Fernandez-Bussy, Sebastian

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide, and despite advances in treatment, immune suppression remains an obstacle to effective therapy. Effector CD4+ T cells (CD4+ Teff) are critical for antitumor immunity, but their function is often inhibited by regulatory T cells (Treg), which accumulate in lung tumors and mediate suppressive functions through multiple mechanisms. This suppression leads to tumor progression and poor patient outcomes. However, the mechanisms underlying Treg-mediated suppression are not fully understood. Herein, we identify the extracellular adenosine 5-triphosphate receptor P2RX7 as a key regulator of Treg function in lung tumors. In a murine lung cancer model induced by Lewis lung carcinoma cells, we found that P2RX7 enhanced the suppressive capacity of tumor-infiltrating Tregs, promoting tumor growth. In T cell–specific P2RX7-knockout (P2RX7-KO) mice, reduced Treg infiltration was accompanied by increased CD4+ Teff accumulation and improved tumor control. Treg-specific P2RX7-KO mice exhibited reduced tumor growth, confirming a Treg-intrinsic role of P2RX7. Suppression assays revealed that tumor-infiltrating wild-type Tregs had greater suppressive activity compared with P2RX7-KO Tregs, which failed to inhibit type 1 and follicular helper T–like responses. This was associated with increased tumor-specific IgG production by lung B cells in P2RX7-KO mice. We also observed that wild-type Tregs expressed higher levels of the immunosuppressive molecule CTLA-4 when compared with P2RX7-KO Tregs. Thus, we conclude that P2RX7 expression on Tregs is essential for their suppressive function in lung cancer and targeting P2RX7 may constitute a strategy to improve lung cancer treatment by alleviating Treg-mediated immune suppression.

ABSTRACTAlthough current treatment strategies for nonmalignant airway stenosis may offer short‐term relief, their effectiveness is limited by high recurrence rates, often requiring additional procedures. While paclitaxel‐coated balloons (PCB) have demonstrated effectiveness in treating stenosis across various vascular and nonvascular conditions, their evidence in recurrent airway stenosis remains limited. Here, we present the case of a 35‐year‐old female with bronchial stenosis who underwent multiple bronchoscopic interventions, all of which were complicated by restenosis. Following the addition of a PCB to the therapeutic regimen, the patient achieved sustained airway patency.

AbstractExpiratory central airway collapse (ECAC) comprising excessive central airway collapse (EDAC) and tracheobronchomalacia. Treatment is challenging for severe cases that are not candidates for surgical management. We report a case of severe ECAC successfully managed with continuous positive airway pressure (CPAP) therapy. A 75‐year‐old female patient status post right pneumonectomy, presented with chronic cough. Dynamic bronchoscopy evaluation showed severe EDAC which improved with intraprocedural noninvasive positive pressure (NIPPV) therapy. Due to patients' comorbidities, she was not a candidate to surgical tracheobronchoplasty. Therefore, we attempted pneumatic stenting with long‐term CPAP therapy resulting in improvement of symptoms and functional capacity. The long‐term efficacy of pneumatic stenting has not been clearly established yet. Literature review of management of ECAC with NIPPV consist primarily of case reports and there is only one clinical trial being conducted to assess the efficacy of CPAP therapy in ECAC. While NIPPV arises as a sufficient alternative for management of severe ECAC, larger scale studies are needed to prove the real efficacy of NIPPV in this setting.

AbstractBackground and ObjectiveShape‐sensing robotic‐assisted bronchoscopy (ssRAB) has expanded as an important diagnostic tool for peripheral pulmonary nodules (PPNs), with diagnostic yields ranging from 60% to 88%. However, sampling and diagnosing PPN less than 2 cm in size has historically been challenging. Mobile cone‐beam computed tomography (mCBCT) has been recently integrated into ssRAB to improve diagnostic accuracy, but its added value remains uncertain. We aim to describe the role of mCBCT and determine if it provides any diagnostic advantage.MethodsA multicentre, retrospective study on the use of ssRAB and mCBCT in two tertiary care institutions: Mayo Clinic Florida and Massachusetts General Hospital. The primary outcome was diagnostic yield and sensitivity for malignancy of ssRAB complemented with mCBCT, compared to ssRAB with the standard 2D fluoroscopy.ResultsA total of 192 nodules were biopsied from 173 patients. mCBCT was used in 117 (60.9%) nodules. The overall diagnostic yield was 85.4%. Diagnostic yield between subgroups with and without mCBCT was 83.8% and 88% (p = 0.417), respectively. The mCBCT group had fewer solid nodules (65.8% vs. 81.3%, p = 0.020) and a higher number of ground‐glass nodules (10.3% vs. 1.3%, p = 0.016).ConclusionOverall, diagnostic yield between subgroups with and without mCBCT was similar. The complementary use of mCBCT to ssRAB allows proceduralists to target more complex and subsolid PPNs with a diagnostic yield comparable to simple solid PPNs while maintaining an excellent safety profile.

AbstractTracheobronchial stenosis (TBS) in adults derives from congenital and acquired conditions, including prolonged mechanical intubation, expiratory central airway collapse, infectious or inflammatory disease, and malignancy. The most common clinical presentation is shortness of breath, recurrent infections, and chronic cough. TBS is usually diagnosed via computed tomography or bronchoscopy, with the latter doubling as a therapeutic tool. We present a case of an atypical fibrotic bridge connecting the walls of the distal trachea and fibrotic bronchial stenosis treated with electrocautery knife and balloon dilation, in an adult patient with bronchopulmonary dysplasia.

AbstractLung cancer is the deadliest cancer worldwide, therefore, early and prompt diagnosis is essential for better patient outcomes. It is known to have a high predilection for metastasis to the adrenal glands; however, two‐thirds of adrenal masses in patients with lung cancer will turn out to be benign, so timely detection is crucial. We present a case of a lung squamous cell carcinoma diagnosed by shape‐sensing robotic‐assisted bronchoscopy (ssRAB), negative mediastinal and hilar staging with endobronchial ultrasound (EBUS) and transbronchial needle aspiration (TBNA), and a pheochromocytoma diagnosed through endoscopic ultrasound with bronchoscope (EUS‐B) fine needle aspiration (FNA) all in the same endoscopic procedure.

AbstractRobotic‐assisted bronchoscopy (RAB) improves endoscopic diagnostic yield of solitary pulmonary nodules (SPN). Needle‐based confocal laser endomicroscopy (nCLE) is an emerging technology that allows high‐resolution, in‐vivo, real‐time assessment of living tissues at a cellular and subcellular level. Their combined use has been scarcely reported. We used them simultaneously in three patients with SPNs. For each, the nodule was evaluated with nCLE and sampled for pathology, followed by mediastinal staging. Median age was 77 years (67% male). Median nodule minimum size was 1.8 cm and maximum was 2.1 cm. nCLE detected abnormal patterns suggestive of malignancy for all nodules and pathology confirmed primary lung adenocarcinomas in two patients and lung primary squamous cell carcinoma in the other. The combined use of RAB with nCLE may potentially enhance the differentiation of malignant cells in real‐time and increase sample adequacy, accuracy, and diagnostic yield when biopsying a suspicious pulmonary lesion.