Susceptibility of Human Airway Tissue Models Derived From Different Anatomical Sites to Bordetella pertussis and Its Virulence Factor AdenyRaylate Cyclase Toxin

To study the interaction of human pathogens with their host target structures, human tissue models based on primary cells are considered suitable. Complex tissue models of the human airways have been used as infection models for various viral and bacterial pathogens. The Gram-negative bacterium Bordetella pertussis is of relevant clinical interest since whooping cough has developed into a resurgent infectious disease. In the present study, we created three-dimensional tissue models of the human ciliated nasal and tracheo-bronchial mucosa. We compared the innate immune response of these models towards the B. pertussis virulence factor adenylate cyclase toxin (CyaA) and its enzymatically inactive but fully pore-forming toxoid CyaA-AC-. Applying molecular biological, histological, and microbiological assays, we found that 1 µg/ml CyaA elevated the intracellular cAMP level but did not disturb the epithelial barrier integrity of nasal and tracheo-bronchial airway mucosa tissue models. Interestingly, CyaA significantly increased interleukin 6, interleukin 8, and human beta defensin 2 secretion in nasal tissue models, whereas tracheo-bronchial tissue models were not significantly affected compared to the controls. Subsequently, we investigated the interaction of B. pertussis with both differentiated primary nasal and tracheo-bronchial tissue models and demonstrated bacterial adherence and invasion without observing host cell type-specific significant differences. Even though the nasal and the tracheo-bronchial mucosa appear similar from a histological perspective, they are differentially susceptible to B. pertussis CyaA in vitro. Our finding that nasal tissue models showed an increased innate immune response towards the B. pertussis virulence factor CyaA compared to tracheo-bronchial tissue models may reflect the key role of the nasal airway mucosa as the first line of defense against airborne pathogens.

Bronchial brush cytology, endobronchial biopsy, and SALSA immunohistochemistry in severe equine asthma

Horses with severe equine asthma (SEA), also known as heaves and recurrent airway obstruction, have persistent neutrophilic inflammation of the lower airways. Cytologic evaluation of bronchoalveolar lavage (BAL) fluid is commonly used to confirm the clinical diagnosis of SEA. However, the utility of microscopic assessment of bronchial brushings, endobronchial biopsies, and immunohistochemical detection of disease-associated biomarkers for the diagnosis of SEA remain poorly characterized. Salivary scavenger and agglutinin (SALSA) has anti-inflammatory properties and downregulated gene expression in SEA; therefore, it was investigated as a tissue biomarker for airway and systemic inflammation. Six asthmatic and 6 non-asthmatic horses were exposed to an inhaled challenge. Before and after challenge, samples of BAL fluid, bronchial brushing, and endobronchial biopsy were collected. Location of SALSA in biopsies was determined, and immunohistochemical label intensity was computed using image analysis software. Serum amyloid A (SAA) was measured to assess systemic inflammation. After challenge, neutrophil proportions were significantly higher in asthmatic versus non-asthmatic horses in BAL fluid (least squares means, 95% confidence interval: 80.9%, 57.2% to 93.1%, vs 3.6%, 1.1% to 10.7%) and in brush cytology slides (39.5%, 7.7% to 83.6%, vs 0.2%, 0% to 2.3%), illustrating the potential of brush cytology as an alternate modality to BAL for assessing intraluminal inflammation. Bronchial histopathologic findings and intensity of SALSA immunolabeling in surface and glandular epithelium were similar in asthmatic and non-asthmatic horses, indicating limited changes in bronchial tissue from the inhaled challenge. Increases in SAA indicated systemic inflammation, but SALSA immunolabeling did not change significantly.

A Prospective Observational Study between the Value of Sputum Cytology and FNAC of Bronchial Growth in Diagnosing Lung Cancer at Chattogram Medical College Hospital, Bangladesh

Background: Lung disease is viewed as perhaps the most far reaching and deadly malignancies all throughout the planet. The most seasoned and most crucial technique is based on sputum cytology. The last outskirts for getting sufficient material are fine needle yearning cytology (FNAC) of bronchial development. Aims and Objective: To relate the meaning of sputum cytology and fine needle goal cytology of bronchial tissue under CT rules for diagnosing cellular breakdown in the lungs. Materials and Methods: This potential observational investigation was completed by the division of medication in Chattogram Medical College Hospital, Chattogram, Bangladesh. Where data was collected from January 2019 to June 2020. A total of 50 patients with a suspected history, symptoms, and risk profile of having primary lung cancer, as demonstrated by chest radiography and CT scan, were chosen for the research population. Fifty patients with clinical and biochemical verification of suspected. All collected data were coding and input in SPSS-25 for further analysis. Both descriptive and inferential statistics were tested. Results: Among the 50 patients the vast majority of the patients were 51-60 years of age and the biggest number of the (94 %) patients were male. Sputum cytology is 8% touchy which isn’t steady with different examinations and CT guided FNAC is 94% sensitive. Conclusion: A definitive point of picture guided histological or cytological examination is to stay away from unnecessary thoracotomy and accomplish a particular determination with sensible exactness and least results. So, in this examination we found that sputum cytology is 8% delicate which isn’t steady with different investigations and CT guided FNAC is 94% touchy to last histological analysis of lung cancer. The discoveries recommended that CT guided FNAC discovered to be protected, feasible and viable.

Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma

Eosinophilic asthma is the most prevalent phenotype of asthma. Although most asthmatics are adequately controlled by corticosteroid therapy, a subset (5–10%) remain uncontrolled with significant therapy-related side effects. This indicates the need for a consideration of alternative treatment strategies that target airway eosinophilia with corticosteroid-sparing benefits. A growing body of evidence shows that a balance between systemic differentiation and local tissue eosinophilopoietic processes driven by traffic and lung homing of bone marrow-derived hemopoietic progenitor cells (HPCs) are important components for the development of airway eosinophilia in asthma. Interleukin (IL)-5 is considered a critical and selective driver of terminal differentiation of eosinophils. Studies targeting IL-5 or IL-5R show that although mature and immature eosinophils are decreased within the airways, there is incomplete ablation, particularly within the bronchial tissue. Eotaxin is a chemoattractant for mature eosinophils and eosinophil-lineage committed progenitor cells (EoP), yet anti-CCR3 studies did not yield meaningful clinical outcomes. Recent studies highlight the role of epithelial cell-derived alarmin cytokines, IL-33 and TSLP, (Thymic stromal lymphopoietin) in progenitor cell traffic and local differentiative processes. This review provides an overview of the role of EoP in asthma and discusses findings from clinical trials with various therapeutic targets. We will show that targeting single mediators downstream of the inflammatory cascade may not fully attenuate tissue eosinophilia due to the multiplicity of factors that can promote tissue eosinophilia. Blocking lung homing and local eosinophilopoiesis through mediators upstream of this cascade may yield greater improvement in clinical outcomes.

Evaluation of the Agreement Between the Tissue Sample and Bronchoalveolar Lavage (BAL) Fluid in the Diagnosis of Tuberculosis in Patients with Anthracosis

Background: Black dust deposited in the lungs is called anthracosis. By damaging bronchial mucosa, anthracosis can affect the mucociliary cleaning function. Initial reports indicate that there is a relationship between anthracosis and pulmonary tuberculosis. Due to obstructive effects of anthracosis on distal airways and disruption in a proper sampling of bronchoalveolar lavage (BAL), other diagnostic methods are necessary for estimating the tuberculosis prevalence in these patients. The aims of this study was to evaluate tissue samples adjacent to an anthracotic plaque for acid-fast bacilli smear and culture. Methods: his is a cross-sectional analysis study on 100 patients referred to Shahid Sadoughi Hospital who required bronchoscopy and anthracotic plaque based on bronchoscopy results. Bronchial fluid lavage, two biopsy samples for culture, and a smear of Mycobacterium tuberculosis from the surrounding of these plaques were prepared. Data analyses were carried out using SPSS (version 18). Results: One-hundred patients og the age range 46-91years were studied. The patients with tuberculosis diagnosis based on the smear of BAL and bronchial tissue samples and culture of BAL and bronchial tissue samples were 7%, 13%, 6% and 8% respectively. The presence of granuloma in histopathology was seen in 15 patients infected with tuberculosis. (κ > 0.04, p-value <0.05). In patients with positive tuberculosis, culture of bronchoalveolar lavage was superior to other methods. Conclusions: Diagnostic value of BAL method and tissue biopsy in anthracosis patients with tuberculosis did not show a statistically significant difference. As compared with other methods, BAL culture was more positive. Therefore, tissue biopsy is not a good alternative to BAL.

