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.

COVID-19 Pneumonia Presenting As Solitary Pulmonary Lesion.

Common findings of COVID-19 pneumonia on chest CT images include ground-glass opacities and organizing pneumonia. Here, we present a patient with a history of lung cancer who came to our center for re-staging CT studies, which showed a solitary peripheral lung mass suggestive of lung cancer. While being evaluated for the mass, the patient developed respiratory failure due to COVID-19 pneumonia. After treatment for COVID-19 and recovery, CT showed complete resolution of the solitary peripheral lung mass. This case highlights that COVID-19 can, on occasion, present with CT findings that mimic those of lung cancer.

Allergic Bronchopulmonary Aspergillosis Mimicking Lung Cancer: A Case Report.

Patients with allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity reaction to Aspergillus fumigatus, typically present with asthma; the common imaging findings are central bronchiectasis, mucoid impaction, and tree-in-bud opacities. In this report, we discuss the case of a heavy smoker who presented with a large pulmonary mass that was initially presumed to be primary lung cancer and who was ultimately diagnosed with ABPA, which responded favorably to steroid treatment.

Reporting Standards for Diagnostic Testing: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Diagnostic testing is fundamental to medicine. However, studies of diagnostic testing in respiratory medicine vary significantly in terms of their methodology, definitions, and reporting of results. This has led to often conflicting or ambiguous results. To address this issue, a group of 20 respiratory journal editors worked to develop reporting standards for studies of diagnostic testing based on a rigorous methodology to guide authors, peer reviewers, and researchers when conducting studies of diagnostic testing in respiratory medicine. Four key areas are covered, including defining the reference standard of truth, measures of dichotomous test performance when used for dichotomous outcomes, measures of multichotomous test performance for dichotomous outcomes, and what constitutes a useful definition of diagnostic yield. The importance of using contingency tables for reporting results is addressed with examples from the literature. A practical checklist is provided as well for reporting studies of diagnostic testing.

The Impact of Anticoagulation on Indwelling Pleural Catheter Removal due to Pleurodesis in Patients with Malignant Pleural Effusion.

BACKGROUND: A well-recognized therapy to improve the symptoms of patients with malignant pleural effusion (MPE), indwelling pleural catheters (IPCs) can also achieve spontaneous pleurodesis. Chemical pleurodesis is associated with a significant pro-coagulation and fibrinolytic environment. Hence, anticoagulation could theoretically interfere with this process. OBJECTIVE: The aim of this study was to evaluate if anticoagulation can interfere with successful spontaneous pleurodesis in patients treated with IPC. METHODS: This was a cohort study of all patients with MPE treated with IPC. The primary objective was to determine if anticoagulant use after IPC placement decreased the rate of spontaneous pleurodesis. The secondary objective was to identify other factors associated with spontaneous pleurodesis. We used a Fine-Gray subdistribution hazard model and a direct acyclic graph to identify variables associated with time to spontaneous pleurodesis. RESULTS: Of the included 410 patients, 210 patients (51.2%) achieved pleurodesis and had their IPC removed. We found no association between anticoagulation and likelihood of pleurodesis. Multivariate analyses revealed that prior chemotherapy, ECOG score of 2-4 were associated with unsuccessful pleurodesis, while chemotherapy or radiotherapy after IPC placement remained associated with increased likelihood of spontaneous pleurodesis. CONCLUSIONS: We failed to demonstrate an association between anticoagulation and pleurodesis. We found that better performance status and chemotherapy or radiotherapy after IPC placement can increase the rate of pleurodesis and catheter removal.

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.

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.

Cytologic Investigations for the Diagnosis of Malignant Pleural Effusion in Non-small Cell Lung Cancer: State-of-the-art Review for Pulmonologists.

Lung cancer is the current leading cause of cancer-related deaths worldwide, and malignant pleural effusion, an indicator of the advanced stage of this disease, portends a poor prognosis. Thus, making an accurate diagnosis of malignant pleural effusion is of paramount importance. During the past decade, the prognosis of patients with advanced non-small cell lung cancer has improved substantially, especially in those treated with targeted therapy and immunotherapy. The use of pleural fluid cytology should not only provide diagnoses but also aid in the selection of targeted therapies, especially when obtaining a histologic specimen is too difficult. In this evidence-based review, we address the importance of pleural fluid cytology in non-small cell lung cancer patients, from making the diagnosis to making treatment-related decisions when only pleural fluid is available.

Optimizing Diagnostic and Staging Pathways for Suspected Lung Cancer: A Decision Analysis.

BACKGROUND: The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known. RESEARCH QUESTION: What diagnostic and staging strategies are most cost-effective for lung cancer? STUDY DESIGN AND METHODS: A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes. RESULTS: For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay. INTERPRETATION: The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified.

Tracheomediastinal Fistula Formation After Endobronchial Ultrasound Transbronchial Needle Aspiration While on Bevacizumab Treatment.

