Incremental Application of Positive End-Expiratory Pressure for the Evaluation of Atelectasis During RP-EBUS and Bronchoscopy (I-APPEAR).

BACKGROUND: CT-to-body divergence-described as the difference between preprocedural CT scans and intraprocedural lung architecture-is a significant barrier to improving diagnostic yield during navigational bronchoscopy. A major proposed contributor to CT-to-body divergence is the development of atelectasis, which can confound visualization of peripheral lung lesions via radial probe endobronchial ultrasound (RP-EBUS). High positive end-expiratory pressure (PEEP) ventilatory strategies have been used to decrease atelectasis, allowing the lesion to re-APPEAR on intraprocedure imaging. However, standardized PEEP levels may not be appropriate for all patients due to hemodynamic and ventilatory impacts. METHODS: We performed a multicenter, prospective observational study in which patients were imaged with RP-EBUS under general anesthesia to determine if subsegmental atelectasis would resolve as incremental increases in PEEP were applied. Resolution of atelectasis was based on the transition from a non-aerated pattern to an aerated appearance on RP-EBUS. RP-EBUS images were reviewed by 3 experienced operators to determine correlation. RESULTS: Forty-three patients underwent RP-EBUS examination following navigational bronchoscopy. Thirty-seven patients underwent incremental PEEP application and subsequent RP-EBUS imaging. Atelectasis was determined to have resolved in 33 patients (88.2%) following increased PEEP. The intraclass correlation coefficient between reviewers was 0.76. A recruitment maneuver was performed in 7 (16.3%) patients after atelectasis persisted at maximal PEEP. Atelectasis was not identified in the examined subsegments in 6 (10.8%) patients despite zero PEEP. CONCLUSION: RP-EBUS is an effective tool to monitor what pressure atelectasis within a lung segment has resolved with increasing levels of PEEP.

Endobronchial ultrasound: A novel screening test for pulmonary hypertension prior to major pulmonary surgery.

Objectives: Pulmonary hypertension (PH) is an important physiologic variable in the assessment of patients undergoing major thoracic operations but all too often neglected because of the need for right heart catheterization (RHC) due to the inaccuracy of transthoracic echocardiography. Patients with lung cancer often require endobronchial ultrasound (EBUS) as part of the staging of the cancer. We sought to investigate whether EBUS can be used to screen these patients for PH. Methods: Patients undergoing a major thoracic operation requiring EBUS for staging were included prospectively in the study. All patients had also a RHC (gold standard). We aimed to compare the pulmonary artery pressure measurements by EBUS with the RHC values. Results: A total of 20 patients were enrolled in the study. The prevalence of abnormal pulmonary artery pressure was 65% based on RHC. All patients underwent measurement of the pulmonary vascular acceleration time (PVAT) by EBUS with no adverse events. Linear regression analysis comparing PVAT and RHC showed a correlation (r = -0.059, -0.010 to -0.018, P = .007). A receiver operator characteristic curve (area under the curve = 0.736) was used to find the optimal PVAT threshold (140 milliseconds) to predict PH; this was used to calculate a positive and negative likelihood ratio following a positive diagnosis of 2.154 and 0.538, respectively. Conclusions: EBUS interrogation of pulmonary artery hemodynamic is safe and feasible. EBUS may be used as a screening test for PH in high-risk individuals.

Severity of Atelectasis during Bronchoscopy: Descriptions of a New Grading System (AtelectasisSeverity Scoring System-"ASSESS") and At-Risk-Lung Zones.

Atelectasis during bronchoscopy under general anesthesia is very common and can have a detrimental effect on navigational and diagnostic outcomes. While the intraprocedural incidence and anatomic location have been previously described, the severity of atelectasis has not. We reviewed chest CT images of patients who developed atelectasis in the VESPA trial (Ventilatory Strategy to Prevent Atelectasis). By drawing boundaries at the posterior chest wall (A), the anterior aspect of the vertebral body (C), and mid-way between these two lines (B), we delineated at-risk lung zones 1, 2, and 3 (from posterior to anterior). An Atelectasis Severity Score System ("ASSESS") was created, classifying atelectasis as "mild" (zone 1), "moderate" (zones 1-2), and "severe" (zones 1-2-3). A total of 43 patients who developed atelectasis were included in this study. A total of 32 patients were in the control arm, and 11 were in the VESPA arm; 20 patients (47%) had mild atelectasis, 20 (47%) had moderate atelectasis, and 3 (6%) had severe atelectasis. A higher BMI was associated with increased odds (1.5 per 1 unit change; 95% CI, 1.10-2.04) (p = 0.0098), and VESPA was associated with decreased odds (0.05; 95% CI, 0.01-0.47) (p = 0.0080) of developing moderate to severe atelectasis. ASSESS is a simple method used to categorize intra-bronchoscopy atelectasis, which allows for a qualitative description of this phenomenon to be developed. In the VESPA trial, a higher BMI was not only associated with increased incidence but also increased severity of atelectasis, while VESPA had the opposite effect. Preventive strategies should be strongly considered in patients with risk factors for atelectasis who have lesions located in zones 1 and 2, but not in zone 3.

