomized controlled trials (RCTs) were obtained via a search of PubMed, Embase, Cochrane Library, Wanfang, and CNKI databases. A random-effects model was used to pool the results if significant heterogeneity was observed. Otherwise, a fixed-effects model was used. Results: Sixteen RCTs were included. Compared to general sputum suction, sputum suction with FOB was associated with a significantly reduced risk of VAP (risk ratio [RR]: 0.56, 95% CI: 0.47 to 0.67, p < 0.001; I2 = 0%). Subgroup analyses showed that the combination of FOBassisted sputum suction with bronchoalveolar lavage (BAL) further reduced the risk of VAP as compared to FOB-assisted sputum suction alone (p for subgroup difference = 0.04). In addition, FOB-assisted treatment was also associated with a reduced MV time (mean difference [MD]: -2.19 days, 95% CI: -2.69 to -1.68, p < 0.001; I2 = 18%), a shorter ICU stay (MD: 2.9 days, 95% CI: -3.68 to -2.13, p < 0.001; I2 = 34%), and a reduced mortality risk (RR: 0.46, 95% CI: 0.24 to 0.90, p = 0.02; I2 = 0%) in patients with invasive MV. Conclusions: FOB for sputum suction and BAL in patients with invasive MV is effective in reducing the incidence of VAP. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) is a type of single-stranded RNA that forms a covalently closed continuous loop, unlike linear RNA. The expression of circRNAs in mammals is often conserved across species and shows tissue and cell specificity. Some circRNA serve as gene regulators. However, the biological function of most circRNAs is unclear. CircRNA does not have 5′ or 3′ ends. The unique structure of circRNAs provides them with a much longer half-life and more resistance to RNase R than linear RNAs. Inflammatory lung responses occur in the pathogenesis and recovery of many lung diseases. Macrophages form the first line of host defense/innate immune responses and initiate/mediate lung inflammation. For example, in bacterial pneumonia, upon pro-inflammatory activation, they release early response cytokines/chemokines that recruit neutrophils, macrophages, and lymphocytes to sites of infection and clear pathogens. The functional effects and mechanisms by which circRNAs exert physiological or pathological roles in macrophage activation and lung inflammation remain poorly understood. In this article, we will review the current understanding and progress of circRNA biogenesis, regulation, secretion, and degradation. Furthermore, we will review the current reports on the role of circRNAs in macrophage activation and polarization, as well as in the process of inflammatory lung responses. [ABSTRACT FROM AUTHOR]

To investigate the carcinogenicity of anatase-type nano-titanium dioxide (aNTiO2), F344/DuCrlCrlj rats were exposed to aNTiO2 aerosol at concentrations of 0, 0.5, 2, and 8 mg/m³. The rats were divided into 2 groups: carcinogenicity study groups were exposed for two years, and satellite study groups were exposed for one year followed by recovery for 1 day, 26 weeks, and 52 weeks after the end of exposure. In the carcinogenicity groups, bronchiolo-alveolar carcinomas were observed in two 8 mg/m³-exposed males, showing an increasing trend by Peto's test. However, this incidence was at the upper limit of JBRC's historical control data. Bronchiolo-alveolar adenomas were observed in 1, 2, 3, and 4 rats of the 0, 0.5, 2, and 8 mg/m³-exposed females and were not statistically significant. However, the incidence in the 8 mg/m³-exposed females exceeded JBRC's historical control data. Therefore, we conclude there is equivocal evidence for the carcinogenicity of aNTiO2 in rats. No lung tumors were observed in the satellite groups. Particle-induced non-neoplastic lesions (alveolar epithelial hyperplasia and focal fibrosis) were observed in exposed males and females in both the carcinogenicity and satellite groups. Increased lung weight and neutrophils of bronchoalveolar lavage fluid were observed in the 8 mg/m³-exposed carcinogenicity groups. The aNTiO2 deposited in the lungs of the satellite group rats was decreased at 26 weeks after the end of exposure compared to 1 day after the end of exposure. At 52 weeks after the end of exposure, the decreased level was the same at 26 weeks after the end of exposure. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) remains a significant global health challenge, particularly with the rise of drug-resistant strains. Heteroresistance, where subpopulations of bacteria show varying levels of resistance within the same patient, complicates diagnosis and treatment. This study aims to assess the prevalence of heteroresistance to rifampicin and isoniazid in clinical samples from patients with presumptive drug-resistant tuberculosis. Materials and Methods A cross-sectional study was conducted from January to June 2024 at a tertiary care hospital. Clinical samples, including sputum and bronchial lavage, were collected from 200 patients suspected of having drug-resistant TB. Samples were processed using the GeneXpert MTB/RIF assay and Löwenstein-Jensen culture for drug susceptibility testing. Isolates were tested for heteroresistance to rifampicin and isoniazid using the BACTEC MGIT 960 system and molecular techniques like whole-genome sequencing. Results Out of 200 samples, 150 (75%) were confirmed to have Mycobacterium tuberculosis complex. Among these, 60 samples (40%) exhibited heteroresistance to rifampicin, while 45 samples (30%) showed heteroresistance to isoniazid. Dual heteroresistance to both drugs was observed in 20 samples (13.3%). Whole-genome sequencing revealed mutations in the rpoB and katG genes associated with resistance. The presence of heteroresistant populations was associated with prior TB treatment history and poor treatment outcomes. Conclusion The study highlights a substantial prevalence of heteroresistance to rifampicin and isoniazid in patients with presumptive drug-resistant TB. This underscores the need for advanced diagnostic techniques to detect heteroresistant strains and guide effective treatment regimens. Tailored therapeutic strategies are crucial to managing and controlling the spread of drugresistant TB. [ABSTRACT FROM AUTHOR]

