{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T20:02:24Z","timestamp":1784404944127,"version":"3.55.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":172,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inflammatory biomarkers are used as surrogate endpoints in obstructive sleep apnea trials, assuming the measured signal originates from the airway or systemic response to intermittent hypoxia. Periodontitis\u2014a common, extrapulmonary inflammatory reservoir\u2014elevates systemic active matrix metalloproteinase-8 independently of obstructive sleep apnea. This Perspective examines whether unmeasured oral inflammation confounds biomarker attribution in obstructive sleep apnea trials. Epidemiological and interventional evidence indicates that periodontitis is highly prevalent, is more common in individuals with obstructive sleep apnea, and substantially elevates circulating active matrix metalloproteinase-8. Moreover, non-surgical periodontal therapy reduces this signal to a degree comparable to early Continuous Positive Airway Pressure (CPAP) effects. In published CPAP trials that reported inflammatory or cardiovascular outcomes, periodontal status has not been reported or incorporated into primary analyses. We propose a heuristic conceptual model: measured circulating active matrix metalloproteinase-8\u2009=\u2009obstructive sleep apnea-related component + periodontal-derived component + measurement noise. Without adjustment for periodontal status, observed changes cannot be uniquely attributed to obstructive sleep apnea treatment. The ORBIT heuristic framework (Oral Reservoir Bias Inflammatory Trial) is introduced as a conceptual prompt for reporting oral inflammatory burden. Inflammatory biomarker responses in obstructive sleep apnea trials are consistent with a composite signal that includes an unmeasured oral component. A testable prediction is that adjusting for periodontal status would reduce between-trial heterogeneity of matrix metalloproteinase-8effect estimates without altering within-subject respiratory outcomes. Prospective validation is warranted. The framework extends beyond active matrix metalloproteinase-8 to any circulating inflammatory marker influenced by extra-target inflammatory reservoirs.<\/jats:p>","DOI":"10.1093\/sleepadvances\/zpag063","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:50:21Z","timestamp":1781869821000},"source":"Crossref","is-referenced-by-count":0,"title":["Hidden oral inflammation and biomarker misclassification in obstructive sleep apnea trials"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-8092","authenticated-orcid":false,"given":"Solomon Olusegun","family":"Nwhator","sequence":"first","affiliation":[{"name":"Department of Preventive and Community Dentistry, Faculty of Dentistry, Obafemi Awolowo University , Ile-Ife ,","place":["Nigeria"]},{"name":"Obafemi Awolowo University Teaching Hospitals Complex , Ile-Ife 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