Obstructive sleep apnea is more severe in men but not women with refractory hypertension compared with controlled resistant hypertension.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension (RHTN) and may contribute to refractory hypertension (RfHTN). The objective of the current study was to test the hypothesis that patients with RfHTN have more severe OSA compared with patients with controlled RHTN. METHODS: Patients (n = 187) referred to the University of Alabama at Birmingham Hypertension Clinic for evaluation and treatment of RHTN, defined as uncontrolled blood pressure (BP) (SBP ≥ 130 mmHg or DBP ≥ 80 mmHg) despite the use of at least three antihypertensive medications including a diuretic, were enrolled following completion of at least three follow-up clinic visits. RfHTN was defined as uncontrolled high BP despite treatment with five or more antihypertensive agents of different classes, including a long-acting thiazide-type diuretic and a mineralocorticoid receptor antagonist. Following enrollment, all patients (n = 130) completed 24-h ambulatory BP measurement and overnight diagnostic polysomnography during normal nightly use of continuous positive airway pressure. Analyses examined the severity of OSA and related sleep characteristics among patients with RfHTN versus controlled RHTN. RESULTS: Of the 130 evaluated patients, 37 (28.5%) had RfHTN and 93 (71.5%) had controlled RHTN. In unadjusted analyses, there was not a significant difference in OSA severity, oxygen saturation, or hypoxemia time in patients with RfHTN versus controlled RHTN (P > 0.05). Men with RfHTN had more severe OSA compared with men with controlled RHTN (P = 0.044). In adjusted analyses, OSA severity was associated with sex (P < 0.0001), but not hypertension phenotype (P = 0.17). CONCLUSION: The severity of OSA may contribute to RfHTN status in men but not women.

Effects of subthalamic nucleus deep brain stimulation on objective sleep outcomes in Parkinson's disease.

BACKGROUND: Sleep dysfunction is a common and disabling non-motor symptom in Parkinson's disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms and subjective sleep in PD, but alternative stimulation parameters to optimize sleep have not been explored. We hypothesized that low frequency STN DBS would improve objective sleep more than conventional settings. METHODS: Twenty PD subjects with STN DBS (18 unilateral, 2 bilateral) underwent 3 non-consecutive nights of polysomnography: DBS off; DBS high frequency (≥130 Hz); and DBS low frequency (60 Hz). Motor symptom tolerability was assessed 30 minutes after resumption of baseline settings the morning following polysomnography. The primary outcome was change in sleep efficiency between high and low frequency nights measured with repeated measures ANOVA. RESULTS: There was no difference in sleep efficiency between nights at high frequency (82.1% (72.6-90.1)) (median (IQR)), low frequency (81.2% (56.2-88.8)), or DBS off (82.8% (75.7-87.4)), p=0.241. Additionally, there was no difference in sleep stage percent, arousals, limb movements, subjective sleep quality, or objective vigilance measures. These outcomes did not change after adjusting for age, sex, disease duration, or side of surgery. No residual adverse motor effects were noted. CONCLUSIONS: Although well tolerated, low frequency STN DBS did not improve objective sleep in PD. Remarkably, objective measures of sleep were not worse with DBS off. These observations point to the potential for adaptive stimulation approaches, through which DBS settings could be optimized during sleep to meet individual needs. Additionally, these changes could preserve battery life without compromising patient outcomes.

Chronic Cough Due to Gastroesophageal Reflux in Adults: CHEST Guideline and Expert Panel Report.

BACKGROUND: We updated the 2006 ACCP clinical practice guidelines for management of reflux-cough syndrome. METHODS: Two population, intervention, comparison, outcome (PICO) questions were addressed by systematic review: (1) Can therapy for gastroesophageal reflux improve or eliminate cough in adults with chronic and persistently troublesome cough? and (2) Are there minimal clinical criteria to guide practice in determining that chronic cough is likely to respond to therapy for gastroesophageal reflux? RESULTS: We found no high-quality studies pertinent to either question. From available randomized controlled trials (RCTs) addressing question #1, we concluded that (1) there was a strong placebo effect for cough improvement; (2) studies including diet modification and weight loss had better cough outcomes; (3) although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, proton pump inhibitors (PPIs) demonstrated no benefit when used in isolation; and (4) because of potential carryover effect, crossover studies using PPIs should be avoided. For question #2, we concluded from the available observational trials that (1) an algorithmic approach to management resolved chronic cough in 82% to 100% of instances; (2) cough variant asthma and upper airway cough syndrome (UACS) (previously referred to as postnasal drip syndrome) from rhinosinus conditions were the most commonly reported causes; and (3) the reported prevalence of reflux-cough syndrome varied widely. CONCLUSIONS: The panelists (1) endorsed the use of a diagnostic/therapeutic algorithm addressing causes of common cough, including symptomatic reflux; (2) advised that although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated no benefit when used in isolation; and (3) suggested that physiological testing be reserved for refractory patients being considered for antireflux surgery or for those in whom there is strong clinical suspicion warranting diagnostic testing.

