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Published ahead of print on January 29, 2009, doi:10.1164/rccm.200810-1639OC
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American Journal of Respiratory and Critical Care Medicine Vol 179. pp. 791-798, (2009)
© 2009 American Thoracic Society
doi: 10.1164/rccm.200810-1639OC

Original Article

Biologic Lung Volume Reduction in Advanced Upper Lobe Emphysema

Phase 2 Results

Gerard J. Criner1, Victor Pinto-Plata2, Charlie Strange3, Mark Dransfield4, Mark Gotfried5, William Leeds6, Geoffrey McLennan7, Yael Refaely8, Sanjiv Tewari9, Mark Krasna10 and Bartolome Celli2

1 Temple University, Philadelphia, Pennsylvania; 2 Caritas-St. Elizabeth's Medical Center, Boston, Massachusetts; 3 Medical University of South Carolina, Charleston, South Carolina; 4 University of Alabama Birmingham, Birmingham, Alabama; 5 Pulmonary Associates, Phoenix, Arizona; 6 Veritas Clinical Specialties, Topeka, Kansas; 7 University of Iowa, Iowa City, Iowa; 8 Rabin Medical Center, Tel Aviv, Israel; 9 Akron Medical Center, Akron, Ohio; and 10 St. Joseph's Medical Center, Baltimore, Maryland

Correspondence and requests for reprints should be addressed to Gerard J. Criner, M.D., Temple Lung Center, Temple University School of Medicine, 745 Parkinson Pavilion, 3401 North Broad Street, Philadelphia, PA 19140. E-mail: crinerg{at}tuhs.temple.edu

Rationale: Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling.

Objectives: Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema.

Methods: Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life.

Measurements and Main Results: After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (–6.4 ± 9.3%; P = 0.002) and HD (–5.5 ± 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: {Delta}FEV1 = +15.6%; P = 0.002; {Delta}FVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: {Delta}FEV1 = +6.7%; P = 0.021; {Delta}FVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life.

Conclusions: BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing.

Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

Key Words: emphysema • biologic lung volume reduction • bronchoscopic lung volume reduction • lung volume reduction • lung volume reduction surgery


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Lung hyperinflation in moderate to severe emphysema is associated with expiratory airflow limitation, reduced exercise capacity, and dyspnea that is only partially responsive to bronchodilator therapy. Biologic lung volume reduction (BioLVR) is a novel endobronchial therapy that reduces lung volume via administration of a fibrinogen biopharmaceutical suspension and thrombin solution that polymerize in situ to form a hydrogel.

What This Study Adds to the Field
We show that BioLVR reagents instilled in eight subsegments can reduce lung volumes and improve pulmonary function in patients with advanced upper lobe emphysema with an acceptable side-effect profile.

 



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