title: Soluble receptor for advanced glycation end products in COPD: relationship with emphysema and chronic cor pulmonale: a case-control study.
abstract: BACKGROUND
  The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation. Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation. With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method. We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method. In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography. Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid conditions on the three quartiles of sRAGE.
  
  
  RESULTS
  sRAGE was significantly lower (p = 0.007) in COPD patients (median 652 pg/mL, interquartile range 484 to 1076 pg/mL) than in controls (median 869 pg/mL, interquartile range 601 to 1240 pg/mL), and was correlated with the severity of emphysema (p < 0.001), the lower the level of sRAGE the greater the degree of emphysema on CT. The relationship remained statistically significant after adjusting for smoking history and comorbid conditions. In addition, sRAGE was significantly lower in COPD patients with chronic cor pulmonale than in those without (p = 0.002). Such difference remained statistically significant after adjusting for smoking history, comorbidities, and emphysema severity. There was no significant difference in the plasma levels of the two RAGE ligands between cases and controls.
  
  
  CONCLUSIONS
  sRAGE is significantly lower in patients with COPD than in age- and sex-matched individuals without airflow obstruction. Emphysema and chronic cor pulmonale are independent predictors of reduced sRAGE in COPD.
authors: Department of Medical and Surgical Critical Care, University of Florence, 50134 Florence, Italy. massimo.miniati@unifi.it
authors: Massimo
authors: M
authors: Miniati
authors: Simonetta
authors: S
authors: Monti
authors: Giuseppina
authors: G
authors: Basta
authors: Franca
authors: F
authors: Cocci
authors: Edo
authors: E
authors: Fornai
authors: Matteo
authors: M
authors: Bottai
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D015897:Comorbidity; D015536:Down-Regulation; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007558:Italy; D016014:Linear Models; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D011660:Pulmonary Heart Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012720:Severity of Illness Index; D012907:Smoking / Q000453:epidemiology; D013147:Spirometry; D014057:Tomography, X-Ray Computed; D014797:Vital Capacity
chemical_list: D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic