COPD is associated with increased pro-inflammatory CD28null CD8 T and NKT-like cells in the small airways

We previously showed increased steroid resistant CD28null CD8+ senescent lymphocyte subsets in peripheral blood from COPD patients. These cells expressed decreased levels of the glucocorticoid receptor (GCR), suggesting their contribution to the steroid resistant property of these cells. COPD is a disease of the small airways. We therefore hypothesized that there would be a further increase in these steroid resistant lymphocytes in the lung, particularly in the small airways. We further hypothesized that the pro-inflammatory/cytotoxic potential of these cells could be negated using prednisolone with low-dose cyclosporin A. Blood, bronchoalveolar lavage, large proximal and small distal airway brushings were collected from 11 COPD patients and 10 healthy aged-matched controls. The cytotoxic mediator granzyme b, pro-inflammatory cytokines IFNγ/TNFα, and GCR were determined in lymphocytes subsets before and after their exposure to 1µM prednisolone and/or 2.5ng/mL cyclosporin A. Particularly in the small airways, COPD subjects showed an increased percentage of CD28null CD8 T-cells and NKT-like cells, with increased expression of granzyme b, IFNγ and TNFα and a loss of GCR, compared with controls. Significant negative correlations between small airway GCR expression and IFNγ/TNFα production by T and NKT-like cells (eg, T-cell IFNγ R= -.834, p=.031) and with FEV1 (R= -890) were shown. Cyclosporine A and prednisolone synergistically increased GCR expression and inhibited pro-inflammatory cytokine production by CD28null CD8- T and NKT-like cells. COPD is associated with increased pro-inflammatory CD28null CD8+ T and NKT-like cells in the small airways. Treatments that increase GCR in these lymphocyte subsets may improve efficacy of clinical treatment.

Virtual Bronchoscopy as the Guide for Fiberoptic Bronchoscopy in Evaluating Tracheobronchial Disorders in the Bronchogenic Carcinoma

Fiberoptic bronchoscopy (FOB) is one of the important modalities in helping to uphold the diagnosis and stadium of bronchogenic carcinoma. However, FOB has some limitations, namely invasive, time-consuming, requiring sedation, intolerable in patients who are critically ill, and difficult to evaluate distal airway side of severe stenosis. To identify the imaging capability of virtual bronchoscopy (VB) examinations in evaluating abnormalities in the tracheobronchial in bronchogenic carcinoma. Observational study with total sampling. Data was obtained from the histopathologic with diagnosis of bronchogenic carcinoma in 1 year. Retrospectively, the data were obtained from the archives of thoracic CT examinations in Radiology and FOB examination in Lung Operating Room. The variables assessed were the finding of mass of endobronchial based on its location, the main bronchi constriction, lobar bronchi constriction, segmental bronchi constriction, and compression/tracheal deformity. The results of VB were examined by three radiologists independently and were then compared with the results of FOB. The observation results of VB and FOB were used to analyse the degree of conformity. There is a low level of agreement on the finding of endobronchial mass, lobar bronchi and segmental bronchi constriction, sufficient level of agreement on the main bronchial constriction finding. VB has a limited capacity to evaluate abnormalities of the tracheobronchial compared with FOB, but VB has an advantage in evaluating the patency of the distal airway of severe obstruction.

Complicated Paediatric Bronchial Foreign Body: A Novel Extraction Technique

A paediatric bronchoscopy procedure for foreign body inhalation is indeed a highly challenging procedure due to multiple risk factors such as lower physiological functional residual capacity and adverse pulmonary function effects by anaesthetic agents in addition to concurrent active lungs infection. Here we elucidate a novel technique of foreign body removal located at the distal airway in a paediatric patient and in a situation where a paediatric flexible bronchoscopy with built-in working channel is not available. A 1-year 7-months-old boy presented with acute respiratory distress syndrome following a one-week history of active respiratory infection. On examination, he was tachypnoeic with audible soft inspiratory stridor and intermittent barking cough despite being supplemented with 3 liters /minute oxygen mask. Chest x-ray showed right upper lobe collapse. He was referred to the otorhinolaryngology team after a suspicious history of foreign body aspiration obtained from his mother. Bedside flexible nasopharyngolaryngoscopy showed granulation tissue at the junction of laryngeal surface of epiglottis and anterior commissure. He underwent emergency direct laryngoscopy, tracheoscopy, bronchoscopy, excision of granulation tissue and removal of foreign body under general anaesthesia. Herein, some of complicated bronchoscopy demand critical thinking of alternative or modified techniques to achieve a successful and safe surgery. Bangladesh J Otorhinolaryngol 2021; 27(2): 177-183

Stable Long-Term Culture of Human Distal Airway Stem Cells for Transplantation

There is a population of p63+/Krt5+ distal airway stem cells (DASCs) quiescently located in the airway basal epithelium of mammals, responding to injury and airway epithelial regeneration. They hold the ability to differentiate into multiple pulmonary cell types and can repopulate the epithelium after damage. The current study aims at gaining further insights into the behavior and characteristics of the DASCs isolated from the patient lung and exploring their clinical translational potential. Human DASCs were brushed off through the bronchoscopic procedure and expanded under the pharmaceutical-grade condition. Their phenotype stability in long-term cell culture was analyzed, followed by safety evaluation and tumorigenic analysis using multiple animal models including rodents and nonhuman primate. The chimerism of the human-mouse lung model indicated that DASC pedigrees could give rise to multiple epithelial types, including type I alveolar cells as well as bronchiolar secretory cells, to regenerate the distal lung. Taken together, the results suggested that DASC transplantation could be a promising therapeutic approach for unmet needs in respiratory medicine including the COVID-19-related diseases.

COPD is associated with increased pro-inflammatory CD28null CD8 T and NKT-like cells in the small airways

We previously showed increased steroid resistant CD28null CD8+ senescent lymphocyte subsets in peripheral blood from COPD patients. These cells expressed decreased levels of the glucocorticoid receptor (GCR), suggesting their contribution to the steroid resistant property of these cells. COPD is a disease of the small airways. We therefore hypothesized that there would be a further increase in these steroid resistant lymphocytes in the lung, particularly in the small airways. We further hypothesized that the pro-inflammatory/cytotoxic potential of these cells could be negated using prednisolone with low-dose cyclosporin A. Blood, bronchoalveolar lavage, large proximal and small distal airway brushings were collected from 11 COPD patients and 10 healthy aged-matched controls. The cytotoxic mediator granzyme b, pro-inflammatory cytokines IFNγ/TNFα, and GCR were determined in lymphocytes subsets before and after their exposure to 1µM prednisolone and/or 2.5ng/mL cyclosporin A. Particularly in the small airways, COPD subjects showed an increased percentage of CD28null CD8 T-cells and NKT-like cells, with increased expression of granzyme b, IFNγ and TNFα and a loss of GCR, compared with controls. Significant negative correlations between small airway GCR expression and IFNγ/TNFα production by T and NKT-like cells (eg, T-cell IFNγ R= -.834, p=.031) and with FEV (R= -890) were shown. Cyclosporine A and prednisolone synergistically increased GCR expression and inhibited pro-inflammatory cytokine production by CD28null CD8- T and NKT-like cells. COPD is associated with increased pro-inflammatory CD28null CD8+ T and NKT-like cells in the small airways. Treatments that increase GCR in these lymphocyte subsets may improve morbidity in COPD patients.

Ventilating through Mobile and Migrated Montgomery T-tube: an Enigma

Montgomery T-tube used to maintain a patent airway in post tracheostomised patients can act like a double edged sword. We report a case where a T-tube migrated into distal airway leading a precarious situation.

Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

The airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.