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Pulmonary alveolar proteinosis (PAP) is a rare disease which involves the accumulation of insoluble lipoproteinaceous material in the alveoli leading to impaired gas exchange and even respiratory failure. Autoimmune PAP is the most common type and is characterized by the presence of anti-granulocyte-monocyte colony stimulating factor (anti GM-CSF) antibody. Whole lung lavage has been traditionally used as first-line management of PAP but there is a lack of clarity especially in the treatment of relapsing cases of PAP. Rituximab is an anti Cluster of Differentiate 20 (CD 20) monoclonal antibody that has been tried as salvage therapy for relapsing cases of PAP. We present a case of 35 years old female patient who was diagnosed as a case of relapsing PAP who was managed initially with neoadjuvant rituximab. This is a retrospective observational report showing novel use of neoadjuvant rituximab in a difficult case of relapsing PAP. [ABSTRACT FROM AUTHOR]

The article focuses on normal blood eosinophil counts in humans, exploring their significance in respiratory diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD), alongside the impact of smoking on eosinophil levels. It discusses the relationship between blood eosinophil counts and airway diseases, the emerging role of blood eosinophils in clinical practice, and the influence of smoking on eosinophil counts.

Abstract Background Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease (ILD) associated with smoking, whose definitive diagnosis requires the exclusion of other forms of ILD and a compatible surgical lung biopsy. Bronchoalveolar lavage (BAL) is commonly proposed for the diagnosis of ILD, including PLCH, but the diagnostic value of this technique is limited. Here, we have analyzed the levels of a panel of cytokines and chemokines in BAL from PLCH patients, in order to identify a distinct immune profile to discriminate PLCH from other smoking related-ILD (SR-ILD), and comparing the results with idiopathic pulmonary fibrosis (IPF) as another disease in which smoking is considered a risk factor. Methods BAL samples were collected from thirty-six patients with different ILD, including seven patients with PLCH, sixteen with SR-ILD and thirteen with IPF. Inflammatory profiles were analyzed using the Human Cytokine Membrane Antibody Array. Principal component analysis (PCA) was performed to reduce dimensionality and protein–protein interaction (PPI) network analysis using STRING 11.5 database were conducted. Finally, Random forest (RF) method was used to build a prediction model. Results We have found significant differences (p

Hospitalized patients with a high suspicion of pulmonary tuberculosis (HS-PTB) are isolated until a definite diagnosis can be determined. If doubt remains after negative sputum samples, bronchoscopy with bronchoalveolar lavage (BAL) is often sought. Still, evidence of the added value of BAL in this patient population is scarce. To address this issue, we included consecutive HS-PTB patients with negative sputum samples who underwent BAL between 2017 and 2018. Chest X-rays (CXR) and CT scans were evaluated by a chest radiologist blind to the final diagnosis. Independent predictors for PTB were assessed by multivariate regression, using all positive PTB patients between 2017 and 2019 (by sputum or BAL) as a control group (n = 41). Overall, 42 HS-PTB patients were included (mean age 51 ± 9, 36% female). BAL was a viable diagnostic for PTB in three (7%) cases and for other clinically relevant pathogens in six (14%). Independent predictors for PTB were ≥2 sub-acute symptoms (adjusted OR 3.18, 95% CI 1.04–9.8), CXR upper-lobe consolidation (AOR 8.70, 95% CI 2.5–29), and centrilobular nodules in chest CT (AOR 3.96, 95% CI 1.20–13.0, p = 0.02). In conclusion, bronchoscopy with BAL in hospitalized patients with HS-PTB had a 7% added diagnostic value after negative sputum samples. Our findings highlight specific predictors for PTB diagnosis that could be used in future controlled studies to personalize the diagnostic evaluation.

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in significant morbidity and mortality. As COPD progresses, patients develop more frequent and severe exacerbations. Several scores have been tested in AECOPD, but none of them is yet widely accepted or recommended to be used in practice due to a lack of data and evidence. Aim and Objectives: (1) To compare neutrophil-to-lymphocyte ratio (NLR) between stable COPD patients and patients with acute exacerbation of COPD and (2) correlation of NLR with severity of acute exacerbation of disease as per clinical, spirometric, and arterial blood gas criteria. Materials and Methods: A total of 100 patients, 50 with acute exacerbation of COPD and 50 stable patients attending the casualty and Outpatient Department of Government Medical College and Associated Group of Hospitals, Kota, were included in the study. Results: The level of NLR was raised in patients with acute exacerbation of COPD (35.28 ± 34.66) as compared to stable COPD patients (2.23 ± 0.63) (P = 0.0001). Levels of this inflammatory marker (NLR) were also positively correlated with the duration of hospitalization (8.14 ± 5.99 days) (P = 0.0010). High NLR was found to be significantly associated with the need for mechanical ventilation (nine patients) and mortality (nine patients), and significantly associated with low forced expiratory volume 1/forced-vital capacity (0.49 ± 0.07) in cases with acute exacerbation of COPD. Conclusion: NLR can be used as a marker of acute exacerbation of COPD, as it was found to be significantly elevated in acute exacerbation patients and found within normal limits in stable patients.

Abstract Background Feline lower airway disease (FLAD) is frequently associated with radiographic abnormalities. Objectives To evaluate whether radiographic changes in cats with naturally occurring FLAD improve with treatment and if radiographic changes correlate with clinical signs. Animals Twenty‐four client‐owned cats newly diagnosed with FLAD, based on medical history, typical clinical signs, radiographic findings, and examination of bronchoalveolar lavage fluid, were included in the prospective study. Methods At 2 examination time points (days 0 and 60), an owner questionnaire, clinical examination, and thoracic radiography were carried out. Information from the questionnaire and clinical examination were evaluated on the basis of a 12‐point clinical score. Radiographs were assessed using a 10‐point radiographic score. Individual treatment was given to all cats over the study period, based on severity of the disease and compliance of the cat. Clinical and radiographic scores were compared statistically for both examination time points and evaluated for correlation. Results All cats showed radiographic abnormalities at initial presentation. In addition to significant improvement in clinical variables, the total radiographic score improved significantly (P = .01) during the study period, with significant improvement in the severity of bronchial (P = .01) and interstitial lung pattern (P = .04). Improvement of the clinical and radiographic score was not correlated. Conclusion and Clinical Importance In addition to clinical signs, repeated radiographic examination can be used as a diagnostic tool to evaluate treatment response in cats with FLAD.

Abstract Background Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis. Methods The dynamics of lung uptake of 18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF). Results Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPα levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels. Conclusions Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAPα in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease.

Abstract Background Immunosuppressed bone marrow transplant patients with pulmonary infiltrates routinely undergo bronchoscopy with bronchoalveolar lavage (BAL) to investigate potential etiologies. Cytokine release syndrome after BAL is unreported in the literature in general and in this patient population. Case presentation We report on an allogeneic bone marrow transplant patient with non-infectious organizing pneumonia of the lungs who developed delayed and rapidly progressive shock and hypoxia post-procedure over the course of 12 h resulting in intensive care unit admission for supportive care. BAL was characterized by a marked lymphocytic, cytotoxic T cell infiltrate on pathology and flow cytometry without clear evidence of infection. The patient’s clinical status improved quickly only after the initiation of high dose intravenous steroids and returned to baseline as an outpatient. Conclusion The patient’s clinical data and course suggest a cytotoxic T cell response from the lung and BAL as the etiology. With an increasing number of cellular therapies for cancer entering the clinic, the potential for unusual but morbid complications from routine bronchoscopy should be considered.

