Differences in microenvironment of lung cancer and pleural effusions by single-cell RNA sequencing.

BACKGROUND: Direct comparison of tumor microenvironment of matched lung cancer biopsies and pleural effusions (PE) from the same patients is critical in understanding tumor biology but has not been performed. This is the first study to compare the lung cancer and PE microenvironment by single-cell RNA sequencing (scRNA-seq). METHODS: Matched lung cancer biopsies and PE were obtained prospectively from ten patients. We isolated CD45+ cells and performed scRNA-seq to compare the biopsies and PE. RESULTS: PE had a higher proportion of CD4+ T cells but lower proportion of CD8+ T cells (False detection rate, FDR = 0.0003) compared to biopsies. There was a higher proportion of naïve CD4+ T cells (FDR = 0.04) and naïve CD8+ T cells (FDR = 0.0008) in PE vs. biopsies. On the other hand, there was a higher proportion of Tregs (FDR = 0.04), effector CD8+ (FDR = 0.006), and exhausted CD8+ T cells (FDR = 0.01) in biopsies. The expression of inflammatory genes in T cells was increased in biopsies vs. PE, including TNF, IFN-É£, IL-1R1, IL-1R2, IL-2, IL-12RB2, IL-18R1, and IL-18RAP (FDR = 0.009, 0.013, 0.029, 0.043, 0.009, 0.013, 0.004, and 0.003, respectively). The gene expression of exhaustion markers in T cells was also increased in tumor biopsies including PDCD1, CTLA4, LAG 3, HAVCR2, TIGIT, and CD160 (FDR = 0.008, 0.003, 0.002, 0.011, 0.006, and 0.049, respectively). CONCLUSIONS: There is a higher proportion of naïve T cells and lower proportion of exhausted T cells and Tregs in PE compared to lung cancer biopsies, which can be leveraged for prognostic and therapeutic applications.

High Yield of Pleural Cell-Free DNA for Diagnosis of Oncogenic Mutations in Lung Adenocarcinoma.

BACKGROUND: Pleural cytology is currently used to assess targetable mutations in patients with advanced lung adenocarcinoma. However, it is fraught with low diagnostic yield. RESEARCH QUESTION: Can pleural cell-free DNA (cfDNA) be used to assess targetable mutations in lung adenocarcinoma patients with malignant pleural effusions (MPE)? STUDY DESIGN AND METHODS: Patients with lung adenocarcinoma MPE were recruited prospectively between January 2017 and September 2021. Oncogenic mutations were assessed by treating providers using pleural fluid cytology or lung cancer biopsies. Pleural and plasma cfDNA were used to assess the mutations using next-generation sequencing (NGS). RESULTS: Fifty-four pleural fluid samples were collected from 42 patients. The diagnostic yield to detect oncogenic mutations for pleural cfDNA, pleural cytology, biopsy, and plasma cfDNA was 49/54 (90.7%), 16/33 (48.5%), 22/25 (88%), and 24/32 (75%), respectively, P < .001. The agreement of mutations in positive samples between pleural cfDNA and pleural cytology was 100%, whereas the agreement of pleural cfDNA with biopsies was 89.4%. The median concentration (interquartile range) of pleural cfDNA was higher than plasma: 28,444 (4,957-67,051) vs 2,966.5 (2,167-5,025) copies of amplifiable DNA per mL, P < .01. Median of 5 mL (interquartile range, 4.5-5) of pleural fluid supernatant was adequate for cfDNA testing. INTERPRETATION: The diagnostic yield of pleural cfDNA NGS for oncogenic mutations in lung adenocarcinoma patients is comparable to tumor biopsies and higher than pleural cytology and plasma cfDNA. The pleural cfDNA can be longitudinally collected, can be readily incorporated in clinical workflow, and may decrease the need for additional biopsies.

Implementation and Effectiveness of a Veterans Affairs-Based Comprehensive Lung Cancer Survivorship Program.