Introduction: The study explored the effects of SHOX2 and RASSF1A DNA methylation in lung cancer (LC). Method: Bronchoalveolar lavage fluid (BALF) samples as well as LC and normal adjacent tissues were collected from 72 LC patients and 35 patients with benign pulmonary nodules. Quantitative analysis of SHOX2 and RASSF1A DNA methylation was performed in benign pulmonary nodules and different stages of LC. The diagnostic value of SHOX2 and RASSF1A DNA methylation in LC and benign pulmonary nodules was determined by receiver operating characteristics analysis. Gain/loss-of-function experiments were constructed in LC cells and mouse models of xenograft and pulmonary nodule metastasis. The levels of SHOX2 and transfer-associated genes were tested through quantitative reverse transcription polymerase chain reaction and Western blot. Malignant phenotype of LC cells was assessed by functional experiment. The tumor volume and weight of mice in xenograft models were measured. Pulmonary nodule metastasis was determined through HE staining assay. 5-azacytidine appeared as a positive control drug. Result: SHOX2 DNA methylation or RASSF1A DNA methylation had diagnostic efficiency in pulmonary nodules and early LC, with the two combined having better diagnostic value. SHOX2 expression was upregulated in LC. Similar to 5-azacytidine, SHOX2 knockdown inhibited LC cell viability, migration, and invasion in vitro as well as restrained LC tumorigenesis and pulmonary nodule metastasis in vivo, whereas overexpressed SHOX2 had the opposite effects. Conclusion: The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early LC. SHOX2 positively modulated the tumorigenesis and metastasis of LC by regulating DNA methylation processes. [ABSTRACT FROM AUTHOR]

Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are increasingly recognised as important complications in patients requiring intensive care for severe viral pneumonia. The diagnosis can typically be made in 10–20% of patients with severe influenza or COVID-19, but only when appropriate diagnostic tools are used. Bronchoalveolar lavage sampling for culture, galactomannan testing, and PCR forms the cornerstone of diagnosis, whereas visual examination of the tracheobronchial tract during bronchoscopy is required to detect invasive Aspergillus tracheobronchitis. Azoles are the first-choice antifungal drugs, with liposomal amphotericin B as an alternative in settings where azole resistance is prevalent. Despite antifungal therapy, IAPA and CAPA are associated with poor outcomes, with fatality rates often exceeding 50%. In this Review, we discuss the mechanistic and clinical aspects of IAPA and CAPA. Moreover, we identify crucial knowledge gaps and formulate directions for future research. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection typically relies on reverse transcription-polymerase chain reaction (RT-PCR) technology. However, there is a certain rate of missed detection of SARS-CoV-2 in nasopharyngeal samples, particularly among immunosuppressed individuals. Methods: In this case, SARS-CoV-2 was detected in nasopharyngeal swabs and bronchoalveolar lavage fluid (BALF) using RT-PCR. Pulmonary imaging was performed using computed tomography (CT). Patient clinical data were retrieved from the Laboratory Information System (LIS) . Results: SARS-CoV-2 was negative in two nasopharyngeal tests of the patient, but was finally detected in BALF, confirming that the lung lesions were infected by SARS-CoV-2. Conclusions: In the post-epidemic era, it is necessary to use BALF to identify SARS-CoV-2 infection in cases where other factors have been ruled out in immunosuppressed individuals with pulmonary infections, especially when the nasopharyngeal test yields a negative result. [ABSTRACT FROM AUTHOR]

