Background-Previous studies have documented a high prevalence of atrial fibrillation (AF) in individuals with obstructive sleep apnea (OSA). Central sleep apnea (CSA) has been associated with AF in patients with heart failure. However, data from prospective cohorts are sparse and few studies have distinguished the associations of obstructive sleep apnea from CSA with AF in population studies. Methods and Results-We assessed the association of obstructive sleep apnea and CSA with incident AF among 2912 individuals without a history of AF in the SHHS (Sleep Heart Health Study), a prospective, community-based study of existing ("parent") cohort studies designed to evaluate the cardiovascular consequences of sleep disordered breathing. Incident AF was documented by 12-lead ECG or assessed by the parent cohort. obstructive sleep apnea was defined by the obstructive apnea-hypopnea index (OAHI). CSA was defined by a central apnea index >= 5 or the presence of Cheyne Stokes Respiration. Logistic regression was used to assess the association between sleep disordered breathing and incident AF. Over a mean of 5.3 years of follow-up, 338 cases of incident AF were observed. CSA was a predictor of incident AF in all adjusted models and was associated with 2-to 3-fold increased odds of developing AF (central apnea index >= 5 odds ratio [OR], 3.00, 1.40-6.44; Cheyne-Stokes respiration OR, 1.83, 0.95-3.54; CSA or Cheyne-Stokes respiration OR, 2.00, 1.16-3.44). In contrast, OAHI was not associated with incident AF (OAHI per 5 unit increase OR, 0.97, 0.91-1.03; OAHI 5 to <15 OR, 0.84, 0.59-1.17; OAHI 15 to <30 OR, 0.93, 0.60-1.45; OAHI >= 30 OR, 0.76, 0.42-1.36). Conclusions-In a prospective, community-based cohort, CSA was associated with incident AF, even after adjustment for cardiovascular risk factors.

Patients undergoing surgery with unrecognized obstructive sleep apnea (OSA) are at greater risk of complications. Ninety percent of those affected in the United States remain undiagnosed. To improve identification, screening tools such as the STOP-Bang questionnaire (Chung et al. 2008), provide anesthesia providers a method of detecting undiagnosed OSA. The purpose of this study is to assess anesthesia providers' practice of preoperative screening for OSA. An email survey was conducted at a Level-III trauma center in Phoenix, Arizona. The survey consisted of a 13 question, 5-point Likert scale questionnaire. It was sent to 29 Certified Registered Nurse Anesthetists (CRNA). A total of 8 CRNA's responded. Respondents were either neutral or disagreed that current methods of OSA screening works well and generally agree that the STOP-Bang tool would provide an advantage over the current methods, accurately detect OSA, and inform their anesthetic plan over current methods. Respondents leaned towards strong agreement that improving the recognition of undiagnosed OSA is needed. However, they were generally neutral on agreement that the STOP-Bang is necessary at their facility. Respondents agreed that the STOP-Bang tool is easy to use and interpret. However, most agreed that integrating the tool would add complexity to the preanesthesia evaluation but they remained neutral on whether it would add significant time to this process. Respondents were neutral on their observations that the STOP-Bang tool would improve early detection of OSA or reduce perianesthesia complications. Just 25% of respondents reported being aware of the existence of the STOP-Bang tool and none reported having used it. In conclusion, this project demonstrates that some providers have not used the STOP-Bang screening tool to detect undiagnosed OSA, but agree this tool is preferred over their current method. Results from the survey brought insight to a potential quality improvement strategy related to improving the perianesthesia care of patients with undiagnosed OSA. Improving knowledge through dissemination of evidence illustrates the value of the STOP-Bang prior to piloting the tool. The rates of perioperative complications justify the implementation of perioperative strategies such as the STOP-Bang as a tool for anesthesia providers.

