Faculty Bibliography

Background: Aspiration is associated with non-tuberculous mycobacterial (NTM) pulmonary disease and airway dysbiosis is associated with increased inflammation. We examined whether NTM disease was associated with a distinct airway microbiota and immune profile.Methods: 297 oral wash and induced sputum samples were collected from 106 participants with respiratory symptoms and imaging abnormalities compatible with NTM. Lower airway samples were obtained in 20 participants undergoing bronchoscopy. 16S rRNA gene and a nested mycobacteriome sequencing approaches characterised microbiota composition. Inflammatory profiles of lower airway samples were also examined.Results: The prevalence of NTM+ cultures was 58%. Few changes were noted in microbiota characteristic or composition in oral wash and sputum samples among groups. Among NTM+ samples, 27% of the lower airway samples were enriched with Mycobacterium A mycobacteriome approach identified Mycobacterium in a greater percentage of samples, including some non-pathogenic strains. In NTM+ lower airway samples, taxa identified as oral commensals were associated with increased inflammatory biomarkers.Conclusions: The 16S rRNA gene sequencing approach is not sensitive in identifying NTM among airway samples which are culture positive. However, associations between lower airway inflammation and microbiota signatures suggest a potential role for these microbes in the inflammatory process in NTM disease.

Interventional pulmonology is an innovative branch of pulmonary medicine that uses minimally invasive diagnostic and therapeutic approaches to airway, parenchymal, and pleural disease. The author reviews recent high-impact trials including randomized trials describing the use of endobronchial coils and valves in the management of severe emphysema. Novel approaches to the palliation of malignant and benign pleural effusion including increasing the frequency of drainage and instillation of talc via tunneled pleural catheters are also presented. In addition, a recent consensus paper discussing the optimal use and technique of cryobiopsy in diffuse parenchymal disease is reviewed, as well as a systematic review and meta-analysis of its diagnostic yield. The final trial reviewed in this article describes the preliminary safety and efficacy study of a novel endobronchial, balloon, and injection catheter for the local administration of chemotherapy into the airway mucosa so as to minimize the systemic absorption of these agents.

Background: There is growing appreciation for the role of tumordraining lymph nodes (TDLN) in the dynamic of immuno-editing orchestrated by non-small cell lung cancers (NSCLC). By comparing Tcell subsets and gene expression in TDLN and non-draining lymph nodes (NDLN), we aim to determine whether there is tumor-regional variation in immunophenotype. Method: Patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis/staging of NSCLC were recruited. Aspirates were obtained from TDLN (N1/N2 nodes with increased fluorodeoxyglucose-F-18 (FDG) avidity and/or enlarged >1cm) and NDLN (non-enlarged/non- FDG-avid N2/N3 nodes) along with peripheral blood. Samples were stained with fluorophore-conjugated antibodies (CD4-FITC, CD8-V450, CD25-PECy7, CD127-APCR700, CD45RO-PECF594) and analyzed by flow cytometry. CD4+CD25- and CD8+ effector T-cells (Teff) were sorted. Gene expression profiling was performed on sorted Teff using the NanostringTM platform to measure differential expression between TDLN and NDLNs. Result: We compared T-cell subpopulations in TDLN and paired NDLN from 16 subjects. There were significantly fewer CD4+ T-cells in TDLN vs NDLN (10.1% vs 28.9%, p=0.0039), with more Tregs (12.1% vs 7.3%, p=0.1563) suggesting a pattern of tumorregional immunosuppression in the TDLN. This was more consistent when tumor histology was adenocarcinoma compared to squamous cell cancer with respect to both depletion of Teff and higher proportion of Tregs (Fig 1). A more immunosuppressive TDLN phenotype was also observed with high tumor PD-L1 expression (>50%), with 36% fewer CD4+ T-cells in TDLN relative to paired NDLN when PD-L1 expression was high relative to just 3.2% fewer CD4+ T-cells with low PD-L1 expression. Gene expression in Teff has preliminarily demonstrated upregulation of genes mediating T-cell exhaustion (CTLA-4, PD-1, TGFb) and downregulation of co-stimulatory/recruitment factors (CD28, ICOS, ICAM2) in TDLN suggesting impaired activation of tumorregional Teff. Conclusion: Our findings suggest that TDLNs in patients with NSCLC display a tolerogenic phenotype, with more marked immunosuppression in the setting of adenocarcinoma and high tumor PD-L1 expression. (Figure Presented)

INTRODUCTION: We describe the evaluation and management of a patient with airway obstruction due to retained surgical material who was being treated as refractory asthma. CASE PRESENTATION: A 61 year old woman was referred for wheezing, dyspnea, and cough. She was steroid dependent in the setting of "poorly controlled asthma" and recurrent pneumonias. Fourteen years earlier she had undergone left lower lobectomy for "carcinoid". Given her refractory symptoms and lack of recent imaging, a CT chest was ordered. CT scan showed left mainstem obstruction. Bronchoscopy revealed complete left mainstem obstruction due to retained surgical pledgets. Extraction was not attempted given potential for major bleeding or loss of airway integrity. Intra-operative thoracic surgery consult was requested, leading to a decision to defer removal until a surgical team was available for urgent rescue completion pneumonectomy. A ventilation-perfusion (V/Q) scan was performed to characterize left lung physiology prior to interventions including relief of airway obstruction and possible completion pneumonectomy. There was decreased ventilation and perfusion of the left lung with split function of eight percent. A rigid bronchoscope was advanced into the left main bronchus. A needle knife at 20 watts was used to cut sutures retaining the pledgets and forceps were used for pledget and suture removal. The patient was extubated soon after the procedure and was discharged the following day. She was seen in follow-up and reported resolution of her symptoms and improved exercise tolerance. Repeat V/Q scan showed improved ventilation and perfusion with split function of twenty two percent. DISCUSSION: Transbronchial erosion of surgical material is rare, and literature describing removal of these foreign bodies is limited 1. Here we describe an approach including multi-disciplinary decision making, preparing for emergent complications during removal of the material, assessment of the patient's ability to tolerate foreign body removal and possible completion pneumonectomy, as well as rigid bronchoscope techniques for definitive removal. CONCLUSIONS: Foreign bodies due to transbronchial erosion are best approached with proper preparation and planning as we have described here