Advanced diagnostic technologies have made accurate and precise diagnosis of pathogens easy. Herein, we present a new diagnostic method, droplet digital PCR (ddPCR), to detect and quantify Acinetobacter baumannii in mini bronchoalveolar lavage (mini-BAL) samples. A. baumannii causes ventilator-associated pneumonia (VAP), a severe healthcare infection affecting patients' lungs. VAP carries a high risk of morbidity and mortality, making its timely diagnosis crucial for prompt and effective management. Methodology. The assay performance was evaluated by comparing colonization data, quantitative culture results, and different generations of PCR (traditional PCR and Real-Time PCR—qPCR Taqman® and SYBR® Green). The ddPCR and qPCR Taqman® prove to be more sensitive than other molecular techniques. Reasonable analytical specificity was obtained with ddPCR, qPCR TaqMan®, and conventional PCR. However, qPCR SYBR® Green technology presented a low specificity, making the results questionable in clinical samples. DdPCR detected/quantified A. baumanni in more clinical samples than other methods (38.64% of the total samples). This emerging ddPCR technology offers promising advantages such as detection by more patients and direct quantification of pathogens without calibration curves. [ABSTRACT FROM AUTHOR]

Aim: To clarify the usefulness of intraoperative lavage cytology in patients undergoing curative resection for pStage II‐III colorectal cancer in a prospective multicenter study. Methods: Patients preoperatively diagnosed with stage II‐III colorectal cancer between 2013 and 2017 from 20 hospitals were enrolled. Lavage cytology was performed twice during the surgery. The primary endpoint was the effect of lavage cytology on the 5‐year relapse‐free survival (RFS) in patients with pStage II‐III colorectal cancer. The secondary endpoint was the effect of lavage cytology on the 5‐year overall survival (OS) and peritoneal recurrence. Results: A total of 1378 patients were eligible for analysis. The number of patients with pStage II‐III colorectal cancer was 670 and 708, respectively. Fifty‐four patients (3.9%) had positive cytological results. In pStage II patients, the 5‐year RFS rates with positive and negative cytology were 61.1% and 81.6%, respectively (p = 0.023). The 5‐year OS rates were 67.1% and 91.7%, respectively (p = 0.0083). However, there was no difference in RFS or OS between pStage III patients with positive and negative cytology results. The peritoneal recurrence rates were 11.8% and 1.5% in pStage II patients with positive and negative cytology results, respectively (p = 0.032). These rates were 10.5% and 2.5% in patients with stage III disease, respectively (p = 0.022). Conclusion: Stage II colorectal cancer patients with negative cytology had better outcomes than those with positive cytology. Peritoneal lavage cytology is useful for predicting peritoneal recurrence after curative resection of stage II‐III colorectal cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Equine asthma is a common, non-infectious, chronic lung disease that affects up to 80% of the horse population. Strict phenotyping and identification of subclinically asthmatic horses can be challenging. The aim of this study was to describe equine asthma phenotypes (mild, moderate, and severe asthma) defined by BALF cytology and occurrence of clinical signs in a population of privately owned horses and to identify the variables and examination steps with best discriminative potential. The standardised examination protocol included clinical examinations, blood work, airway endoscopy with bronchoalveolar lavage fluid analysis, arterial blood gas analysis and radiography under clinical conditions performed by one veterinarian. Results Out of 26 horses, four were diagnosed with mild (subclinical), seven with moderate, and seven with severe asthma based on clinical examination and BALF cytology. Eight horses served as controls. Cough with history of coughing was the strongest variable in phenotype differentiation. Factor analysis revealed an increasing clinical variability with disease severity and an overlapping of clinical presentations between phenotypes. Elevated mast cell (4/4 horses) and neutrophil counts (3/4 horses) in bronchoalveolar lavage cytology differentiated mild asthmatic horses from healthy horses. Moderate and severe asthmatic horses were characterised by clinical signs and neutrophil counts. Conclusions The results indicate that medical history, clinical examination and bronchoalveolar lavage cytology are minimum indispensable steps to diagnose equine asthma and that phenotypes are clinically overlapping. A differentiation of three phenotypes without neutrophil and mast cell counts in bronchoalveolar lavage cytology is not sufficient for clinical diagnostics. A comparably exact diagnosis cannot be achieved by relying on alternative examinations used in this study. Screenings of inconspicuous horses with bronchoalveolar lavage can aid in diagnosing subclinically affected animals, however, group size was small, the procedure is invasive and clinical relevance of slightly elevated cells in bronchoalveolar lavage remains unclear. Clinical relevance could not be clarified in this study, since follow-up examinations or lung function testing were not performed.

