Emphysematous Lung Sealant Therapy Attenuates the Chronic Inflammatory State of Advanced Emphysema

Abstract

Background: Patients with advanced emphysema often have elevated markers of systemic inflammation, a phenotype associated with greater clinical compromise and increased mortality. We hypothesized that endoscopic lung volume reduction using emphysematous lung sealant therapy might attenuate the state of inflammation in patients with advanced emphysema by eliminating damaged tissue; similar to what has previously been reported following lung volume reduction surgery. Methods: To explore this hypothesis, serum C-reactive protein (CRP) was measured at baseline, 12, 24 and 48 weeks following ELVR therapy with Emphysematous Lung Sealant (ELS) at 5 centers participating in clinical trial NCT00884962 (www.clinicaltrials.gov). Results were correlated with post-treatment changes in BODE Index, systemic white cell count, and vital status out to 3 years. Results: Baseline CRP for the 29 patient cohort was elevated (5.3 ± 8.7 mg/L) compared to normal. Sixteen (16) of 29 patients (55%) had serum levels above the “high risk threshold” (3 mg/L). ELS therapy was associated with a transient increase in CRP followed by a progressive decline. At 48 weeks, the CRP level of the cohort had decreased to 2.2 ± 3.2 mg/L (p=0.041); only 9 of 29 (31%) showed persistently elevation. 3 years post treatment, 28 of 29 patients were alive (3.4% mortality), while 24 and 36 month mortality for this cohort predicted from baseline BODE Index was 12% and 35% respectively. Conclusions: ELS therapy reduces chronic inflammation in patients with advanced emphysema, manifest as a reduction in CRP. Model predictions suggest this is associated with a reduction in long term mortality risk. Larger prospective studies are needed to further evaluate this question.