Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration: A pilot study.

OBJECTIVES: 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: 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: TDLN had significantly fewer CD4+ T cells (12.68% vs 27%, p = 0.002) and significantly more regulatory T cells (Treg, 12.03% vs 9.52%, p = 0.03) relative to paired NDLN suggesting tumor-regional immunosuppression. There were significantly more Treg in NDLN relative to paired PBMC (9.52% vs 5.6%, p = 0.016). Patients with PD-L1 expression ≥50% had significantly greater tumor-regional CD4+ 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.

Multiple epinephrine doses for stinging insect hypersensitivity reactions treated in the emergency department.

BACKGROUND: Data are sparse on epinephrine treatment for stinging insect hypersensitivity (SIH) reactions. OBJECTIVE: To establish the frequency of receiving more than 1 dose of epinephrine in patients presenting to the emergency department (ED) with SIH reactions. METHODS: We performed a medical record review of all 153 patients with SIH reactions presenting to 3 EDs in Boston, Massachusetts, between January 1, 2001, and December 31, 2006. Patients were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes (989.5, 995.0, and 995.3). We focused on clinical presentations and treatments, including epinephrine treatments given before and during the ED visit. RESULTS: The cohort was 54% male, with a median age of 33 years. Bees were the most frequently reported triggering insect (74%). A total of 59% of patients experienced large local reactions, whereas 36% had systemic reactions (10% cutaneous systemic and 26% anaphylaxis). The remaining 5% presented with normal local reactions to insect stings. Among patients with systemic reactions, 82% were stung within 3 hours of arrival at the ED. Most (60%) received treatments before arrival at the ED, including 26% who received epinephrine. While in the ED, these patients received antihistamines (76%), systemic corticosteroids (55%), and epinephrine (9%). Overall, 35% of patients with systemic reactions received epinephrine, and among this subset, 16% received more than 1 dose. Most patients with systemic reactions (67%) were discharged to home. At ED discharge, 68% received a prescription for self-injectable epinephrine, but only 11% had documentation of referral to an allergist. CONCLUSIONS: Among patients with systemic SIH reactions who received epinephrine, 16% received a second dose. Physicians should consider prescribing 2 doses of self-injectable epinephrine for patients at risk for systemic SIH reactions.