Abstract Rationale Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. Objective Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. Methods We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). Results Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen’s Kappa = 0.47 ± 0.07; P

Antimicrobial activity of antibacterial agents (benzylpenicillin, methicillin, amoxicillin, cefazolin, ceftriaxone, cefquinome, cefepime, gentamicin, tylosin, lincomycin, enrofloxacin, marbofloxacin) and herbal medicines (extracts ofEleutherococcus,Echinacea purpureaandHypericum perforatum) was studied. The purpose of the research was to determine sensitivity to antibiotics and phytobiotics in microorganisms isolated from bronchoalveolar lavage fluid collected from calves with acute catarrhal bronchopneumonia. Calves with acute catarrhal bronchopneumonia (n= 37) aged 13 months were studied in the research. Bronchoalveolar lavage was collected into sterile test tubes from sick calves using silicone sterile catheter. Bacteriological studies were carried out in LLC Vettest, using generally accepted methods. Determining the sensitivity of isolated opportunistic microorganisms to antibacterial drugs showed that the vast majority of them have rather low efficiency. It was found that all 115 isolated microorganisms were sensitive only to three antibacterial drugs: fourth-generation cephalosporin antibiotics cefquinome and cephepime, and third-generation fluoroquinolone antibiotic marbofloxacin. Of the phytobiotics studied,Hypericum perforatumextract had the most pronounced antimicrobial properties against the main initiators of acute catarrhal bronchopneumonia in the calves. Moreover, it showeda more powerful antimicrobial effect against gram-positive bacteria. This makes it possible to use it widely in complex therapy in calves.

Abstract Background Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). Methods This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. Results Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (−), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (−) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. Conclusion Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

History of Present Illness: The patient is a 57-year-old woman who presented to the emergency department with increasing cough and shortness of breath over several days. She has a history of ulcerative colitis complicated by toxic megacolon with subsequent colectomy. Past Medical History, Family History and Social History • Ulcerative colitis with history of toxic megacolon (4 years prior), s/p total colectomy • History of recent respiratory failure thought secondary to ustekinumab (Stelara). The respiratory failure responded well to steroid therapy. • She has a history of latent Tb treated with rifampin • Anxiety Medications • Clonazepam 1.0 mg daily at bedtime • Gabapentin 300 mg TID • Pantoprazole 40 mg BID • Prednisone 5 mg daily Physical Examination • Mild-moderate respiratory distress • Afebrile. SpO2 87% on room air. Oxygen saturation 94% on 2 lpm supplemental oxygen. • Chest: crackles noted at left base • Cardiovascular: regular rhythm, no murmur • Extremities: scarring and erythema on both ankles consistent with resolving pyoderma …

