Noninvasive, MultiOmic, and Multicompartmental Biomarkers of Reflux Disease: A Systematic Review

Overview

Journal Gastro Hep Adv

Specialty Gastroenterology

Date 2023 Nov 27

PMID 38009162

Authors

Muhammad S Farooqi

Sanjiti Podury

George Crowley

Urooj Javed

Yiwei Li

Mengling Liu

Sophia Kwon

Gabriele Grunig

Abraham R Khan

Fritz Francois

Anna Nolan

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder that may complicate conditions such as obstructive airway disease. Our group has identified predictive biomarkers of GERD in particulate exposed first responders with obstructive airway disease. In addition, GERD diagnosis and treatment is costly and invasive. In light of these clinical concerns, we aimed to systematically review studies identifying noninvasive, multiOmic, and multicompartmental biomarkers of GERD.

Methods: A systematic review of PubMed and Embase was performed using keywords focusing on reflux disease and biomarkers and registered with PROSPERO. We included original human studies in English, articles focusing on noninvasive biomarkers of GERD published after December 31, 2009. GERD subtypes (non-erosive reflux disease and erosive esophagitis) and related conditions (Barrett's Esophagus [BE] and Esophageal Adenocarcinoma). Predictive measures were synthesized and risk of bias assessed (Newcastle-Ottawa Scale).

Results: Initial search identified n = 238 studies andn 13 articles remained after applying inclusion/exclusion criteria. Salivary pepsin was the most studied biomarker with significant sensitivity and specificity for GERD. Serum assessment showed elevated levels of Tumor Necrosis Factor-alpha in both GERD and Barrett's. Exhaled breath volatile sulfur compounds and acetic acid were associated with GERD. Oral Microbiome: Models with , , and showed the greatest discrimination between BE and controls vs ; ROC 0.94 (95% confidence interval; 0.85-1.00).

Conclusion: Prior studies identified significant multiOmic, multicompartmental noninvasive biomarker risks for GERD and BE. However, studies have a high risk of bias and the reliability and accuracy of the biomarkers identified are greatly limited, which further highlights the need to discover and validate clinically relevant noninvasive biomarkers of GERD.

Citing Articles

Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN) in World Trade Center exposed firefighters: a case-control observational study protocol.

Javed U, Podury S, Kwon S, Liu M, Kim D, Fallahzadeh A BMC Gastroenterol. 2024; 24(1):255.

PMID: 39123126 PMC: 11312152. DOI: 10.1186/s12876-024-03294-9.

The oral microbiome and oral and upper gastrointestinal diseases.

Liu S, Wang S, Zhang N, Li P J Oral Microbiol. 2024; 16(1):2355823.

PMID: 38835339 PMC: 11149586. DOI: 10.1080/20002297.2024.2355823.

Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN): a Case-Control Observational Study Protocol.

Javed U, Podury S, Kwon S, Liu M, Kim D, Zadeh A Res Sq. 2024; .

PMID: 38798396 PMC: 11118699. DOI: 10.21203/rs.3.rs-4355584/v1.

References

Lim S, Lee J, Kim J, Kim J, Kim H, Jeon S . Management of Asymptomatic Erosive Esophagitis: An E-Mail Survey of Physician's Opinions. Gut Liver. 2013; 7(3):290-4. PMC: 3661960. DOI: 10.5009/gnl.2013.7.3.290. View

Shaheen N, Hansen R, Morgan D, Gangarosa L, Ringel Y, Thiny M . The burden of gastrointestinal and liver diseases, 2006. Am J Gastroenterol. 2006; 101(9):2128-38. DOI: 10.1111/j.1572-0241.2006.00723.x. View

Numans M, Lau J, de Wit N, Bonis P . Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med. 2004; 140(7):518-27. DOI: 10.7326/0003-4819-140-7-200404060-00011. View

McDonnell M, Hunt E, Ward C, Pearson J, OToole D, Laffey J . Current therapies for gastro-oesophageal reflux in the setting of chronic lung disease: state of the art review. ERJ Open Res. 2021; 6(4). PMC: 7927787. DOI: 10.1183/23120541.00190-2019. View

Lagergren J, Bergstrom R, Lindgren A, Nyren O . Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999; 340(11):825-31. DOI: 10.1056/NEJM199903183401101. View