Outcomes of Pleural Space Infections in Patients With Indwelling Pleural Catheters for Active Malignancies.

BACKGROUND: Pleural infections related to indwelling pleural catheters (IPCs) are an uncommon clinical problem. However, management decisions can be complex for patients with active malignancies due to their comorbidities and limited life expectancies. There are limited studies on the management of IPC-related infections, including whether to remove the IPC or use intrapleural fibrinolytics. METHODS: We conducted a retrospective cohort study of patients with active malignancies and IPC-related empyemas at our institution between January 1, 2005 and May 31, 2021. The primary outcome was to evaluate clinical outcomes in patients with malignant pleural effusions and IPC-related empyemas treated with intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) compared with those treated with tPA alone or no intrapleural fibrinolytic therapy. The secondary outcome evaluated was the incidence of bleeding complications. RESULTS: We identified 69 patients with a malignant pleural effusion and an IPC-related empyema. Twenty patients received tPA/DNase, 9 received tPA alone, and 40 were managed without fibrinolytics. Those treated with fibrinolytics were more likely to have their IPCs removed as part of the initial management strategy ( P =0.004). The rate of surgical intervention and mortality attributable to the empyema were not significantly different between treatment groups. There were no bleeding events in any group. CONCLUSION: In patients with IPC-related empyemas, we did not find significant differences in the rates of surgical intervention, empyema-related mortality, or bleeding complications in those treated with intrapleural tPA/DNase, tPA alone, or no fibrinolytics. More patients who received intrapleural fibrinolytics had their IPCs removed, which may have been due to selection bias.

Preventing atelectasis during bronchoscopy under general anesthesia.

Atelectasis is a well-defined phenomenon in patients having surgery under general anesthesia. Recently, this phenomenon was also reported in patients having bronchoscopy under general anesthesia, with dedicated studies demonstrating a high incidence of up to 89%. Not surprisingly, time under general anesthesia and a higher body mass index (BMI) were found to be two significant factors that influenced the development of intraprocedural atelectasis. Atelectasis poses a significant obstacle in peripheral bronchoscopy since it can result in false positive radial probe ultrasound images, create computed tomography to body divergence, as well as obscure the target lesion on intraprocedural cone beam computed tomography (CBCT) images, thereby affecting both the navigational and diagnostic yield of the procedure. Bronchoscopists should be aware of this phenomenon and make efforts to prevent it when peripheral bronchoscopy under general anesthesia is planned. Ventilatory strategies to reduce intraprocedural atelectasis have been studied and proven to be effective and well-tolerated. Other strategies, such as patient positioning and preprocedural strategies have also been described but need further investigation. This article aims to summarize the recent history regarding the discovery and significance of intraprocedural atelectasis during bronchoscopy under general anesthesia and the various state-of-the-art strategies that have been proposed to mitigate the development of this entity.

Airway stenting for central airway obstruction: a review.

Central airway obstruction is a serious complication of various diseases, most often malignancy. Malignant etiologies include primary lung cancer as most common though metastases from various other cancers can obstruct the airways as well. Benign etiologies include inflammatory or fibrotic changes due to prior airway interventions (e.g., endotracheal intubation or tracheostomy) or specific autoimmune conditions. Different interventional modalities exist including various electrosurgical or mechanical debulking tools, though these are sometimes insufficient or contraindicated for the purpose of restoration of airway patency. The placement of stents is thus needed in certain particularly complex or refractory cases. Airway stenting requires careful patient selection and stent selection along with a thorough knowledge of relevant anatomy and procedural technique. Indeed, certain clinical presentations are better suited for stent placement and more likely to achieve a symptomatic benefit. Moreover, a variety of stents exist with each having different attributes that may better fit specific conditions. Complications must be managed properly as well. These include stent migration, granulation tissue formation, and stent-related infection which can have clinically significant consequences. In this review, we will discuss airway stenting for central airway obstruction with regard to these various subject areas as well as conclude with discussion of future research directions.

