Christopher R. Gilbert

Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry.

RATIONALE Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy. OBJECTIVES To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations. METHODS We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions. MEASUREMENTS AND MAIN RESULTS Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16). CONCLUSIONS Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.

Vitamin D Deficiency and Chronic Lung Disease

Vitamin D deficiency is increasingly being recognized as a prevalent problem in the general population. Patients with chronic lung diseases such as asthma, cystic fibrosis, chronic obstructive lung disease and interstitial pneumonia appear to be at increased risk for vitamin D deficiency for reasons that are not clear. Several studies indicate that vitamin D possesses a range of anti-inflammatory properties and may be involved in processes other than the previously believed functions of calcium and phosphate homeostasis. Various cytokines, cellular elements, oxidative stress and protease/antiprotease levels appear to affect lung fibroproliferation, remodelling and function, which may be influenced by vitamin D levels. Chronic lung diseases such as asthma and chronic obstructive lung disease have also been linked to vitamin D on a genetic basis. This immune and genetic influence of vitamin D may influence the pathogenesis of chronic lung diseases. A recent observational study notes a significant association between vitamin D deficiency and decreased pulmonary function tests in a large ambulatory population. The present review will examine the current literature regarding vitamin D deficiency, its prevalence in patients with chronic lung disease, vitamin D anti-inflammatory properties and the role of vitamin D in pulmonary function.

Cryoprobe Transbronchial Lung Biopsy in Patients After Lung Transplantation: A Pilot Safety Study

BACKGROUND Transbronchial biopsies using standard forceps (FTBBxs) are often limited by crush artifact and their small size. To date, there have been no studies aimed at assessing the safety and efficacy of cryoprobe biopsies (CPBxs) in the population of patients who have undergone lung transplants. We present the safety profile and biopsy results from the fi rst 21 procedures in a pilot study comparing CPBx to FTBBx in patients after lung transplantation. METHODS Patients who had undergone lung transplant and who were scheduled for bronchoscopy were sequentially enrolled between November 2011 and September 2012. Inclusion criteria included age . 18 years and bilateral, orthotopic lung transplant. Exclusion criteria were coagulopathy, FEV 1 < 0.8 L, diffuse bullous disease, hemodynamic instability, and severe hypoxemia (Pa(O2) < 55 mm Hg or Sp(O2) < 92% on room air). Twenty-one procedures were performed, 10 using rigid bronchoscopy followed by 11 via flexible bronchoscopy. Patients were monitored for complications including pneumothorax, hemodynamic instability, and/or respiratory distress. Bleeding was categorized on an adapted grading system. RESULTS Twenty-one procedures in 17 patients (median age: 52 years; 12 male patients) were performed. Specimen area and percent open alveoli were significantly greater using CPBx compared with FTBBx ( P < .05). No clinically significant procedural complications occurred and all patients were discharged the day of the procedure. CONCLUSIONS The use of the cryoprobe is a safe, alternative technique to FTBBx during post-lung transplant bronchoscopy. Further studies are needed to determine if larger samples obtained with CPBx translate to an increased diagnostic yield.

Optimizing Endobronchial Ultrasound for Molecular Analysis. How Many Passes Are Needed

BACKGROUND The current oncologic management of non-small cell lung cancer (NSCLC) requires pathologic differentiation between adenocarcinoma and squamous cell carcinoma. Furthermore, novel therapies for adenocarcinoma are clinically available for specific mutation profiles. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been shown to adequately obtain specimens for molecular profiling. However, it remains unclear what quantity of specimens is needed to provide suitable mutational genotyping for adenocarcinoma. The objective of this study was to determine the optimal number of aspirations per EBUS-TBNA procedure required in the presence of rapid on-site cytopathology evaluation (ROSE) for maximal diagnostic yield for molecular mutational analysis. METHODS From March 2010 to February 2012, cytopathologic data were collected from consecutive cases of adenocarcinoma or NSCLC not otherwise specified (NSCLC-NOS), diagnosed by EBUS-TBNA and ROSE. Samples of material obtained were air-dried and wet-fixed. Samples were tested for the KRAS, EGFR, and/or ALK mutations. MEASUREMENTS AND MAIN RESULTS Eighty-five patients who underwent EBUS-TBNA and were diagnosed with adenocarcinoma or NSCLC-NOS were identified. Of the 85 cases identified, 77 (90.6%) were classified as adenocarcinoma with the remaining 8 (9.4%) classified as NSCLC-NOS. Eighty-one of 85 (95.3%) were found to be adequate for molecular profiling. The median number of sites sampled was one. A median of four passes was needed to obtain adequate molecular profiling of 95.3%, using EBUS in conjunction with ROSE. CONCLUSIONS With the use of EBUS-TBNA and ROSE, a minimum of four needle passes may provide an adequate amount of specimen for advanced molecular marker analysis.

