The Role of Obstructive Sleep Apnea in Hypercapnic Respiratory Failure Identified in Critical Care, Inpatient, and Outpatient Settings.

An emerging body of literature describes the prevalence and consequences of hypercapnic respiratory failure. While device qualifications, documentation practices, and previously performed clinical studies often encourage conceptualizing patients as having a single "cause" of hypercapnia, many patients encountered in practice have several contributing conditions. Physiologic and epidemiologic data suggest that sleep-disordered breathing-particularly obstructive sleep apnea (OSA)-often contributes to the development of hypercapnia. In this review, the authors summarize the frequency of contributing conditions to hypercapnic respiratory failure among patients identified in critical care, emergency, and inpatient settings with an aim toward understanding the contribution of OSA to the development of hypercapnia.

Chronic Cough and Obstructive Sleep Apnea.

Chronic cough, defined as a cough lasting more than 8 weeks, is a common medical condition occurring in 5% to 10% of the population. Its overlap with another highly prevalent disorder, obstructive sleep apnea (OSA), is therefore not surprising. The relationship between chronic cough and OSA extends beyond this overlap with higher prevalence of OSA in patients with chronic cough than in the general population. The use of continuous positive airway pressure can result in improvement in chronic cough although further studies are needed to understand which patients will experience benefit in their cough from the treatment of comorbid OSA.

Laryngeal Dysfunction Manifesting as Chronic Refractory Cough and Dyspnea: Laryngeal Physiology in Respiratory Health and Disease.

TOPIC IMPORTANCE: Laryngeal dysfunction as a cause of chronic refractory cough and episodic dyspnea is often missed, which results in unnecessary testing and delays in diagnosis. Understanding laryngeal roles in breathing and airway protection can help to appreciate the propensity to laryngeal dysfunction with aging, chronic lung disease, and sleep apnea. REVIEW FINDINGS: The human larynx is a complex muscular structure that is responsible for multiple roles of breathing, vocalization, coughing, and swallowing. To undertake these activities, the larynx has a high density of sensory and motor innervation. In addition to common embryological origins with the pharynx and esophagus, with which many laryngeal activities are shared, somatomotor and autonomic pathways regulate emotional, cognitive, and complex motor sequence-planning activities within the larynx. Due to its unique location, the larynx is susceptible to infectious and gastroesophageal reflux-related insults. Couple this with key roles in regulation of airflow and mediation of airway protective reflexes, it is not surprising that neuropathic abnormalities and muscle dysfunction frequently develop. The expression of laryngeal dysfunction as hypersensitivity to mechanical, thermal, chemical, and other stimuli leads to exaggerated airway protective reflexes (laryngeal adductor reflex and cough reflex) manifesting as dyspnea and cough. SUMMARY: Pulmonologists should incorporate assessment of laryngeal dysfunction during evaluation of chronic refractory cough and dyspnea. Recognition of laryngeal hypersensitivity in the patient with chronic refractory cough can identify patients who may benefit from cough suppression therapies. Similarly, timely identification of inducible laryngeal obstruction may not only resolve episodic dyspnea but lessen the need for unnecessary testing and treatments.

Prevalence of Anxiety as a Variable in Treatment Outcomes for Individuals With Chronic Refractory Cough.

PURPOSE: Anxiety is a mental state characterized by an intense sense of tension, worry, or apprehension relative to something adverse that might happen in the future. Anxiety is a known comorbidity in cough patients, yet its prevalence among those with chronic refractory cough (CRC) is unknown. Anxiety is not typically assessed during evaluation for CRC, but treatments for CRC such as neuromodulators and behavioral cough suppression therapy (BCST) may potentially attenuate anxiety. This preliminary study investigates the potential prevalence of anxiety in CRC and its possible role in treatment outcomes. METHOD: CRC patients seen in a specialty clinic at the University of Utah or the University of Montana completed the Leicester Cough Questionnaire (LCQ) pre- and post-BCST treatment. Participants were dichotomized into positive anxiety screen (PAS) and negative anxiety screen (NAS) groups based on presence or absence of documented anxiety within electronic medical records at the University of Utah and based on a Generalized Anxiety Disorder-7 score > 5 at the University of Montana. RESULTS: Of the 86 total participants, 37 (43%) were in the PAS group (29 females, Mage = 56 ± 13) and 49 (57%) were in the NAS group (36 females, Mage = 64 ± 14). Eighty-nine percent of CRC participants with a PAS reported a clinically meaningful improvement in LCQ total score following treatment compared to 65% of NAS participants. Furthermore, mean pre- to posttreatment change scores on the LCQ were significantly greater within the PAS group (p = .002, Cohen's d = 0.7, indicating a moderate to large effect size). CONCLUSION: This preliminary study suggests that (a) anxiety may be prevalent among those with CRC and (b) those patients who screen positive for anxiety report greater benefit from BCST.