Somatic Cough Syndrome (Previously Referred to as Psychogenic Cough) and Tic Cough (Previously Referred to as Habit Cough) in Adults and Children: CHEST Guideline and Expert Panel Report.

BACKGROUND: We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic. METHODS: We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology. RESULTS: The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate. CONCLUSIONS: Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

Long-Term Effectiveness and Safety of Maxillomandibular Advancement for Treatment of Obstructive Sleep Apnea.

STUDY OBJECTIVE: To determine the long-term clinical effectiveness and safety of maxillomandibular advancement (MMA) for the treatment of moderate to severe obstructive sleep apnea (OSA). METHODS: A prospective two-center cohort study design was used to evaluate OSA patients who underwent MMA > 2 years ago. The primary outcome measure was the apnea-hypopnea index (AHI). Secondary outcome measures included blood pressure (BP), sleepiness (Epworth Sleepiness Scale [ESS]), and quality of life (Functional Outcomes of Sleep Questionnaire [FOSQ]). RESULTS: 30 adult patients (80% men, age 50.5 ± 9.6 years [mean ± SD]) participated in the study. The AHI decreased from a mean of 49 to 10.9 events/h (p < 0.0001) at the time of long-term evaluation (6.6 ± 2.8 years after MMA), with 46.7% of patients obtaining an AHI < 5 and 83.4% of patients attaining an AHI ≤ 15 events/h. The mean diastolic BP decreased from 83.7 to 79.0 mm Hg (p < 0.05). ESS decreased from a mean of 12.1 to 6.0 (p < 0.01). FOSQ increased from a mean of 12.6 to 17.3 (p < 0.05). Few long-term treatment-related adverse events occurred, which had minimal impact on quality of life (QOL). CONCLUSIONS: MMA is a clinically effective and safe long-term treatment for most patients with moderate-to-severe OSA as demonstrated by significant decreases in AHI, diastolic BP, and subjective sleepiness, with concomitant significant improvements in QOL. The results of this small cohort study suggest that MMA should be considered as the alternative treatment of choice for patients with severe OSA who cannot fully adhere to CPAP therapy.

Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult: CHEST Guideline and Expert Panel Report.

BACKGROUND: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators. METHODS: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology. RESULTS: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48). CONCLUSIONS: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

Respiratory manifestations of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is highly associated with a range of respiratory symptoms, arising from a variety of etiologies. The following commentaries on respiratory manifestations of GERD address evidence for a role of a vagally mediated bronchoconstriction reflex in the development of asthma; the direct effects of airway obstruction on lower esophageal sphincter (LES) pressure and reflux episodes; the mechanisms by which reflux may play roles in chronic cough and airway stenosis; the limited efficacy of laparoscopic antireflux surgery (LARS) in improving GERD-related respiratory symptoms; the search for a marker for microaspiration and reflux-induced airway disease; and the potential of proton pump inhibitor (PPI) treatment for patients presenting with asthma and GERD.

Computational fluid dynamic analysis of the posterior airway space after maxillomandibular advancement for obstructive sleep apnea syndrome.

PURPOSE: This study evaluated the soft tissue change of the upper airway after maxillomandibular advancement (MMA) using computational fluid dynamics. MATERIALS AND METHODS: Eight patients with obstructive sleep apnea syndrome who required MMA were recruited into this study. All participants underwent pre- and postoperative computed tomography and then MMA by a single oral and maxillofacial surgeon. Upper airway computed tomographic datasets for these 8 patients were created with high-fidelity 3-dimensional numerical models for computational fluid dynamics. The 3-dimensional models were simulated and analyzed to study how changes in airway anatomy affect the pressure effort required for normal breathing. Airway dimensions, skeletal changes, apnea-hypopnea index, and pressure effort of pre- and postoperative 3-dimensional models were compared and correlations were interpreted. RESULTS: After MMA, laminar and turbulent air flows were significantly decreased at every level of the airway. The cross-sectional areas at the soft palate and tongue base were significantly increased. CONCLUSIONS: This study showed that MMA increased airway dimensions by increasing the distance from the occipital base to the pogonion. An increase of this distance showed a significant correlation with an improvement in the apnea-hypopnea index and a decreased pressure effort of the upper airway. Decreasing the pressure effort will decrease the breathing workload. This improves the condition of obstructive sleep apnea syndrome.

Increased dietary sodium is related to severity of obstructive sleep apnea in patients with resistant hypertension and hyperaldosteronism.