The pathogenesis of acute lung injury is complex. Studies have demonstrated the role of neutrophil extracellular traps (NETs) in the process of lipopolysaccharide (LPS)‐induced acute lung injury (ALI). However, the underlying mechanism remains unclear. In this study, the regulation of Nrf2 in the formation of NETs, which was pathogenic in LPS‐induced ALI, was identified by analyzing the levels of Cit‐H3, lung function, lung tissue pathology, lung wet/dry ratio, the inflammatory cells, cytokines and proteins in the bronchoalveolar lavage fluid (BALF) and in addition, the activity of lung myeloperoxidase (MPO) was also measured. Results showed that the levels of Cit‐H3 measured by western blot in Nrf2‐knockout (KO) mice were higher compared with the WT mice after LPS stimulation. To further investigate the NETs formation was pathogenic during LPS‐induced ALI, the Nrf2‐KO mice were treated with DNase I. Results showed that DNase I improved lung function and lung tissue pathology and significantly reduced lung wet/dry ratio and proteins in the BALF. Besides, DNase I also attenuated the infiltration of inflammatory cells and the cytokines (TNF‐α, IL‐1β) production in the BALF and the activity of lung MPO. Therefore, these results together indicate that Nrf2 may intervene in the release of NETs during LPS‐induced ALI in mice. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to evaluate the clinical utility of Metagenomic Next-Generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) in diagnosis of Lower Respiratory Tract Infections (LRTIs). Methods: In this study, we retrospectively analyzed 186 hospitalized patients who were suspected with LRTIs and performed mNGS (DNA) test of BALF simultaneously at The Fifth Affiliated Hospital of Sun Yat-Sen University from March 2023 to August 2023. Suspected LRTI was based on LRTI related clinical manifestations or imaging examination. Among them, 155 patients had undergone conventional culture and mNGS (DNA) testing simultaneously. Finally, 138 cases (89.03%,138/155) were diagnosed as LRTI and 17 cases (10.97%,17/155) were diagnosed as non-LRTI. Both detecting rate and diagnostic efficacy of mNGS and conventional culture were compared. Results: The positive detection rates of pathogens between mNGS and conventional culture were significant different (81.29% VS 39.35%, P < 0.05). Compared with paired conventional culture result, the sensitivity of mNGS in diagnosis of LRTIs was more superior (88.41% VS 43.48%; P < 0.05), the specificity was opposite (76.47% VS 94.12%; P > 0.05). Furthermore, 77.54% and 35.51% of LRTI cases were being etiologically diagnosed by mNGS and culture respectively. Importantly, mNGS directly led to a change of treatment regimen in 58 (37.42%) cases, including antibiotic adjustment (29.68%) and ruling out active infection (7.74%). Moreover, treatment regimen remained unchanged in 97 (62.58%) cases, considering the current antibiotic therapy already covered the detected pathogens (36.13%) or empirical treatment was effective (11.61%). Conclusions: mNGS can identify a wide range of pathogens in LRTIs, with improved sensitivity and being more superior at diagnosing LRTIs etiologically. mNGS has the potential to enhance clinical outcomes by optimizing the treatment regimens. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the diagnostic value of IL-17 detection in bronchoalveolar lavage fluid (BALF) and plasma samples from nonneutropenic patients with invasive pulmonary aspergillosis. Methods: We retrospectively collected data on non-neutropenic patients who were suspected to have IPA admitted to the Third Affiliated Hospital of Soochow University between March 2020 to January 2023. IL-17 and GM were measured using enzyme-linked immunosorbent assays. Results: A total of 281 patients were enrolled in this study, of which 62 had proven or probable IPA and the remaining 219 patients were controls. The plasma and BALF IL-17 levels were significantly higher in the IPA group compared with the control group. The plasma GM, plasma IL17, BALF GM, and BALF IL17 assays had sensitivities of 56.5%, 72.6%, 68.7%, and 81.2%, respectively, and specificities of 87.7%, 69.4%, 91.9%, and 72.6%, respectively. The sensitivity of IL17 in plasma and BALF was higher than that of GM. Plasma GM in combination with IL-17 increases the sensitivity but does not decrease the diagnostic specificity of GM testing. The diagnostic sensitivity and specificity of BALF GM combined with IL-17 for IPA in non-neutropenic patients were greater than 80% and there was a significant increase in sensitivity compared with BALF GM. Conclusions: Plasma and BALF IL-17 levels were significantly higher in nonneutropenic patients with IPA. The sensitivity of plasma and BLAF IL-17 for diagnosing IPA in non-neutropenic patients was superior to that of GM. Combined detection of lavage fluid GM and IL17 significantly improves the diagnosis of IPA in non-neutropenic patients. The combined detection of GM and IL-17 in plasma also contributes to the diagnosis of IPA in patients who cannot tolerate invasive procedures. [ABSTRACT FROM AUTHOR]

Background: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). Methods: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. Results: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (−), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (−) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. Conclusion: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO. [ABSTRACT FROM AUTHOR]

Plastic bronchitis is a relatively uncommon illness that has been reported in all age groups. This case report describes a specific manifestation of plastic bronchitis in two pediatric brothers influenced by both smoke inhalation and influenza A virus infection. The therapeutic approach mainly involved symptomatic supportive care, antiviral therapy, repeated bronchoscopic alveolar lavage, and bronchial cast removal. Eventually, both patients went into remission. Bronchoscopy proved to be helpful in diagnosing and treating these cases. [ABSTRACT FROM AUTHOR]

