Elsevier

Sleep Medicine Reviews

Volume 23, October 2015, Pages 28-45
Sleep Medicine Reviews

Clinical review
Biomarkers associated with obstructive sleep apnea: A scoping review

https://doi.org/10.1016/j.smrv.2014.11.004Get rights and content

Summary

The overall validity of biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. We conducted a scoping review to provide assessments of biomarkers characteristics in the context of obstructive sleep apnea (OSA) and to identify gaps in the literature. A scoping review of studies in humans without age restriction that evaluated the potential diagnostic value of biological markers (blood, exhaled breath condensate, salivary, and urinary) in the OSA diagnosis was undertaken. Retained articles were those focused on the identification of biomarkers in subjects with OSA, the latter being confirmed with a full overnight or home-based polysomnography (PSG). Search strategies for six different databases were developed. The methodology of selected studies was classified using an adaptation of the evidence quality criteria from the American Academy of Pediatrics. Additionally the biomarkers were classified according to their potential clinical application. We identified 572 relevant studies, of which 117 met the inclusion criteria. Eighty-two studies were conducted in adults, 34 studies involved children, and one study had a sample composed of both adults and children. Most of the studies evaluated blood biomarkers. Potential diagnostic biomarkers were found in nine pediatric studies and in 58 adults studies. Only nine studies reported sensitivity and specificity, which varied substantially from 43% to 100%, and from 45% to 100%, respectively. Studies in adults have focused on the investigation of IL-6, TNF-α and hsCRP. There was no specific biomarker that was tested by a majority of authors in pediatric studies, and combinatorial urine biomarker approaches have shown preliminary promising results. In adults IL-6 and IL-10 seem to have a favorable potential to become a good biomarker to identify OSA.

Introduction

Obstructive sleep apnea (OSA) has now been widely recognized as a major public health concern with numerous and widespread societal consequences that include among others, motor vehicle accidents, increased cardiovascular morbidity, heightened risk for metabolic dysfunction, and mood, behavioral and cognitive deficits leading to impaired work performance and productivity [1]. Although healthcare costs are not normally distributed, i.e., the costliest and the sickest tertile of patients consume 65–82% of all medical-related costs, it has now become apparent that OSA significantly adds to the healthcare cost burden, in addition to its adverse impact on the economy [2], [3]. It is notable that sleep disorders have been assigned as playing a causative role in an estimated 9.1% of work-related injuries [4].

The prevalence of OSA varies widely, ranging from 14.7% to 36.5%, depending on gender and nationality [5]. It is higher in males (34.2%) than in females (14.7%) [5]. Although the prevalence of OSA in Hispanics (36.5%) is similar to American Whites (33.3%), increased risk of OSA occurs in both African American and Asian ethnic groups [5], [6], [7], [8]. In contrast, the prevalence of pediatric OSA is reported to be between 1 and 4%, with the caveat that prospective community-based studies using overnight polysomnography (PSG) are lacking [9], [10].

The standard diagnostic procedure for establishing the presence of OSA is the overnight polysomnography [11]. Except for the a priori reported consensus [11], an original publication or study that provided definitive validation on the use of overnight PSG as the gold standard in OSA diagnosis could not be found even after an extensive literature search. However, notwithstanding the great progress in our understanding of sleep disorders that PSG have afforded over the years, it has also become apparent that overnight PSG are onerous and labor-intensive tests that impose substantial inconvenience to the patients, and are relatively inaccessible. Indeed, waiting times between referral for evaluation to diagnosis commonly take 3–6 mo across the United States and around the world [12].

The relative complexity and high costs associated with overnight PSG as the gold standard approach employed for diagnosing the vast majority of sleep disorders has spurred the quest for alternative diagnostic methods [12]. The development of simple, cheap, and reliable screening tools that permit precise screening of at-risk populations is paramount. If accurate identification of those subjects with or without definitive disease is accomplished using such simplified and less onerous tools, then timely access to clinical care would be possible to a large sector of the population [12].

During the search for this elusive screening tool, special interest has centered around potential OSA biomarkers. The ideal biomarker should be highly sensitive and specific for OSA, should be dose-responsive and correlate to severity of disease, and should be involved in an important causal pathway, so that changes in the biomarker levels reliably predict improvements in the outcome [13]. Several different OSA biomarkers have been proposed over the last 14 y. However, to the best of our knowledge, no scoping review has been conducted thus far to critically examine what we currently know on the potential viability and use of biomarkers in OSA diagnosis and management. Therefore, the purpose of this study was to map our current understanding regarding biomarkers, and provide assessments of their characteristics in the context of OSA in both adults and children, to identify gaps in the research and help with the dissemination of the findings, and to determine the value of conducting a full systematic review related to this topic.

Section snippets

Methods

This scoping review was done adhering to Arksey and O'Malley's scoping review proposed reporting framework [14].

Study selection

In phase 1, we found 572 citations across the five electronic databases. After duplicate articles were removed, 279 remaining different citations were retained. A comprehensive evaluation of the abstracts was performed and resulted in a final number of 104 articles after phase 1. We found 40 citations in Google Scholar, but only four articles from Google Scholar met our phase 1 inclusion criteria. We identified 29 additional studies from the hand-search of reference lists of these studies, and

Discussion

The present scoping review investigated the available evidence regarding biomarkers for the diagnosis of OSA. The gold standard for OSA-PSG-imposes several important limitations, such as cost and reduced widespread availability. Moreover, this technique is potentially inconvenient since it requires that the patient will sleep outside the home environment [158]. Therefore, we need to develop methods that would allow for the large-scale screening of at-risk populations, and enable the accurate

Conclusions

The majority of pediatric studies have been performed in the USA and Greece, while adult studies were primarily conducted in China, USA and Japan. Most of studies used blood biomarkers. Studies in adults primarily explored the investigation of IL-6, TNF-α, and hsCRP as potentially promising biomarkers. There was not a specific biomarker that was tested by a majority of authors in pediatric studies, i.e., each paper evaluated different non-overlapping types of biomarkers.

Only the combination of

Conflicts of interest

The authors have no conflict of interest to declare.

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