Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis

BACKGROUND: The diagnosis of pulmonary sarcoidosis can be established by a variety of techniques. Transbronchial lung biopsy is often the preferred approach, but it is frequently nondiagnostic and carries a risk of pneumothorax and bleeding. Mediastinoscopy is often suggested as the next diagnostic step but entails significant cost and associated morbidity. Endobronchial ultrasound (EBUS) with transbronchial needle aspiration (TBNA) is emerging as a safe, minimally invasive tool for the primary diagnosis of mediastinal and hilar lymphadenopathy. The purpose of this study was to assess the utility of EBUS-TBNA for pulmonary sarcoidosis. METHODS: Fifty consecutive patients who had been referred for EBUS-TBNA for suspected pulmonary sarcoidosis were included in the study. On-site cytology was used to assess the adequacy of the samples. The presence of noncaseating granulomas without necrosis in the appropriate clinical setting was deemed to be adequate for the diagnosis of pulmonary sarcoidosis. Patients with a negative EBUS-TBNA underwent further histologic biopsy or clinical follow-up to determine the final diagnosis. RESULTS: Eighty-two lymph nodes with a median size of 16 mm (range, 4 to 40 mm) were punctured. EBUS-TBNA demonstrated noncaseating granulomas without necrosis in 41 of 48 patients (85%) with a final diagnosis of sarcoidosis. EBUS-TBNA, therefore, has a sensitivity of 85% for the primary diagnosis of pulmonary sarcoidosis. CONCLUSIONS: EBUS-TBNA is a safe, minimally invasive tool for the primary diagnosis of pulmonary sarcoidosis that has a high diagnostic yield. EBUS-TBNA should be considered an appropriate alternative diagnostic technique for patients with suspected pulmonary sarcoidosis.     

Endobronchial biopsy for sarcoidosis: a prospective study.

STUDY OBJECTIVES: To determine the yield of endobronchial biopsy (EBB) for suspected sarcoidosis, and to evaluate if EBB increases the diagnostic value of fiberoptic bronchoscopy (FOB) when added to transbronchial biopsy (TBB). DESIGN: Prospective study of consecutive patients. SETTING: Pulmonary clinic of a tertiary-care, academic medical center. PATIENTS: Patients consecutively referred for suspected pulmonary sarcoidosis. INTERVENTIONS: All patients having FOB performed underwent an evaluation that included history, physical examination, a chest radiograph, and spirometry. During FOB, airway appearance was recorded and both TBB and EBB were performed in a standardized fashion. Six TBB specimens were obtained, as were six EBB samples. For patients with abnormal-appearing airways, four specimens were obtained from the abnormal-appearing airways and two specimens were obtained from the main carina. In patients with normal-appearing airways, four specimens were obtained from a secondary carina and two specimens were obtained from the main carina. A biopsy finding was considered positive if it demonstrated nonnecrotizing granulomas with special stains that were negative for fungal and mycobacterial organisms. Measurements and results: The study cohort included 34 subjects (mean +/- SD age, 37.9 +/- 6.8 years; 58.8% were male; 64.7% were African American). EBB findings were positive in 61.8% of patients, while TBB showed nonnecrotizing granulomas in 58.8% of subjects. The addition of EBB increased the yield of FOB by 20.6%. Although EBB findings were more frequently positive in abnormal-appearing airways (p = 0.014), EBB provided diagnostic tissue in 30.0% of patients with normal-appearing endobronchial mucosa. There were no complications resulting from the addition of EBB to TBB. CONCLUSIONS: Endobronchial involvement is common in sarcoidosis. EBB has a yield comparable to TBB and can safely increase the diagnostic value of FOB. Pulmonologists should consider routinely performing EBB in cases of suspected sarcoidosis.     

Endobronchial ultrasound in therapeutic bronchoscopy.