PURPOSE: Few programs exist to address persistent impairment in functional status, quality of life, and mental health in lung cancer survivors. We aimed to determine whether a 12-wk multimodal survivorship program imparts clinical benefit. METHODS: Any patient at the Durham Veterans Affairs Medical Center with lung cancer and a Karnofsky score of ≥60 could participate. Chronic obstructive pulmonary disease medications were optimized at the enrollment visit. Participants with a Hospital Anxiety and Depression Scale (HADS) score of >8 were offered pharmacotherapy and mental health referral. Participants did home-based exercise with a goal of 1 hr/d, 5 d/wk. They were called weekly to assess exercise progress and review depression/anxiety symptoms. Participants were offered pharmacotherapy for smoking cessation. RESULTS: Twenty-three (50%) of the first 46 enrollees completed the full 12-wk program. Paired changes from enrollment to completion (mean ± SD) were observed in 6-min walk test (73.6 ± 96.9 m, P = .002), BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index (-1.45 ± 1.64 points, P < .001), Duke Activity Status Index (3.84 ± 7.12 points, P = .02), Fried Frailty Index (-0.588 ± 0.939 points, P = .02), modified Medical Research Council dyspnea scale (-0.619 ± 1.284 points, P = .04), Functional Assessment of Cancer Therapy-Lung Emotional subscale score (1.52 ± 2.96 points, P = .03), HADS total score (-2.63 ± 4.34 points, P = .02), and HADS Anxiety subscale score (-1.47 ± 2.29 points, P = .01). CONCLUSIONS: A comprehensive Lung Cancer Survivorship Program provides clinically meaningful improvements in functional status, quality of life, and mental health.

Comparison of Forceps, Cryoprobe, and Thoracoscopic Lung Biopsy for the Diagnosis of Interstitial Lung Disease - The CHILL Study.

RATIONALE: Transbronchial lung cryobiopsy (TBLC) has emerged as a less invasive method to obtain a tissue diagnosis in patients with interstitial lung disease (ILD). The diagnostic yield of TBLC compared to surgical lung biopsy (SLB) remains uncertain. OBJECTIVES: The aim of this study was to determine the diagnostic accuracy of forceps transbronchial lung biopsy (TBLB) and TBLC compared to SLB when making the final diagnosis based on multidisciplinary discussion (MDD). METHODS: Patients enrolled in the study underwent sequential TBLB and TBLC followed immediately by SLB. De-identified cases, with blinding of the biopsy method, were reviewed by a blinded pathologist and then discussed at a multidisciplinary conference. MAIN RESULTS: Between August 2013 and October 2017, we enrolled 16 patients. The raw agreement between TBLC and SLB for the MDD final diagnosis was 68.75% with a Cohen's kappa of 0.6 (95% CI 0.39, 0.81). Raw agreement and Cohen's kappa of TBLB versus TBLC and TBLB versus SLB for the MDD final diagnosis were much lower (50%, 0.21 [95% CI 0, 0.42] and 18.75%, 0.08 [95% CI -0.03, 0.19], respectively). TBLC was associated with mild bleeding (grade 1 bleeding requiring suction to clear) in 56.2% of patients. CONCLUSIONS: In patients with ILD who have an uncertain type based on clinical and radiographic data and require tissue sampling to obtain a specific diagnosis, TBLC showed moderate correlation with SLB when making the diagnosis with MDD guidance. TBLB showed poor concordance with both TBLC and SLB MDD diagnoses.

Variable Learning Curve of Basic Rigid Bronchoscopy in Trainees.

BACKGROUND: Despite increased use of rigid bronchoscopy (RB) for therapeutic indications and recommendations from professional societies to use performance-based competency, an assessment tool has not been utilized to measure the competency of trainees to perform RB in clinical settings. OBJECTIVES: The aim of the study was to evaluate a previously developed assessment tool - Rigid Bronchoscopy Tool for Assessment of Skills and Competence (RIGID-TASC) - for determining the RB learning curve of interventional pulmonary (IP) trainees in the clinical setting and explore the variability of learning curve of trainees. METHODS: IP fellows at 4 institutions were enrolled. After preclinical simulation training, all RBs performed in patients were scored by faculty using RIGID-TASC until competency threshold was achieved. Competency threshold was defined as unassisted RB intubation and navigation through the central airways on 3 consecutive patients at the first attempt with a minimum score of 89. A regression-based model was devised to construct and compare the learning curves. RESULTS: Twelve IP fellows performed 178 RBs. Trainees reached the competency threshold between 5 and 24 RBs, with a median of 15 RBs (95% CI, 6-21). There were differences among trainees in learning curve parameters including starting point, slope, and inflection point, as demonstrated by the curve-fitting model. Subtasks that required the highest number of procedures (median = 10) to gain competency included ability to intubate at the first attempt and intubation time of <60 s. CONCLUSIONS: Trainees acquire RB skills at a variable pace, and RIGID-TASC can be used to assess learning curve of IP trainees in clinical settings.

