{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T06:53:17Z","timestamp":1781506397804,"version":"3.54.1"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Eustachian tube dysfunction (ETD) and related pressure-mediated otologic disorders often present with fluctuating auditory, vestibular, and pressure-related symptoms that are difficult to explain using static structural or symptom-based diagnostic labels alone. This conceptual review proposes the Neuro\u2013Vascular\u2013Mechanical\u2013Inflammatory\u2013Autonomic (NVMIA) framework as a hypothesis-generating architecture for organizing such variability. Within this framework, middle ear pressure (MEP) is interpreted as a clinically measurable physiologic variable through which interacting neural, vascular, mechanical, inflammatory, and autonomic influences may become mechanically expressed and clinically observable. The framework does not present NVMIA-based patterns as validated diagnostic categories, clinical decision tools, or treatment algorithms. Rather, it proposes provisional regulatory patterns that may help generate testable hypotheses regarding pressure-regulatory instability, cross-axis coupling, symptom fluctuation, and physiologic reversibility. Mechanical impedance may function as an accessible reference plane for future empirical assessment, while neural, vascular, inflammatory, and autonomic domains are conceptualized as modulatory axes that may alter symptom expression and response variability. The review further outlines future validation needs, including dynamic MEP measurement, patient-reported outcome integration, longitudinal response assessment, and cautious computational modeling. By reframing ETD as a model of state-dependent regulatory instability, the NVMIA framework provides a conceptual basis for future studies in precision otology while emphasizing that prospective validation is required before clinical implementation.<\/jats:p>","DOI":"10.3390\/jpm16060315","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:59:47Z","timestamp":1781503187000},"page":"315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Pressure-Centered Mechanistic Framework for Precision Otology: The Neuro\u2013Vascular\u2013Mechanical\u2013Inflammatory\u2013Autonomic (NVMIA) Regulatory Architecture"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9400-3098","authenticated-orcid":false,"given":"Hee-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Professional, Corporate, and Continuing Education, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Center for Executive and Continuing Professional Education, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Otolaryngology, Kim Ear, Nose and Throat Clinic, Seoul 08753, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","unstructured":"National Research Council (2011). Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease, National Academies Press."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/msb4100163","article-title":"Human disease classification in the postgenomic era","volume":"3","author":"Loscalzo","year":"2007","journal-title":"Mol. Syst. Biol."},{"key":"ref_3","first-page":"1661","article-title":"Why an animal needs a brain","volume":"26","author":"Sterling","year":"2023","journal-title":"Anim. Cogn."},{"key":"ref_4","unstructured":"Bluestone, C.D. (2018). 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