Early bone loss in patients with obstructive sleep apnea: a cross-sectional study.

BACKGROUND: Obstructive sleep apnea (OSA) and osteoporosis are both prevalent diseases with shared pathophysiological mechanisms and risk factors. However, the association between the two diseases is seldom studied. This study aimed to identify the link between OSA and bone metabolism. METHODS: Male participants aged 30-59-years who visited the sleep clinic were continuously recruited. Polysomnography was used to evaluate sleep and respiratory conditions. Blood samples were collected to detect metabolic, inflammatory and bone turnover indicators. High-resolution peripheral quantitative computer tomography was used to measure the non-dominant lateral radius and tibia. RESULTS: Ninety subjects were recruited. The cortical area (Ct.Ar) of tibia of the severe OSA group was significantly higher than that of the mild and moderate OSA groups (P = 0.06 and P = 0.048). There were significant differences between the four groups in terms of total volumetric bone mineral density (vBMD) (F = 2.990, P = 0.035), meta trabecular vBMD (F = 3.696, P = 0.015), trabecular thickness (Tb.Th) (F = 7.060, P = 0.000) and cortical thickness (Ct.Th) (F = 4.959, P = 0.003). The mean values of the OSA groups were lower than control group. Hypopnea index and percentage of total sleep time with SpO2 < 90% were both positively correlated with alkaline phosphatase (R = 0.213, P = 0.044; R = 0.212, P = 0.045). Sleep efficiency was correlated with multiple indicators of the radius. CONCLUSIONS: In non-elderly male populations, OSA patients tended to have lower vBMD, Tb.Th and Ct.Th than non-OSA patients. The negative effect of OSA may mainly affect the osteogenesis process, and is presumed to be related to sleep-related hypoxemia and sleep efficiency.

Current medical education improves OSA-related knowledge but not confidence in residents: An underappreciated public health risk.

Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and induces a growing health care burden. However, a large proportion of patients with OSA do not receive appropriate treatment and are underdiagnosed or misdiagnosed in primary care. A contributing factor to the phenomenon is the lack of education, which reflects the current inadequacies in medical education. Therefore, assessing the level of knowledge and attitudes toward OSA and associated factors among resident physicians is highly warranted. Methods: A validated questionnaire, the OSA Knowledge and Attitudes (OSAKA) questionnaire was distributed to residents who had already completed undergraduate education and were attending an internal medicine residency training program. The questionnaire consists of 2 parts: including an assessment of (1) OSA-related knowledge involving epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment; (2) the importance of OSA and confidence in diagnosing and treating OSA patients. Other information including demographics, training experience, and questions exploring the future form of the sleep breathing disorder course was collected together. Results: Of the 160 residents who participated in the survey, 153 (95.6%) completed the survey and the mean total knowledge score was 12.6/18 (70% correct). Although all respondents believed that OSA was an important clinical disorder, only a minority of the residents felt confident in identifying patients at risk for OSA (38%), managing OSA patients (27.5%), or continuous positive airway pressure therapy (CPAP) (26.2%). We found that OSA training experience significantly increased knowledge scores (p = 0.002) but not confidence scores (p = 0.248). As for the specific form of medical education, "Small classes during residency training" was the most popular form of sleep-breathing disorder educational training in the future of the resident training program. Conclusion: Despite adequate knowledge of OSA, there was still a generalized lack of confidence in the management of OSA patients among residents. Current medical education can not build enough confidence for physicians, which may in turn affect patients' trust and reduce long-term compliance. Untreated OSA places a significant health threat and economic burden on not only the patients but also their families and society, causing an underappreciated public health risk. In the future, merely increasing OSA courses is not sufficient, a more specific focus on the course format and training effect is required.

Exome and Sputum Microbiota as Predictive Markers of Frequent Exacerbations in Chronic Obstructive Pulmonary Disease.