BACKGROUND: Obstructive sleep apnea (OSA) is a strong and independent risk factor for the development of hypertension, particularly resistant hypertension, and cardiovascular diseases. Patients with resistant hypertension have a high prevalence of OSA in association with elevated aldosterone levels, high salt intake, and salt-sensitive BP. The objective of this study was to determine whether dietary salt and aldosterone are associated with severity of OSA in patients with resistant hypertension. METHODS: Ninety-seven patients with resistant hypertension were prospectively evaluated by overnight polysomnography and 24-h urinary sodium and aldosterone levels while maintaining their usual diet. Hyperaldosteronism was defined as a plasma renin activity of < 1 ng/mL/h and urinary aldosterone level of ≥ 12 µg/24 h. RESULTS: Overall, patients' mean clinic BP was 156.3 ± 22.4/88.9 ± 13.3 mm Hg while taking an average of 4.3 ± 1.1 antihypertensive medications. Prevalence of OSA was 77.3%. Twenty-eight (28.9%) patients had hyperaldosteronism. Urinary sodium level was an independent predictor of severity of OSA only in patients with hyperaldosteronism. CONCLUSIONS: The findings suggest that dietary salt is related to the severity of OSA in patients with resistant hypertension and hyperaldosteronism. The results support dietary salt restriction as a treatment strategy for reduction of OSA severity in these patients.

Development and growth of a large multispecialty certification examination: sleep medicine certification--results of the first three examinations.

This paper summarizes the results of the first three examinations (2007, 2009, and 2011) of the Sleep Medicine Certification Examination, administered by its six sponsoring American Board of Medical Specialty Boards. There were 2,913 candidates who took the 2011 examination through one of three pathways-self-attested practice experience, previous certification by the American Board of Sleep Medicine, or formal Sleep Medicine fellowship training. The 2011 exam was the last administration in which candidates who had not previously been admitted could take it without completion of formal Sleep Medicine fellowship training. As expected, the number of candidates admitted to the 2011 examination through the practice experience pathway increased, and the overall scores of these candidates were on average lower than the other candidates. Consequently, the pass rate for all first takers of the 2011 examination (65%) was lower than that observed from the 2009 examination (78%) and the 2007 examination (73%). For each administration, candidates admitted through the fellowship training pathway scored the highest; over 90% of them passed the 2011 and 2009 examinations.

Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension.

BACKGROUND: We previously described a significant correlation between plasma aldosterone concentration (PAC) and severity of obstructive sleep apnea (OSA) in patients with resistant hypertension. This investigation examines the relationship between aldosterone status and OSA in patients with resistant hypertensive-with and without hyperaldosteronism. METHODS AND RESULTS: One hundred and nine consecutive patients with resistant hypertension were prospectively evaluated with plasma renin activity (PRA), PAC, 24-hour urinary aldosterone excretion (UAldo), and polysomnography. Hyperaldosteronism (PRA < 1 ng x mL(-1) x h(-1) and UAldo > or = 12 microg/24-h) prevalence was 28% and OSA prevalence was 77%. In patients with hyperaldosteronism, OSA prevalence was 84%, compared with 74% in hypertensive patients with normal aldosterone levels. There were no significant differences in body mass index or neck circumference between aldosterone groups. PAC and UAldo were both significantly correlated with apnea-hypopnea index (AHI) in the high-aldosterone group (p = 0.568, p = 0.0009; p = 0.533, p = 0.002, respectively). UAldo correlated weakly with apnea-hypopnea index in the normal-aldosterone group, but there was no significant correlation between PAC and AHI in the normal-aldosterone group (p = 0.224, p = 0.049; p = 0.015, p = 0.898, respectively). CONCLUSIONS: Our analysis of patients with resistant hypertension confirms a markedly high prevalence of OSA in this group. Furthermore, severity of OSA was greater in those patients with hyperaldosteronism and related to the degree of aldosterone excess. The correlation between OSA severity and aldosterone supports the hypothesis that aldosterone excess contributes to greater severity of OSA.

Sleep and hypertension.

Ambulatory BP studies indicate that even small increases in BP, particularly nighttime BP levels, are associated with significant increases in cardiovascular morbidity and mortality. Accordingly, sleep-related diseases that induce increases in BP would be anticipated to substantially affect cardiovascular risk. Both sleep deprivation and insomnia have been linked to increases in incidence and prevalence of hypertension. Likewise, sleep disruption attributable to restless legs syndrome increases the likelihood of having hypertension. Observational studies demonstrate a strong correlation between the severity of obstructive sleep apnea (OSA) and the risk and severity of hypertension, whereas prospective studies of patients with OSA demonstrate a positive relationship between OSA and risk of incident hypertension. Intervention trials with continuous positive airway pressure (CPAP) indicate a modest, but inconsistent effect on BP in patients with severe OSA and a greater likelihood of benefit in patients with most CPAP adherence. Additional prospective studies are needed to reconcile observational studies suggesting that OSA is a strong risk factor for hypertension with the modest antihypertensive effects of CPAP observed in intervention studies.

Development and results of the first ABMS subspecialty Certification Examination in Sleep Medicine.

In November 2007, the first Certification Examination in Sleep Medicine was administered to 1,882 candidates under the cosponsorship of five member boards of the American Board of Medical Specialties (ABMS)--the American Board of Internal Medicine, the American Board of Family Medicine, the American Board of Otolaryngology, the American Board of Pediatrics, and the American Board of Psychiatry and Neurology. The pass rate was 73%. This paper chronicles the history of a certification examination in Sleep Medicine and the development of this new ABMS examination.