Abstract Background Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The COVID-19 pandemic required rapid action to curb transmission and mitigate its lethiferous impact. Non-pharmaceutical interventions (NPIs) were globally adopted. We hypothesized that these measures reduced the transmission and acquisition of P. jirovecii in both hospital and community settings. Methods We conducted a retrospective observational study on 2950 respiratory specimens from patients with suspected pulmonary infection, analyzed at the Laboratory of Parasitology Unit of the Policlinico Tor Vergata of Rome, Italy, from January 2014 to December 2022. Results We show a significant reduction in the frequency of PCP in the COVID-19 pandemic era compared to the previous period. Among the four sequence types of P. jirovecii identified, genotype 1 was the most prevalent (37%). We observed a non-significant trend of decreasing cases with genotype 1 and increasing cases with genotype 3 over the study period. Conclusions The nationwide implementation of NPIs against COVID-19 may have changed the microbiological landscape of exposure, thereby decreasing the exposure to P. jirovecii and consequently reducing the incidence of PCP.

Abstract Background Diagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD). Methods Prospective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose. Results Of the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%. Conclusions Using a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA.

Single-cell RNA sequencing (scRNA-seq) is an important tool for understanding disease pathophysiology, including airway diseases. Currently, the majority of scRNA-seq studies in airway diseases have used invasive methods (airway biopsy, surgical resection), which carry inherent risks and thus present a major limitation to scRNA-seq investigation of airway pathobiology. Bronchial brushing, where the airway mucosa is sampled using a cytological brush, is a viable, less invasive method of obtaining airway cells for scRNA-seq. Here we describe the development of a rapid and minimal handling protocol for preparing single-cell suspensions from bronchial brush specimens for scRNA-seq. Our optimized protocol maximizes cell recovery and cell quality and facilitates large-scale profiling of the airway transcriptome at single-cell resolution.

BackgroundLung transplant recipients undergo bronchoalveolar lavage (BAL) to detect antecedents of chronic lung allograft dysfunction (CLAD), but routine assessment of BAL cytology is controversial. We hypothesized that inflammation on BAL cytology would predict CLAD-free survival.MethodsIn a single-center retrospective cohort, associations between cytology results and clinical characteristics were compared using generalized-estimating equation-adjusted regression. The association between BAL inflammation and CLAD or death risk was assessed using time-dependent Cox models.ResultsIn 3365 cytology reports from 451 subjects, inflammation was the most common finding (6.2%, 210 cases), followed by fungal forms (5.3%, 178 cases, including 24 cases of suspected Aspergillus). Inflammation on BAL cytology was more common in procedures for symptoms (8.5%) versus surveillance (3.2%, p

Background: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease (ILD) associated with smoking, whose definitive diagnosis requires the exclusion of other forms of ILD and a compatible surgical lung biopsy. Bronchoalveolar lavage (BAL) is commonly proposed for the diagnosis of ILD, including PLCH, but the diagnostic value of this technique is limited. Here, we have analyzed the levels of a panel of cytokines and chemokines in BAL from PLCH patients, in order to identify a distinct immune profile to discriminate PLCH from other smoking related-ILD (SR-ILD), and comparing the results with idiopathic pulmonary fibrosis (IPF) as another disease in which smoking is considered a risk factor. Methods: BAL samples were collected from thirty-six patients with different ILD, including seven patients with PLCH, sixteen with SR-ILD and thirteen with IPF. Inflammatory profiles were analyzed using the Human Cytokine Membrane Antibody Array. Principal component analysis (PCA) was performed to reduce dimensionality and protein–protein interaction (PPI) network analysis using STRING 11.5 database were conducted. Finally, Random forest (RF) method was used to build a prediction model. Results: We have found significant differences (p < 0.05) on thirty-two cytokines/chemokines when comparing BAL from PLCH patients with at least one of the other ILD. Four main groups of similarly regulated cytokines were established, identifying distinct sets of markers for each cluster. Exploratory analysis using PCA (principal component analysis) showed clustering and separation of patients, with the two first components capturing 69.69% of the total variance. Levels of TARC/CCL17, leptin, oncostatin M (OSM) and IP-10/CXCL10 were associated with lung function parameters, showing positive correlation with FVC. Finally, random forest (RF) algorithm demonstrates that PLCH patients can be differentiated from the other ILDs based solely on inflammatory profile (accuracy 96.25%). Conclusions: Our results show that patients with PLCH exhibit a distinct BAL immune profile to SR-ILD and IPF. PCA analysis and RF model identify a specific immune profile useful for discriminating PLCH. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acupoint catgut embedding can alleviate airway inflammation in asthma, which is related to regulating the imbalance of Th1/Th2 in the p38 MAPK pathway. Whether the above process is affected by the functional state of type II alveolar epithelial cells at the same time remains to be further studied. OBJECTIVE: To observe the effect of acupoint catgut embedding on p38 MAPK pathway, interleukin-4, γ-interferon and type II alveolar epithelial cells in lung tissue of asthma rats. METHODS: Forty male Wistar rats were randomly divided into blank control group, asthma model group, dexamethasone group and acupoint catgut embedding group (n=10 per group). Asthma models of asthma were prepared by intraperitoneal injection of ovalbumin and aluminum hydroxide suspension on days 1 and 8 and aerosol inhalation of ovalbumin solution from day 15 was given to induce symptoms of airway inflammatory responses, once a day for 2 weeks, in the latter three groups. Meanwhile, the dexamethasone group began to receive intraperitoneal injection of dexamethasone on day 15, once a day for 2 weeks; and the acupoint catgut embedding group received embedding treatment at Feishu, Dingchuan, and Danzhong acupoints on day 15. At the end of aerosol inhalation, the relative content of eosinophils in the alveolar lavage fluid was counted by Richter-Kimsa staining, the ultrastructural changes of type II alveolar epithelial cells in lung tissue were observed by transmission electron microscopy, the positive expression of interleukin-4 and γ-interferon in lung tissue was detected by immunohistochemistry, and the protein and gene expression of p-p38 MAPK, interleukin-4 and γ-interferon in lung tissue were detected by western blot and PCR respectively. RESULTS AND CONCLUSION: Compared with the asthma model group, the relative content of eosinophils in the bronchoalveolar lavage fluid was significantly reduced in the dexamethasone group and acupoint catgut embedding group (P < 0.01), while compared with the dexamethasone group, the relative content of eosinophils in the bronchoalveolar lavage fluid was significantly higher in the acupoint catgut embedding group (P < 0.05). Under the transmission electron microscopy, damage to lamellar vesicles and mitochondria in type II alveolar epithelial cells was alleviated in the dexamethasone and acupoint catgut embedding groups compared with the asthma model group. Immunohistochemical detection showed that compared with the asthma model group, the expression of interleukin-4 in lung tissue was decreased (P < 0.01) and that of γ-interferon was increased (P < 0.01) in the dexamethasone and acupoint catgut embedding group; compared with the dexamethasone group, the expression of interleukin-4 in lung tissue was increased (P < 0.01) and that of γ-interferon was decreased (P < 0.01) in the acupoint catgut embedding group. Compared with the asthma model group, the protein and mRNA expressions of p-p38 MAPK and interleukin-4 in the lung tissue of the dexamethasone and acupoint catgut embedding groups were decreased (P < 0.01, P < 0.05), while the protein and mRNA expressions of γ-interferon were increased (P < 0.01). To conclude, acupoint catgut embedding may upregulate γ-Interferon and downregulate interleukin-4 by inhibiting the p38 MAPK signal pathway, thereby reducing stress damage in type II alveolar epithelial cells and alleviating the airway inflammatory response in asthma. [ABSTRACT FROM AUTHOR]

