Endosonography vs Conventional Bronchoscopy for the Diagnosis of Sarcoidosis: The GRANULOMA Randomized Clinical Trial | Allergy and Clinical Immunology | JAMA | JAMA Network
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Original Contribution
June 19, 2013

Endosonography vs Conventional Bronchoscopy for the Diagnosis of Sarcoidosis: The GRANULOMA Randomized Clinical Trial

Author Affiliations

Author Affiliations: From the Departments of Pulmonology (Drs von Bartheld, Rabe, and Annema), Clinical Epidemiology (Dr Dekkers), and Medical Statistics (Dr van Zwet), Leiden University Medical Center, Leiden, the Netherlands; Department of Pulmonology, Academical Medical Center, University of Amsterdam, the Netherlands (Dr Annema); Endoscopy Unit of John Paul II Hospital, Krakow, and Endoscopy Unit of Pulmonary Hospital Zakopane, Zakopane, Poland (Dr Szlubowski); Department of Pneumonology, Thoraxclinic Heidelberg, Heidelberg, Germany (Drs Eberhardt and Herth); Department of Pulmonology, Sint Franciscus Gasthuis, Rotterdam (Dr in ‘t Veen); Department of Pulmonology, Rijnstate Hospital, Arnhem, the Netherlands (Dr de Jong); Department of Pulmonology, Radboud University Medical Center, Nijmegen, the Netherlands (Dr van der Heijden); Department of Pulmonology, Ghent University Hospital, Ghent, and Onze-Lieve- Vrouw Hospital Aalst, Belgium (Dr Tournoy); Department of Pneumonology, Hospital Grosshansdorf, Grosshansdorf, Germany (Drs Claussen and Rabe); Department of Pulmonology, Erasmus Medical Center, Rotterdam, the Netherlands (Dr van den Blink); Department of Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom (Drs Shah and Zoumot); Department of Chest Medicine, Copenhagen University Hospital, Gentofte, Denmark (Drs Clementsen and Porsbjerg); Department of Pathology, University of São Paulo, Brazil (Drs Mauad and Bernardi); and the Medical Sciences School of Santa Casa de São Paulo, Brazil (Dr Bernardi).

JAMA. 2013;309(23):2457-2464. doi:10.1001/jama.2013.5823
Abstract

Importance 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.

Design, Setting, and Patients 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.

Interventions 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.

Main Outcomes and Measures 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.

Conclusion and Relevance 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.

Trial Registration clinicaltrials.gov Identifier: NCT00872612

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