Hyperbaric oxygen therapy to prevent central airway stenosis after lung transplantation.

BACKGROUND: Central airway stenosis (CAS) is a severe airway complication after lung transplantation associated with bronchial ischemia and necrosis. We sought to determine whether hyperbaric oxygen therapy (HBOT), an established treatment for tissue ischemia, attenuates post-transplant bronchial injury. METHODS: We performed a randomized, controlled trial comparing usual care with HBOT (2 atm absolute for 2 hours × 20 sessions) in subjects with extensive airway necrosis 4 weeks after transplantation. Endobronchial biopsies were collected at 4, 7, and 10 weeks after transplantation for a quantitative polymerase chain reaction. Coprimary outcomes were incidence of airway stenting and acute cellular rejection (ACR) at 1 year. RESULTS: The trial was stopped after enrolling 20 subjects (n = 10 per group) after a pre-planned interim analysis showed no difference between usual care and HBOT groups in stenting (both 40%), ACR (70% and 40%, respectively), or CAS (40% and 60%, respectively). Time to first stent placement (median [interquartile range]) was significantly shorter in the HBOT group (150 [73-150] vs 186 [167-206] days, p < 0.05). HIF gene expression was significantly increased in donor tissues at 4, 7, and 10 weeks after transplantation but was not altered by HBOT. Subjects who developed CAS or required stenting had significantly higher HMOX1 and VEGFA expression at 4 weeks (both p < 0.05). Subjects who developed ACR had significant FLT1, TIE2, and KDR expression at 4 weeks (all p < 0.05). CONCLUSIONS: Incidence of CAS is high after severe, established airway necrosis after transplantation. HBOT does not reduce CAS severity or stenting. Elevated HMOX1 and VEGFA expressions appear to associate with airway complications.

Clinical and radiographic predictors of successful therapeutic bronchoscopy for the relief of malignant central airway obstruction.

BACKGROUND: Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO. METHODS: We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival. RESULTS: During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015). CONCLUSIONS: Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.

Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry.

Background: Accurate staging for small cell lung cancer (SCLC) is critical for determining appropriate therapy. The clinical impact of increasing PET adoption and stage migration is well described in non-small cell lung cancer but not in SCLC. The objective of this study was to evaluate temporal trends in PET staging and survival in the Veterans Affairs Central Cancer Registry and the impact of PET on outcomes. Patients and Methods: Patients diagnosed with SCLC from 2001 to 2010 were identified. PET staging, overall survival (OS), and lung cancer-specific survival (LCSS) were assessed over time. The impact of PET staging on OS and LCSS was assessed for limited-stage (LS) and extensive-stage (ES) SCLC. Results: From 2001 to 2010, PET use in a total of 10,135 patients with SCLC increased from 1.1% to 39.2%. Median OS improved for all patients (from 6.2 to 7.9 months), those with LS-SCLC (from 10.9 to 13.2 months), and those with ES-SCLC (from 5.0 to 7.0 months). Among staged patients, the proportion of ES-SCLC increased from 63.9% to 65.7%. Among 1,536 patients with LS-SCLC treated with concurrent chemoradiotherapy, 397 were staged by PET. In these patients, PET was associated with longer OS (median, 19.8 vs 14.3 months; hazard ratio [HR], 0.78; 95% CI, 0.68-0.90; P<.0001) and LCSS (median, 22.9 vs 16.7 months; HR, 0.74; 95% CI, 0.63-0.87; P<.0001) with multivariate adjustment and propensity-matching. In the 6,143 patients with ES-SCLC, PET was also associated with improved OS and LCSS. Conclusions: From 2001 to 2010, PET staging increased in this large cohort, with a corresponding relative increase in ES-SCLC. PET was associated with greater OS and LCSS for LS-SCLC and ES-SCLC, likely reflecting stage migration and stage-appropriate therapy. These findings emphasize the importance of PET in SCLC and support its routine use.