Positive Airway Pressure Therapy Predicts Lower Mortality and Major Adverse Cardiovascular Events Incidence in Medicare Beneficiaries with Obstructive Sleep Apnea.

Background: Obesity is associated with obstructive sleep apnea (OSA) and cardiovascular risk. Positive airway pressure (PAP) is the first line treatment for OSA, but evidence on its beneficial effect on major adverse cardiovascular events (MACE) prevention is limited. Using claims data, the effects of PAP on mortality and incidence of MACE among Medicare beneficiaries with OSA were examined. Methods: A cohort of Medicare beneficiaries with ≥2 distinct OSA claims was defined from multi-state, state-wide, multi-year (2011-2020) Medicare fee-for-service claims data. Evidence of PAP initiation and utilization was based on PAP claims after OSA diagnosis. MACE was defined as a composite of myocardial infarction, heart failure, stroke, or coronary revascularization. Doubly robust Cox proportional hazards models with inverse probability of treatment weights estimated treatment effects controlling for sociodemographic and clinical factors. Results: Among 888,835 beneficiaries with OSA (median age 73 years; 43.9% women; median follow-up 1,141 days), those with evidence of PAP initiation (32.6%) had significantly lower all-cause mortality (HR [95%CI]: 0.53 [0.52-0.54]) and MACE incidence risk (0.90 [0.89-0.91]). Higher quartiles of annual PAP claims were progressively associated with lower mortality (Q2: 0.84 [0.81-0.87], Q3: 0.76 [0.74-0.79], Q4: 0.74 [0.72-0.77]) and MACE incidence risk (Q2: 0.92 [0.89-0.95], Q3: 0.89 [0.86-0.91], Q4: 0.87 [0.85-0.90]). Conclusion: PAP utilization was associated with lower all-cause mortality and MACE incidence among Medicare beneficiaries with OSA. Results might inform trials assessing the importance of OSA therapy towards minimizing cardiovascular risk and mortality in older adults.

Predictors of Initial CPAP Prescription and Subsequent Course with CPAP in Patients with Central Sleep Apneas at a Single Center.

PURPOSE: Guidelines recommend considering an initial trial of continuous positive airway pressure (CPAP) to treat central sleep apnea (CSA). However, practice patterns vary widely. This study investigated predictors for an initial trial of CPAP in patients with central apneas and whether those factors predict adequate treatment response in patients receiving an initial CPAP trial. METHODS: Charts of patients receiving a diagnostic code for CSA following a sleep study during 2016-2018 at a single center were reviewed. Patient factors, initial treatment prescriptions, and subsequent changes to therapy were extracted from electronic health records. Regression models were used to estimate factors associated with an initial CPAP prescription and the likelihood of an adequate CPAP response (no subsequent therapy change and no discontinuation of therapy) among patients prescribed CPAP. RESULTS: 429/588 (73%) patients with central apneas received an initial trial of CPAP. Younger age, diagnosis by home sleep testing, non-opiate etiology of central apneas, and a lower proportion of central apneas at diagnosis were independently associated with a higher likelihood of an initial CPAP trial. A lower proportion of central apneas was associated with a higher probability of adequate response, while current smoking and opiate-related central apneas predicted an unsuccessful CPAP trial. A new finding was that older age predicted a lower likelihood of an initial CPAP prescription but did not predict an unsatisfactory response to CPAP. CONCLUSION: Clinicians may incorrectly weigh certain clinical and sleep study characteristics when deciding whether to trial CPAP for patients with central apneas.

Depicting and defining sleep disturbed breathing associated with vagal nerve stimulation.