Endobronchial ultrasound (EBUS) has been introduced as an adjunct to diagnostic bronchoscopy as it allows evaluation of the submucosal and parabronchial structures. Its use in therapeutic bronchoscopy has not been assessed. A large observational study of the value of EBUS in therapeutic bronchoscopy is presented here. From January 1998-January 2001 all patients undergoing therapeutic bronchoscopy and EBUS were evaluated prospectively. Patient demographics, indication for bronchoscopy, interventional treatments used and changes in therapy as influenced by the use of EBUS were documented. A total 2,446 therapeutic bronchoscopies were performed. In 1,174 cases EBUS was used (29% mechanical tumour debridement, 20% airway stenting, 13% Neodymium:yttrium aluminium garnet (Nd:YAG) laser use, 23% argon plasma coagulation, 11% brachytherapy, 2% foreign body removal and 2% endoscopic abscess drainage). EBUS guided or changed therapy significantly in 43% of cases. Changes included adjustment of stent dimensions, termination of tumour debridement when nearing vessels, and referral for surgical interventions rather than endoscopic treatment. Complications associated with EBUS use were minimal. No patient undergoing EBUS guided tumour destruction experienced severe bleeding or fistula formation. In summary, endobronchial ultrasound was easily performed and changed or guided therapeutic decisions during therapeutic bronchoscopic procedures in a substantial number of cases. As this may result in better outcomes, it has become a standard adjunct in the authors practice.     

Endobronchial ultrasound‐guided transbronchial needle aspiration for diagnosis of sarcoidosis in clinically unselected study populations

Literature suggests that ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) has excellent performance characteristics for diagnosis of sarcoidosis. However, many authors challenge the external validity of EBUS‐TBNA results, as most studies were performed in referral centres by highly experienced investigators, and included populations with very high sarcoidosis prevalence. We performed a systematic review and meta‐analysis to estimate the role of EBUS‐TBNA for diagnosis of sarcoidosis in studies enrolling consecutive patients with lymphadenopathy detected at imaging studies, regardless of the suspected underlying clinical aetiology. The Pubmed, Embase, Cinahl, Web of Science and Cochrane Library databases were screened to identify the pertinent literature. Quality of eligible studies was assessed by Quality Assessment, Data Abstraction and Synthesis‐2 criteria. Pooled diagnostic yield, sensitivity and specificity were calculated, and a summary receiver operating characteristic curve was constructed. Subgroup analysis was planned to identify possible sources of study heterogeneity. Fourteen studies, collectively involving 2097 patients, fulfilled eligibility criteria. The median prevalence of sarcoidosis was 15%. EBUS‐TBNA had a pooled diagnostic yield of 0.79 (standard deviation, 0.24), a pooled sensitivity of 0.84 (95% confidence interval (CI), 0.79–0.88) and a pooled specificity of 1.00 (95% CI, 0.99–1.00). Only subgroup analysis exploring the influence of study design seemed to influence the observed inter‐study heterogeneity for sensitivity, retrospective studies showing worst sensitivity than prospective ones. The results of EBUS‐TBNA for diagnosis of sarcoidosis in clinically unselected populations are excellent and compare favourably with published results from studies conducted in selected populations. High‐quality trials would be needed to evaluate factors possibly explaining the observed heterogeneity in sensitivity.     

Esophageal sarcoidosis: an unusual diagnosis.

We report a 48-year-old patient who developed secondary achalasia because of esophageal sarcoidosis. Sarcoidosis can involve many gastrointestinal tract organs and can affect the esophagus in different ways. We describe how achalasia was diagnosed and treated in our patient and provide a review of the presentations of esophageal sarcoidosis.     

Endobronchial ultrasound (EBUS): the state of the art

Endobronchial ultrasound (EBUS) is a technique which allows the endoscopist to sample mediastinal and/or hilar lymph nodes for complete staging of thoracic malignancy without recourse to surgery. Originally developed at the beginning of the 21st century, EBUS has become a well developed practice within France in recent years. As the technique requires high tech, expensive and fragile equipment, it has been important to develop an approach that is appropriate for the specific features and constraints of the French health system, including access to anaesthesia, imaging modalities and costing. The first centers to adopt EBUS had to adapt quickly and develop their own practices for its use. Training seminars were carried out in order to pass on this experience. After the passage of several years, it seems helpful to give a progress report on this technique through the stages of its development, taking account of the specificities of the French system and thus to transmit this accumulated experience. In this article, the authors review the literature concerning all the essential aspects needed to apply this technique under the best conditions in the French health system.     

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis.