Frequent acute exacerbations are the leading cause of high rates of hospitalization and mortality in chronic obstructive pulmonary disease (COPD). Despite the enormous worldwide medical burden, reliable molecular markers for effective early diagnosis and prognosis of acute exacerbations are still lacking. Both the host genetics and airway microbiome are known to play potential roles in the pathogenesis of frequent exacerbations. Here, we performed whole exome sequencing (WES) and 16S rRNA gene sequencing to explore the interaction between these two factors and their implications in the pathogenesis of frequent exacerbations. We collected peripheral blood (n = 82), sputum samples (n = 59) and clinical data from 50 frequent-exacerbation phenotype (FE) COPD patients and 32 infrequent-exacerbation phenotype (IE) as controls. Based on filtering the deleterious sites, candidate mutated genes shared only in FE patients and did not occur in the IE group were identified. Microbiota analysis revealed significant differences in bacterial diversity and composition between FE and IE groups. We report the underlying pathogenic gene including, AATF, HTT, CEP350, ADAMTS9, TLL2 genes, etc., and explore their possible genotypic-phenotypic correlations with microbiota dysbiosis. Importantly, we observed that AATF gene mutations were significantly negatively correlated with microbial richness and diversity. Our study indicated several deleterious mutations in candidate genes that might be associated with microbial dysbiosis and the increased risk of frequent acute exacerbations in COPD patients. These results provide novel evidence that exomes and related microbiomes may potentially serve as biomarkers for predicting frequent acute exacerbations in COPD patients.

[Advances and Application of Genomics in Chronic Obstructive Pulmonary Disease].

Chronic obstructive pulmonary disease (COPD) is a common and frequently-occurring disease in the department of respiratory medicine,the pathogenesis of which involves both environmental factors and genetic factors.In recent years,with the application of new methods such as genome-wide association study,researchers have discovered a large number of gene mutations associated with lung function and COPD,providing a new perspective on the pathogenesis of COPD and potential therapeutic targets.This article reviews the research achievements and application progress of genomics in COPD.

The Relationship Between HIF1α and Clock Gene Expression in Patients with Obstructive Sleep Apnea.

Purpose: In this study, we aimed to investigate the precise relationship between hypoxia-inducible factor 1α (HIF1α), circadian clock genes, and OSA. Methods: We recruited 21 patients with OSA and 22 age-matched controls who underwent polysomnography and had their peripheral blood collected on the evening before and the morning after sleep. OSA was defined as an apnea hypopnea index (AHI) ≥15 events/h. Patients in which T90 > 0 were defined as having nocturnal hypoxemia (NH) and were referred to as the NH group. The mRNA levels of HIF1α, HIF1ß and several clock genes (Timeless, Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2, Ck1δ, Rorα, NR1D1, and NPAS2) were determined by RT-qPCR. The percentage difference in gene expression levels when compared between the morning and evening was then determined as referred to as morning-evening variation (MEV). Results: The MEV for HIF1α mRNA expression in OSA patients increased significantly by 23% (P = 0.008) when compared to patients without OSA. The gene expression levels of Timeless (P = 0.038) and Cry2 (P = 0.012) decreased with AHI. The MEV of Bmal1, Rorα, and HIF1α mRNA levels were upregulated by 16% (P = 0.006), 14% (P = 0.027), and 25% (P = 0.005), respectively, in participants with NH when compared to those without NH. Furthermore, the MEV for HIF1α mRNA levels was positively correlated with the MEV of Bmal1, Cry1, and CK1δ mRNA levels (R = 0.638, P < 0.001; R = 0.327, P = 0.002; R = 0.332, P = 0.001, respectively) and negatively correlated with LSpO2 (R = -0.464, P =0.009) and Mean SpO2 (R = -0.500, P = 0.003). Conclusion: Our data suggest that patients with OSA or NH tend to develop circadian rhythm disorders that may be induced by the hypoxia-mediated augmentation of HIF1α gene expression in OSA.