Clinical Risk Factors for Death in Patients With Empyema and Active Malignancy.

Background Pleural infection is a common clinical problem resulting in prolonged hospitalization and increased mortality. In patients with active malignancy, management decisions are based on the need for further immunosuppressive therapies, the ability to tolerate surgery, and consideration of the limited life expectancy. Identifying patients at risk for death or poor outcomes is very important as it will guide care. Study design and methods This is a retrospective cohort study of all patients with active malignancy and empyema. The primary outcome was time to death from empyema at three months. The secondary outcome was surgery at 30 days. Standard Cox regression model and cause-specific hazard regression model were used to analyze the data. Results A total of 202 patients with active malignancy and empyema were included. The overall mortality rate at three months was 32.7%. On multivariable analysis, female gender and higher urea were associated with an increased risk of death from empyema at three months. The area under the curve (AUC) of the model was 0.70. The risk factors for surgery at 30 days included the presence of frank pus and postsurgical empyema. The AUC of the model was 0.76. Interpretation Patients with active malignancy and empyema have a high probability of death. In our model, the risk factors for death from empyema included female gender and higher urea.

Sarcoidosis and Airway Disease After Immune Checkpoint Inhibitor Therapy: Case Study and Review of the Literature.

Pulmonary toxicity from immune checkpoint inhibitor therapy is typically a severe and potentially fatal complication, but these observations are driven by the most common toxicity, pneumonitis. Rarer pulmonary immune related adverse events, like airway disease and sarcoidosis, may have a more benign course. In this case report, we present a patient in whom therapy with the PD-1 inhibitor pembrolizumab resulted in severe eosinophilic asthma and sarcoidosis. This is the first case showing that anti-IL-5 inhibition may be safe in patients who develop eosinophilic asthma after ICI therapy. We further show that sarcoidosis does not necessarily require treatment cessation. This case highlights relevant nuances when clinicians face pulmonary toxicities other than pneumonitis.

Mobile Cone-Beam CT-Assisted Bronchoscopy for Peripheral Lung Lesions.

Peripheral bronchoscopy with the use of thin/ultrathin bronchoscopes and radial-probe endobronchial ultrasound (RP-EBUS) has been associated with a fair diagnostic yield. Mobile cone-beam CT (m-CBCT) could potentially improve the performance of these readily available technologies. We retrospectively reviewed the records of patients undergoing bronchoscopy for peripheral lung lesions with thin/ultrathin scope, RP-EBUS, and m-CBCT guidance. We studied the performance (diagnostic yield and sensitivity for malignancy) and safety (complications, radiation exposure) of this combined approach. A total of 51 patients were studied. The mean target size was 2.6 cm (SD, 1.3 cm) and the mean distance to the pleura was 1.5 cm (SD, 1.4 cm). The diagnostic yield was 78.4% (95 CI, 67.1-89.7%), and the sensitivity for malignancy was 77.4% (95 CI, 62.7-92.1%). The only complication was one pneumothorax. The median fluoroscopy time was 11.2 min (range, 2.9-42.1) and the median number of CT spins was 1 (range, 1-5). The mean Dose Area Product from the total exposure was 41.92 Gy·cm2 (SD, 11.35 Gy·cm2). Mobile CBCT guidance may increase the performance of thin/ultrathin bronchoscopy for peripheral lung lesions in a safe manner. Further prospective studies are needed to corroborate these findings.

Safety and Feasibility of Photodynamic Therapy for Ablation of Peripheral Lung Tumors.

BACKGROUND: Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors. METHODS: Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630 nm wavelength) was applied at 200 J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study). RESULTS: There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%. CONCLUSION: PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.

Anesthetic Management of Gas Embolism During Rigid Bronchoscopy with Argon Plasma Coagulation: A Case Report.