Background and Purpose: Acute lung injury (ALI) is a serious, life-threatening inflammation of the lungs that still lacks effective treatment. We previously showed that serine protease inhibitor B1 (SerpinB1) protects against ALI induced by orthotopic autologous liver transplantation. However, the role of SerpinB1 in lipopolysaccharide (LPS)-induced ALI and its regulatory mechanisms are not known. Experimental Approach: Wild-type (WT) and SerpinB1 knockout (KO) mice were treated with intratracheal LPS stimulation to induce ALI. Some of the WT and KO mice were injected i.p. with melatonin, a rhythm-related protein Rev-erbα agonist. The circadian rhythm in WT mice was disrupted by exposing mice to 24 h of continuous dark or light conditions after intratracheal LPS. Neutrophils were isolated from alveolar lavage fluid of WT and KO mice, and from human peripheral blood. Neutrophils were treated with LPS and melatonin. Key Results: Disruption of circadian rhythm by either 24-h dark or light conditions exacerbated LPS-induced ALI and decreased expression of Rev-erbα and SerpinB1 protein in lung, whereas melatonin treatment increased SerpinB1 expression and attenuated LPS-induced ALI in WT mice, but not in KO mice. In isolated neutrophils, Rev-erbα was co-localized with SerpinB1 and bound to its promoter to trigger SerpinB1 transcription. Furthermore, LPS stimulation increased formation of neutrophil extracellular traps, which was reversed by melatonin treatment in neutrophils from WT mice, but not from KO mice. Conclusion and Implications: In mice, SerpinB1 is rhythmically regulated by Reverbα, and its down-regulation exacerbates LPS-induced ALI by inducing formation of neutrophil extracellular traps. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CP) is an antineoplastic drug commonly used worldwide. Despite its spread, it causes fatal organ toxicity. Lung toxicity is a serious side effect of CP. Actually, in the past three years the world has been facing an un-predicted crisis following COVID-19 pandemic and the associated high-mortality rates attributed to respiratory distress. Accordingly; this study aimed to probe the potential prophylactic role of levocetrizine against CP-induced lung injury. Animals were allocated into three sets; control; CP and CP/Levo. CP was intraperitoneally injected in rats 150 mg/kg once on day 7. Levocetrizine was given orally for 14 days starting 7 days before CP injection. On the last day, all rats were sacrificed and lung tissues were kept for analysis. CP significantly elevated lung/body weight index, inflammatory cell counts, LDH, total protein, TNF-α, IL-1β, TGF-β and histamine levels in bronchoalveolar lavage (BAL). Moreover, it markedly increased expression of MMP-9 and contents of MDA, hydroxyproline, collagen and NOx besides decreasing GSH level and SOD activity in lung tissues. These biochemical results were further confirmed by histopathological examination. In contrast, treatment with levocetrizine significantly attenuated CP-induced pathological alterations. These findings propose that levocetrizine can attenuate CP-induced lung injury via exerting antioxidant, anti-inflammatory and anti-fibrotic effects. [ABSTRACT FROM AUTHOR]

Background: Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). Methods: Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. Results: Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. Conclusion: Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive. [ABSTRACT FROM AUTHOR]

Background: Ventilator-induced lung injury (VILI) is a clinical complication of mechanical ventilation observed in patients with acute respiratory distress syndrome. It is characterized by inflammation mediated by inflammatory cells and their secreted mediators. Methods: To investigate the mechanisms underlying VILI, a C57BL/6J mouse model was induced using high tidal volume (HTV) mechanical ventilation. Mice were pretreated with Clodronate liposomes to deplete alveolar macrophages or administered normal bone marrow-derived macrophages or Group V phospholipase A2 (gVPLA2) intratracheally to inhibit bone marrow-derived macrophages. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected to assess lung injury and measure Ca2 + concentration, gVPLA2, downstream phosphorylated cytoplasmic phospholipase A2 (p-cPLA2), prostaglandin E2 (PGE2), protein expression related to mitochondrial dynamics and mitochondrial damage. Cellular experiments were performed to complement the animal studies. Results: Depletion of alveolar macrophages attenuated HTV-induced lung injury and reduced gVPLA2 levels in alveolar lavage fluid. Similarly, inhibition of alveolar macrophage-derived gVPLA2 had a similar effect. Activation of the cPLA2/PGE2/Ca2 + pathway in alveolar epithelial cells by gVPLA2 derived from alveolar macrophages led to disturbances in mitochondrial dynamics and mitochondrial dysfunction. The findings from cellular experiments were consistent with those of animal experiments. Conclusions: HTV mechanical ventilation induces the secretion of gVPLA2 by alveolar macrophages, which activates the cPLA2/PGE2/Ca2 + pathway, resulting in mitochondrial dysfunction. These findings provide insights into the pathogenesis of VILI and may contribute to the development of therapeutic strategies for preventing or treating VILI. [ABSTRACT FROM AUTHOR]

The β-tubulin (benA) gene is a promising target for the identification of Aspergillus species. Assessment of the clinical implementation and performance of benA gene-based Aspergillus polymerase chain reaction (PCR) remains warranted. In this study, we assessed the analytical performance of the BenA probe PCR in comparison with the Aspergenius kit. We prospectively collected bronchoalveolar lavage (BAL) fluid via diagnostic bronchoscopy from adult patients with hematologic diseases. BenA gene-based multiplex real-time PCR and sequential melting temperature analysis were performed to detect the azole resistance of Aspergillus fumigatus. In total, 76 BAL fluids in 75 patients suspicious of invasive pulmonary aspergillosis (IPA) were collected. Before the application of PCR, the prevalence of proven and probable IPA was 32.9%. However, after implementing the benA gene-based PCR, 15.8% (12 out of 76) of potential IPA cases were reclassified as probable IPA. The analytical performance of the BenA probe PCR in BAL samples was comparable to that of the Aspergenius kit. The diagnostic performance was as follows: sensitivity, 52.0%; specificity, 64.7%; positive predictive value, 41.9%; negative predictive value, 73.3%; positive likelihood ratio, 1.473; and negative likelihood ratio, 0.741. Moreover, benA gene-based Aspergillus PCR discriminated all major sections of Aspergillus, including cryptic species such as Aspergillus tubingensis. Sequential melting temperature analysis successfully detected 2 isolates (15.4%) of A. fumigatus carrying resistant mutations. BenA gene-based Aspergillus PCR with melting temperature analysis enhances diagnostic accuracy and detects not only cryptic species but also resistant mutations of A. fumigatus. It shows promise for clinical applications in the diagnosis of IPA. [ABSTRACT FROM AUTHOR]