Characteristics of the sputum microbiome in COPD exacerbations and correlations between clinical indices.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent, progressive respiratory disease, and acute exacerbations of COPD (AECOPD) can accelerate the deterioration of the disease. Increasing evidence suggests that airway bacterial dysbiosis is associated with AECOPD. However, the exact relationship between changes in the sputum microbiome during AECOPD and clinical indices remains unclear. METHODS: In this study, a total of 76 sputum samples were collected from patients with AECOPD (n = 28), stable COPD (n = 23), recovery (n = 15) and healthy controls (HCs; n = 10). The sputum microbiome profile was analysed by sequencing the V3­V4 amplicon of the 16S rRNA (ribosomal RNA) gene. RESULTS: The bacterial diversity (Shannon and Simpson's index) was found to be significantly decreased in the AECOPD and recovery groups when compared to that in the stable COPD and HC groups. The most dominant phylum identified in the sputum samples of AECOPD patients was Proteobacteria, accounting for 30% of the microbiome. Compared to the stable COPD groups, the relative abundances of Firmicutes and Bacteroidetes were decreased, whereas those of Proteobacteria and Actinobacteria were increased in AECOPD patients. Furthermore, discriminative bacteria, such as Haemophilus, were identified as being specific taxa in AECOPD patients. Functional analysis showed that genes involved in membrane transport and signal transduction metabolism were enriched in the AECOPD group. Importantly, the proportions of Veillonella were positively correlated with lung function, and Staphylococcus was positively correlated with inflammatory indices. CONCLUSION: Our study revealed variations in the sputum microbiome of AECOPD (based on composition and function) in a Chinese cohort and highlighted its correlation to clinical indices. These results indicated that microbial dysbiosis may contribute to disease progression and provide microbial biomarkers for the diagnosis of AECOPD.

Endothelial Function and Arterial Stiffness Should Be Measured to Comprehensively Assess Obstructive Sleep Apnea in Clinical Practice.

Objective: An effective clinical tool to assess endothelial function and arterial stiffness in patients with obstructive sleep apnea (OSA) is lacking. This study evaluated the clinical significance of subclinical markers for OSA management in males without serious complications. Patients/Methods: Males without serious complications were consecutively recruited. Clinical data, biomarker tests, reactive hyperemia index (RHI), and augmentation index at 75 beats/min (AIx75) measured by peripheral arterial tonometry were collected. An apnea hypopnea index (AHI) cutoff of ≥15 events/h divided the patients into two groups. Results: Of the 75 subjects, 42 had an AHI ≥15 events/h. Patients with an AHI ≥15 events/h had higher high-sensitivity C-reactive protein, tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor, and AIx75 values than the control group but no statistical difference in RHI was observed. After controlling for confounders, TNF-α was negatively correlated with the average oxygen saturation (r = -0.258, P = 0.043). RHI was correlated with the rapid eye movement (REM) stage percentage (r = 0.306, P = 0.016) but not with AHI (P > 0.05). AIx75 was positively correlated with the arousal index (r = 0.289, P = 0.023) but not with AHI (r = 0.248, P = 0.052). Conclusions: In males with OSA without severe complications, TNF-α and AIx75 are independently related to OSA. The role of RHI in OSA management requires further elucidation. These markers combined can comprehensively evaluate OSA patients to provide more evidence for the primary prevention of coronary heart disease and treatment response assessment.

Application of personalized medicine to obstructive sleep apnea in China.

Obstructive sleep apnea (OSA) is a common sleep disorder whose prevalence is increasing in China consistent with rising obesity trends. OSA is a heterogeneous disorder depends on anatomical and nonanatomical risk factors. Ethnicity differentially influences the attribution of these OSA risk factors. Chinese patients had more craniofacial bony restriction and Caucasians were more obese. This suggests ethnic differences in potential applications for diagnostics and therapeutics. However, current strategies for the management of OSA reflect a one-size-fits-all approach based on the apnea-hypopnea index (AHI). Although continuous positive airway pressure (CPAP) remains the first-line and most efficacious treatment for OSA, the acceptance is unacceptably low in China. Therefore, targeted therapies to treat OSA need to be developed. This review summarizes the differences in OSA pathogenesis of Chinese patients and analyzes the current condition of personalized medicine to patients with OSA in China. The application of personalized medicine to OSA in the Chinese population is still a long way off.