Receptor for Advanced Glycation End Products (RAGE) Contributes to World Trade Center Particulate Matter (WTC-PM)-Associated Lung Function Loss

BackgroundAdvanced glycation end-products (AGEs) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the association between AGE accumulation in the skin measured by skin autofluorescence (SAF) and lung function in healthy subjects has not been explored in detail. We use a population-based study of 50–64-year-olds to assess spirometry, diffusing capacity of the lung for carbon monoxide (DLCO) and impulse oscillometry (IOS) in relation to SAF.MethodsParticipants with information on SAF, lung function and potential confounding variables were included from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) cohort (spirometry, n=4111; DLCO, n=3889; IOS, n=3970). Linear regression was used to assess changes in lung function (as measured by spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC), DLCO and IOS (resistance measured at 5 (R5) and 20 Hz (R20), R5−R20, area of reactance, reactance measured at 5 Hz (X5), and resonant frequency)) by a 1-sd increase in SAF.ResultsFEV1, FVC and DLCO were significantly and inversely associated with SAF after adjustment for potential confounding factors (per 1-sd increase in SAF: FEV1 −0.03 L (95% CI −0.04– −0.02 L), p<0.001; FVC −0.03 L (95% CI −0.05– −0.02 L), p<0.001; DLCO −0.07 mmol·min−1·kPa−1 (95% CI −0.11– −0.03 mmol·min−1·kPa−1), p<0.001). This association was also found in nonsmokers and in non-COPD subjects. Pulmonary reactance (X5) but not pulmonary resistance (R5, R20 and R5−R20) was significantly associated with SAF (per 1-sd increase in SAF: X5 −0.001 kPa·L−1·s (95% CI −0.003–0.00 kPa·L−1·s), p=0.042), which was mirrored in non-COPD patients but not in current nonsmokers.ConclusionsAGE accumulation, as measured by SAF, is significantly associated with lung function decrements indicative of changes in the lung parenchyma

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Receptor for advanced glycation end-products and environmental exposure related obstructive airways disease: a systematic review

European Respiratory Review ◽

10.1183/16000617.0096-2018 ◽

2019 ◽

Vol 28 (151) ◽

pp. 180096 ◽

Cited By ~ 1

Author(s):

Syed H. Haider ◽

Assad Oskuei ◽

George Crowley ◽

Sophia Kwon ◽

Rachel Lam ◽

...

Keyword(s):

Systematic Review ◽

Particulate Matter ◽

Lung Disease ◽

Environmental Exposure ◽

Advanced Glycation End Products ◽

Advanced Glycation ◽

Soluble Rage ◽

Glycation End Products ◽

End Products ◽

Obstructive Airways Disease

BackgroundOur group has identified the receptor for advanced glycation end-products (RAGE) as a predictor of World Trade Center particulate matter associated lung injury. The aim of this systematic review is to assess the relationship between RAGE and obstructive airways disease secondary to environmental exposure.MethodsA comprehensive search using PubMed and Embase was performed on January 5, 2018 utilising keywords focusing on environmental exposure, obstructive airways disease and RAGE and was registered with PROSPERO (CRD42018093834). We included original human research studies in English, focusing on pulmonary end-points associated with RAGE and environmental exposure.ResultsA total of 213 studies were identified by the initial search. After removing the duplicates and applying inclusion and exclusion criteria, we screened the titles and abstracts of 61 studies. Finally, 19 full-text articles were included. The exposures discussed in these articles include particulate matter (n=2) and cigarette smoke (n=17).ConclusionRAGE is a mediator of inflammation associated end-organ dysfunction such as obstructive airways disease. Soluble RAGE, a decoy receptor, may have a protective effect in some pulmonary processes. Overall, RAGE is biologically relevant in environmental exposure associated lung disease. Future investigations should focus on further understanding the role and therapeutic potential of RAGE in particulate matter exposure associated lung disease.

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