Variations of inflammatory mediators and alpha1-antitrypsin levels after lung volume reduction surgery for emphysema.
BACKGROUND
In emphysema, chronic inflammation, including protease-antiprotease imbalance, is responsible for declining pulmonary function and progressive cachexia.


OBJECTIVE
To evaluate variations of inflammatory mediators and alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared with respiratory rehabilitation.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Mineo
Davide
D
Division of Thoracic Surgery, Tor Vergata University of Rome and Policlinic, 00133 Rome, Italy. d.mineo@med.uniroma2.it
Ambrogi
Vincenzo
V
Cufari
Maria Elena
ME
Gambardella
Stefano
S
Pignotti
Laura
L
Pompeo
Eugenio
E
Mineo
Tommaso Claudio
TC
D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D004646:Emphysema / Q000097:blood / Q000150:complications / Q000534:rehabilitation / Q000601:surgery*; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D010446:Peptide Fragments / Q000097:blood*; D011013:Pneumonectomy / Q000379:methods*; D012129:Respiratory Function Tests / Q000379:methods / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D000515:alpha 1-Antitrypsin / Q000097:blood*
D015415:Biomarkers; C508153:C105Y peptide; D010446:Peptide Fragments; D000515:alpha 1-Antitrypsin