Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation.
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ABSTRACT: Rationale
Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome.Objectives
To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers.Methods
Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated.Measurements and main results
In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota.Conclusions
We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.
SUBMITTER: Wu BG
PROVIDER: S-EPMC6353011 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Study objectiveTo investigate whether low levels of physical activity were associated with an increased occurrence of obstructive sleep apnea (OSA), OSA-related symptoms, and cardiometabolic risk.MethodsA case-control study design was used. OSA cases were patients referred to a sleep clinic for suspected OSA (n = 2,340). Controls comprised participants from the Busselton community (n = 1,931). Exercise and occupational activity were derived from questionnaire data. Associations were modelled using logistic and linear regression and adjusted for confounders.ResultsIn comparison with moderate exercise, the high, low, and nil exercise groups had an odds ratio (OR) for moderate-severe OSA of 0.6 (95% CI 0.5-0.8), 1.6 (95% CI 1.2-2.0), and 2.7 (95% CI 1.9-3.7), respectively. Relative to men in heavy activity occupations, men in medium, light and sedentary occupations had an OR for moderate-severe OSA of 1.7 (95% CI 1.1-2.5), 2.1 (95% CI 1.4-3.2), and 1.8 (95% CI 1.2-2.8), respectively. Relative to women in medium activity occupations, women in light and sedentary occupations had an OR for moderate-severe OSA of 4.2 (95% CI 2.6-7.2) and 3.5 (2.0-6.0). OSA patients who adequately exercised had lower: levels of doctor-diagnosed depression (p = 0.047); symptoms of fatigue (p < 0.0001); systolic (p = 0.015) and diastolic blood pressure (p = 0.015); and C-reactive protein (CRP) (p = 0.003).ConclusionsLow levels of physical activity were associated with moderate-severe OSA. Exercise in individuals with OSA is associated with lower levels of depression, fatigue, blood pressure and CRP.
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Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:Purpose:Obstructive sleep apnea (OSA) is less prevalent among women and is associated with different symptoms and consequences to OSA in men. The reasons for these differences are unknown and difficult to tease apart in clinical populations. If OSA could be temporarily induced in healthy men and women, the causes of some of these differences could be investigated. Nasal blocking has been used to induce OSA in healthy men but its effect in women has not been reported. Patients and Methods:A total of 14 healthy individuals (10 women) underwent in-laboratory diagnostic sleep studies on two occasions separated by a week. On one occasion, the nasal passages were blocked, whereas on the other occasion, participants slept naturally. In both conditions, a full-face mask was used to monitor respiratory events. Participants' self-reported sleepiness, mood and performance on a motor learning task were assessed in the evening and morning of both sleep studies. Furthermore, endothelial function and self-reported sleep quality were assessed in the morning following each study. Results:Nasal blockage induced OSA in healthy young (age=22±3 years) and slim (BMI=22.2±3.2 kg/m2) women (control AHI=2.0±2.6, blocked AHI=33.1±36.7 events/hr, p=0.02). One night of OSA was associated with poorer self-reported sleep quality (p<0.001) and increased self-reported snoring (p<0.04), choking and gasping during sleep (p<0.001) but was not associated with alterations in mood, neurocognitive or endothelial function on the following morning. Conclusion:Nasal blockage induces OSA in healthy, young, and normal weight women. However, whether the induced OSA is representative of naturally occurring OSA and the technique useful for future studies is unclear.
| S-EPMC7319502 | biostudies-literature
Project description:The direct pathophysiological effects of obstructive sleep apnea (OSA) have been well described. However, the systemic and metabolic consequences of OSA are less well understood. The aim of this secondary analysis was to translate recent findings in healthy subjects on vigilance-state-dependent metabolism into the context of OSA patients and answer the question of how symptomatic OSA influences metabolism and whether these changes might explain metabolic and cardiovascular consequences of OSA. Patients with suspected OSA were assigned according to their oxygen desaturation index (ODI) and Epworth Sleepiness Scale (ESS) score into symptomatic OSA and controls. Vigilance-state-dependent breath metabolites assessed by high-resolution mass spectrometry were used to test for a difference in both groups. In total, 44 patients were eligible, of whom 18 (40.9%) were assigned to the symptomatic OSA group. Symptomatic OSA patients with a median [25%, 75% quartiles] ODI of 40.5 [35.0, 58.8] events/h and an ESS of 14.0 [11.2, 15.8] showed moderate to strong evidence for differences in 18 vigilance-state-dependent breath compounds compared to controls. These identified metabolites are part of major metabolic pathways in carbohydrate, amino acid, and lipid metabolism. Thus, beyond hypoxia per se, we hypothesize that disturbed sleep in OSA patients persists as disturbed sleep-dependent metabolite levels during daytime.
| S-EPMC9694615 | biostudies-literature
Project description:Study objectivesTo explore and analyze diversity and abundance of oropharyngeal microbiota in patients with obstructive sleep apnea (OSA).MethodsThis was a cross-sectional study. Middle-aged men, suspected to have OSA, referred to full-night polysomnography, and willing to provide oropharyngeal swab samples, were consecutively enrolled. OSA severity was assessed by apnea-hypopnea index (AHI) as non-OSA (AHI < 5 events/h) and OSA (AHI ≥ 15 events/h). Bacterial DNA of oropharyngeal samples was extracted and quality test performed. Oropharyngeal microbiota was analyzed using 16S ribosomal DNA (rDNA) sequencing, and bioinformatic analysis carried out after sequencing.ResultsSamples from 51 men (25 in the non-OSA group and 26 in the OSA group) were sent for examination. Of these, 40 samples were found to have sufficient concentration of DNA and were analyzed for bioinformatics. In alpha diversity analysis, the OSA group exhibited significantly lower sobs (198.33 ± 21.71 versus 216.57 ± 26.21, P = .022), chao (221.30 ± 26.62 versus 243.86 ± 26.20, P = .014), ace (222.17 ± 27.15 versus 242.42 ± 25.81, P = .028) and shannon index (3.14 ± 0.23 versus 3.31 ± 0.26, P = .035), suggesting a reduction in microbial species diversity. We further divided participants into non-OSA, moderate OSA, and severe OSA groups and observed a significant decrease in the bacterial biodiversity of OSA groups compared with the non-OSA group, with the most significant decrease occurring in the moderate OSA group. Principal coordinate analysis showed two extremely different oropharyngeal microbial communities in non-OSA and OSA groups. More interestingly, proportion of Neisseria was slightly higher in the severe OSA group (20.64%), followed by the moderate OSA and non-OSA groups (12.57% and 9.69%, respectively). Glaciecola was not detected in the OSA groups compared to the non-OSA group (0 versus 0.772 ± 0.4754, P < .001).ConclusionsMiddle-aged men with OSA showed less oropharyngeal species diversity and altered abundance, on which further confirmation is warranted.
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