Lysophosphatidic acid and apolipoprotein A1 predict increased risk of developing World Trade Center-lung injury: a nested case-control study

Tsukiji, Jun; Cho, Soo Jung; Echevarría, Ghislaine C.; Kwon, Sophia; Joseph, Peter M.; Schenck, Edward J.; Naveed, Bushra; Prezant, David J.; Rom, William N.; Schmidt, Ann Marie; Weiden, Michael D.; Nolan, Anna

doi:10.3109/1354750x.2014.891047

Cited by 19 publications

(19 citation statements)

References 45 publications

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“…At their MMTP visit spirometry was performed and serum was collected and processed as previously described. [ 10 , 11 , 51 – 53 ] A subset of n = 1720 presented with pulmonary symptoms between 9/11/2001 and March 2008 and were referred to subspecialty pulmonary evaluation (SPE) which included pulmonary function testing.…”

Section: Methodsmentioning

confidence: 99%

“…Lysophosphatidic Acid (LPA) was quantified in human-serum and, murine-BAL and plasma by ELISA (Echelon-Biosciences). [ 11 ]…”

Section: Methodsmentioning

confidence: 99%

“…Finally, our group has identified elevated serum lysophosphatidic acid (LPA), a product of low-density lipoprotein (LDL) and known ligand of RAGE, as a WTC-LI biomarker in the FDNY-cohort. [ 11 , 46 , 47 ] Here we investigate if sRAGE is a WTC-LI biomarker in the FDNY WTC exposed-cohort. Our prior in vitro work showed that WTC-PM exposure mediated an inflammatory phenotype 24 hours after exposure.…”

Section: Introductionmentioning

confidence: 99%

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Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure

Caraher¹,

Kwon²,

Haider³

et al. 2017

PLoS ONE

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World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE)≥97pg/mL, CRP≥2.4mg/L, and MMP-9≤397ng/mL, respectively, assessed in a multivariate logistic regression model (ROCAUC of 0.72). Wild type(WT) and RAGE-deficient(Ager-/-) mice were exposed to PM or PBS-control by oropharyngeal aspiration. Lung function, airway hyperreactivity, bronchoalveolar lavage, histology, transcription factors and plasma/BAL cytokines were quantified. WT-PM mice had decreased FEV and compliance, and increased airway resistance and methacholine reactivity after 24-hours. Decreased IFN-γ and increased LPA were observed in WT-PM mice; similar findings have been reported for firefighters who eventually develop WTC-LI. In the murine model, lack of RAGE was protective from loss of lung function and airway hyperreactivity and was associated with modulation of MAP kinases. We conclude that in a multivariate adjusted model increased sRAGE is associated with WTC-LI. In our murine model, absence of RAGE mitigated acute deleterious effects of PM and may be a biologically plausible mediator of PM-related lung disease.

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Section: Methodsmentioning

confidence: 99%

“…Lysophosphatidic Acid (LPA) was quantified in human-serum and, murine-BAL and plasma by ELISA (Echelon-Biosciences). [ 11 ]…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure

Caraher¹,

Kwon²,

Haider³

et al. 2017

PLoS ONE

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“…Finally, our group has identified elevated serum lysophosphatidic acid (LPA), a product of low-density lipoprotein and a known ligand of RAGE and sRAGE, as World Trade Center-Lung Injury (WTC-LI) biomarkers in the Fire Department of New York (FDNY) cohort [32][33][34]. Therefore, we have focused this systematic review on RAGE, a biologically plausible mediator and biomarker of environmentally associated OAD.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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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“…Pulmonary vascular injury occurs early in obstruction, prior to the development of abnormal FEV 1 [ 59 , 60 ]. We have published that enlarged pulmonary artery/aorta ratio by CT scan and dyslipidemia are biomarkers of WTC-LI [ 61 ]. FeNO, a clinically accepted, indirect biomarker of lung disease activity, will be a valuable measure in our population.…”

Section: Discussionmentioning

confidence: 99%

Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE) Protocol: A Randomized Clinical Trial

Kwon

Riggs

Crowley

et al. 2020

IJERPH

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Fire Department of New York (FDNY) rescue and recovery workers exposed to World Trade Center (WTC) particulates suffered loss of forced expiratory volume in 1 s (FEV1). Metabolic Syndrome increased the risk of developing WTC-lung injury (WTC-LI). We aim to attenuate the deleterious effects of WTC exposure through a dietary intervention targeting these clinically relevant disease modifiers. We hypothesize that a calorie-restricted Mediterranean dietary intervention will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI. To assess our hypothesis, we developed the Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE), a randomized controlled clinical trial (RCT). Male firefighters with WTC-LI and a BMI > 27 kg/m2 will be included. We will randomize subjects (1:1) to either: (1) Low Calorie Mediterranean (LoCalMed)—an integrative multifactorial, technology-supported approach focused on behavioral modification, nutritional education that will include a self-monitored diet with feedback, physical activity recommendations, and social cognitive theory-based group counseling sessions; or (2) Usual Care. Outcomes include reduction in body mass index (BMI) (primary), improvement in FEV1, fractional exhaled nitric oxide, pulse wave velocity, lipid profiles, targeted metabolic/clinical biomarkers, and quality of life measures (secondary). By implementing a technology-supported LoCalMed diet our FIREHOUSE RCT may help further the treatment of WTC associated pulmonary disease.

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Lysophosphatidic acid and apolipoprotein A1 predict increased risk of developing World Trade Center-lung injury: a nested case-control study

Abstract: Rationale Metabolic syndrome, inflammatory and vascular injury markers measured in serum after WTC exposures predict abnormal FEV1. We hypothesized that elevated LPA levels predict FEV1 Show more

Cited by 19 publications

References 45 publications

Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure

Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure

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

Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE) Protocol: A Randomized Clinical Trial

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