Management of Lung Transplant Bronchial Stenosis With Mitomycin C.

BACKGROUND: Bronchial stenosis is a significant source of morbidity among lung transplant recipients, with etiologies including infection and ischemia of the airways. Current management with balloon bronchoplasty and stents is imperfect and a subset of patients requires multiple procedures to maintain airway patency. Mitomycin C (MMC) has been utilized for its antifibrotic properties in nonmalignant tracheobronchial stenosis but its application is not well studied in post-lung transplant stenosis. We performed this study to assess if MMC application decreases the need for repeated balloon bronchoplasty in lung transplant-related airway stenosis. METHODS: This is a retrospective cohort study of all lung transplant recipients who developed airway stenosis and who were treated with MMC over 4 years. MMC was injected submucosally into the stenotic airway. We compared the rate of bronchoscopic dilation at intervals of 3 and 6 months before and after MMC therapy. RESULTS: Eleven lung transplant recipients, with airway stenosis were included in our study, who required recurrent balloon dilation, despite airway stents in place in 73% of these patients. At 3 months after MMC treatment the median number of dilations decreased from 3 to 1 (P=0.023), and at 6 months from 3 to 2 dilations (P=0.004). There was a trend toward improvement in forced expiratory volume in one second and forced vital capacity, although it was not statistically significant. No adverse events related to MMC therapy was observed CONCLUSION:: Application of MMC is safe and is associated with a reduction in frequency of bronchoscopic balloon dilation in patients with post-lung transplant airway stenosis.

Yield of Malignant Pleural Effusion for Detection of Oncogenic Driver Mutations in Lung Adenocarcinoma.

BACKGROUND: Pleural fluid can be used to assess targetable mutations in patients with lung adenocarcinoma. The primary objective of this study was to assess the yield of pleural fluid cytology for targetable oncogenic mutations (EGFR, KRAS, BRAF, ALK, and ROS1 gene rearrangements). We also assessed pleural fluid volume necessary for molecular testing. METHODS: Retrospective review was performed of 134 consecutive patients with lung adenocarcinoma associated malignant pleural effusions. EGFR and KRAS testing was done using PCR amplification followed by DNA sequencing, or next generation sequencing in more recent cases that included BRAF assessment. Fluorescence in situ hybridization employing break-apart probes was used to test for ALK and ROS1 rearrangements. RESULTS: Mutation analysis on pleural fluid cell-block was performed on 56 patients. It was adequate for complete analysis ordered including EGFR, KRAS, BRAF, ALK, and ROS1 rearrangements on 40 (71.4%) samples. For individual mutations, EGFR testing was possible in 38 of 49 (77.6%); KRAS 22 of 28 (78.6%); BRAF 10 of 13 (76.9%), ALK gene rearrangement 42 of 51 (82.4%) and ROS1 gene rearrangement in 21 of 28 (75%) pleural fluid specimens. The analysis was satisfactory in 13 of 19 (68.4%) samples with ≤100 mL versus 27 of 37 (72.9%) with >100 mL of fluid tested (P-value=0.7). CONCLUSION: Genetic mutation analysis can be performed on malignant pleural effusions secondary to lung adenocarcinoma, independent of fluid volume.

Safety of hyperbaric oxygen therapy for management of central airway stenosis after lung transplant.

