Breath of Fresh Air: Toward Unraveling the Molecular Underpinnings of Sleep Apnea.
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ABSTRACT:
SUBMITTER: Cade BE
PROVIDER: S-EPMC9757082 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Breath of Fresh Air: Toward Unraveling the Molecular Underpinnings of Sleep Apnea.
Cade Brian E BE Gharib Sina A SA
American journal of respiratory and critical care medicine 20221201 12
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Project description:RATIONALE: Panic disorder (PD) has been shown to be associated with worse asthma outcomes in individuals with asthma, but the psychophysiological mechanisms underlying this association remain unclear. Some theories suggest that asthmatics with PD have worse underlying asthma severity and some argue that they simply report more symptoms based on their tendency to catastrophize bodily sensations. METHODS: A total of 39 patients (19 with and 20 without PD) with physician-diagnosed asthma underwent standard metacholine challenge testing (MCT). Demographic and medical/asthma history information was collected at baseline. Pre and post MCT patients completed the Panic symptom scale (PSS), the Modified Borg Scale (MBS), and the Subjective distress visual analogue scale (SD-VAS). Heart rate (HR), systolic, and diastolic blood pressure (SBP/DBP) were recorded pre, during, and post MCT. RESULTS: There were no differences in PC20 values between asthmatics with and without PD (F=0.21, p=0.652). PD patients had a higher number of panic symptoms (from the PSS) at post-test compared to those without PD ([M (SD)] PD pre = 2.21 (2.42), PD post = 5.00 (3.32); non-PD pre = 0.75 (1.07), non-PD post = 2.25 (1.89): F=5.05, p=0.031). There were no differences in MBS (F=0.70, p=0.407), SD-VAS anxiety (F=0.36, p=0.554), SD-VAS worry (F=0.84, p=0.366), HR (F=0.06, p=0.805), SBP (F=0.49, p=0.487), or DBP (F=0.01, p=0.942) between PD and non-PD patients. CONCLUSIONS: Results suggest that having PD is associated with increased subjective responses during MCT, with no impact on objective measures of asthma. Future research should focus on the potential impact of these increased panic attack-like symptoms on long-term asthma care and if intervening on them influences outcomes such as emergency room visits.
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Project description:The worldwide burden of tuberculosis has continued to rise. The management of TB has become more difficult with the emergence of MDR-TB (multidrug resistant tuberculosis) and XDR-TB (extensively drug resistant tuberculosis). MDR/XDR-TB has rendered the treatment of this disease extremely challenging as the treatment requires the use of medications that are less effective, more toxic, more costly, and have to be given for a longer duration (usually at least 18 months). MDR-TB is associated with decreased cure rates and increased rates of relapse than fully susceptible tuberculosis. XDR-TB is associated with even worse treatment outcomes than MDR-TB. There is an urgent need for new anti-TB drugs. Fortunately, new medications for the treatment of tuberculosis are currently completing phase III trials and can be released on a compassionate basis to tuberculosis centres. We present a case of a patient with XDR-TB in which bedaquiline, one such medication, was included in his treatment regimen. The drug was released from Janssen Pharmaceutica on compassionate grounds. We believe that this is the first case in Canada in which bedaquiline was used. Our patient is a 22-year-old male with XDR-TB isolated from pleural fluid. Because of the pattern of drug resistance and numerous drug adverse effects (ototoxicity from amikacin, bone marrow suppression from linezolid and severe neuropathy from clarithromycin and cycloserine), his treatment was very difficult. Bedaquiline was added in April 2013 to his treatment regimen following the recommended schedule. He completed 6 months of bedaquiline without any untoward side effects in October 2013. Follow-up computed tomography scans and chest radiography have shown resolution of the pleural effusion with no parenchymal or lymphatic disease.