Expression of aquaporins in bronchial tissue and lung parenchyma of patients with chronic obstructive pulmonary disease

Background: Aquaporins AQP1 and AQP5 are highly expressed in the lung. Recent studies have shown that the expression of these proteins may be mechanistically involved in the airway inflammation and in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma of patients with COPD and COPD-resistant smokers. Methods: Using a case–control design, we selected a group of 15 subjects with COPD and 15 resistant smokers (smokers without COPD) as a control, all of whom were undergoing lung resection surgery due to a lung neoplasm. We studied the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma by means of immunohistochemistry and reverse-transcription real-time polymerase chain reaction. Tissue expression of AQP1 and AQP5 was semi-quantitatively assessed in terms of intensity and expression by immunohistochemistry using a 4-point scale ranging from 0 (none) to 3 (maximum). Results: There were no significant differences in gene expression between COPD patients and resistant smokers both in the bronchial tissue and in the lung parenchyma. However, AQP1 gene expression was 2.41-fold higher in the parenchyma of smokers with COPD compared to controls, whereas the AQP5 gene showed the opposite pattern, with a 7.75-fold higher expression in the bronchus of smokers with COPD compared with controls. AQP1 and AQP5 proteins were preferentially expressed in endothelial cells, showing a higher intensity for AQP1 (66.7% of cases with an intensity of 3, and 93.3% of subjects with an extension of 3 among patients with COPD). Subtle interstitial disease was associated with type II pneumocyte hyperplasia and an increased expression of AQP1. Conclusions: This study provides pilot observations on the differences in AQP1 and AQP5 expression between COPD patients and COPD-resistant smokers. Our findings suggest a potential role for AQP1 in the pathogenesis of COPD.

Expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$ in nasal polyps and bronchial tissue of patients with aspirin exacerbated airway disease

Background Aspirin exacerbated respiratory disease (AERD) is a disease of the upper and lower airways. It is characterized by severe asthma, chronic sinusitis with nasal polyps (CRSwNP) and intolerance towards nonsteroidal analgesics (NSAR). Arachidonic acid (AA) metabolites play an important role in the pathogenesis of AERD. It is still unknown, whether metabolism of AA is comparable between the upper and lower airways as well as between patients with and without NSAR intolerance. Objective We sought to analyze differences in the expression of cyclooxygenases type 1 and 2 (COX-1, COX-2), arachidonate 5-lipoxygenase (5-LOX) and cysteinyl leukotriene receptor type 2 ($$\hbox {CysLT}_2$$CysLT2) in nasal polyps and the bronchial mucosa of patients with aspirin intolerant asthma (AIA, $$n=23$$n=23) as compared to patients with aspirin tolerant asthma (ATA, $$n=17$$n=17) and a control group with nasal polyps, but without asthma (NPwA, $$n=15$$n=15). Methods Tissue biopsies from nasal polyps and bronchial mucosa were obtained during surgical treatment of nasal polyps by endonasal functional endoscopic sinus surgery (FESS) under general anesthesia from intubated patients. Immunohistochemistry was used to analyze the expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$CysLT2 in nasal and bronchial mucosa. Categorization into the different patient groups was performed according to the patient history, clinical and laboratory data, pulmonary function and provocation tests, as well as allergy testing. Results We observed a stronger expression of 5-LOX and $$\hbox {CysLT}_2$$CysLT2 in submucosal glands of nasal and bronchial tissue compared to epithelial expression. The expression of COX-1 and COX-2 was stronger in epithelia compared to submucosal glands. There was a similar expression of the enzymes and $$\hbox {CysLT}_2$$CysLT2 between upper and lower airways in all patient groups. We did not detect any significant differences between the patient groups. Conclusions The AA-metabolizing enzymes and the $$\hbox {CysLT}_2$$CysLT2 were expressed in a very similar way in different microscopic structures in samples of the upper and lower airways of individual patients. We did not detect differences between the patient groups indicating the pathogenetic role of AA metabolism in these disorders is independent of the presence of NSAR-intolerance.