A 63-year-old male with non-small-cell lung cancer (NSCLC) developed a tracheomediastinal fistula after endobronchial ultrasound transbronchial needle aspiration while on treatment with bevacizumab. This vascular endothelial growth factor-specific angiogenesis inhibitor is a first-line treatment for unresectable or metastatic NSCLC and has been reported to cause fatal non-gastrointestinal fistulas. Respiratory tract fistulas are a known rare complication after bevacizumab therapy characterized by a high mortality rate.

Predicting Lymph Node Metastasis in Non-small Cell Lung Cancer: Prospective External and Temporal Validation of the HAL and HOMER Models.

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

A Case of Laryngeal Tuberculosis Mimicking Lymphoma.

The incidence of laryngeal tuberculosis has steadily increased due to rising prevalence of HIV infection, immunosuppressive diseases and treatments, and the emergence of multidrug-resistant organisms and atypical mycobacteria. We report on a woman with a unique presentation of laryngeal tuberculosis mimicking lymphoma to remind clinicians that the diagnosis of laryngeal tuberculosis merits awareness and that delay in diagnosis poses a serious threat to the patient due to delayed treatment and further complications.

Breast and Lung Effusion Survival Score Models: Improving Survival Prediction in Patients With Malignant Pleural Effusion and Metastasis.

BACKGROUND: Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates. RESEARCH QUESTION: Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates? STUDY DESIGN AND METHODS: Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell's C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors' performances. RESULTS: The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P < .0001), pleural fluid lactate dehydrogenase (P = .029), and bilateral effusion (P = .002). DSMs for lung, breast, and hematologic malignancies showed C-statistics of 0.72, 0.72, and 0.62, respectively; the combined model's C-statistics was 0.67. LENT-D (C-statistic, 0.60) and LENT-C (C-statistic, 0.65) models underperformed. INTERPRETATION: EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions.

Use of fibrinolytics and deoxyribonuclease in adult patients with pleural empyema: a consensus statement.

Although our understanding of the pathogenesis of empyema has grown tremendously over the past few decades, questions still remain on how to optimally manage this condition. It has been almost a decade since the publication of the MIST2 trial, but there is still an extensive debate on the appropriate use of intrapleural fibrinolytic and deoxyribonuclease therapy in patients with empyema. Given the scarcity of overall guidance on this subject, we convened an international group of 22 experts from 20 institutions across five countries with experience and expertise in managing adult patients with empyema. We did a literature and internet search for reports addressing 11 clinically relevant questions pertaining to the use of intrapleural fibrinolytic and deoxyribonuclease therapy in adult patients with bacterial empyema. This Position Paper, consisting of seven graded and four ungraded recommendations, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience when necessary. Panel members participated in the development of the final recommendations using the modified Delphi technique. Our Position Paper aims to address the existing gap in knowledge and to provide consensus-based recommendations to offer guidance in clinical decision making when considering the use of intrapleural therapy in adult patients with bacterial empyema.

Is Biopsy of Contralateral Hilar N3 Lymph Nodes With Negative PET-CT Scan Findings Necessary When Performing Endobronchial Ultrasound Staging?

BACKGROUND: Systematic endobronchial ultrasound (EBUS)-guided lung cancer staging starts with hilar N3 nodes, proceeding sequentially to mediastinal N3, N2, and N1 nodes, with sampling of all enlarged nodes (size, ≥ 5 mm) by EBUS. However, procedure time is limited by patient comfort when moderate sedation is used. It is unclear if EBUS staging should start with hilar N3 nodes or whether starting with mediastinal N3 nodes suffices. Knowing the probability of hilar N3 nodes with PET-CT scan negative findings harboring occult metastasis can inform this decision. RESEARCH QUESTION: What proportion of patients with hilar N3 nodes showing negative PET-CT scan findings have malignancy by EBUS? STUDY DESIGN AND METHODS: This retrospective observational, single-center cohort study included consecutive patients with clinical-radiographic T1-3, N0-3, M0 non-small cell lung cancer undergoing systematic EBUS staging with biopsy of hilar N3 nodes with negative PET-CT scan findings. The primary outcome was the proportion of patients with malignant hilar N3 nodes showing negative PET-CT scan findings. Based on expert opinion, a threshold probability of malignancy of less than 5% was considered sufficient to skip hilar N3 nodes. We used the binomial exact test to compare the observed proportion vs threshold probability of 5%. RESULTS: Of 1,737 consecutive patients undergoing EBUS staging, 1,567 showed negative PET-CT scan findings of the hilar N3 nodes. These nodes were enlarged by EBUS and were sampled in 739 patients. Malignancy was found in the hilar N3 nodes of 5 of 739 patients (0.68%; 95% CI, 0.22%-1.57%). The proportion was significantly less than the threshold probability (P < .001). Patients with positive PET scan results of the mediastinal N3 nodes were at higher risk of having occult hilar N3 nodal metastasis (P = .003), found in 3 of 46 patients (6.5%; 95% CI, 1.4%-17.9%) with positive PET scan results of the mediastinal N3 nodes. INTERPRETATION: When using moderate sedation, because time is limited, it is reasonable to start with the mediastinal N3 nodes if the hilar and mediastinal N3 nodes show negative PET scan results. Patients with positive PET scan findings of the mediastinal N3 nodes probably should undergo hilar N3 node sampling.