Gas embolism is a procedure-related complication and has been reported during endoscopy, surgical procedures, intravenous catheterization, positive pressure ventilation, and a multitude of scenarios. Recognizing the potential for gas embolus and a high level of suspicion are paramount to timely intervention to prevent significant morbidity and mortality. There is such rapid decompensation that only clinical suspicion can guide timely intervention; it is not uncommon for gas embolus to be diagnosed postmortem. It then must be determined whether the gas embolus has a venous or systemic entry point. Overall management is similar for both forms of gas emboli with focus on hemodynamic support and preservation of organ function. This case report discusses an occurrence of presumed systemic gas embolus from argon plasma coagulation and management of a patient under general anesthesia during rigid bronchoscopy.

Ventilatory Strategy to Prevent Atelectasis During Bronchoscopy Under General Anesthesia: A Multicenter Randomized Controlled Trial (Ventilatory Strategy to Prevent Atelectasis -VESPA- Trial).

BACKGROUND: Atelectasis negatively influences peripheral bronchoscopy, increasing CT scan-body divergence, obscuring targets, and creating false-positive radial-probe endobronchial ultrasound (RP-EBUS) images. RESEARCH QUESTION: Can a ventilatory strategy reduce the incidence of atelectasis during bronchoscopy under general anesthesia? STUDY DESIGN AND METHODS: Randomized controlled study (1:1) in which patients undergoing bronchoscopy were randomized to receive standard ventilation (laryngeal mask airway, 100% Fio2, zero positive end-expiratory pressure [PEEP]) vs a ventilatory strategy to prevent atelectasis (VESPA) with endotracheal intubation followed by a recruitment maneuver, Fio2 titration (< 100%), and PEEP of 8 to 10 cm H2O. All patients underwent chest CT imaging and a survey for atelectasis with RP-EBUS bilaterally on bronchial segments 6, 9, and 10 after artificial airway insertion (time 1) and 20 to 30 min later (time 2). Chest CT scans were reviewed by a blinded chest radiologist. RP-EBUS images were assessed by three independent, blinded readers. The primary end point was the proportion of patients with any atelectasis (either unilateral or bilateral) at time 2 according to chest CT scan findings. RESULTS: Seventy-six patients were analyzed, 38 in each group. The proportion of patients with any atelectasis according to chest CT scan at time 2 was 84.2% (95% CI, 72.6%-95.8%) in the control group and 28.9% (95% CI, 15.4%-45.9%) in the VESPA group (P < .0001). The proportion of patients with bilateral atelectasis at time 2 was 71.1% (95% CI, 56.6%-85.5%) in the control group and 7.9% (95% CI, 1.7%-21.4%) in the VESPA group (P < .0001). At time 2, 3.84 ± 1.67 (mean ± SD) bronchial segments in the control group vs 1.21 ± 1.63 in the VESPA group were deemed atelectatic (P < .0001). No differences were found in the rate of complications. INTERPRETATION: VESPA significantly reduced the incidence of atelectasis, was well tolerated, and showed a sustained effect over time despite bronchoscopic nodal staging maneuvers. VESPA should be considered for bronchoscopy when atelectasis is to be avoided. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04311723; URL: www. CLINICALTRIALS: gov.

Three-dimensionally printed navigational template: a promising guiding approach for lung biopsy.

Background: Percutaneous transthoracic lung biopsy is customarily conducted under computed tomography (CT) guidance, which primarily depends on the conductors' experience and inevitably contributes to long procedural duration and radiation exposure. Novel technique facilitating lung biopsy is currently demanded. Methods: Based on the reconstructed anatomical information of CT scans, a three-dimensionally printed navigational template was customized to guide fine-needle aspiration (FNA). The needle insertion site and angle could be indicated by the template after proper placement according to the reference landmarks. From June 2020 to August 2020, patients with peripheral indeterminate lung lesions ≥30 mm in diameter were enrolled in a pilot trial. Cases were considered successful when the virtual line indicated by the template in the first CT scan was pointing at the target, and the rate of success was recorded. The insertion deviation, procedural duration, radiation exposure, biopsy-related complications, and diagnostic yield were documented as well. Results: A total of 20 patients consented to participate, and 2 withdrew. The remaining 18 participants consisting of 11 men and 7 women with a median age of 63 [inter-quartile range (IQR), 50-68] years and a median body mass index (BMI) of 23.5 (IQR, 20.8-25.8) kg/m2 received template-guided FNA. The median nodule size of the patients was 41.2 (IQR, 36.2-51.9) mm and 17 lesions were successfully targeted (success rate, 94.4%). One lesion was not reached through the designed trajectory due to an unpredictable alteration of the lesion's location resulting from pleural effusion. The median deviation between the actual position of the needle tip and the designed route was 9.4 (IQR, 6.8-11.7) mm. The median procedural duration was 10.7 (IQR, 9.7-11.8) min, and the median radiation exposure was 220.9 (IQR, 198.6-249.5) mGy×cm. No major biopsy-related complication was encountered. Definitive diagnosis of malignancy was reached in 13 of the 17 (76.5%) participants. Conclusions: The feasibility and safety of navigational template-guided FNA were preliminarily validated in lung biopsy cohort. Nonetheless, patients with pleural effusion were not recommended to undergo FNA guided by such technique. Trial Registration: This study was registered with ClinicalTrials.gov (identifier: NCT03325907).

