title: Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results.
abstract: BACKGROUND
  Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling.
  
  
  OBJECTIVE
  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.
  
  
  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: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +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).
authors.affiliation: Temple Lung Center, Temple University School of Medicine, 745 Parkinson Pavilion, 3401 North Broad Street, Philadelphia, PA 19140. crinerg@tuhs.temple.edu
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Criner
authors.forename: Victor
authors.initials: V
authors.lastname: Pinto-Plata
authors.forename: Charlie
authors.initials: C
authors.lastname: Strange
authors.forename: Mark
authors.initials: M
authors.lastname: Dransfield
authors.forename: Mark
authors.initials: M
authors.lastname: Gotfried
authors.forename: William
authors.initials: W
authors.lastname: Leeds
authors.forename: Geoffrey
authors.initials: G
authors.lastname: McLennan
authors.forename: Yael
authors.initials: Y
authors.lastname: Refaely
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Tewari
authors.forename: Mark
authors.initials: M
authors.lastname: Krasna
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
mesh_terms: D000368:Aged; D001999:Bronchoscopy; D004417:Dyspnea / Q000628:therapy; D005221:Fatigue / Q000209:etiology; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000009:adverse effects; D007964:Leukocytosis / Q000209:etiology; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000628:therapy; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000628:therapy*; D011788:Quality of Life; D011859:Radiography; D012129:Respiratory Function Tests
chemical_list: C540466:BioLVR hydrogel; D020100:Hydrogels