BACKGROUND: Central airway stenosis (CAS) is common after lung transplantation and causes significant post-transplant morbidity. It is often preceded by extensive airway necrosis, related to airway ischemia. Hyperbaric oxygen therapy (HBOT) is useful for ischemic grafts and may reduce the development of CAS. METHODS: The purpose of this study was to determine whether HBOT could be safely administered to lung transplant patients with extensive necrotic airway plaques. Secondarily, we assessed any effects of HBOT on the incidence and severity of CAS. Patients with extensive necrotic airway plaques within 1-2 months after lung transplantation were treated with HBOT along with standard care. These patients were compared with a contemporaneous reference group with similar plaques who did not receive HBOT. RESULTS: Ten patients received HBOT for 18.5 (interquartile range, IQR 11-20) sessions, starting at 40.5 (IQR 34-54) days after transplantation. HBOT was well tolerated. Incidence of CAS was similar between HBOT-treated patients and reference patients (70% vs 87%, respectively; P=.34), but fewer stents were required in HBOT patients (10% vs 56%, respectively; P=.03). CONCLUSIONS: This pilot study is the first to demonstrate HBOT safety in patients who develop necrotic airway plaques after lung transplantation. HBOT may reduce the need for airway stent placement in patients with CAS.

Development of a Tool to Assess Basic Competency in the Performance of Rigid Bronchoscopy.

RATIONALE: Rigid bronchoscopy is increasingly used by pulmonologists for the management of central airway disorders. However, an assessment tool to evaluate the competency of operators in the performance of this technique has not been developed. We created the Rigid Bronchoscopy Tool for Assessment of Skills and Competence (RIGID-TASC) to serve as an objective, competency-oriented assessment tool of basic rigid bronchoscopic skills, including rigid bronchoscopic intubation and central airway navigation. OBJECTIVES: To assess whether RIGID-TASC scores accurately distinguish the basic rigid bronchoscopy skills of novice, intermediate, and expert operators, and to determine whether RIGID-TASC has adequate interrater reliability when used by different independent testers. METHODS: At two academic medical centers in the United States, 30 physician volunteers were selected in three categories: 10 novices at rigid bronchoscopy (performed at least 50 flexible, but no rigid, bronchoscopies), 10 operators with intermediate experience (performed 5-20 rigid bronchoscopies), and 10 experts (performed ≥100 rigid bronchoscopies). Participants included pulmonary and critical care fellows, interventional pulmonology fellows, and faculty interventional pulmonologists. Each subject then performed rigid bronchoscopic intubation and navigation on a manikin, while being scored independently by two testers, using RIGID-TASC. MEASUREMENTS AND MAIN RESULTS: Mean scores for three categories (novice, intermediate, and expert) were 58.10 (±4.6 [SE]), 78.15 (±3.8), and 94.40 (±1.1), respectively. There was significant difference between novice and intermediate (20.05, 95% confidence interval [CI] = 7.77-32.33, P = 0.001), and intermediate and expert (16.25, 95% CI = 3.97-28.53, P = 0.008) operators. The interrater reliability (intraclass correlation coefficient) between the two testers was high (r = 0.95, 95% CI = 0.90-0.98). CONCLUSIONS: RIGID-TASC showed evidence of construct validity and interrater reliability in this setting and group of subjects. It can be used to reliably and objectively score and classify operators from novice to expert in basic rigid bronchoscopic intubation and navigation.

Hypoxic Gene Expression of Donor Bronchi Linked to Airway Complications after Lung Transplantation.

RATIONALE: Central airway stenosis (CAS) after lung transplantation has been attributed in part to chronic airway ischemia; however, little is known about the time course or significance of large airway hypoxia early after transplantation. OBJECTIVES: To evaluate large airway oxygenation and hypoxic gene expression during the first month after lung transplantation and their relation to airway complications. METHODS: Subjects who underwent lung transplantation underwent endobronchial tissue oximetry of native and donor bronchi at 0, 3, and 30 days after transplantation (n = 11) and/or endobronchial biopsies (n = 14) at 30 days for real-time polymerase chain reaction of hypoxia-inducible genes. Patients were monitored for 6 months for the development of transplant-related complications. MEASUREMENTS AND MAIN RESULTS: Compared with native endobronchial tissues, donor tissue oxygen saturations (Sto2) were reduced in the upper lobes (74.1 ± 1.8% vs. 68.8 ± 1.7%; P < 0.05) and lower lobes (75.6 ± 1.6% vs. 71.5 ± 1.8%; P = 0.065) at 30 days post-transplantation. Donor upper lobe and subcarina Sto2 levels were also lower than the main carina (difference of -3.9 ± 1.5 and -4.8 ± 2.1, respectively; P < 0.05) at 30 days. Up-regulation of hypoxia-inducible genes VEGFA, FLT1, VEGFC, HMOX1, and TIE2 was significant in donor airways relative to native airways (all P < 0.05). VEGFA, KDR, and HMOX1 were associated with prolonged respiratory failure, prolonged hospitalization, extensive airway necrosis, and CAS (P < 0.05). CONCLUSIONS: These findings implicate donor bronchial hypoxia as a driving factor for post-transplantation airway complications. Strategies to improve airway oxygenation, such as bronchial artery re-anastomosis and hyperbaric oxygen therapy merit clinical investigation.