BACKGROUND: Vagal nerve stimulators (VNS), which have been approved for management of refractory epilepsy and depression, induce unique disturbances of breathing during sleep (SDBVNS) that are not captured well using standard criteria. The primary purpose of this retrospective study was to compare AASM definitions with alternative criteria to more accurately measure SDBVNS We also sought to assess outcome variables that may be clinically relevant and response to positive airway pressure therapy. METHODS: We analyzed the electronic medical records and comprehensive polysomnography results of all adult subjects with active VNS for epilepsy who were referred to the sleep center for suspected sleep apnea (2015-2020). We compared standard AASM criteria for defining apneas/hypopnea index (AHIAASM) with three novel scoring criteria for hypopnea according to degree of oxygen desaturation associated with VNS events: AHIVNS0 (none required); AHIVNS2 (2% required); and AHIVNS3 (3% required). RESULTS: Twenty-six subjects were included in the final analysis with 35 PSGs (14 females/12 males). The mean age was 33.6 years and mean body mass index (BMI) of 32.2 kg/m2. AHIAASM measured ≥ 15/hour in 7 (26.9%) subjects versus 21 (80.8%) by AHIVNS0; 15 (70.0%) by AHIVNS2; and 5 (19.2%) by AHIVNS3. Clinically significant hypoxemia was not present. The mean time SpO2<89% was 7 (20.8) minutes. Oximetry tracings often showed a desaturation pattern that resembled a sawfish rather than sawtooth. Arousals specifically linked to VNS activation were not elevated (2.9/hour). The baseline AHIVNS0 was 27.7/hour with a lowest AHIVNS0 on PAP of 27.9/hr. CONCLUSIONS: AASM scoring criteria significantly underestimated the degree of VNS induced respiratory disturbances. VNS events were not associated with increased arousals or significant hypoxemia. PAP therapy was an ineffective treatment in this population. This study adds to the increasing body of evidence of sleep disordered breathing related to VNS and questions the clinical significance of this finding.

Predictors of Initial CPAP Prescription and Subsequent Course with CPAP in Patients with Central Sleep Apneas.

Purpose: Guidelines recommend considering an initial trial of continuous positive airway pressure (CPAP) to treat central sleep apnea (CSA). However, practice patterns vary widely. This study investigated predictors for an initial trial of CPAP in patients with central apneas and whether those factors predict adequate treatment response in patients receiving an initial CPAP trial. Methods: Charts of patients receiving a diagnostic code for CSA following a sleep study during 2016-2018 at a single center were reviewed. Patient factors, initial treatment prescriptions, and subsequent changes to therapy were extracted from electronic health records. Regression models were used to estimate factors associated with an initial CPAP prescription and the likelihood of an adequate CPAP response (no subsequent therapy change or nonadherence) among patients prescribed CPAP. Results: 429/588 (73%) patients with central apneas received an initial trial of CPAP. Younger age, diagnosis by home sleep testing, non-opiate etiology of central apneas, and a lower proportion of central apneas at diagnosis were independently associated with a higher likelihood of an initial CPAP trial. A lower proportion of central apneas was associated with a higher probability of adequate response, while current smoking and opiate-related central apneas predicted an unsuccessful CPAP trial. A new finding was that older age predicted a lower likelihood of an initial CPAP prescription but did not predict a suboptimal response to CPAP. Conclusion: Clinicians may incorrectly weigh certain clinical and sleep study characteristics when deciding whether to trial CPAP for patients with central apneas.

Increased blood reactive oxygen species and hepcidin in obstructive sleep apnea precludes expected erythrocytosis.

Obstructive sleep apnea (OSA) causes intermittent hypoxia during sleep. Hypoxia predictably initiates an increase in the blood hemoglobin concentration (Hb); yet in our analysis of 527 patients with OSA, >98% did not have an elevated Hb. To understand why patients with OSA do not develop secondary erythrocytosis due to intermittent hypoxia, we first hypothesized that erythrocytosis occurs in these patients, but is masked by a concomitant increase in plasma volume. However, we excluded that explanation by finding that the red cell mass was normal (measured by radionuclide labeling of erythrocytes and carbon monoxide inhalation). We next studied 45 patients with OSA before and after applying continuous positive airway pressure (CPAP). We found accelerated erythropoiesis in these patients (increased erythropoietin and reticulocytosis), but it was offset by neocytolysis (lysis of erythrocytes newly generated in hypoxia upon return to normoxia). Parameters of neocytolysis included increased reactive oxygen species from expanded reticulocytes' mitochondria. The antioxidant catalase was also downregulated in these cells from hypoxia-stimulated microRNA-21. In addition, inflammation-induced hepcidin limited iron availability for erythropoiesis. After CPAP, some of these intermediaries diminished but Hb did not change. We conclude that in OSA, the absence of significant increase in red cell mass is integral to the pathogenesis, and results from hemolysis via neocytolysis combined with inflammation-mediated suppression of erythropoiesis.

Normative Values for the Leicester Cough Questionnaire in Healthy Individuals.

