| Selected Publications： |
◆Su MC, Chin CH, Chen YC, Hsieh YT, Wang CC, Huang YC, Lin MC. Chang Gung Med J. 2008 May-Jun;31(3):297-303. Diurnal change of respiratory muscle strength in patients with sleep-disordered breathing.
◆Su MC, Chen YC, Huang KT, Wang CC, Lin MC, Lin HC. Association of metabolic factors with high-sensitivity C-reactive protein in patients with sleep-disordered breathing. Eur Arch Otorhinolaryngol. 2013 Feb; 270(2):749-54.
◆Lai CC, Friedman M, Lin HC, Wang PC, Hsu CM, Yalamanchali S, Lin MC, Chen YC. Objective versus subjective measurements of palatine tonsil size in adult patients with obstructive sleep apnea/hypopnea syndrome. Eur Arch Otorhinolaryngol. 2014 Aug; 271(8):2305-10.
◆Huang KT, Chin CH, Tseng CC, Chang HC, Chen YC, Wang CC, Lin MC, Lin HC, Su MC. The influence of obesity on different genders in patients with obstructive sleep apnea. Scientific World Journal. 2014;2014:487215.
◆Chen YC, Su MC, Liou CW, Liu SF, Chen CJ, Lin HC, Hsiao CC, Wang TY, Wang CC, Chin CH, Huang KT, Lin AS, Lin MC. Co-upregulation of Toll-like receptors 2 and 6 on peripheral blood cells in patients with obstructive sleep apnea. Sleep Breath. 2015;19(3):873-82.
◆Chen YC, Chen TW, Su MC, Chen CJ, Chen KD, Liou CW, Tang P, Wang TY, Chang JC, Wang CC, Lin HC, Chin CH, Huang KT, Lin MC, Hsiao CC. Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype. Sleep. 2016 Apr 1;39(4):743-55.
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| Abstract： |
Obstructive sleep apnea (OSA) should be personalized in that there are different structural and physiological pathways to disease. Structural risk factors include craniofacial dimensions, increased size of upper airway soft tissue structures, and obesity, while physiological risk factors include (1) Critical upper airway pressure: the collapsibility of the passive upper airway; (2) high loop gain: instability of the overall ventilatory control system; (3) decreased arousal threshold to hypoxia and hypercapnia; and (4) inadequate reflex response of upper airway dilator muscles.
Unsupervised approaches identified three clusters of OSA patients: “excessive daytime sleepiness”, “disturbed sleep/insomnia’’ and ‘‘minimally symptomatic’’. Supervised analytic methods identified several clinical phenotypes with single or multiple features. Symptom or polysomnography based phenotypes include excessive daytime sleepiness (EDS), elderly, rapid eye movement-predominant, and position-dependent. Outcome based phenotypes include complete concentric collapse at level of the palate for failure of upper airway neuro-stimulation therapy, long soft palate / large cranial base angulation for failure of mandibular advancement device treatment, EDS for compliance of continuous positive airway pressure (CPAP) treatment, Friedman stage III / low hyoid position for failure of uvulopalatopharyngoplasty, and a very high BMI for indication of bariatric surgery.
Although randomized, controlled trials have shown that CPAP can improve
EDS, resistant hypertension, endothelial function and insulin sensitivity, it did not prevent cardiovascular events in OSA patients in either primary or secondary prevention settings. Previous researches revealed that chronic intermittent hypoxia with re-oxygenation cause a series of oxidative stress responses, inflammatory reactions, oxygen sensor activation, and increased sympathetic activity, which in turn contribute to the development of adverse consequences of OSA. Vascular endothelial growth factor levels are elevated in OSA patients, particularly in the older and more serious patients. OSA is independently associated with higher C-reactive protein, and lower vitamin D in several cohorts. CPAP can reduce leptin levels in OSA patients without concomitant weight loss. Recently, DNA methylation and microRNA changes have been linked to EDS/high hypoxic load and resistant hypertension, respectively. The findings of these potential biological phenotypes open the possibility of using biologic agents to prevent adverse consequences of OSA.
Evidence is accumulating that apnea H\hypopnea index alone is insufficient for diagnosis and management of OSA patients. Complementary to molecular phenotyping, clinical phenotyping may serve as an intermediate step towards personalized medicine in OSA. Further studies may focus on anchoring these phenotypes to meaningful outcomes and assessing their temporal stability.
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