Role of precision medicine in obstructive sleep apnoea.

Obstructive sleep apnoea is a substantial clinical and public health problem because it contributes to harmful effects on quality of life, daytime symptoms, road traffic incidents, and cardiometabolic disease. Increasingly, obstructive sleep apnoea is recognised as a heterogeneous disease, and patients have varied susceptibility to long term complications and different responses to treatment. This narrative review summarises the current knowledge of precision medicine in obstructive sleep apnoea, particularly the role of symptom clusters, polysomnogram phenotypes, physiological endotypes, and circulating biomarkers in defining subtypes. In the near future, the prognostic accuracy of these measures in predicting long term complications in obstructive sleep apnoea will likely be improved, together with better matching of treatments to disease subtypes.

The rs579459 ABO gene polymorphism and risk of incident cardiovascular events in obstructive sleep apnea: a pilot study.

PURPOSE: We have previously shown that the TT genotype (rs579459 location of the ABO gene) is significantly associated with circulating levels of e-selectin in patients with suspected obstructive sleep apnea (OSA). We hypothesized that this genotype would be associated with incident cardiovascular disease (CVD). METHODS: Patients with suspected OSA who had a full diagnostic polysomnogram from 2003 to 2011 were recruited; CV events occurring within 8 years of polysomnography were identified by linkage to provincial health databases. Cox proportional hazards models were used to evaluate the incidence of first CV events as a function of the rs579459 genotype. RESULTS: In this targeted study, 408 patients were studied, and 39 incident events were identified. A larger proportion of patients with the TT genotype had an event (31/247; 12.6%) than the CT and CC genotypes (8/161; 5.0%); in univariate analysis, the TT genotype was significantly associated with CV events (HR = 2.53; 95% CI = 1.16-5.51, p = 0.02). After adjustment for age, AHI, sex, smoking, diabetes, statin use, and BMI, the TT genotype remained a significant predictor (HR = 2.35; 95% CI = 1.02-5.42, p = 0.046). No events were found in patients with an absence of both OSA and the TT genotype (N = 30). The effect of the SNP was partially (16.2%) mediated by e-selectin levels. CONCLUSION: This is the first study to examine genetic variants as a risk factor for incident CVD in the context of OSA. Although these results are preliminary and in need of replication, it suggests that genetic markers may become useful in helping to guide precision clinical care.

Circulating markers of oxidative stress and risk of incident cardiovascular events in obstructive sleep apnea.

The identification of which patients with obstructive sleep apnea (OSA) are more likely to develop cardiovascular disease (CVD) remains a challenge. OSA causes oxidative stress (OS) which may contribute to CVD pathogenesis. Therefore, OS markers could be useful in risk-stratifying cardiovascular (CV) risk in OSA patients. The purpose of this pilot study was to assess whether three OS marker levels could be associated with incident CVD in suspected OSA patients. Morning plasma levels of 8-isoprostane, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and superoxide dismutase (SOD) were measured in patients with suspected OSA referred for a polysomnogram (PSG). A composite outcome of CV events was defined by linkage with provincial administrative health databases. Cox proportional hazards models were used to assess the relationship between the levels of OS markers and events. 352 patients were included (mean age of 51.4 years, 68% male, median apnea hypopnea index of 16/h). Thirty-one first CV events occurred over an 8-year follow-up. In univariate or fully adjusted models, none of the OS markers were significantly associated with incident CV events (hazard ratio in adjusted models of: 1.25 (95% CI 0.56-2.80, p = 0.59), 1.15 (0.52-2.57, p = 0.73), 0.77 (0.37-1.61, p = 0.48), for 8-OHdG, 8-isoprostane and SOD; however, confidence intervals were wide. In this small preliminary study, oxidative stress markers were not significantly associated with risk of CV events. However, moderate associations between these markers and risk of CV events are possible and should be the focus of future larger studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00399-0.

Microfluidics-based fabrication of cell-laden microgels.

Microfluidic principles have been extensively utilized as powerful tools to fabricate controlled monodisperse cell-laden hydrogel microdroplets for various biological applications, especially tissue engineering. In this review, we report recent advances in microfluidic-based droplet fabrication and provide our rationale to justify the superiority of microfluidics-based techniques over other microtechnology methods in achieving the encapsulation of cells within hydrogels. The three main components of such a system-hydrogels, cells, and device configurations-are examined thoroughly. First, the characteristics of various types of hydrogels including natural and synthetic types, especially concerning cell encapsulation, are examined. This is followed by the elucidation of the reasoning behind choosing specific cells for encapsulation. Next, in addition to a detailed discussion of their respective droplet formation mechanisms, various device configurations including T-junctions, flow-focusing, and co-flowing that aid in achieving cell encapsulation are critically reviewed. We then present an outlook on the current applications of cell-laden hydrogel droplets in tissue engineering such as 3D cell culturing, rapid generation and repair of tissues, and their usage as platforms for studying cell-cell and cell-microenvironment interactions. Finally, we shed some light upon the prospects of microfluidics-based production of cell-laden microgels and propose some directions for forthcoming research that can aid in overcoming challenges currently impeding the translation of the technology into clinical success.