TABLE 2

Associations between receptor for advanced glycation end-products (RAGE), soluble (s)RAGE and disease state

RAGEsRAGESummary
OADPositiveNegative
  • Lungs of patients with OAD (COPD and CF) have increased levels of RAGE [4, 21]

    OAD-associated airway inflammation is associated with lower levels of sRAGE in CF patients [22, 23]

    None of the identified studies focused or included asthma as a clinical end-point

AsthmaPositiveNegative
  • Neutrophilic asthma in humans is associated with lower levels of sRAGE [13]

    RAGE expression is associated with increased downstream inflammatory effects, reflective of an asthmatic profile [15, 16]

COPDPositiveNegative
  • COPD is associated with RAGE overexpression [48]

    sRAGE levels are reduced in COPD patients [43]

    RAGE SNPs are positively associated with COPD [55, 56]

CVDInconsistent
  • sRAGE and CVD outcome are inconsistent [44]

EmphysemaNegativeNegative
  • Lower RAGE is associated with more emphysema [45]

    Higher sRAGE is associated with less emphysema and less disease progression [48]

WTC-LIPositivePositive
  • Absence of RAGE is protective against loss of lung function in a murine model [6]

    Increased sRAGE is associated with WTC-LI development [6]

Pulmonary fibrosisNegative
  • AGER−/− mice develop fibrosis in an asbestos-exposure model [30]

NO generationPositiveNegative
  • COPD smokers had higher RAGE and NO levels [47]

    In vitro cigarette smoke exposure led to low sRAGE and high RAGE and NO levels [47]

FEV1 and FEV1/FVCPositiveInconsistent
  • Ser82 RAGE variant is associated with higher FEV1 [57]

    Lower sRAGE levels are associated with longitudinal decline of FEV1 in COPD smokers and FEV1/FVC in all subjects [46]

    COPD patients with lower sRAGE levels had higher FEV1 [43]

OAD: obstructive airways disease; COPD: chronic obstructive pulmonary disease; CVD: cardiovascular disease; WTC-LI: World Trade Center lung injury; NO: nitric oxide; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; CF: cystic fibrosis; SNP: single nucleotide polymorphism; AGER: advanced glycation end-products receptor.