At present, metagenomic next-generation sequencing (mNGS) based on Illumina platform has been widely reported for pathogen detection. There are few studies on the diagnosis of major pathogens and treatment regulation using mNGS based on Illumina versus Nanopore. We aim to evaluate the clinical value of metagenomic next-generation sequencing (mNGS) by Illumina and Nanopore for the detection of pathogens in bronchoalveolar lavage fluid (BALF) in suspected community-acquired pneumonia (CAP) patients. BALF samples collected from 66 suspected CAP patients within 48 hours of hospitalization were divided into two parts, one for conventional culture and the other for mNGS by two platforms (Illumina and Nanopore). The clinical value based on infection diagnosis, diagnostic performance for main pathogens and treatment guidance were assessed. More types of species were detected by Nanopore than Illumina, especially in viruses, fungus and mycobacterium. Illumina and Nanopore showed similar detectability in bacterium except for mycobacterium tuberculosis complex/nontuberculosis mycobacteria. Pathogenic infection was established or excluded in 53 of 66 patients. There was little difference in the coincidence rate between Illumina and Nanopore with the clinical diagnosis, but both were superior to the culture (57.81%, 59.38%, 25%, respectively). Compared with Illumina, the diagnostic area under the curve of Nanopore was higher in fungi, but lower in bacteria and Chlamydia psittaci. There was no statistically significant difference between Illumina and Nanopore in guiding drug treatment (56.1% vs. 50%, p=0.43), but both were superior to the culture (56.1% vs. 28.8%, p=0.01; 50% vs. 28.8%, p=0.01). Single inflammatory indicators could not be used to determine whether the patients with culture-negative BALF were established or excluded from infection. The species detected at 1 h and 4 h by Nanopore were consistent to some extent, and its turn-around time (TAT) was significantly shorter than Illumina (p<0.01). Illumina and Nanopore both have its own advantages in pathogenic diagnosis and play similar roles in infection diagnosis and guiding clinical treatment. Nanopore has a relatively short TAT, which may be promising in rapid etiological diagnosis of acute and critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Sepsis is associated with a highest mortality rate in the ICU. Present study tests the efficacy of combined therapy with vitamin C, hydrocortisone and thiamine (combined therapy) in the ovine model of sepsis induced by Pseudomonas aeruginosa. In this study, sepsis was induced in sheep by instillation of Pseudomonas aeruginosa (1 × 1011 CFU) into the lungs via bronchoscope, under anesthesia. Nine hours after injury, intravenous infusion of vitamin C (0.75 g every 6 h), hydrocortisone (25 mg every 6 h), and thiamine (100 mg every 12 h) or saline was given to the treatment and control groups. Cardiopulmonary variables were recorded. Results: The survival rate was 16.7% in control and 33.3% in treatment groups. In the control group, mean arterial pressure dropped from 93.6 ± 8.6 to 75.5 ± 9.7 mmHg by 9 h, which was not affected by the combined therapy. Pulmonary dysfunction was not attenuated by the combined therapy either. The combined therapy had no effect on increased extravascular lung water content and fluid effusion into thoracic cavity. The bacterial number in the bronchoalveolar lavage fluid was significantly increased in the treatment group than the control group. The blood bacterial number remained comparable between groups. Conclusions: Combined vitamin C, hydrocortisone, and thiamine did not attenuate severity of ovine sepsis. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic accuracy of matrix-assisted laser desorption ionization time-of-flight mass spectrometry based on nucleotide (nucleotide MALDI-TOF MS) on bronchoalveolar lavage fluid (BALF) from suspected pulmonary tuberculosis (PTB) patients. A retrospective study was conducted on suspected PTB patients (total of 960) admitted to Chongqing Public Health Medical Center between May 2021 and January 2022. The sensitivity, specificity, positive predictive value, negative predictive value (NPV) and area under the curve values of nucleotide MALDI-TOF MS as well as smear microscopy, Mycobacterium Growth Indicator Tube 960 culture (MGIT culture), and Xpert MTB/RIF were calculated and compared. Total of 343 presumed PTB cases were enrolled. Overall, using the clinical diagnosis as reference, the sensitivity and NPV of nucleotide MALDI-TOF MS was 71.5% and 43.1%, respectively, significantly higher than smear microscopy (22.6%, 23.2%), MGIT culture (40.6%, 18.9%), Xpert MTB/RIF (40.8%, 27.9%). Furthermore, nucleotide MALDI-TOF MS also outperformed over Xpert MTB/RIF and MGIT culture on smear-negative BALFs. Approximately 50% and 30% of patients benefited from nucleotide MALDI-TOF MS compared with smear and MGIT culture or Xpert MTB/RIF, respectively. This study demonstrated that the analysis of BALF with nucleotide MALDI-TOF MS provided an accurate and promising tool for the early diagnosis of PTB. [ABSTRACT FROM AUTHOR]