The expression of the programmed cell death protein 1 (PD-1) has been shown to be markedly increased in tumor-infiltrating lymphocytes. However, the proportion of PD-1 + T cells in the bronchoalveolar lavage (BAL) of lung cancer patients has not been sufficiently evaluated so far. In this prospective study, the proportion of PD-1 + CD4 + as well as PD-1 + CD8 + T cells in BAL samples, isolated from patients with lung cancer, asthma or interstitial lung disease (ILD), were determined via flow cytometry and compared for differences. Bronchoalveolar lavage was performed in 34 patients (14 patients with lung cancer, 10 patients with asthma, 10 patients with ILD). The highest median proportion of PD-1 + CD4 + or PD-1 + CD8 + T cells were found in patients with ILD (83.1% [IQR 72.1; 87.5] and 73.8% [IQR 60.3; 86.3]) followed by patients with lung cancer (66.4% [IQR 59; 69] and 77.1% [IQR 35.8; 82.3]) and patients with asthma (61.3% [IQR 57.4; 70.5] and 57.3% [IQR 46; 65]). Thereby, the difference in the proportion of PD-1 + CD3 + CD4 + BAL cells between ILD patients and asthmatics was significantly different (p = 0.04). The proportion of PD-1 + CD4 + and PD-1 + CD8 + T cells in the BAL of patients with lung cancer did not differ significantly to patients with benign lung diseases. The highest proportion was observed in ILD patients suggesting further research to evaluate the role of the PD-1/PD-L1 pathway in ILD patients. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii (A. baumannii) has become a global pathogen relevant to healthcare. Carbapenems are among the last resort classes of antibiotics having the greatest efficacy against severe infections caused by bacteria that are resistant to many other antibiotics. This research was done in order to detecte the frequency of carbapenememase genes in A. baumannii isolated from Surgical Wards and Intensive Care Units (ICUs) in Minia, Egypt by phenotypic and genotypic methods. Methods: 310 patients who were undergoing surgery and receiving care in ICUs participated in the current study between August 2017 and October 2020. The isolates were obtained from a variety of clinical samples, including sputum, bronchial lavage, Pus and wound fluid. All clinical samples have been collected under complete aseptic conditions. A. baumannii isolates were identified by standard microbiological tests. The resistance patterns of the obtained isolates were detected by the disc diffusion method. Production of carbapenemresistant genes was determined by phenotypic tests the Modified Hodge Test (MHT) and confirmed by the modified carbapenem inactivation method (mCIM). Various carbapenem-resistant genes were detected by PCR. Results:Out of 310 samples, Twenty-Five 25 (8%) isolates of A. baumannii were obtained. Antibiotic and sensitivity tests detect that 16(64%) and 12(48%) of A.baumannii isolates were resistant to meropenem and imipenem respectively. Out of the Carbapenem-resistant A. baumannii (CRAB): 9(56%) were (MHT) positive, and 13 (81%) were (mCIM) positive. Regarding resistance genes, blaOXA-23like and blaOXA-51like were detected in 94% and 100% of CRAB isolates respectively, while blaOXA-24like, blaoxa-48like, blaoxa-58like and blaNDM were not detected in CRAB isolates. [ABSTRACT FROM AUTHOR]

Background and Objective: The importance of extracellular traps (ETs) in chronic respiratory conditions is increasingly recognized but their role in paediatric bronchiectasis is poorly understood. The specialized techniques currently required to study ETs preclude routine clinical use. A simple and cost‐effective ETs detection method is needed to support diagnostic applications. We aimed to determine whether ETs could be detected using light microscopy‐based assessment of Romanowsky‐stained bronchoalveolar lavage (BAL) slides from children with bronchiectasis, and whether the ETs cellular origin could be determined. Methods: Archived Romanowsky‐stained BAL slides from a cross‐sectional study of children with bronchiectasis were examined for ETs using light microscopy. The cellular origin of individual ETs was determined based on morphology and physical contact with surrounding cell(s). Results: ETs were observed in 78.7% (70/89) of BAL slides with neutrophil (NETs), macrophage (METs), eosinophil (EETs) and lymphocyte (LETs) ETs observed in 32.6%, 51.7%, 4.5% and 9%, respectively. ETs of indeterminate cellular origin were present in 59.6% of slides. Identifiable and indeterminate ETs were co‐detected in 43.8% of slides. Conclusion: BAL from children with bronchiectasis commonly contains multiple ET types that are detectable using Romanowsky‐stained slides. While specialist techniques remain necessary to determining the cellular origin of all ETs, screening of Romanowsky‐stained slides presents a cost‐effective method that is well‐suited to diagnostic settings. Our findings support further research to determine whether ETs can be used to define respiratory endotypes and to understand whether ETs‐specific therapies may be required to resolve airway inflammation among children with bronchiectasis. [ABSTRACT FROM AUTHOR]

The article focuses on the case of a previously healthy 6-month-old infant who presented with severe respiratory distress and was ultimately diagnosed with Pneumocystis jirovecii pneumonia (PJP), a rare opportunistic infection. It discusses the diagnostic challenges, genetic testing, and treatment options for the patient, highlighting the importance of considering immunodeficiencies in such cases.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of large amounts of phospholipid protein-like surfactant material in the alveolar spaces, leading to severe hypoxemia and respiratory failure. The disease has an insidious onset and is difficult to diagnose in the early stages. Its clinical manifestations primarily include progressive dyspnea and coughing. Currently, whole lung lavage (WLL) is the preferred and effective treatment for PAP, as it improves alveolar ventilation function. Granulocyte colony-stimulating factor is used clinically in the treatment of a variety of disease. Nebulized granulocyte-macrophage colony-stimulating factor (GM-CSF) has a certain therapeutic effect on PAP. Here, we report a case of PAP treated with WLL combined with nebulized GM-CSF, which achieved good therapeutic effects during a 4-year follow-up period, to enhance understanding of the disease. [ABSTRACT FROM AUTHOR]

The melanoma antigen gene (MAGE) belongs to the group of cancer-testis antigens that are exclusively expressed in germ cells but may be re-expressed in cancer cells. The highly expressed MAGE-A subfamily in lung cancer may potentially be a diagnostic and prognostic biomarker. This study aimed to identify MAGE-A11 and MAGE-A12 expressions in lung tumors obtained from core biopsy, forceps biopsy, and bronchoalveolar lavage specimens. A cross-sectional observational study was conducted on 90 patients clinically diagnosed with lung tumors. These patients received core biopsy, forceps biopsy, and bronchoalveolar lavage interventions after ethical approval was obtained. The complementary deoxyribonucleic acid (cDNA) quality was assessed by the polymerase chain reaction (PCR) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The assessment was performed to ascertain if all specimens exhibited positive PCR amplification of the GAPDH gene. MAGE-A11 and MAGE-A12 were identified through a semi-nested reverse transcription PCR. The positive results were detected by measuring the PCR products, with MAGE-A11 and MAGE-A12 at base pairs (bp) of 858 and 496 in the first and second rounds, respectively. The expressions of MAGE-A11 and MAGE-A12 were observed in 3 (3.33%) and 40 (44.44%) out of 90 specimens, respectively. The prevalence rate of non-small cell lung cancer (NSCLC) was 31.11% (28/90). Among these cases, 3.57% (1/28) showed the expression of MAGE-A11, while 32.14% (9/28) exhibited the expression of MAGE-A12. Sixty-two (68.89%) out of 90 patients were diagnosed with no tumor cell malignancy. Out of 62 cases, 2 (3.23%) exhibited the expression of MAGE-A11, while 31 (50%) demonstrated the expression of MAGE-A12. MAGE-A11 and MAGE-A12 were detected in NSCLC and certain specimens with a pathological diagnosis that indicated the absence of malignant cells. In conclusion, MAGE A11 and MAGE A12 have potential markers to improve the pathological diagnosis of lung cancer. Further investigation is necessary to explore the expression of MAGE-A in correlation with lung cancer progression. [ABSTRACT FROM AUTHOR]

