Salivary biomarkers associated with obstructive sleep apnea: a systematic review

ABSTRACT

Introduction: This study aimed to define and characterize current literature describing salivary biomarker changes with the goal of improving diagnosis and treatment outcomes for sleep apnea.

Area Covered: A search of six databases yielded 401 peer-reviewed articles published through October 2019 corresponded to 221 unique references following deduplication. Twenty studies were selected. The sample size ranged from 17 to 99. The samples were mostly whole saliva and selected glandular areas.

Expert Opinion: Most targeted studies focused on the level of salivary cortisol and ɑ-amylase. One study used RNA transcriptome analysis of 96 genes. Only two explored novel targets using mass spectrometry. ɑ-amylase, myeloperoxidase, and IL-6 were among those biomarkers found associated with OSA. Cytokeratin, CystatinB, calgranulin A, and alpha-2-HS-glycoprotein are upregulated in OSA patients based on non-targeting mass spectrometry. Salivary cortisol and ɑ-amylase and others appeared to be associated with severity of OSA and OSA treatment. There were inconsistencies in saliva collection and processing protocols. More studies are needed in exploring novel biomarkers to examine if these biomarkers are capable of diagnosing and monitoring OSA through proteomics or transcriptomics. Salivary biomarkers have a potential to be a noninvasive measure for the disease diagnosis and treatment outcome monitoring for sleep apnea.

KEYWORDS:

• ɑ-amylase
• biomarker
• diagnosis
• monitoring
• saliva
• salivary cortisol
• sleep apnea
• systematic review

Article Highlights

• Saliva sample collection for biomarker examination can be done successfully during the PSG diagnostic process since the patient will be in the control environment.

• Saliva sample treatment should be based on type of biomarker and analysis. Protease or RNAase inhibitors may be needed to preserve proteins and RNAs. Removing highly abundant proteins such as α-amylase and immunoglobulins can improve the discovery of low abundant protein biomarkers.

• Known salivary biomarkers such as cortisol and α-amylase can be used to diagnose and monitor treatment outcomes for OSA. Using night and morning ratios of these biomarkers seem to be an effective way to reduce individual variations.

• There is a need to explore novel salivary biomarkers through gene arrays, transcriptomics, and proteomics.

• There is also a need to link salivary biomarkers to serum biomarkers.

• Longitudinal studies monitoring the changes of salivary biomarkers are needed to validate the benefit of salivary biomarkers.

Author Contributions

S BENCHARIT ROLES Conceptualization, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing

RG REDENZ ROLES Screening the articles, Extracting Data, Data curation, Formal analysis, Investigation, Methodology, Software, Writing – original draft, Writing – review & editing

ER BRODY ROLES Performing article searches, Formal analysis, Investigation, Writing – original draft

H CHIANG ROLES Conceptualization, Methodology, Screening the articles, Writing – original draft

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.