Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results.

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: 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).

Association between hyperhomocysteinemia and primary pulmonary hypertension.

STUDY OBJECTIVE: This case-control study was conducted to test the hypothesis that fasting homocysteine levels are higher in PPH patients than in healthy controls. DESIGN: Levels of plasma total homocysteine, serum folate, vitamin B-12, and serum creatinine in 18 consecutive patients with PPH were compared with data from 36 age- and sex-matched controls. RESULTS: Eight of the 18 patients (44.4%) and three of the 36 controls (8.3%) had elevated plasma total homocysteine (tHcy) levels (> or = 15 mol/l, odds ratio 8.8; 95% CI: 2.0-39.6; P = 0.005). There was an inverse correlation between tHcy levels and creatinine clearance in patients with PPH (P = 0.036). CONCLUSION: PPH patients are significantly more likely to have hyperhomocysteinemia, and higher mean plasma total homocysteine levels than in controls. Plasma total homocysteine may be an important factor in the pathogenesis of PPH.