The article investigates the effects of Fe3O4 nanoparticles on respiratory parameters through intravenous injection in Wistar rats, finding that increasing doses of these nanoparticles lead to significant changes in bronchoalveolar lavage parameters, suggesting potential harm. Topics include the methodology for administering nanoparticles to rats, the impact on selected respiratory parameters, and the significance of dose escalation in nanoparticle-induced effects on lung health.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) on nasopharyngeal swab (NPS), remains the most reliable and practical test to diagnose coronavirus disease 2019 (COVID-19). Current literature is sparse regarding the rates of discordance between NPS and bronchoalveolar lavage (BAL) in patients with cancer. Methods We conducted a retrospective cohort study of adult patients with cancer who had BAL samples tested for SARS-CoV-2 at a comprehensive cancer center. Patients without NPS PCR for SARS-CoV-2 before BAL were excluded. Results In a cohort of 345 patients, 12% and 17% tested positive for SARS-CoV-2 on NPS and BAL, respectively. There was a 6.3% NPS−/BAL+ discordance rate and a 9.5% NPS+/BAL− discordance rate. Patients with lymphoma (adjusted odds ratio [aOR] = 4.06; P =.007) and Hispanic patients (aOR = 3.76; P =.009) were more likely to have NPS−/BAL+ discordance on multivariate analysis. Among patients with NPS− /BAL− for SARS-CoV-2, an alternate infectious (23%) and a noninfectious etiology (16%) were identified in BAL. Conclusions Our discordance rates between NPS and BAL were sufficient to recommend BAL in certain patients with cancer with a high clinical suspicion of COVID-19. BAL has value in identifying alternative etiologies of illness in patients with suspected or confirmed COVID-19. [ABSTRACT FROM AUTHOR]

Cryptococcosis typically manifests as pulmonary lesions, with endobronchial lesions occurring rarely. Inhaled corticosteroids (ICS) may be a risk factor for cryptococcosis of the larynx but not of the bronchi. Here, we report a case involving a 73‐year‐old Japanese man who developed endobronchial cryptococcosis during ICS treatment for asthma. Chest computed tomography showed right mainstem bronchial stenosis and asthma control worsening when he received adequate asthma treatments. Bronchoscopy revealed multiple elevated lesions with white slough from the trachea to the right mainstem bronchus and the right mainstem bronchus lumen entrance narrowing. Bronchial lavage culture revealed Cryptococcus neoformans. Combination treatment with the antifungal agent, mepolizumab, and bronchodilation surgery successfully controlled cryptococcosis and asthma. Attention should be paid to central airway lesions during ICS treatment for uncontrolled asthma. [ABSTRACT FROM AUTHOR]

Rationale: Acute eosinophilic pneumonia (AEP) is an acute pulmonary illness caused by eosinophilic infiltration of the lung parenchyma. It can happen after using drugs such as daptomycin and minocycline. AEP induced by imipenem/cilastatin is a rare condition. Patient's Concern: A 45-year-old male patient, who previously suffered from a urinary tract infection and treated with imipenem/cilastatin antibiotic, was presented to us with acute respiratory distress, soon after the initiation of the antibiotic. Computed tomography identified pulmonary infiltrates in the upper and middle lung fields and eosinophils were found to account for 36% of differential count of the broncho-alveolar lavage fluid. He also developed peripheral eosinophilia as the disease progressed. Diagnosis: AEP, secondary to imipenem/cilastatin therapy. Interventions: Steroid therapy was administered and imipenem/cilastatin antibiotic was discontinued. Outcomes: The patient improved completely following the therapy and had clear lung fields on follow-up. Lessons: Imipenem/cilastatin is an uncommon cause of AEP and requires close monitoring during therapy. [ABSTRACT FROM AUTHOR]

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The article employs single-cell Ribonucleic acid (RNA) sequencing (scRNA-Seq) meta-analysis of COVID-19 bronchoalveolar lavage samples. Topics include clustering methods, cell type identification through supervised learning, inference of transcription factor activity, cell-cell communication analysis, differential expression analysis, gene set variability analysis, pseudotime analysis, and the integration of scRNA-Seq data from lung COVID-19 samples.

The implementation of nanotechnology in pulmonary delivery systems might result in better and more specific therapy. Therefore, a nano-sized drug carrier should be toxicologically inert and not induce adverse effects. We aimed to investigate the responses of a polymer nano drug carrier, a lysine poly-hydroxyethyl methacrylate nanoparticle (NP) [Lys-p(HEMA)], loaded with formoterol, both in vitro and in vivo in an ovalbumin (OVA) asthma model. The successfully synthesized nanodrug formulation showed an expectedly steady in vitro release profile. There was no sign of in vitro toxicity, and the 16HBE and THP-1 cell lines remained vital after exposure to the nanocarrier, both loaded and unloaded. In an experimental asthma model (Balb/c mice) of ovalbumin sensitization and challenge, the nanocarrier loaded and unloaded with formoterol was tested in a preventive strategy and compared to treatment with the drug in a normal formulation. The airway hyperresponsiveness (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL), both cellular and biochemical, were assessed. The application of formoterol as a regular drug and the unloaded and formoterol-loaded NP in OVA-sensitized mice followed by a saline challenge was not different from the control group. Yet, both the NP formulation and the normal drug application led to a more deteriorated lung function and increased lung inflammation in the OVA-sensitized and -challenged mice, showing that the use of the p(HEMA) nanocarrier loaded with formoterol needs more extensive testing before it can be applied in clinical settings. [ABSTRACT FROM AUTHOR]

