Kern, Ryan

Abstract Rationale: Airway-stenosing disease is a significant clinical problem in multiple populations. While the immediate endoscopic and clinical response to bronchoscopic interventions are high, rates of clinically significant recurrence are elevated, and often require multiple and frequent reinterventions. Newer strategies to prevent recurrence of central and proximal airway stenosis are needed. Methods: Retrospective review of bronchoscopic balloon bronchoplasties performed at the Mayo Clinic utilizing paclitaxel coated balloons (PCB) in 2023-2024 for recurrent airway stenosis. IN.PACT Admiral and AV balloons (sizes 5-12 mm, 3.5 mcg/mm2 paclitaxel dose) were used with an inflation time of 2-3 minutes. Procedural success was defined as <50% airway stenosis or resolution of the procedural indication. Reintervention was considered only if a therapeutic bronchoscopy was subsequently required to address the same lesion treated with PCB. Only patients with follow-ups >90 days were included in the reintervention inter-procedural time analysis. Results: Thirty-three procedures were performed in 18 patients. Seventeen (51%) for lung transplantation-associated stenosis (29% anastomotic/perianastomotic, 76% lobar and segmental stenoses), 8 (24%) for granulomatous polyangiitis-associated stenosis, 3 for postintubation tracheal stenosis and 2 for chemical/pill injury. Eighteen cases (54%) utilized an additional dilation modality (12 non-coated balloon dilation, 4 rigid dilation), 5 spray cryotherapy, 6 other ablative therapies (4 CO2-laser, 2 electrocautery cuts), and 6 received an airway stent during the same procedure. 57% percent of interventions occurred in the lobar, 27% mainstem/bronchus intermedius, 9% tracheal, 7% segmental airways. Thirty-one (93%) cases had a satisfactory initial endoscopic result. The median number of bronchoscopic therapeutic interventions required before the use pf PCB was 5 (IQR 2.5-11.5), which significantly decreased to 0.1 (IQR 0-1, range 0-9) after PCB (p <0.001). The reintervention-free survival significantly increased after PCB dilation from a median 35 days (IQR 28.7-80.5) to 132 days (IQR 64-197; p=0.004). Twenty-one cases required subsequent bronchoscopies, sixteen (76%) of which demonstrated improvement in lesion severity when compared to the results of prior interventions. Only 16 (48%) required therapeutically addressing the same lesion. Only 2 minor complications occurred (6%, self-limited bleeding and unplanned admission), none related to paclitaxel use. Six-month mortality was 3% from an unrelated cause. Conclusions: The locoregional antiproliferative effects of paclitaxel show promise in preventing recurrence, minimizing the need for repeat procedures, and extending intervals between interventions in patients with recurrent, predominantly benign airway stenosis. Its use is feasible, safe, and future research is warranted, particularly comparing PCB with the currently available strategies.

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with few focusing on samples derived from affected tissues. Furthermore, clinical studies alone often provide correlative insights rather than causal mechanisms. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to understand the etiology of PASC. In this study, we comprehensively compared bronchoalveolar lavage fluid single-cell RNA sequencing data derived from clinical PASC samples and a mouse model of PASC. This revealed a pro-fibrotic monocyte-derived macrophage response in respiratory PASC, as well as abnormal interactions between pulmonary macrophages and respiratory resident T cells, in both humans and mice. Interferon-γ (IFN-γ) emerged as a key node mediating the immune anomalies in respiratory PASC. Neutralizing IFN-γ after the resolution of acute SARS-CoV-2 infection reduced lung inflammation and tissue fibrosis in mice. Together, our study underscores the importance of performing comparative analysis to understand the cause of PASC and suggests that the IFN-γ signaling axis might represent a therapeutic target.