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Project description:Rapid and reliable tools for the diagnosis and monitoring of obstructive sleep apnea (OSA) are currently lacking. Prior studies using a chemical analysis of exhaled breath have suggested the existence of an OSA-specific metabolic signature. Here, we validated this diagnostic approach and the proposed marker compounds, as well as their potential to reliably diagnose OSA. In this cross-sectional observational study, exhaled breath was analyzed using secondary electrospray ionization high-resolution mass spectrometry. The study cohort included untreated OSA patients, OSA patients treated with continuous positive airway pressure and healthy subjects. The robustness of previously reported OSA markers was validated based on detectability, significant differences between groups (Mann-Whitney U test) and classification performance. The breath analysis of 118 participants resulted in 42 previously reported markers that could be confirmed in this independent validation cohort. Nine markers were significantly increased in untreated OSA compared to treated OSA, with a subset of them being consistent with a previous validation study. An OSA prediction based on the confirmed OSA signature performed with an AUC of 0.80 (accuracy 77%, sensitivity 73% and specificity 80%). As several breath markers were clearly found to be repeatable and robust in this independent validation study, these results underscore the clinical potential of breath analysis for OSA diagnostics and monitoring.
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Project description:Background and Objectives: Obstructive sleep apnea syndrome (OSAS) represents an independent risk factor for cardiovascular, metabolic and neurological events. Polysomnography is the gold-standard for the diagnosis, however is expensive and time-consuming and not suitable for widespread use. Breath analysis is an innovative, non-invasive technique, able to provide clinically relevant information about OSAS. This systematic review was aimed to outline available evidence on the role of exhaled breath analysis in OSAS, taking into account the techniques' level of adherence to the recently proposed technical standards. Materials and Methods: Articles reporting original data on exhaled breath analysis in OSAS were identified through a computerized and manual literature search and screened. Duplicate publications, case reports, case series, conference papers, expert opinions, comments, reviews and meta-analysis were excluded. Results: Fractional exhaled Nitric Oxide (FeNO) is higher in OSAS patients than controls, however its absolute value is within reported normal ranges. FeNO association with AHI is controversial, as well as its change after continuous positive airway pressure (C-PAP) therapy. Exhaled breath condensate (EBC) is acid in OSAS, cytokines and oxidative stress markers are elevated, they positively correlate with AHI and normalize after treatment. The analysis of volatile organic compounds (VOCs) by spectrometry or electronic nose is able to discriminate OSAS from healthy controls. The main technical issues regards the dilution of EBC and the lack of external validation in VOCs studies. Conclusions: Exhaled breath analysis has a promising role in the understanding of mechanisms underpinning OSAS and has demonstrated a clinical relevance in identifying individuals affected by the disease, in assessing the response to treatment and, potentially, to monitor patient's adherence to mechanical ventilation. Albeit the majority of the technical standards proposed by the ERS committee have been followed by existing papers, further work is needed to uniform the methodology.
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Project description:This study examines the relationship between sleep apnea and glucose metabolism. Physiological studies have demonstrated that 5 days of exposure to intermittent hypoxia (similar to what occurs with sleep apnea) leads to significant improvements in glucose tolerance. Therefore, this study investigates the hypothesis that intermittent hypoxia may lead to upregulation of some novel peptide(s) that have a powerful glucose lowering action. Keywords: other
2003-07-16 | GSE480 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is a major global cause of morbidity and mortality, projected to become the 3rd cause of disease mortality worldwide by 2020. COPD is characterized by persistent and not fully reversible airflow limitation that is usually progressive and is associated with an abnormal chronic inflammatory response of the lung to noxious agents including cigarette smoke. Currently available therapeutic strategies aim to ease COPD symptoms but cannot prevent its progress or regenerate physiological lung structure or function. The urgently needed new approaches for the treatment of COPD include stem cell therapies among which transplantation of mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) emerges as a promising therapeutic strategy because of the unique properties of these cells. The present review discusses the main biological properties of WJ-MSCs pertinent to their potential application for the treatment of COPD in the context of COPD pathomechanisms with emphasis on chronic immune inflammatory processes that play key roles in the development and progression of COPD.
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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:Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.
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Project description: Not available
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