A 66-year-old male patient diagnosed with small-cell lung cancer received chemotherapy and immunotherapy, resulting in successful tumor control. However, the patient subsequently experienced a fever and rapid progression of the pulmonary cavity. Despite sampling bronchoscopic bronchoalveolar lavage fluid for targeted next-generation sequencing (tNGS), the cause remained unidentified. Adding bronchoalveolar lavage fluid to sense metagenomic next-generation sequencing (mNGS) confirmed the infection caused by actinomycetes. The patient's condition improved after active anti-infection treatment. This case was further analyzed and discussed through a comprehensive literature review, focusing on molecular microbiological diagnosis and treatment processes. The points outlined were as follows: the advancement of molecular microbiology has gradually reduced the challenges associated with diagnosing rare infectious diseases such as pulmonary actinomycosis. Additionally, in immunodeficient individuals, certain infectious diseases with a chronic course may exhibit acute and aggressive characteristics, which is of concern to all colleagues. Currently, tNGS and mNGS are widely employed in clinical settings as practical tools for diagnosing infectious diseases. Notably, these two methods are not substitutes for each other but complement each other. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of targeted nanopore sequencing technology for the detection of Mycobacterium tuberculosis(M.tb.) in bronchoalveolar lavage fluid(BALF) specimens. Methods: A prospective study was used to select 58 patients with suspected pulmonary tuberculosis(PTB) at Henan Chest Hospital from January to October 2022 for bronchoscopy, and BALF specimens were subjected to acid-fast bacilli (AFB) smear, Mycobacterium tuberculosis MGIT960 liquid culture, Gene Xpert MTB/RIF (Xpert MTB/RIF) and targeted nanopore sequencing (TNS) for the detection of M.tb., comparing the differences in the positive rates of the four methods for the detection of patients with different classifications. Results: Among 58 patients with suspected pulmonary tuberculosis, there were 48 patients with a final diagnosis of pulmonary tuberculosis. Using the clinical composite diagnosis as the reference gold standard, the sensitivity of AFB smear were 27.1% (95% CI: 15.3-41.8); for M.tb culture were 39.6% (95% CI: 25.8-54.7); for Xpert MTB/RIF were 56.2% (95% CI: 41.2-70.5); for TNS were 89.6% (95% CI: 77.3-96.5). Using BALF specimens Xpert MTB/RIF and/or M.tb. culture as the reference standard, TNS showed 100% (30/30) sensitivity. The sensitivity of NGS for pulmonary tuberculosis diagnosis was significantly higher than Xpert MTB/RIF, M.tb. culture, and AFB smear. Besides, P values of <0.05 were considered statistically significant. Conclusion: Using a clinical composite reference standard as a reference gold standard, TNS has the highest sensitivity and consistency with clinical diagnosis, and can rapidly and efficiently detect PTB in BALF specimens, which can aid to improve the early diagnosis of suspected tuberculosis patients. [ABSTRACT FROM AUTHOR]

Bovine respiratory disease (BRD) causes morbidity and mortality in cattle. The critical roles of the respiratory microbiota in BRD have been widely studied. The nasopharynx was the most popular sampling niche for BRD pathogen studies. The oral cavity and other niches within the respiratory tract, such as nostrils and lung, are less assessed. In this study, oropharyngeal swabs (OS), nasal swabs (NS), nasopharyngeal swabs (NP), and bronchoalveolar lavage (BAL) were collected from calves located in four countries and analyzed for investigation of the dissimilarities and connections of the respiratory microbiota. The results showed that the microbial diversity, structure, and composition in the upper and lower respiratory tract in beef cattle from China, the USA, Canada, and Italy were significantly different. The microbial taxa for each sampling niche were specific and associated with their local physiology and geography. The signature microbiota for OS, NS, NP, and BAL were identified using the LEfSe algorithm. Although the spatial dissimilarities among the respiratory niches existed, the microbial connections were observed in beef cattle regardless of geography. Notably, the nostril and nasopharynx had more similar microbiomes compared to lung communities. The major bacterial immigration patterns in the bovine respiratory tract were estimated and some of them were associated with geography. In addition, the contribution of oral microbiota to the nasal and lung ecosystems was confirmed. Lastly, microbial interactions were characterized to reveal the correlation between the commercial microbiota and BRD-associated pathogens. In conclusion, shared airway microbiota among niches and geography provides the possibility to investigate the common knowledge for bovine respiratory health and diseases. In spite of the dissimilarities of the respiratory microbiota in cattle, the spatial connections among these sampling niches not only allow us to deeply understand the airway ecosystem but also benefit the research and development of probiotics for BRD. [ABSTRACT FROM AUTHOR]

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT. TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease. [ABSTRACT FROM AUTHOR]

Background: Diagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD). Methods: Prospective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose. Results: Of the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%. Conclusions: Using a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA. [ABSTRACT FROM AUTHOR]

Objective: The lung is implicated as a site for breach of tolerance prior to onset of seropositive rheumatoid arthritis (RA). To substantiate this, we investigated lung‐resident B cells in bronchoalveolar lavage (BAL) samples from untreated early RA patients and anti–citrullinated protein antibody (ACPA)–positive individuals at risk for developing RA. Methods: Single B cells (n = 7,680) were phenotyped and isolated from BAL samples from individuals at risk of RA (n = 3) and at RA diagnosis (n = 9). The immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n = 141). Monoclonal ACPAs were tested for reactivity patterns and binding to neutrophils. Results: Using our single‐cell approach, we found significantly increased proportions of B lymphocytes in ACPA+ compared to ACPA– individuals. Memory and double‐negative B cells were prominent in all subgroups. Upon antibody re‐expression, 7 highly mutated citrulline‐autoreactive clones originating from different memory B cell subsets were identified, both in individuals at risk of RA and early RA patients. Lung IgG variable gene transcripts from ACPA+ individuals carried frequent mutation‐induced N‐linked Fab glycosylation sites (P < 0.001), often in the framework 3 of the variable region. Two of the lung ACPAs bound to activated neutrophils, 1 from an individual at risk of RA and 1 from an early RA patient. Conclusion: T cell–driven B cell differentiation resulting in local class switching and somatic hypermutation are evident in lungs before as well as in early stages of ACPA+ RA. Our findings add to the notion of lung mucosa being a site for initiation of citrulline autoimmunity preceding seropositive RA. [ABSTRACT FROM AUTHOR]

Background: Feline lower airway disease (FLAD) is frequently associated with radiographic abnormalities. Objectives: To evaluate whether radiographic changes in cats with naturally occurring FLAD improve with treatment and if radiographic changes correlate with clinical signs. Animals: Twenty‐four client‐owned cats newly diagnosed with FLAD, based on medical history, typical clinical signs, radiographic findings, and examination of bronchoalveolar lavage fluid, were included in the prospective study. Methods: At 2 examination time points (days 0 and 60), an owner questionnaire, clinical examination, and thoracic radiography were carried out. Information from the questionnaire and clinical examination were evaluated on the basis of a 12‐point clinical score. Radiographs were assessed using a 10‐point radiographic score. Individual treatment was given to all cats over the study period, based on severity of the disease and compliance of the cat. Clinical and radiographic scores were compared statistically for both examination time points and evaluated for correlation. Results: All cats showed radiographic abnormalities at initial presentation. In addition to significant improvement in clinical variables, the total radiographic score improved significantly (P =.01) during the study period, with significant improvement in the severity of bronchial (P =.01) and interstitial lung pattern (P =.04). Improvement of the clinical and radiographic score was not correlated. Conclusion and Clinical Importance: In addition to clinical signs, repeated radiographic examination can be used as a diagnostic tool to evaluate treatment response in cats with FLAD. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) affects West Highland white terriers (WHWTs). Osteopontin (SPP1) and fibronectin (FN1) are associated with human IPF and are overexpressed by bronchoalveolar lavage fluid (BALF) macrophages in dogs with IPF. Objective: To investigate the value of these proteins as biomarkers of IPF. Animals: West Highland white terriers (WHWTs) with IPF, control WHWTs, and terriers. Methods: Cross‐sectional observational study. Immunohistochemistry was used to localize SPP1 and FN1 in lung tissue. Serum and BALF SPP1 and FN1 concentrations were measured using canine ELISA kits and compared between groups. Results: Osteopontin stained ciliated epithelial cells, smooth muscular cells, and macrophages of all included dogs, and type‐II pneumocytes and extracellular matrix of all 12 diseased WHWTs, 4/6 control WHWTs, and none of the 3 terriers. Osteopontin serum concentration was higher in diseased WHWTs (n = 22; 2.15 ng/mL [0.74‐5.30]) compared with control WHWTs (n = 13; 0.63 ng/mL [0.41‐1.63]; P =.005) and terriers (n = 15; 0.31 ng/mL [0.19‐0.51]; P <.0001), and in control WHWTs compared with terriers (P =.005). Osteopontin BALF concentrations were higher in diseased (0.27 ng/mL [0.14‐0.43]) and control WHWTs (0.25 ng/mL [0.14‐0.40]), compared with terriers (0.02 ng/mL [0.01‐0.08]; P <.0001 and P =.003, respectively). Fibronectin (FN1) serum concentrations were lower in diseased dogs (1.03 ng/mL [0.35‐1.48]) and control WHWTs (0.61 ng/mL [0.24‐0.65]) compared with terriers (2.72 ng/mL [0.15‐5.21]; P <.0001 and P =.0001, respectively). There was no difference in FN1 immunostaining and FN1 BALF concentrations between groups. Conclusions: Results suggest that SPP1 is involved in pathogenesis of IPF and could predispose that breed to the disease. Osteopontin serum concentration could serve as a diagnostic biomarker of IPF. [ABSTRACT FROM AUTHOR]