Therapeutic bronchoscopy improves spirometry, quality of life, and survival in central airway obstruction.

BACKGROUND: Central airway obstruction (CAO) occurs in patients with primary or metastatic lung malignancy and nonmalignant pulmonary disorders and results in significant adverse effects on respiratory function and quality of life. OBJECTIVES: The objective of this study was to assess the effect of therapeutic bronchoscopic interventions on spirometry, dyspnea, quality of life, and survival in patients with CAO. METHODS: We prospectively studied patients who underwent therapeutic rigid bronchoscopy for CAO. Spirometry, San Diego Shortness of Breath questionnaire (SOBQ), and SF-36 questionnaire responses were obtained before the procedure and at follow-up 6-8 weeks after the procedure. RESULTS: Fifty-three patients (24 malignant and 29 nonmalignant CAO), who underwent successful rigid bronchoscopic intervention, were enrolled. Airway stent placement and various debulking techniques including mechanical debridement and heat therapy were used. After bronchoscopy, there was a significant increase in forced vital capacity (2.2 ± 0.91 l before, 2.7 ± 0.80 l after, p = 0.009) and forced expiratory volume at 1 s (1.4 ± 0.60 l before, 1.8 ± 0.67 l after, p = 0.002). The SOBQ score improved from 55.8 ± 30.1 before the procedure to 37.9 ± 27.25 after the procedure (p = 0.002). In the SF-36, there was an improvement in almost all domains, with statistically significant improvement seen in several domains. Benefits were seen independent of the etiology of CAO, site of intervention or stent placement. The patients with malignant CAO, in whom airway patency could not be achieved, had a poor survival. CONCLUSIONS: Alleviation of CAO with therapeutic rigid bronchoscopy results in improvement in spirometry, shortness of breath, quality of life, and survival.

Bronchomediastinal fistula caused by endobronchial aspergilloma.

RATIONALE: Endobronchial aspergilloma is a rare condition affecting immunocompromised patients. We present three cases resulting in airway fistulae. CASE PRESENTATIONS: A 68-year-old male with orthotopic heart transplantation presented with fatigue, cough, and dyspnea. A computerized tomography (CT) scan of the chest and bronchoscopy revealed an endobronchial right mainstem mass and airway fistula to the mediastinum. The mass was debrided and biopsy showed Aspergillus fumigatus. He was treated with antifungals and recovered. A 52-year-old male with acquired immunodeficiency syndrome presented with cough, dyspnea, and hypoxemia. Chest CT showed a bronchus intermedius mass and fistula to the mediastinum. Bronchoscopy revealed a necrotic endobronchial mass and pseudomembranes and confirmed the presence of a fistula. The mass was resected bronchoscopically and Aspergillus fumigatus was isolated. He was treated with antifungals and the fistula healed. A 63-year-old male with chronic lymphoid leukemia was admitted for dyspnea, cough, weakness, and dysphagia. Chest CT and bronchoscopy showed a mass causing obstruction of the subglottic trachea and a fistula to the mediastinum. Biopsy showed Aspergillus fumigatus and he was treated with antifungals. The sinus healed but the patient died of leukemia. MAIN RESULTS: Risk factors for airway aspergilloma include immune deficiency, mucosal damage, and ischemia. We report airway fistula formation as a complication of this infection, which has not been previously emphasized. CONCLUSIONS: Endobronchial aspergillomas may form fistulae to the mediastinum. Aggressive treatment with antifungals and bronchoscopic interventions are required.