Background: Obstructive sleep apnea (OSA) consists of repeated, involuntary breathing suspension during sleep. These events induce rapid depletion/repletion of blood/tissue oxygen content, a phenomenon known as intermittent hypoxia. Aside from causing daytime sleepiness, the most important health consequence of OSA is a 2-fold increase in cardiovascular (CVD) risk. Animal studies provide evidence that intermittent hypoxia, a simulating model of OSA, causes important rise in plasma TG, especially in the postprandial state. However, the underpinning mechanisms linking intermittent hypoxia to altered postprandial TG levels remain unknown. As such, the objective of this study was to characterize the effects of acute intermittent hypoxia on postprandial TG levels in 2 distinct lipoprotein subtypes in humans: chylomicrons which are secreted by the intestine and carry dietary lipids, and denser TG carriers (mainly VLDL) which are secreted by the liver and carry endogenous lipids. Methods: The research consisted of a randomized crossover design. In collaboration with the Sleep laboratory at Montfort Hospital, 7 individuals diagnosed with moderate sleep apnea were recruited through phone calls as well as 8 healthy individuals without OSA from the University of Ottawa. While lying on a bed, participants were given a meal after which they were exposed for 6 hours to normoxia or intermittent hypoxia corresponding to moderate OSA, e.g. 15 hypoxic events per hour. Blood lipid levels were measured hourly.  Results: Plasma TG levels increased over time in both experimental conditions and tended to be greater under 6-h exposure to intermittent hypoxia (p=0.093, effect size ηp2= 0.383.). This trend toward higher total plasma TG under intermittent hypoxia was attributable to increased levels in denser TG carrying lipoproteins such as VLDL and CM remnants (p= 0.009, ηp2 = 0.173).  Conclusion: Acute intermittent hypoxia, a simulating model of obstructive sleep apnea, tends to negatively affect postprandial TG levels, which is attributable to an increase in denser TG carrying lipoprotein levels such as VLDL and CM remnants. These results lend support to the increase in blood lipid levels in animal studies observing the effect of acute hypoxia in mice.  Contribution to advancement of knowledge: This proposed research will allow a better understanding of the mechanisms by which obstructive sleep apnea may alter blood lipid profile. This information will be beneficial to the treatment of obstructive sleep apnea related dyslipidemia and contribute to reduce CVD risk in the large proportion of obstructive sleep apnea patients who are reluctant to current treatment avenues.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23097号 / 医博第4724号 / 新制||医||1050(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 近藤 尚己, 教授 稲垣 暢也, 教授 石見 拓 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated. We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD. COPD-PS™ development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5). A national survey of 697 patients was conducted at 12 practitioner sites. Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%). ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity. Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations. For known-groups validation, COPD-PS differences between clinical groups were tested. Test-retest reliability was evaluated in a 20% sample. Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO. Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age. COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91). Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3). Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems. With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%. The COPD-PS accurately classified physicianreported COPD (AUC = 0.89). The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18166号 / 医博第3886号 / 新制||医||1003(附属図書館) / 31024 / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 三森 経世, 教授 佐藤 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Chronic Obstructive Pulmonary Disease (COPD) is the fifth leading cause of death in the United States. COPD is a highly heterogeneous disease, and patients with COPD experience varying degrees of respiratory findings (lung function decline, chronic bronchitis, and emphysema). However, the molecular changes underlying this heterogeneity are not well understood. For my dissertation research I used bronchial airway gene expression to develop a signature of lung function decline, evaluate a molecule for potential anti-COPD properties, and develop a gene expression-based classification of COPD subtypes. Genome-wide gene expression generated from bronchial epithelial brushings of ever smokers with and without COPD were used to identify differences in gene expression associated with the rate of subsequent lung function decline. I validated this lung function decline signature in an independent set of COPD patients and determined that this signature may be driven by changes in the activity of the transcription factor XBP1. I next identified gene expression changes in human derived bronchial epithelial cells (HBECS) when exposed to a potential novel anti-COPD compound. I performed an in silico analysis to determine if these gene expression changes were related to COPD-associated gene expression differences observed in independent datasets of COPD patients. Lastly, I performed unbiased gene expression clustering on bronchial brushings to identify novel molecular COPD subtypes. I then examined these gene expression changes in independent datasets of COPD. Together, these works may lead to better understanding and treatment of COPD. The signature of lung function decline could be used as an intermediary endpoint in studies evaluating COPD therapies, or for patient stratification. Characterizing the relationship between the gene expression changes associated with COPD and those induced by the novel anti-COPD compound helps inform choices around its development as a potential medication. Lastly, the molecular subtypes of COPD may lead to a better understanding of molecular heterogeneity in the pathogenesis of COPD and ultimately more patient-specific treatments that are targeted to these molecular differences. / 2023-05-25T00:00:00Z

No description available.

No description available.