Background: Nonbronchoscopic bronchoalveolar lavage (nBAL) is routinely performed in calves, and airway cytology has great potential in airway disease diagnostics. A good reference framework for nBAL cytology is lacking. Objectives: To distinguish different cytological profiles in nBAL from grouped housed calves using cluster analysis, and characterize these profiles on individual and herd levels. Animals: Three hundred thirty‐eight group‐housed calves from 60 herds (mainly dairy and beef). Methods: Cross‐sectional study. Differential counts of white blood cells were determined on nBAL fluid, followed by differentiation of cytological profiles by K‐means‐based cluster analysis. These profiles were characterized by reference values, decision tree analysis, and associations with clinical, ultrasonographic, bacteriological, and cytological features. Results: A normal (55.9%), a neutrophilic (41.1%), and an eosinophilic profile (3.0%) were identified. The normal profile was characterized by reference values of 2.3% to 47.4% neutrophils, 35.1% to 95.1% macrophages, 0.4 to 22.9% lymphocytes, and 0.0% to 0.9% eosinophils. The neutrophilic profile was characterized by ≥44.5% neutrophils, <1.6% eosinophils, and <11.5% lymphocytes. This profile was associated with the isolation of Pasteurella multocida, the presence of neutrophils with toxic granulation, and the presence of phagocytosed bacteria in neutrophils. The eosinophilic profile was characterized by eosinophils ≥1.6% (neutrophilia present) or ≥2.4% (neutrophilia absent), and associated with the presence of mast cells. On herd level, the neutrophilic and eosinophilic profiles were present in 85.0% and 15.0% of the herds, respectively. Conclusions and Clinical Importance: This study provides a first step in the development of cytological guidelines, aiding the assessment of airway health and inflammation in calves through nBAL fluid cytology. [ABSTRACT FROM AUTHOR]

Noncardiogenic pulmonary edema (NCPE) in hunting dogs is an uncommon and poorly described condition for which no preventive treatment is available. Two dogs were presented for recurrent respiratory distress strictly associated with hunting activities. Diagnosis was based on bilateral, symmetrical, interstitial‐to‐alveolar pattern in the caudodorsal lung fields on thoracic radiographs, exclusion of other causes, and spontaneous clinical and radiographic improvement. Considering that the pathogenesis of exercise‐induced NCPE likely involves α‐ and β‐adrenergic overstimulation, treatment with sympathetic blockers was used in both dogs. The first dog no longer showed respiratory signs during hunting activities. However, treatment failed to prevent respiratory distress in the other dog. Based on the large number of red blood cells in the bronchoalveolar lavage fluid of the second dog, exercise‐induced pulmonary hemorrhage was suspected, as described in racing horses. The loop diuretic furosemide successfully prevented further hunting‐associated respiratory distress episodes in this dog. [ABSTRACT FROM AUTHOR]

OBJECTIVE Evaluate agreement among the antimicrobial susceptibility profiles of Mannheimia haemolytica or Pasteurella multocida obtained by transtracheal wash, nasal swab, nasopharyngeal swab, and bronchoalveolar lavage. ANIMALS 100 Holstein and Holstein-cross bull calves with bovine respiratory disease. METHODS Calves > 30 days old with naturally occurring bovine respiratory disease were sampled sequentially by nasal swab, nasopharyngeal swab, transtracheal wash, and then bronchoalveolar lavage. Samples were cultured, and for each antimicrobial, the MIC of 50% and 90% of isolates was calculated, and isolates were categorized as susceptible or not. Categorical discrepancies were recorded. Percent positive agreement and kappa values were calculated between isolates for each of the sampling methods. RESULTS Antimicrobial susceptibility varied by pathogen and resistance to enrofloxacin, florfenicol, tilmicosin, and spectinomycin was detected. Minor discrepancies were seen in up to 29% of classifications, with enrofloxacin, penicillin, and florfenicol more frequently represented than other drugs. Very major and major discrepancies were seen when comparing florfenicol (1.9%) and tulathromycin (3.8 to 4.9%) across sampling methods. Some variability was seen in agreement for enrofloxacin for several comparisons (8.3 to 18.4%). CLINICAL RELEVANCE Susceptibility testing of isolates from 1 location of the respiratory tract can reliably represent susceptibility in other locations. Nevertheless, the potential for imperfect agreement between sampling methods does exist. The level of restraint available, the skill level of the person performing the sampling, the age and size of the animal, disease status, and treatment history all must be factored into which test is most appropriate for a given situation. [ABSTRACT FROM AUTHOR]