Learning experience of linear endobronchial ultrasound among pulmonary trainees.

BACKGROUND: Linear endobronchial ultrasound (EBUS) allows real-time guidance of transbronchial needle aspiration of thoracic structures and has become an increasingly important diagnostic tool for chest physicians. Little has been published about the learning experience of operators with this technology. The purpose of this study was to define the learning experience of EBUS-guided transbronchial needle aspiration (EBUS-TBNA) among pulmonary trainees. METHODS: This was a multicenter cohort study of fellows in pulmonary medicine over the first 2 years of their training. Prior to performing EBUS-TBNA, all participants had to complete 30 conventional bronchoscopies, an EBUS-specific didactic curriculum, and a simulation session with a plastic airway model. Each consecutive EBUS procedure was scored with a checklist that evaluated the ability to pass a bronchoscope through vocal cords, identify the appropriate node for sampling, acquire adequate ultrasound images, guide the bronchoscopy team through the technical steps of EBUS-TBNA, and obtain adequate tissue samples. RESULTS: Thirteen pulmonary trainees from three training programs were enrolled in the study and were observed over a 2-year period. The majority of trainees were able to perform all essential steps of EBUS-TBNA and obtain adequate tissue after performing an average of 13 (95% CI, 7-16) procedures. CONCLUSIONS: Pulmonary trainees needed an average of 13 procedures to achieve first independent successful performance of EBUS-TBNA following a training protocol that included a didactic curriculum and simulation-based practice. Our findings could guide pulmonary fellowship directors in planning EBUS training and establishing a reasonable juncture to assess EBUS skills with validated assessment tools.

Hemorrhagic complications of thoracentesis and small-bore chest tube placement in patients taking clopidogrel.

RATIONALE: Clopidogrel is a commonly used antiplatelet medication. The risk of local hemorrhage associated with use of this drug during routine thoracentesis or small-bore chest tube placement is not well established. OBJECTIVES: We conducted a prospective cohort study to assess the risk of hemothorax in patients taking clopidogrel while undergoing either pleural procedure. METHODS: Twenty-five consecutive adult patients who were taking clopidogrel at the time they were offered thoracentesis or small-bore (14 Fr) chest tube placement consented to continue taking the drug through their procedure. A control group consisted of 50 patients undergoing these pleural procedures who were not taking clopidogrel at the time they consented to undergo either procedure. All of the pleural procedures were performed under ultrasound guidance by an interventional pulmonologist or a fellow under direct faculty supervision. Hospitalized patients were screened for hemothorax by observing for a post-procedure drop in blood hemoglobin content of 2 g/dl or reaccumulation of their pleural effusion within 24 hours of the procedure. Outpatients were called within 2 weeks after their procedure to determine whether they had any symptoms suggestive of hemothorax. MEASUREMENTS AND MAIN RESULTS: There was one case of hemothorax after thoracentesis in the clopidogrel group versus none in the control group. The one patient with hemothorax required transfusion with 2 units of packed red blood cells and small-bore chest tube placement, and clopidogrel was withheld. There were no other clinically apparent complications of either procedure. CONCLUSIONS: Considered in combination with other small previously published studies, this single-center, nonrandomized, controlled prospective cohort study suggests that the rate of clinically consequential hemorrhage after ultrasound-guided thoracentesis or chest tube placement in patients taking clopidogrel is sufficiently low to warrant a large, randomized clinical trial designed to determine the safety of performing these procedures without interrupting clopidogrel therapy.

Endobronchial fiducial to guide stereotactic body radiotherapy.

Optimal treatment for unresectable central airway tumors is not well established. Stereotactic body radiation therapy has shown efficacy for both peripheral and central lung lesions. However, the treatment of central tumors has been limited because of associated radiation toxicity. We report the use of an endobronchial fiducial to localize hypofractionated stereotactic body radiation therapy treatment of a limited central airways disease in a patient with recurrent metastatic squamous cell lung cancer. The fiducial was instrumental in designing the treatment field and minimizing related treatment toxicity. Future studies may take advantage of this technique in patients with unresectable central airways non-small cell lung cancers.