Background: CO2 Laser (CO2L) technology deployable through flexible endoscopes now allows for their use throughout the airway, although published data are limited. Methods: Retrospective analysis of CO2L bronchoscopic procedures, excluding glottic and subglottic interventions. Procedural success was defined as >50% visual reduction in airway obstruction in the area treated or resolution of the procedural indication. Results: Seventy-two procedures were performed on 36 patients. Nonmalignant indications comprised 66%: stent-associated granulation tissue (28%), granulomatosis with polyangiitis lesions (23%), and lung transplant-related granulation tissue (16%) were the most common. Bronchoscopic access was flexible only in 81% and primarily rigid (combined with flexible) in 18%. The site of intervention was the trachea at 19%, the mainstem at 56%, and lobar/segmental airways at 45%. Procedural success was 89%. CO2L was used exclusively in 19%; in 81%, additional techniques were required, most commonly balloon dilation (59%), cryo-debulking (23%), and rigid dilation (16%). Malignant indications had a nonsignificant trend toward requiring adjuvant techniques (P=0.05). Seventy-six percent of the patients required more than 1 procedure. CO2L exclusive cases had no statistically different needs for subsequent therapeutic bronchoscopies (P=0.10) or time to reintervention (109 vs. 41 days, P=0.07), and reintervention-free survival was similar (P=0.10) and difficult to predict. The complication rate attributable to CO2L was 2.7%. Conclusion: CO2L is a safe and useful tool when precise cutting and vaporization are desired. Its use in multi-modality approaches has high levels of success in adequately selected lesions, adding an ablative potential to dilation techniques. Vasculitis-associated scars/webs and granulation tissue (including stent-associated) appear to be ideal targets.

Background: Prescription opioids are a major cause of the opioid epidemic. Despite the minimally invasive nature of medical thoracoscopy (MT), data on the efficacy of non-opioid-based pain control after MT is lacking. The purpose of this study is to assess the feasibility and efficacy of a non-opioid-based pain management strategy in patients who underwent MT. Methods: We performed a retrospective analysis of all patients who underwent MT in the Mayo Clinic (Minnesota and Arizona) outpatient setting. We assessed their pain level and the need for analgesia post-MT from August 1, 2019, to May 24, 2021. Results: Forty patients were included. In the first 24 hours, 5/40 (12.5%) reported no pain. Twenty-eight patients out of 40 (70%) reported minor pain (pain scale 1-3), and 7/40 (17.5%) reported moderate pain (pain scale 4-6). No patients reported severe pain. Twenty-two out of 35 patients who experienced discomfort (63%) required acetaminophen, 6/35 patients (17%) required nonsteroidal anti-inflammatory drug, and 7/35 patients (20%) did not require analgesia. Of the 7 patients who had moderate pain, 5 (71%) reported that the moderate pain improved to mild at 72 hours post-MT. Zero patients required opioids, and none reported contacting any provider to manage the pain post-MT. Fourteen patients (78%) who had both parietal pleural biopsies and tunneled pleural catheter placed reported minor pain, 3 patients (17%) reported moderate pain, and 1 patient (6%) experienced no discomfort. Conclusion: MT is well-tolerated by patients with non-opioid-based pain management strategy as needed if there is no absolute contraindication.

Abstract Purpose: The purpose of this study was to evaluate the feasibility and specimen quality of lymph node biopsies prepared through a novel automated system for automated fixation, drying and staining compared to standard slide preparation method. Methods: We performed a prospective, single-center study of patients undergoing endobronchial ultrasound. Samples were split into conventional standard of care (SOC) slide preparation and preparation using the device (ASP). Pathologists compared the SOC slides to the slides prepared by the automated system and assessed the following metrics: nuclear and cytoplasmic quality, presence of debris/artifact, staining quality, creation of a monolayer, and ease of adequacy/diagnosis assessment. A score between 1 (lowest quality) and 3 (highest quality) was assigned to the above metrics. Results: 60 patients were recruited. One to three lymph nodes were sampled for each patient with a total of 73 samples collected. The mean scores of each assessment category showed no statistical difference between the two preparation techniques except for improved monolayer creation in the ASP samples. All samples showed diagnostic equivalency between the automated slides and conventional slides except for one which was reported to be suspicious on the ASP sample and atypical on the SOC. Conclusion: Study results suggest that slides prepared by the automated system are of adequate quality for adequacy assessment with diagnostic concordance when compared to SOC slides.

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S–specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19–vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.