Simple Summary: Macrophages are an integral part of the tumor microenvironment, playing a role in immunoregulation. We investigated the antigenic and cytokine macrophages profile derived from bronchoalveolar lavage fluid in lung affected by cancer (cBALF) and healthy lung (hBALF) of 36 patients. Macrophages markers: CD206, CD163, CD80, CD86, CD40, Arginase-1, and CD68 were evaluated by flow cytometry. Cytokines (IL-1 RA, IL-6, IL-10, TNF-α, IL-1β, IL-12, IL-23, and TGF-β) profile was analyzed. There was higher median proportion of macrophages in cBALF than in hBALF. The population of macrophages presented immunophenotype: cCD68+bright CD206+bright CD163+bright CD80+ CD86+ CD40+bright CD45+ cArginase+. We observed some trends in the expression of the analyzed antigens in clBALF and hlBLAF. High concentrations of IL-1RA and IL-6 and correlations between pro- and anti-inflammatory cytokines in cBALF and hBALF supernatants were found. We expanded knowledge of the macrophages polarization, their diversity and unique properties based on the antigenic pattern and cytokine profile. Macrophages play an important role in the suppression and activation of immune anti-cancer response, but little is known about dominant macrophage phenotype in the lung cancer environment, evaluated by bronchoalveolar lavage fluid (BALF). The aim of this study was to characterize macrophages in BALF from a lung affected by cancer (cBALF) and a healthy lung (hBALF) of the same patient regarding their individual macrophage polarization and selected cytokines profile. A total of 36 patients with confirmed lung cancer were investigated. Macrophages markers: CD206 CD163 CD80 CD86 CD40 CD45, Arginase-1, and CD68 were evaluated by flow cytometry. Cytokines (IL-1 RA, IL-6, IL-10, TNF-α, IL-1β, IL-12, IL-23, and TGF-β) profile was analyzed. There was higher median proportion of macrophages in Cbalf than in Hbalf. The population of macrophages presented immunophenotype: Ccd68+bright CD206+bright CD163+bright CD80+ CD86+ CD40+bright CD45+ cArginase+. We observed some trends in the expression of the analyzed antigens in clBALF and hlBLAF. The highest concentrations of IL-1RA and IL-6 were in Cbalf and Hbalf supernatant. There were the correlations between pro- and anti-inflammatory cytokines. The findings showed that macrophages include a diverse and plastic group with the presence of different antigens and cytokines, and determining the target phenotype is a complex and variable process. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung diseases (ILDs) are extremely challenging in terms of diagnosis. Extreme bronchoalveolar lavage (BAL) lymphocytosis is thought to strongly point towards the diagnosis of hypersensitivity pneumonitis (HP). Objectives: Explore the range of different ILD that can present with BAL lymphocytosis, including cases of pronounced lymphocytosis and its diagnostic utility. Methods: Patients with ILD that were subjected to BAL were identified retrospectively from a cohort of consecutive patients. Results: BAL lymphocytosis ≥20% was recorded in 106 patients (27%), while pronounced BAL lymphocytosis ≥40% was recorded in 49 patients (12.5%). The most common diagnoses in patients with BAL lymphocytosis ≥20% and ≥40%, were HP (32.1%), connective tissue disease (CTD)-ILD (26.4%), sarcoidosis (16%), and HP (38.8%), CTD-ILD (24.5%), sarcoidosis (14.3%), respectively. Conclusions: Neither the presence nor the degree of BAL lymphocytosis can point to a specific diagnosis. [ABSTRACT FROM AUTHOR]

Tidal ventilation is essential in supporting the transition to air-breathing at birth, but excessive tidal volume (VT) is an important factor in preterm lung injury. Few studies have assessed the impact of specific VT levels on injury development. Here, we used a lamb model of preterm birth to investigate the role of different levels of VT during positive pressure ventilation (PPV) in promoting aeration and initiating early lung injury pathways. VT was delivered as 1) 7 mL/kg throughout (VTstatic), 2) begun at 3 mL/kg and increased to a final VT of 7 mL/kg over 3 min (VTinc), or 3) commenced at 7 mL/kg, decreased to 3 mL/kg, and then returned to 7 mL/kg (VTalt). VT, inflating pressure, lung compliance, and aeration were similar in all groups from 4 min, as was postmortem histology and lung lavage protein concentration. However, transient decrease in VT in the VTalt group caused increased ventilation heterogeneity. Following TMT-based quantitative mass spectrometry proteomics, 1,610 proteins were identified in the lung. Threefold more proteins were significantly altered with VTalt compared with VTstatic or VTinc strategies. Gene set enrichment analysis identified VTalt specific enrichment of immune and angiogenesis pathways and VTstatic enrichment of metabolic processes. Our finding of comparable lung physiology and volutrauma across VT groups challenges the paradigm that there is a need to rapidly aerate the preterm lung at birth. Increased lung injury and ventilation heterogeneity were identified when initial VT was suddenly decreased during respiratory support at birth, further supporting the benefit of a gentle VT approach. NEW & NOTEWORTHY: There is little evidence to guide the best tidal volume (VT) strategy at birth. In this study, comparable aeration, lung mechanics, and lung morphology were observed using static, incremental, and alternating VT strategies. However, transient reduction in VT was associated with ventilation heterogeneity and inflammation. Our results suggest that rapidly aerating the preterm lung may not be as clinically critical as previously thought, providing clinicians with reassurance that gently supporting the preterm lung maybe permissible at birth. [ABSTRACT FROM AUTHOR]

Pneumonia is the most common cause of mortality in under-five children worldwide. Largely, viral pneumonia is the most common cause of pneumonia in children across all age groups. We need to think outside the jukebox while dealing with cases of recurrent or persistent pneumonia. A few uncommon causes of persistent or recurrent pneumonia are primary or secondary immunodeficiencies, airway anomalies, infection with Mycobacterium tuberculosis complex, aspiration pneumonia, and severe gastroesophageal reflux. We present a few uncommon presentations of pneumonia in children, which can pose a significant diagnostic challenge in a resource-limited setting. [ABSTRACT FROM AUTHOR]

Background: Detection of serum neuron specific enolase (NSE) has high sensitivity and specificity in the diagnosis of lung cancer, especially small cell lung cancer, but sometimes serum NSE provides limited help. We report a case of high-density shadow of the left lung and elevated serum NSE which mimicked lung cancer. It was ultimately confirmed to be pulmonary aspergillosis (PA) by bronchoscopic alveolar lavage fluid (BALF) and next-generation sequencing (NGS). Methods: Appropriate laboratory tests, chest computed tomography (CT) scan, bronchoscopic alveolar lavage fluid, and next-generation sequencing were used to explore latent causes. Results: NSE level was elevated, chest CT scan showed high-density shadow of the left lung, bronchoscopy showed flesh-colored new organisms in the lower lobe of the left lung, BALF and NGS revealed the presence of Aspergillus. Conclusions: Elevated NSE is not a typical manifestation of lung cancer, and we should perform BALF and NGS early to determine whether there is infection with special pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Objective.To investigate the expression of mucin 5AC (MUC5AC) in airway of children with mycoplasma pneumoniae pneumonia(MPP), and to provide clinical value for early diagnosis and treatment of MPP mucus plug. Methods.A total of 94 children with MPP who were hospitalized for alveolar lavage from April 2022 to October 2022 were included in the MPP group. According to whether mucus plug was observed under the first fiberoptic bronchoscope, the MPP group was divided into mucus plug group (n = 41) and non-mucus plug group (n = 53). Relevant clinical data and laboratory examination data were collected. Results.Compared with non mucus plug group, the mucus plug group had a longer heat duration and hospital stay, and the levels of CRP, LDH,PCT, D-dimer, MP-DNA copy value of lavage fluid, IL-17, MUC5AC were all increased,with statistically significant differences (P < 0.05). MUC5AC was positively correlated with LDH and IL-17 levels (r = 0.54, P = 0.002, r = 0.39, P = 0.019). The ROC curve plotted based on the level of MUC5AC had an area under the ROC curve of 0.811, a sensitivity of 86.2% and a specificity of 71.4% for predicting formation of mucus plug in MPP. Conclusions.There was an increase in the level of MUC5AC in children with mucus plug group in MPP, and the level of MUC5AC had a certain value for predicting mucus plug formation. [ABSTRACT FROM AUTHOR]

Background: Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis. Methods: The dynamics of lung uptake of 18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF). Results: Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPα levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels. Conclusions: Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAPα in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease. [ABSTRACT FROM AUTHOR]