Effects of 1,8-cineole (eucalyptol) on the activity of human bronchial tissue

1,8-cineole (eucalyptol) is used for the treatment of bronchial complaints, sinusitis and colds. Experiments have previously shown that 1,8-cineole, a monoterpene (C-10), has a very pronounced spasmolytic effect on smooth muscle fibre. In nearly all clinical applications with 1,8-cineole, especially when used in conjunction with allergic symptoms, histamine receptors prove to be crucial for treatment (use of histamine inhibitors). Results: The desired 1,8-cineole effects are attained through: specifically blocking H1 histamine receptors, without influencing ACh receptors Inhibiting the contractile activity of human bronchial smooth muscle by activating H2 histamine receptors. The ultimate goal of this study was to address the bronchodilatory effect of this compound, using human airway smooth muscle in order to demonstrate a possible role for 1,8-cineole in airway diseases. Keywords: Smooth muscle fibre; 1,8-cineole (eucalyptol); Human bronchial tissue; Bronchitis; Monoterpene

IgG4-related disease with tracheobronchial miliary nodules and asthma: a case report and review of the literature

Background IgG4-related disease (IgG4-RD) is a systemic autoimmune disease that can affect multiple organs of the body. Pulmonary manifestations of IgG4-RD include pulmonary solid nodules, thickening of bronchovascular bundles, interstitial involvement, and ground glass opacities. Here we present a rare case of IgG4-RD with tracheobronchial nodules and review the relevant literature. Case presentation A 52-year-old man was admitted to our hospital with a history of intermittent cough for 27 months and recurrent wheezing for 17 months. He had been diagnosed with asthma prior to admission and was responsive to oral prednisone (30 mg/day, with gradual tapering). Bronchoscopy performed 2 years prior to admission showed tracheal and bronchial mucosal hyperemia, edema, and miliary nodules. Pathological tests showed chronic inflammation with focal lymphocytic infiltration in the bronchial mucosa. The patient had recurrent cough and wheezing after prednisone was stopped or the dose reduced. At the time of admission to our hospital, his serum immunoglobulin G4 (IgG4) level had increased to 7.35 g/L. Following bronchoscopy, the IgG4 expression in the bronchial mucosa was compared with that observed during the last two bronchoscopies. Bronchoscopy performed 7 months prior to admission revealed IgG4+ plasma cell infiltration in the bronchial tissue, with > 10 IgG4+ plasma cells per high power field and an IgG4+/IgG+ cell ratio of > 40%. The current bronchoscopy revealed a decrease in IgG4 expression in the bronchial tissue, probably because of the intermittent prednisone treatment. The case fulfilled the comprehensive clinical diagnostic criteria for IgG4-RD. He received prednisone and azathioprine, and he has never developed recurrence. Conclusions Our case exhibited three important clinical indication: First, tracheobronchial miliary nodules could be the presentation of IgG4-related disease. Second, IgG4-related disease with pulmonary involvement has close connection with asthma. Last, IgG4-related disease can be very sensitive to prednisone, the infiltration of IgG4 positive plasma cells decreased after prednisone treatment and symptoms significantly improved in our case. In conclusion, we reported the first case of IgG4-RD presenting with miliary nodules on the tracheal and bronchial tube walls combined with asthma. The findings will further our understanding of the characteristics of IgG4-RD.