Comparison of Moderate versus Deep Sedation for Endobronchial Ultrasound Transbronchial Needle Aspiration

RATIONALE Most bronchoscopic procedures are performed using moderate sedation achieved by combining a short-acting benzodiazepine with an opioid agent. Propofol (2.6-diisopropylphenol), a short-acting hypnotic agent, has been increasingly used to provide deep sedation in the endoscopy community with an acceptable safety profile. OBJECTIVES To compare the impact of moderate versus deep sedation on the adequacy and diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). METHODS A retrospective review of prospectively collected data was performed at two academic institutions with interventional pulmonary fellowships using two methods of sedation during EBUS (deep vs. moderate sedation). Rapid on-site cytologic evaluation was used on all procedures in both groups. EBUS-TBNA nodal sampling was considered adequate if the aspirate yielded a specific diagnosis or lymphocytes. EBUS-TBNA was considered diagnostic if a lymph node aspirate yielded a specific diagnosis or if subsequent surgical sampling or prolonged radiographic surveillance revealed no nodal pathology. MEASUREMENTS AND MAIN RESULTS No difference was observed in the indication for EBUS-TBNA between the two groups. More lymph nodes were sampled per patient in the deep sedation group (314 nodes from 163 patients; 2.2 nodes per patient) than in the moderate sedation group (181 lymph nodes from 146 patients; 1.4 nodes per patient; P < 0.01). The EBUS-TBNA diagnostic yield was higher for the deep sedation group (80% of patients) than for the moderate sedation group (66% of patients; P < 0.01). CONCLUSIONS Diagnostic yield and number of lymph nodes sampled using deep sedation is superior to moderate sedation in patients undergoing EBUS-TBNA. Prospective studies accounting for other factors including patient selection and cost are needed.

Original ResearchInterventional PulmonologyCryoprobe Transbronchial Lung Biopsy in Patients After Lung Transplantation: A Pilot Safety Study

BACKGROUND Transbronchial biopsies using standard forceps (FTBBxs) are often limited by crush artifact and their small size. To date, there have been no studies aimed at assessing the safety and efficacy of cryoprobe biopsies (CPBxs) in the population of patients who have undergone lung transplants. We present the safety profile and biopsy results from the fi rst 21 procedures in a pilot study comparing CPBx to FTBBx in patients after lung transplantation. METHODS Patients who had undergone lung transplant and who were scheduled for bronchoscopy were sequentially enrolled between November 2011 and September 2012. Inclusion criteria included age . 18 years and bilateral, orthotopic lung transplant. Exclusion criteria were coagulopathy, FEV 1 < 0.8 L, diffuse bullous disease, hemodynamic instability, and severe hypoxemia (Pa(O2) < 55 mm Hg or Sp(O2) < 92% on room air). Twenty-one procedures were performed, 10 using rigid bronchoscopy followed by 11 via flexible bronchoscopy. Patients were monitored for complications including pneumothorax, hemodynamic instability, and/or respiratory distress. Bleeding was categorized on an adapted grading system. RESULTS Twenty-one procedures in 17 patients (median age: 52 years; 12 male patients) were performed. Specimen area and percent open alveoli were significantly greater using CPBx compared with FTBBx ( P < .05). No clinically significant procedural complications occurred and all patients were discharged the day of the procedure. CONCLUSIONS The use of the cryoprobe is a safe, alternative technique to FTBBx during post-lung transplant bronchoscopy. Further studies are needed to determine if larger samples obtained with CPBx translate to an increased diagnostic yield.

The Use of Indwelling Tunneled Pleural Catheters for Recurrent Pleural Effusions in Patients With Hematologic Malignancies: A Multicenter Study

BACKGROUND Malignant pleural effusion is a common complication of advanced malignancies. Indwelling tunneled pleural catheter (IPC) placement provides effective palliation but can be associated with complications, including infection. In particular, hematologic malignancy and the associated immunosuppressive treatment regimens may increase infectious complications. This study aimed to review outcomes in patients with hematologic malignancy undergoing IPC placement. METHODS A retrospective multicenter study of IPCs placed in patients with hematologic malignancy from January 2009 to December 2013 was performed. Inclusion criteria were recurrent, symptomatic pleural effusion and an underlying diagnosis of hematologic malignancy. Records were reviewed for patient demographics, operative reports, and pathology, cytology, and microbiology reports. RESULTS Ninety-one patients (mean ± SD age, 65.4 ± 15.4 years) were identified from eight institutions. The mean × SD in situ dwell time of all catheters was 89.9 ± 127.1 days (total, 8,160 catheter-days). Seven infectious complications were identified, all of the pleural space. All patients were admitted to the hospital for treatment, with four requiring additional pleural procedures. Two patients died of septic shock related to pleural infection. CONCLUSIONS We present, to our knowledge, the largest study examining clinical outcomes related to IPC placement in patients with hematologic malignancy. An overall 7.7% infection risk and 2.2% mortality were identified, similar to previously reported studies, despite the significant immunosuppression and pancytopenia often present in this population. IPC placement appears to remain a reasonable clinical option for patients with recurrent pleural effusions related to hematologic malignancy.

