Impact of Cough Severity on the Diagnostic Yield of Endobronchial Ultrasonography Transbronchial Biopsy with Guide Sheath: A Retrospective Observational Study.

Bronchoscopy is an invasive procedure, and patient coughing during examination has been reported to cause patient distress. This study aimed to clarify the relationship between cough severity and diagnostic yield of endobronchial ultrasonography with guide sheath transbronchial biopsy (EBUS-GS-TBB). Data of patients who underwent bronchoscopy at Kyorin University Hospital between April 2019 and March 2022 were retrospectively evaluated. Bronchoscopists assessed the cough severity upon completion of the procedure using a four-point cough scale. Cough severity was included as a predictive factor along with those reportedly involved in bronchoscopic diagnosis, and their impact on diagnostic yield was evaluated. Predictors of cough severity were also examined. A total of 275 patients were enrolled in this study. In the multivariate analysis, the diagnostic group (n = 213) had significantly more 'within' radial endobronchial ultrasound findings (odds ratio [OR] 5.900, p < 0.001), a lower cough score (cough score per point; OR 0.455, p < 0.001), and fewer bronchial generations to target lesion(s) (OR 0.686, p < 0.001) than the non-diagnostic group (n = 62). The predictive factors for severe cough include the absence of virtual bronchoscopic navigation (VBN) and prolonged examination time. Decreased cough severity was a positive predictive factor for successful EBUS-GS-TBB, which may be controlled using VBN and awareness of the procedural duration.

Myeloid differentiation protein-2 has a protective role in house dust mite-mediated asthmatic characteristics with the proinflammatory regulation of airway epithelial cells and dendritic cells.

BACKGROUND: Myeloid differentiation protein-2 (MD-2) is a lipopolysaccharide-binding protein involved in lipopolysaccharide signalling via Toll-like receptor 4 (TLR4). TLR4 plays an essential role in HDM-mediated allergic airway inflammation. Moreover, MD-2 is structurally similar to Der f 2, a major allergen from house dust mite (HDM). OBJECTIVES: We aimed to clarify the role of MD-2 in the pathogenesis of HDM-mediated allergic airway inflammation. METHODS: Wild-type (WT), TLR4 knockout and MD-2 knockout mice were subjected to intranasal instillation of HDM extract, and asthmatic features were evaluated. We also evaluated gene sets regulated by MD-2 in HDM-treated airway epithelial cells and examined the function of dendritic cells from lymph nodes and from lungs. RESULTS: Aggravated allergic airway inflammation with increased airway hyperresponsiveness was observed in MD-2 knockout mice compared with WT and TLR4 knockout mice. Global gene expression analysis revealed an MD-2 regulated proinflammatory response and reconstituted TLR4 signalling in airway epithelial cells. The ability of dendritic cells to evoke an allergic immune response was enhanced in MD-2 knockout mice. CONCLUSIONS & CLINICAL RELEVANCE: MD-2 plays a protective role in HDM-induced airway allergy with the proinflammatory regulation of airway epithelial cells and dendritic cells. MD-2 may serve as a therapeutic target in the treatment of asthma.

Crucial role of stimulator of interferon genes-dependent signaling in house dust mite extract-induced IgE production.

Stimulator of interferon genes (STING) is a DNA sensor that responds to pathogens and induces type I interferon production. Herein, the role of STING in house dust mite extract (HDM)-induced allergic asthma was investigated. C57BL/6 wild-type (WT) and Sting-/- mice were intratracheally sensitized with HDM, and the bronchoalveolar lavage fluid (BALF), sera, lungs, and mediastinal lymph nodes (MLNs) were analyzed. The total and HDM-specific serum IgE levels were lower in Sting-/- mice than in WT mice. B cell and IgE-positive B cell proportion in BALF and MLNs, respectively, was significantly lower in Sting-/- mice than in WT mice. Additionally, cyclic GMP-AMP, a STING ligand, augmented total and HDM-specific serum IgE levels and B cell proportion in BALF when applied in combination with HDM. To elucidate the role of STING in IgE production, follicular helper T (Tfh) cells, which are involved in B cell maturation, were investigated. Tfh cell proportion in MLNs decreased in Sting-/- mice, and IL-4 and IL-13 production by HDM-restimulated MLN cells from HDM-sensitized mice was decreased in Sting-/- mice compared with WT mice. Thus, STING plays an important role in the maturation and class switching of IgE-producing B cells in allergic inflammation via Tfh cells.

Diagnostic Value of Vascular Endothelial Growth Factor, Transforming Growth Factor-ß, Interleukin-8, and the Ratio of Lactate Dehydrogenase to Adenosine Deaminase in Pleural Effusion.

PURPOSE: We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid. METHODS: Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted. RESULTS: We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-ß was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001). CONCLUSIONS: VEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

Tracheobronchial Amyloidosis in a Patient with Sjögren's Syndrome.

A 65-year-old woman was referred to our respiratory department because of incidentally detected endobronchial deposits. She had been diagnosed with Sjögren's syndrome 12 years earlier. Bronchoscopy showed protrusion of the reddened, shiny or edematous mucosa at the orifice of the lower lobe bronchus, suggesting a submucosal tumor. Based on the pathological findings of the transbronchial biopsied specimens, the patient was diagnosed with non-classified type tracheobronchial amyloidosis associated with Sjögren's syndrome, which was negative for both λ and κ chains, transthyretin and amyloid A. She has remained in good health without a relapse of the tumor.