The objective of the current study was to assess the yield of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) for the diagnosis of sarcoidosis in a large patient group. Bronchoscopy with transbronchial lung biopsy (TBLB) is nondiagnostic in 30% of patients with suspected sarcoidosis and has a risk of pneumothorax and haemoptysis. In order to obtain a diagnosis, mediastinoscopy is often performed as the next diagnostic procedure. EUS-FNA provides a nonsurgical alternative for the demonstration of noncaseating granulomas by aspirating mediastinal lymph nodes from the oesophagus. In total, 51 patients with suspected sarcoidosis stage I and II underwent EUS-FNA. Thirty-six patients (71%) previously underwent a nondiagnostic bronchoscopy. All patients were clinically followed (median 18 months) and surgical-pathological verification occurred in those patients with EUS aspirates that contained unrepresentative material. EUS-FNA demonstrated noncaseating granulomas without necrosis in 41 of 50 patients (82%) with the final diagnosis of sarcoidosis. Specific ultrasound features of clustered, well-demarcated iso-echoic lymph nodes were observed in 64% of patients with sarcoidosis. No complications occurred. Endoscopic ultrasound-guided fine-needle aspiration has a high yield in diagnosing sarcoidosis and qualifies as the next diagnostic step after a nondiagnostic bronchoscopy. The current authors expect that endoscopic ultrasound-guided fine-needle aspiration will reduce the number of mediastinoscopies for the diagnosis of sarcoidosis dramatically.     

Pregnancy and sarcoidosis: an insight into the pathogenesis of hypercalciuria

Hypercalciuria with or without hypercalcemia is a well-known complication of sarcoidosis, the pathogenesis of which is not fully understood. Pregnancy is associated with physiologic alterations in calcium metabolism. These changes can further alter the derangement of calcium metabolism that occurs in sarcoidosis, if the two conditions coexist. We had the opportunity to study prospectively the changes in serum and urine calcium along with all the hormonal changes that occur during pregnancy in a young woman with sarcoidosis, who had hypercalciuria at presentation. We believe that an increased level of calcitriol is central to the calcium abnormalities in our patient. In her case, the increased calcitriol is derived from sarcoid granulomas and renal sources enhanced by the effect of estradiol and prolactin on the conversion of 25(OH)D to 1,25(OH)(2) D. She acquired hypoparathyroidism, with normal serum calcium, which probably was due to the direct suppression of parathyroid hormone (PTH) secretion by calcitriol. Finally, hypercalciuria is the result of the combined effect of hyperabsorption of calcium from the gut (the result of increased calcitriol levels leading to increased filtration of calcium) and decreased tubular reabsorption of calcium, as a result of undetectable PTH.     

支气管结核介入诊治的认识和思考

支气管结核（EBTB）的介入诊断和治疗有了长足的进展,但也面临着诸多的问题,有必要加深认识和思考。EBTB的支气管镜下目前分为5型,即炎症浸润型（Ⅰ型）、溃疡坏死型（Ⅱ型）、肉芽增殖型（Ⅲ型）、瘢痕狭窄型（Ⅳ型）和管壁软化型（Ⅴ型）,建议在原来EBTB＂五型＂的基础上将结核性支气管瘘从第Ⅱ型中分离出来成为单独的类型,即Ⅵ型。在支气管结核的治疗中,应根据不同的类型,采用包括高频电刀、冷冻、氩气刀、激光、支架置入、球囊扩张以及黏膜下穿刺注射抗结核药物等综合介入技术进行治疗。     

Endobronchial biopsy positive sarcoidosis: relation to bronchoalveolar lavage and course of disease

Sixty-two patients with newly diagnosed sarcoidosis were examined with fibreoptic bronchoscopy, endobronchial biopsies and bronchoalveolar lavage (BAL) were analysed. Epithelioid granulomatosis in endobronchial biopsies were found in 28 (45%) of the patients (BPOS). The patients in this BPOS group showed higher inflammatory activity in BAL fluid compared to those with negative biopsies (BNEG), with significant increases in lymphocyte and mast cell counts, and concentrations of procollagen III peptide and albumin. The patients were followed over a period of 2 years. The BPOS group tended to have a worse clinical course with more patients having a progressive disease and more patients requiring treatment with systemic steroids. We conclude that the findings of epithelioid granulomatosis in endobronchial biopsies may reflect a more intense and widespread inflammation in the lung.     