Lysosomal inhibition sensitizes TMEM16A-expressing cancer cells to chemotherapy.

Squamous cell carcinoma of the head and neck (SCCHN) is a devastating disease that continues to have low cure rates despite the recent advances in therapies. Cisplatin is the most used chemotherapy agent, and treatment failure is largely driven by resistance to this drug. Amplification of chromosomal band 11q13 occurs in ∼30% of SCCHN tumors. This region harbors the ANO1 gene that encodes the TMEM16A ion channel, which is responsible for calcium-activated chloride transport in epithelial tissues. TMEM16A overexpression is associated with cisplatin resistance, and high TMEM16A levels correlate with decreased survival. However, the mechanistic underpinning of this effect remains unknown. Lysosomal biogenesis and exocytosis have been implicated in cancer because of their roles in the clearance of damaged organelles and exocytosis of chemotherapeutic drugs and toxins. Here, we show that TMEM16A overexpression promotes lysosomal biogenesis and exocytosis, which is consistent with the expulsion of intracellular cisplatin. Using a combination of genetic and pharmacologic approaches, we find that TMEM16A promotes lysosomal flux in a manner that requires reactive oxygen species, TRPML1, and the activation of the ß-catenin­melanocyte-inducing transcription factor pathway. The lysosomal inhibitor hydroxychloroquine (HCQ) synergizes with cisplatin in killing SCCHN cells in vitro. Using a murine model of SCCHN, we show that HCQ and cisplatin retard the growth of cisplatin-resistant patient-derived xenografts in vivo. We propose that TMEM16A enables cell survival by the up-regulation of lysosomal sequestration and exocytosis of the cytotoxic drugs. These results uncover a model of treatment for resistance in cancer, its reversal, and a role for TMEM16A.

Predicting malignant pleural effusion during diagnostic pleuroscopy with biopsy: A prospective multicentre study.

BACKGROUND AND OBJECTIVE: Pleuroscopy with pleural biopsy has a high sensitivity for malignant pleural effusion (MPE). Because MPEs tend to recur, concurrent diagnosis and treatment of MPE during pleuroscopy is desired. However, proceeding directly to treatment at the time of pleuroscopy requires confidence in the on-site diagnosis. The study's primary objective was to create a predictive model to estimate the probability of MPE during pleuroscopy. METHODS: A prospective observational multicentre cohort study of consecutive patients undergoing pleuroscopy was conducted. We used a logistic regression model to evaluate the probability of MPE with relation to visual assessment, rapid on-site evaluation (ROSE) of touch preparation and presence of pleural nodules/masses on computed tomography (CT). To assess the model's prediction accuracy, a bootstrapped training/testing approach was utilized to estimate the cross-validated area under the receiver operating characteristic curve. RESULTS: Of the 201 patients included in the study, 103 had MPE. Logistic regression showed that higher level of malignancy on visual assessment is associated with higher odds of MPE (OR = 34.68, 95% CI = 9.17-131.14, p < 0.001). The logistic regression also showed that higher level of malignancy on ROSE of touch preparation is associated with higher odds of MPE (OR = 11.63, 95% CI = 3.85-35.16, p < 0.001). Presence of pleural nodules/masses on CT is associated with higher odds of MPE (OR = 6.61, 95% CI = 1.97-22.1, p = 0.002). A multivariable logistic regression model of final pathologic status with relation to visual assessment, ROSE of touch preparation and presence of pleural nodules/masses on CT had a cross-validated AUC of 0.94 (95% CI = 0.91-0.97). CONCLUSION: A prediction model using visual assessment, ROSE of touch preparation and CT scan findings demonstrated excellent predictive accuracy for MPE. Further validation studies are needed to confirm our findings.