Novel bronchoscopic strategies for the diagnosis of peripheral lung lesions: Present techniques and future directions

The diagnosis of the peripheral lung lesion has been a long‐standing clinical challenge—balancing accuracy with patient safety. With recent data revealing mortality benefits with lung cancer screening via low‐dose computed tomography, now more than ever, clinicians will be challenged with the task of providing the means to provide a safe and minimally invasive method of obtaining accurate tissue diagnostics for the pulmonary nodule. In this review, we present available technologies to aid clinicians in attempts at minimally invasive techniques and the data supporting their use. In addition, we review novel tools under investigation that may further increase yield and provide additional benefit in obtaining an early diagnosis of lung cancer.

Novel Applications of an Injectable Radiopaque Hydrogel Tissue Marker for Management of Thoracic Malignancies

BACKGROUND Radiopaque markers (otherwise known as fiducials) are used clinically to mark sites of biopsy or resection, which aids with targeting of local therapy, including surgery and radiation therapy. We performed a human cadaveric imaging series with a novel, injectable, radiopaque, absorbable hydrogel marker to demonstrate its potential in the management of thoracic malignancies. METHODS Baseline CT imaging was performed on three unfixed cadaveric specimens. Hydrogel marker implants were placed in the submucosa of the esophagus, the mediastinum, and lung parenchyma by an endoscopic approach with real-time endobronchial and esophageal ultrasound guidance. Subpleural implants in peripheral lung parenchyma were also performed through an anterolateral thoracotomy. Postimplant simulation CT imaging, T2-weighted MRI, and cone-beam CT imaging were performed. Gross dissection of the lung parenchyma was used to evaluate localization of the hydrogel. RESULTS Transthoracic and endoscopic marker placement was readily achieved. The hydrogel appeared hyperechoic by ultrasound, hyperenhancing on T2-weighted MRI, and demonstrated radiopacity of ~300 Hounsfield Units in simulation CT imaging and cone-beam CT imaging. Gross dissection of the lung revealed well-localized blebs of hydrogel marker within lung parenchyma. CONCLUSIONS This cadaveric series demonstrates the excellent visibility of a radiopaque injectable hydrogel marker in the human thorax by multiple common imaging techniques. The hydrogel marker forms a well-localized bleb within tissue, which can assist with triangulation of disease during minimally invasive thoracic surgery. Esophageal applications include radiographic delineation of tumor defined by endoscopy and image guidance for radiotherapy. Future in vivo studies are warranted because radiopaque injectable compounds are promising alternatives to metal fiducials.

Safety and Feasibility of Interventional Pulmonologists Performing Bedside Percutaneous Endoscopic Gastrostomy Tube Placement

BACKGROUND Prior to the 1980s, permanent feeding tube placement was limited to an open surgical procedure until Gauderer and colleagues described the safe placement of percutaneous endoscopic gastrostomy (PEG) tubes. This procedure has since expanded beyond the realm of surgeons to include gastroenterologists, thoracic surgeons, and interventional radiologists. In some academic centers, interventional pulmonologists (IPs) also perform this procedure. We describe the safety and feasibility of PEG tube placement by IPs in a critically ill population. METHODS Prospectively collected data of patients in a medical ICU undergoing PEG tube placement from 2003 to 2007 at a tertiary-care center were reviewed. Inclusion criteria included all PEG tube insertions performed or attempted by the IP team. Data were collected on mortality, PEG tube removal rate, total number of days with PEG tube, and complication rates. Follow-up included hospital length of stay and phone contact after discharge. Procedural and long-term PEG-related complications were recorded. RESULTS Seventy-two patients were studied. PEG tube insertion was completed successfully in 70 (97.2%), with follow-up data in 69 of these 70. Thirty-day mortality was 11.7%. No deaths or immediate complications were attributed to PEG tube placement. PEG tube removal occurred in 27 patients, with a median time to removal of 76 days. CONCLUSIONS Bedside PEG tube placement can be performed safely and effectively by trained IPs. Because percutaneous tracheostomy is currently performed by IPs, the ability to place both PEG and tracheostomy tubes at the same time has the potential for decreased costs, anesthesia exposure, procedural times, ventilator times, and ICU days.