TABLE 2

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

	RAGE	sRAGE	Summary
OAD	Positive	Negative	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
Asthma	Positive	Negative	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]
COPD	Positive	Negative	COPD is associated with RAGE overexpression [48] sRAGE levels are reduced in COPD patients [43] RAGE SNPs are positively associated with COPD [55, 56]
CVD		Inconsistent	sRAGE and CVD outcome are inconsistent [44]
Emphysema	Negative	Negative	Lower RAGE is associated with more emphysema [45] Higher sRAGE is associated with less emphysema and less disease progression [48]
WTC-LI	Positive	Positive	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 fibrosis	Negative		AGER^−/− mice develop fibrosis in an asbestos-exposure model [30]
NO generation	Positive	Negative	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/FVC	Positive	Inconsistent	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.