title: Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis: the GRANULOMA randomized clinical trial.
abstract: OBJECTIVE
  Tissue verification of noncaseating granulomas is recommended for the diagnosis of sarcoidosis. Bronchoscopy with transbronchial lung biopsies, the current diagnostic standard, has moderate sensitivity in assessing granulomas. Endosonography with intrathoracic nodal aspiration appears to be a promising diagnostic technique.
  
  
  OBJECTIVE
  To evaluate the diagnostic yield of bronchoscopy vs endosonography in the diagnosis of stage I/II sarcoidosis.
  
  
  METHODS
  Randomized clinical multicenter trial (14 centers in 6 countries) between March 2009 and November 2011 of 304 consecutive patients with suspected pulmonary sarcoidosis (stage I/II) in whom tissue confirmation of noncaseating granulomas was indicated.
  
  
  METHODS
  Either bronchoscopy with transbronchial and endobronchial lung biopsies or endosonography (esophageal or endobronchial ultrasonography) with aspiration of intrathoracic lymph nodes. All patients also underwent bronchoalveolar lavage.
  
  
  METHODS
  The primary outcome was the diagnostic yield for detecting noncaseating granulomas in patients with a final diagnosis of sarcoidosis. The diagnosis was based on final clinical judgment by the treating physician, according to all available information (including findings from initial bronchoscopy or endosonography). Secondary outcomes were the complication rate in both groups and sensitivity and specificity of bronchoalveolar lavage in the diagnosis of sarcoidosis.
  
  
  RESULTS
  A total of 149 patients were randomized to bronchoscopy and 155 to endosonography. Significantly more granulomas were detected at endosonography vs bronchoscopy (114 vs 72 patients; 74% vs 48%; P < .001). Diagnostic yield to detect granulomas for endosonography was 80% (95% CI, 73%-86%); for bronchoscopy, 53% (95% CI, 45%-61%) (P < .001). Two serious adverse events occurred in the bronchoscopy group and 1 in the endosonography group; all patients recovered completely. Sensitivity of the bronchoalveolar lavage for sarcoidosis based on CD4/CD8 ratio was 54% (95% CI, 46%-62%) for flow cytometry and 24% (95% CI, 16%-34%) for cytospin analysis.
  
  
  CONCLUSIONS
  Among patients with suspected stage I/II pulmonary sarcoidosis undergoing tissue confirmation, the use of endosonographic nodal aspiration compared with bronchoscopic biopsy resulted in greater diagnostic yield.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00872612.
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martin B
authors.initials: MB
authors.lastname: von Bartheld
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.forename: Artur
authors.initials: A
authors.lastname: Szlubowski
authors.forename: Ralf
authors.initials: R
authors.lastname: Eberhardt
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Herth
authors.forename: Johannes C C M
authors.initials: JC
authors.lastname: in 't Veen
authors.forename: Ynze P
authors.initials: YP
authors.lastname: de Jong
authors.forename: Erik H F M
authors.initials: EH
authors.lastname: van der Heijden
authors.forename: Kurt G
authors.initials: KG
authors.lastname: Tournoy
authors.forename: Martin
authors.initials: M
authors.lastname: Claussen
authors.forename: Bernt
authors.initials: B
authors.lastname: van den Blink
authors.forename: Pallav L
authors.initials: PL
authors.lastname: Shah
authors.forename: Zaid
authors.initials: Z
authors.lastname: Zoumot
authors.forename: Paul
authors.initials: P
authors.lastname: Clementsen
authors.forename: Celeste
authors.initials: C
authors.lastname: Porsbjerg
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
authors.forename: Fabiola D
authors.initials: FD
authors.lastname: Bernardi
authors.forename: Erik W
authors.initials: EW
authors.lastname: van Zwet
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.forename: Jouke T
authors.initials: JT
authors.lastname: Annema
mesh_terms: D000328:Adult; D001706:Biopsy; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D019160:Endosonography; D005260:Female; D006099:Granuloma / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis*; D012680:Sensitivity and Specificity