Faculty Bibliography

Malignant pleural effusions (MPE) complicate malignancies and portend worse outcomes. MPE is comprised of various components, including immune cells, cancer cells, and cell-free DNA/RNA. There have been investigations into using these components to diagnose and prognosticate MPE. We hypothesize that the microbiome of MPE is unique and may be associated with diagnosis and prognosis. We compared the microbiota of MPE against microbiota of pleural effusions from non-malignant and paramalignant states. We collected a total of 165 pleural fluid samples from 165 subjects; Benign (n = 16), Paramalignant (n = 21), MPE-Lung (n = 57), MPE-Other (n = 22), and Mesothelioma (n = 49). We performed high throughput 16S rRNA gene sequencing on pleural fluid samples and controls. We showed that there are compositional differences among pleural effusions related to non-malignant, paramalignant, and malignant disease. Furthermore, we showed differential enrichment of bacterial taxa within MPE depending on the site of primary malignancy. Pleural fluid of MPE-Lung and Mesothelioma were associated with enrichment with oral and gut bacteria that are commonly thought to be commensals, including Rickettsiella, Ruminococcus, Enterococcus, and Lactobacillales. Mortality in MPE-Lung is associated with enrichment in Methylobacterium, Blattabacterium, and Deinococcus. These observations lay the groundwork for future studies that explore host-microbiome interactions and their influence on carcinogenesis.

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.

BACKGROUND:In March 2020, the United States Centers for Disease Control and Prevention recommended cancelation of elective medical services in response to the COVID-19 pandemic. The daily case rate is now declining in many states and there is a need for guidance about the resumption of elective clinical services for patients with lung disease or sleep conditions. METHODS:Volunteers were solicited from the Association of Pulmonary, Critical Care, and Sleep Division Directors (APCCSDD) and American Thoracic Society (ATS). Working groups developed plans by discussion and consensus for resuming elective services in pulmonary and sleep medicine clinics, pulmonary function testing laboratories, bronchoscopy and procedural suites, polysomnography laboratories, and pulmonary rehabilitation facilities. RESULTS:The community new case rate should be consistently low or have a downward trajectory for at least 14 days before resuming elective clinical services. In addition, institutions should have an operational strategy that consists of patient prioritization, screening, diagnostic testing, physical distancing, infection control, and follow-up surveillance. The goals are to protect patients and staff from exposure to the virus, account for limitations in staff, equipment, and space that are essential for the care of COVID-19 patients, and provide access to care for patients with acute and chronic conditions. CONCLUSIONS:Transmission of SARS-CoV-2 is a dynamic process and, therefore, it is likely that the prevalence of COVID-19 in the community will wax and wane. This will impact an institution's mitigation needs. Operating procedures should be frequently reassessed and modified as needed. The suggestions provided are those of the authors and do not represent official positions of the APCCSDD or the ATS.

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:Our objectives are to present our outcomes of robotic segmentectomy and our preferred technique for nodule localization using indocyanine green both bronchoscopically and intravenously. METHODS:This is a retrospective review of a consecutive series of patients scheduled for robotic segmentectomy from a single surgeon's prospectively collected database. RESULTS:Between January 2010 and October 2018, there were 245 consecutive patients who underwent planned robotic segmentectomy by one surgeon, of which 93 (38%) received indocyanine green via electromagnetic navigational bronchoscopy and all 245 received intravenous indocyanine green. Median time for navigational bronchoscopy was 9 minutes. Navigational bronchoscopy with indocyanine green correctly identified the lesion in 80 cases (86%). Our preferred technique is: 0.5 mL of 25 mg of indocyanine green diluted in 10 mL of saline given bronchoscopically, followed by a 0.5 mL saline flush, staying at least 4 mm from the pleural surface. The remaining 9.5 mL of indocyanine green is administered intravenously after pulmonary artery ligation. An R0 resection was achieved in all 245 patients, a median of 17 lymph nodes were resected, and the average length of stay was 3.1 days (range 1-21 days). Major morbidity occurred in 3 patients and there were no 30 or 90-day mortalities. CONCLUSIONS:Robotic segmentectomy is safe with excellent early clinical outcomes. In our series, electromagnetic navigational bronchoscopy and indocyanine green localization is efficient and effective at identifying the target lesion. Intravenous indocyanine green delineates the intersegmental plane.

As many as 25% of all patients undergoing invasive pulmonary procedures are receiving at least one antiplatelet or anticoagulant agent. For those undergoing elective procedures, the decision-making process is uncomplicated and the procedure may be postponed until the antiplatelet or anticoagulant agent may be safely held. However, many invasive pulmonary procedures are semi-elective or emergent in nature in which case a risk-benefit calculation and discussion occur between the provider and patient or surrogate decision-maker. Therefore, it is critical for providers to have an awareness of the risk of bleeding complications with different pulmonary procedures on various antiplatelet and anticoagulant agents. This systematic review summarizes the bleeding complications associated with different pulmonary procedures in patients on various antiplatelet or anticoagulant agents in the literature and reveals a paucity of high-quality evidence across a wide spectrum of pulmonary procedures and antiplatelet or anticoagulant agents. The results of this review can help inform providers of the bleeding risk in these patients to aid in the shared decision-making process and risk vs benefit discussion.

BACKGROUND:In lung cancer, upregulation of the PI3K pathway is an early event that contributes to cell proliferation, survival, and tissue invasion. Upregulation of this pathway was recently described as associated with enrichment of the lower airways with bacteria identified as oral commensals. We hypothesize that host-microbe interactions in the lower airways of subjects with lung cancer affect known cancer pathways. METHODS:Airway brushes were collected prospectively from subjects with lung nodules at time of diagnostic bronchoscopy, including 39 subjects with final lung cancer diagnoses and 36 subjects with non-cancer diagnosis. Additionally, samples from 10 healthy control subjects were included. 16S rRNA gene amplicon sequencing and paired transcriptome sequencing (RNAseq) were performed on all airway samples. In addition, an in vitro model with airway epithelial cells exposed to bacteria/bacterial products was performed. RESULTS:The composition of the lower airway transcriptome in the cancer patients was significantly different from the controls, which included upregulation of ERK and PI3K signaling pathways. The lower airways of lung cancer patients were enriched for oral taxa (Streptococcus and Veillonella), which was associated with upregulation of the ERK and PI3K signaling pathways. In vitro exposure of airway epithelial cells to Veillonella, Prevotella, and Streptococcus led to upregulation of these same signaling pathways. CONCLUSIONS:The data presented here shows that several transcriptomic signatures previously identified as relevant to lung cancer pathogenesis are associated with enrichment of the lower airway microbiota with oral commensals.