Endobronchial ultrasound‐guided transbronchial needle aspiration in sarcoidosis: Beyond the diagnostic yield

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is the commonly used technique for pathological confirmation of clinically suspected sarcoidosis, mostly owing to its consistently high success rate in the detection of granulomas. However, other possible advantages, which are less appreciated and often poorly studied, may also contribute to the wider use of EBUS‐TBNA in the future. These advantages include refinement of differential diagnoses through the study of lymph node characteristics during B‐mode examination; reduction of complications associated with bronchoscopy, as well as improved triage of the specimen for ancillary studies with the use of rapid on‐site evaluation; optimization of the quality of the sample through the selection of a target area for biopsy with minimal vascularity and absence of calcifications by using the colour Doppler and the B‐mode; and prediction of the presence of extensive lymph node fibrosis by using the strain elastography module. Yet, limitations and possible clinical drawbacks should also be acknowledged. Indeed, due to the lack of specificity of the pathology findings in EBUS‐derived samples, the diagnosis of sarcoidosis is one of the exclusion and should remain essentially clinical. The external validity of EBUS‐TBNA results in sarcoidosis is questionable, as they mainly derive from studies in populations with a high disease prevalence. Finally, the risk exists that the low morbidity and high diagnostic yield of EBUS‐TBNA may lead to its overuse in patients with clinical/radiological findings specific enough to secure a clinical diagnosis of sarcoidosis.     

Endobronchial ultrasound and positron emission tomography positive mediastinal lymph nodes.

Positron emission tomography with 18F-fluoro-2-deoxy-d-glucose (FDG-PET) is more accurate than computed tomography for staging of mediastinal (hilar) lymph nodes. In the case of positive findings, tissue sampling of lymph nodes is required. The diagnostic/staging yield of transbronchial needle aspiration (TBNA) following endobronchial ultrasound (EBUS) localisation was assessed in this particular clinical setting. The number of avoided surgical procedures was evaluated. All consecutive patients referred for staging and/or diagnosis of mediastinal FDG-PET positive lesions were included. Data were prospectively collected. TBNA sampling of lymph nodes was performed after EBUS localisation. If no diagnosis was reached, further surgical sampling or adequate follow-up was performed. From January 2003 to June 2004, 33 patients were included. The average number of TBNA samples per patient was 4.2+/-1.5. Cytological or histological diagnoses were obtained in 27 (82%) of the patients, of which 78% were obtained after previous EBUS localisation. In 25 (76%) of the 33 patients, surgical staging procedures were suppressed. In conclusion, transbronchial needle aspiration after endobronchial ultrasound localisation should be considered as a primary method of evaluation of lymph nodes positive by positron emission tomography with 18F-fluoro-2-deoxy-d-glucose, and may replace the majority of surgical mediastinal staging/diagnostic procedures.     

Endobronchial ultrasound morphology of expiratory central airway collapse

Abstract:   Differences in central airway wall structure in patients with various forms of expiratory central airway collapse can be identified by endobronchial ultrasound using a 20 MHz radial probe. In tracheobronchomalacia due to relapsing polychondritis, the cartilage is thick and irregular while the membranous portion is normal. In malacia due to chronic inflammation after tracheotomy, the cartilage is thick and irregular and the membranous portion is also thick. In excessive dynamic airway collapse associated with COPD, on the contrary, the cartilage is normal and the posterior membrane is thin when compared to the normal airway wall structures identified in a patient with physiological dynamic airway collapse. These findings may support the hypothesis that various clinical forms of expiratory central airway collapse are not only different morphologically, physiologically and aetiologically, but also structurally.     

Therapeutic options for sarcoidosis: new and old

The treatment of patients with sarcoidosis remains an important part of management. The role of corticosteroids has been questioned by some, while others have reported its value even in asymptomatic patients with interstitial lung disease. Cytotoxic agents have become standard therapy for some forms of chronic disease. Newer agents that modulate the immune response have been studied. A key cytokine in chronic sarcoidosis appears to be tumor necrosis factor. Drugs that inhibit its release or block its effect have been reported as effective for sarcoidosis.