Purpose: Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy. Patients and Methods: We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the Fleischner Society classification. Results: From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4– 51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam cell-like macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity. Conclusion: Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN. [ABSTRACT FROM AUTHOR]

Introduction: Talaromyces marneffei (T. marneffei), a kind of endemic opportunistic pathogen, was previously thought to occur in HIV-positive individuals and non-HIV hosts with impaired immune function. However, the infection of T. marneffei in patient with normal immune function was rarely reported. Case Presentation: We report a case of severe pneumonia caused by T. marneffei in an immunocompetent and HIV-negative patient, which was rapidly confirmed by metagenomics next-generation sequencing (mNGS) and treated successfully. The patient was a previously healthy 63-year-old male, who was admitted to hospital with fever for 11 days, cough and sputum for 1 week, and chest distress for 4 days. The infection of T. marneffei was quickly determined by alveolar lavage under bedside bronchoscope and mNGS test. Results: Patient’s condition improved rapidly after voriconazole treatment, and he was evaluated as a HIV-negative case of T. marneffei infection with normal immune function. This is a sporadic case of T. marneffei in non-endemic areas, and mNGS played a very important role in the treatment of the disease. The patient’s immune function was relatively normal which was rare in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxidative stress generates harmful oxygen radicals that activate biomolecules in the lungs of asthmatics. The effects of these mediators are not directly targeted by first-line therapeutics. Using a clinically relevant murine model of allergic asthma, this study reveals that immuno-pharmacological neutralization of oxidized phospholipids in the lung can ameliorate inflammation and asthma symptoms. This suggests that specifically targeting mediators generated by oxidative stress could offer new therapeutic options for asthma to complement conventional therapies. Oxidative stress is associated with asthma pathobiology. We reported that oxidized phosphatidylcholines (OxPCs) are mediators of oxidative stress and accumulate in the lung in response to allergen challenge. The current study begins to unravel mechanisms for OxPC accumulation in the lung, providing the first insights about how OxPCs underpin allergic airway pathophysiology, and pre-clinical testing of selective neutralization of OxPCs in a murine model of allergic asthma. We hypothesized that intranasal delivery of E06, a natural IgM antibody that neutralizes the biological activity of OxPCs, can ameliorate allergen-induced airway inflammation and airway hyperresponsiveness. Adult BALB/c mice were intranasally (i.n.) challenged with house dust mite (HDM) (25 μg/mouse, 2 weeks). Some animals also received E06 monoclonal antibody (mAb) (10 µg) i.n. 1 hr before each HDM challenge. HDM challenge reduced mRNA for anti-oxidant genes (SOD1, SOD2, HO-1, and NFE2L2) in the lung by several orders of magnitude (p < 0.05). Concomitantly, total immune cell number in bronchoalveolar lavage fluid (BALF) increased significantly (p < 0.001). E06 mAb treatment prevented allergen-induced BALF immune cell number by 43% (p < 0.01). This included a significant blockade of eosinophils (by 48%, p < 0.001), neutrophils (by 80%, p < 0.001), macrophages (by 80%, p < 0.05), and CD4 (by 30%, p < 0.05) and CD8 (by 42%, p < 0.01) lymphocytes. E06 effects correlated with a significant reduction in TNF (by 64%, p < 0.001) and IL-1β (by 75%, p < 0.05) and a trend to diminish accumulation of other cytokines (e.g., IL-4, -10, and -33, and IFN-γ). E06 mAb treatment also inhibited HDM exposure-induced increases in total respiratory resistance and small airway resistance by 24% and 26%, respectively. In conclusion, prophylactic treatment with an OxPC-neutralizing antibody significantly limits allergen-induced airway inflammation and airway hyperresponsiveness, suggesting that OxPCs are important mediators of oxidative stress-associated allergic lung pathophysiology. [ABSTRACT FROM AUTHOR]