Prezant D, Weiden M, Banauch G, McGuinness G, Rom W, Aldrich T . Cough and bronchial responsiveness in firefighters at the World Trade Center site. N Engl J Med. 2002; 347(11):806-15. DOI: 10.1056/NEJMoa021300. View

Ronkainen J, Aro P, Storskrubb T, Lind T, Bolling-Sternevald E, Junghard O . Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study. Aliment Pharmacol Ther. 2006; 23(12):1725-33. DOI: 10.1111/j.1365-2036.2006.02952.x. View

Guo Z, Wu Y, Chen J, Zhang S, Zhang C . The Role of Salivary Pepsin in the Diagnosis of Gastroesophageal Reflux Disease (GERD) Evaluated Using High-Resolution Manometry and 24-Hour Multichannel Intraluminal Impedance-pH Monitoring. Med Sci Monit. 2020; 26:e927381. PMC: 7687924. DOI: 10.12659/MSM.927381. View

Branski R, Bhattacharyya N, Shapiro J . The reliability of the assessment of endoscopic laryngeal findings associated with laryngopharyngeal reflux disease. Laryngoscope. 2002; 112(6):1019-24. DOI: 10.1097/00005537-200206000-00016. View

10.

Amir I, Konikoff F, Oppenheim M, Gophna U, Half E . Gastric microbiota is altered in oesophagitis and Barrett's oesophagus and further modified by proton pump inhibitors. Environ Microbiol. 2013; 16(9):2905-14. DOI: 10.1111/1462-2920.12285. View

11.

Commisso A, Lim F . Lifestyle Modifications in Adults and Older Adults With Chronic Gastroesophageal Reflux Disease (GERD). Crit Care Nurs Q. 2018; 42(1):64-74. DOI: 10.1097/CNQ.0000000000000239. View

12.

Stoikes N, Drapekin J, Kushnir V, Shaker A, Brunt L, Gyawali C . The value of multiple rapid swallows during preoperative esophageal manometry before laparoscopic antireflux surgery. Surg Endosc. 2012; 26(12):3401-7. PMC: 4098863. DOI: 10.1007/s00464-012-2350-0. View

13.

Long J, Orlando R . Nonerosive reflux disease. Minerva Gastroenterol Dietol. 2007; 53(2):127-41. View

14.

Vakil N, van Zanten S, Kahrilas P, Dent J, Jones R . The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006; 101(8):1900-20. DOI: 10.1111/j.1572-0241.2006.00630.x. View

15.

Segal L, Rom W, Weiden M . Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs. Ann Am Thorac Soc. 2014; 11(1):108-16. PMC: 3972985. DOI: 10.1513/AnnalsATS.201310-339FR. View

16.

Liu X, Yip J, Zeig-Owens R, Weakley J, Webber M, Schwartz T . The Effect of World Trade Center Exposure on the Timing of Diagnoses of Obstructive Airway Disease, Chronic Rhinosinusitis, and Gastroesophageal Reflux Disease. Front Public Health. 2017; 5:2. PMC: 5296346. DOI: 10.3389/fpubh.2017.00002. View

17.

Yan X, Zhu S, Zhang H . miR-203 Expression in Exfoliated Cells of Tongue Coating Represents a Sensitive and Specific Biomarker of Gastroesophageal Reflux Disease. Gastroenterol Res Pract. 2016; 2016:2349453. PMC: 5030450. DOI: 10.1155/2016/2349453. View

18.

Haider S, Kwon S, Lam R, Lee A, Caraher E, Crowley G . Predictive Biomarkers of Gastroesophageal Reflux Disease and Barrett's Esophagus in World Trade Center Exposed Firefighters: a 15 Year Longitudinal Study. Sci Rep. 2018; 8(1):3106. PMC: 5814524. DOI: 10.1038/s41598-018-21334-9. View

19.

Yuksel E, Hong S, Strugala V, Slaughter J, Goutte M, Garrett C . Rapid salivary pepsin test: blinded assessment of test performance in gastroesophageal reflux disease. Laryngoscope. 2012; 122(6):1312-6. DOI: 10.1002/lary.23252. View

20.

Bor S, Capanoglu D, Vardar R, Woodcock A, Fisher J, Dettmar P . Validation of Peptest™ in Patients with Gastro-Esophageal Reflux Disease and Laryngopharyngeal Reflux Undergoing Impedance Testing. J Gastrointestin Liver Dis. 2019; 28(4):383-387. DOI: 10.15403/jgld-335. View