Faculty Bibliography

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in group IIIB-IV TNM stage lung cancer and is associated with poor prognosis, as shown by decreased survival among subjects with early stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with IIIB-IV stage disease. In addition, this lower airway microbiota signature was associated with upregulation of IL-17, PI3K, MAPK and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL-17 inflammatory phenotype and activation of checkpoint inhibitor markers.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Rigid tracheobronchoscopy (RTB) has seen an increasing interest over the last decades with the development of the field of IPM but no benchmark exists for complication rates in RTB. We aimed to establish benchmarks for complication rates in RTB. METHODS:A multicentric retrospective analysis of RTB performed between 2009 and 2015 in eight participating centres was performed. RESULTS:A total of 1546 RTB were performed over the study period. One hundred and thirty-one non-lethal complications occurred in 103 procedures (6.7%, 95% CI: 5.5-8.0%). The periprocedural mortality rate was 1.2% (95% CI: 0.6-1.8%). The 30-day mortality rate was 5.6% (95% CI: 4.5-6.8%). Complication rate increases further when procedures were performed in an emergency setting. Procedures in patients with MAO are associated with a higher 30-day mortality (8.1% vs 2.7%, P < 0.01) and a different complication profile when compared to procedures performed for BAS. CONCLUSION/CONCLUSIONS:RTB is associated with a 6.7% non-lethal complication rate, a 1.2% periprocedural mortality rate and a 5.6% 30-day mortality in a large multicentre cohort of patients with benign and malignant airway disease.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine in a 3- to 4-year recurring cycle of topics. The topics of the 2020 Pulmonary Core Curriculum include pulmonary vascular disease (submassive pulmonary embolism, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension) and pulmonary infections (community-acquired pneumonia, pulmonary nontuberculous mycobacteria, opportunistic infections in immunocompromised hosts, and coronavirus disease [COVID-19]).

BACKGROUND:COVID-19 is a worldwide pandemic, with many patients requiring prolonged mechanical ventilation. Tracheostomy is not recommended by current guidelines as it is considered a super-spreading event due to aerosolization that unduly risks healthcare workers. METHODS:Patients with severe COVID-19 that were on mechanical ventilation ≥ 5 days were evaluated for percutaneous dilational tracheostomy. We developed a novel percutaneous tracheostomy technique that placed the bronchoscope alongside the endotracheal tube, not inside it. This improved visualization during the procedure and continued standard mechanical ventilation after positioning the inflated endotracheal tube cuff in the distal trachea. This technique offers a significant mitigation for the risk of virus aerosolization during the procedure. RESULTS:From March 10 to April 15, 2020, 270 patients with COVID-19 required invasive mechanical ventilation at New York University Langone Health Manhattan's campus of which 98 patients underwent percutaneous dilational tracheostomy. The mean time from intubation to the procedure was 10.6 days (SD ±5 days). Currently, thirty-two (33%) patients do not require mechanical ventilatory support, 19 (19%) have their tracheostomy tube downsized and 8 (8%) were decannulated. Forty (41%) patients remain on full ventilator support, while 19 (19%) are weaning from mechanical ventilation. Seven (7%) died as result of respiratory and multiorgan failure. Tracheostomy related bleeding was the most common complication (5 patients). None of health care providers have developed symptoms or tested positive for COVID-19. CONCLUSIONS:Our percutaneous tracheostomy technique appears to be safe and effective for COVID-19 patients and safe for healthcare workers.

OBJECTIVES/OBJECTIVE:Tumor draining lymph nodes (TDLN) are key sites of early immunoediting in patients with non-small cell lung cancer (NSCLC) and play an important role in generating anti-tumor immunity. Immune suppression in the tumor microenvironment has prognostic implications and may predict therapeutic response. T cell composition of draining lymph nodes may reflect an immunophenotype with similar prognostic potential which could be measured during standard-of-care bronchoscopic assessment. In this study, we compared the immunophenotype from different sites within individuals to primary tumor characteristics in patients with NSCLC to see whether there were tumor-regional differences in immunophenotype which could be evaluated from transbronchial needle aspirates. MATERIALS AND METHODS/METHODS:Twenty patients were enrolled in this study and had tissue (lymph node aspirates and/or peripheral blood) obtained during standard of care bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis or staging of known or suspected NSCLC. Aspirates and blood underwent flow-assisted cell sorting and a subset of sorted effector T cells underwent RNA quantitation to determine feasibility of this approach. Immunophenotypic patterns from twelve patients with paired data from tumor-draining and non-tumor draining lymph nodes (NDLN) were compared relative to one another and based on PD-L1 immunohistochemistry and primary tumor histology. RESULTS: T cell depletion compared to patients with PD-L1 expression <50% (-35.98% vs -1.89%, p = 0.0357; negative values represent absolute difference between paired TDLN and NDLN). CONCLUSIONS:In patients with NSCLC, TDLN have a suppressive immunophenotype correlating with tumor PD-L1 status and can be assessed during routine EBUS-TBNA.

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.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Intratumoral administration of chemotherapeutic agents is a treatment modality that has proven efficacious in reducing the recurrence of tumours and increases specificity of treatment while minimizing systemic side effects. Direct intratumoral injection of malignant airway obstruction has potential therapeutic benefits but tissue drug concentrations and side-effect profiles are poorly understood. METHODS:Bronchial wall injection of generic paclitaxel (PTX) (102 injections of 0.05, 0.5, 1.5 or 2.5 mg/mL in 10 healthy pigs), saline (14 injections in 2 healthy pigs) or Abraxane (ABX) (24 injections of 0.5 mg/mL in 4 healthy pigs) was performed with a microneedle infusion catheter. Local histopathology, plasma and tissue PTX concentrations were evaluated at 7, 20 or 28 days post-injection. RESULTS:of 6300 ng h/mL for the approved intravenous dose. At 7 and 28 days post-injection, bronchial PTX tissue concentrations were above a 10-nmol/L cancer therapeutic level. PTX was not found in peripheral tissues. Similar results were observed between ABX and generic PTX. CONCLUSION/CONCLUSIONS:Results of these studies confirm the administration of PTX directly into the bronchial wall is safe and feasible. PTX was detectable in plasma for <7 days but tissue concentrations remained therapeutic throughout the follow-up period.