Division of Thoracic Surgery, Tor Vergata University of Rome and Policlinic, 00133 Rome, Italy.
Am J Respir Crit Care Med. 2010 Apr 15;181(8):806-14. doi: 10.1164/rccm.200910-1476OC. Epub 2010 Jan 7.
In emphysema, chronic inflammation, including protease-antiprotease imbalance, is responsible for declining pulmonary function and progressive cachexia.
To evaluate variations of inflammatory mediators and alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared with respiratory rehabilitation.
A total of 28 patients with moderate to severe emphysema, who underwent video-assisted thoracoscopic LVRS, were compared with 26 similar patients, who refused operation and followed a standardized rehabilitation program, and to a matched healthy group. Respiratory function, body composition, circulating inflammatory mediators, and alpha(1)-antitrypsin levels were evaluated before and 12 months after treatment. Gene expression levels of inflammatory mediators and protease-antiprotease were assessed in emphysematous specimens from 17 operated patients by matching to normal tissue from resection margins.
Significant improvements were only obtained after surgery in respiratory function (FEV(1), +25.2%, P < 0.0001; residual volume [RV], -19.5%, P < 0.0001; diffusing lung capacity for carbon monoxide, +3.3%, P < 0.05) and body composition (fat-free mass, +6.5%, P < 0.01; fat mass, +11.9%, P < 0.01), with decrement of circulating inflammatory mediators (TNF-alpha, -22.2%, P < 0.001; IL-6, -24.5%, P < 0.001; IL-8, -20.0%, P < 0.001) and increment of antiprotease levels (alpha(1)-antitrypsin, +27.0%, P < 0.001). Supportive gene expression analysis demonstrated active inflammation and protease hyperactivity in the resected emphysematous tissue. Reduction of TNF-alpha and IL-6 and increment of alpha(1)-antitrypsin levels significantly correlated with reduction of RV (P = 0.03, P = 0.009, and P = 0.001, respectively), and partially with increment of fat-free mass (P = 0.03, P = 0.02, and P = 0.09, respectively).
LVRS significantly reduced circulating inflammatory mediators and increased antiprotease levels over respiratory rehabilitation, also improving respiratory function and nutritional status. Correlations of inflammatory mediators and antiprotease levels with RV and, partly, with body composition suggest that elimination of inflammatory emphysematous tissue may explain clinical improvements after surgery.
在肺气肿中，慢性炎症，包括蛋白酶-抗蛋白酶失衡，导致肺功能下降和进行性恶病质。
评估肺减容术（LVRS）与呼吸康复治疗后炎症介质和α1-抗胰蛋白酶水平的变化。
总共 28 例中重度肺气肿患者接受电视辅助胸腔镜下 LVRS，与 26 例相似的拒绝手术并接受标准化康复计划的患者以及 1 例匹配的健康组进行比较。治疗前和治疗后 12 个月评估呼吸功能、身体成分、循环炎症介质和α1-抗胰蛋白酶水平。通过与切除边缘的正常组织相匹配，评估 17 例手术患者的肺气肿标本中炎症介质和蛋白酶-抗蛋白酶的基因表达水平。
仅在手术后呼吸功能（FEV1，+25.2%，P <0.0001；残气量[RV]，-19.5%，P <0.0001；一氧化碳弥散量，+3.3%，P <0.05）和身体成分（去脂体重，+6.5%，P <0.01；脂肪量，+11.9%，P <0.01）显著改善，循环炎症介质（TNF-α，-22.2%，P <0.001；IL-6，-24.5%，P <0.001；IL-8，-20.0%，P <0.001）减少，抗蛋白酶水平（α1-抗胰蛋白酶，+27.0%，P <0.001）增加。支持性基因表达分析表明，切除的肺气肿组织中存在活跃的炎症和蛋白酶过度活跃。TNF-α和 IL-6 的减少以及 α1-抗胰蛋白酶水平的增加与 RV 的减少显著相关（P = 0.03，P = 0.009 和 P = 0.001），部分与去脂体重的增加相关（P = 0.03，P = 0.02 和 P = 0.09）。
LVRS 显著降低循环炎症介质并增加抗蛋白酶水平，优于呼吸康复治疗，也改善呼吸功能和营养状况。炎症介质和抗蛋白酶水平与 RV 的相关性，部分与身体成分的相关性提示，消除炎症性肺气肿组织可能解释手术后的临床改善。