INTRODUCTION: The primary self-assessment questionnaire used for patients with chronic cough is the Leicester Cough Questionnaire (LCQ). The LCQ is a validated questionnaire that ranges in total score from 3 to 21. While it is known that a higher score on the LCQ reflects a better quality of life, normative data have not been reported for this questionnaire. OBJECTIVE: The purpose of this study was to determine normative LCQ scores on a healthy population without cough. METHODS: The LCQ was distributed via electronic survey to the authors' universities, professional affiliation email lists, and personal contacts. Participants were included if they were at least 18, nonsmokers, and without abnormal cough, without pulmonary disease, and without neurological disease. Participants answered questions regarding age, gender, and race/ethnicity, and completed the 19 LCQ questions. RESULTS: One hundred forty-three (118 women) LCQ responses were analyzed. Average participant age was 47 years (SD = 13) and 133 (93%) were Caucasian. The mean LCQ Total score was 20.23 (SD = 0.85) with scores ranging from 17.05 to 21. CONCLUSIONS: This study determined the following LCQ scores should be considered normal threshold scores: Total score - 17.68, Physical domain - 5.36, Psychological domain - 5.81, and Social domain - 6.06. The findings of this study will assist clinicians in determining severity of cough impact on quality of life using the LCQ. Further research is needed to ensure more complete participant demographic representation.

Couples-based interventions to promote PAP adherence among older adults: a qualitative study of patients, partners, and providers.

STUDY OBJECTIVES: Bed partners play a critical role in the treatment of obstructive sleep apnea and are affected by the treatment (or lack thereof) of their partner's obstructive sleep apnea, but few studies have included partners formally in treatment. In this qualitative study, we examine key stakeholder perspectives (patient, bedpartner, and sleep medicine provider) to inform the development of a novel, couples-based intervention to promote adherence to positive airway pressure (PAP) and sleep health among older adult couples. METHODS: We conducted 3 focus group discussions with patients with obstructive sleep apnea/using PAP and their partners and 3 focus group discussions with sleep medicine providers. A standard interview guide was used to gather stakeholder input: (1) to understand interdependence of sleep among couples with sleep apnea; (2) to understand collaborative strategies that couples are currently using to address their sleep health challenges, including their perceptions of what is helpful vs not helpful; and (3) feasibility of the intervention design and delivery. Interviews were transcribed and thematically analyzed. RESULTS: Participants (n = 25) included 9 patients, 7 partners, and 9 providers. Analysis of the discussion identified themes within the 3 topics addressed in the focus group discussions: (1) interdependence of sleep health among couples, (2) collaboration and other dyadic strategies for increasing PAP use, and (3) facilitators and barriers to a couples-based PAP adherence intervention. Results of the focus group discussions provided new insights into collaborative strategies that could be used to enhance the sleep health of both patients and partners. Patient/partners reported that a couples-based treatment could reduce common frustrations experienced by new PAP users, thereby benefiting their relationship. However, barriers to couples-based treatment included patients and partners feeling overwhelmed and reluctance to discuss intimacy. Providers recognized the benefits of involving partners but reported concern about exacerbating conflict in the couple. CONCLUSIONS: Results indicate that couples and providers are enthusiastic about couples-based treatment that addresses their individual and dyadic sleep health challenges and identified important barriers that will need to be addressed to enhance uptake by clinicians and participation/retention of couples. CITATION: Baron KG, Troxel WM, Galway S, et al. Couples-based interventions to promote PAP adherence among older adults: a qualitative study of patients, partners, and providers. J Clin Sleep Med. 2022;18(11):2627-2634.

Rationale and study protocol for We-PAP: a randomized pilot/feasibility trial of a couples-based intervention to promote PAP adherence and sleep health compared to an educational control.

BACKGROUND: Obstructive sleep apnea (OSA) is a serious health condition that affects approximately 30-50% of older adults and contributes to risk for cardiometabolic disorders and dementia. Despite the well-documented role of partners in treatment seeking and adherence to positive airway pressure (PAP), treatments for OSA have nearly exclusively focused on the patient and current treatments for OSA do not address co-existing sleep problems such as insomnia that are prevalent in both patients with OSA and their partners. Therefore, the goal of this study is to develop and test a novel couples-based sleep health intervention to promote adherence to PAP and improve sleep health of the couple. METHODS: We are conducting a two-arm, parallel group, single blind, randomized controlled pilot/feasibility trial to compare our novel couples-based sleep health intervention (We-PAP) to an information control group (IC). We-PAP is based on a transdiagnostic model and uses a dyadic approach including increasing effective partner support, communication skills, and couple-level goal-setting. We-PAP involves 3 sessions and delivered via telehealth in weekly sessions. The IC includes standardized patient educational materials. Both groups receive the usual follow-up with their medical team. The study involves assessments at pre-treatment, post-intervention (approximately 1 month after starting PAP and completing We-PAP sessions or IC) and 3 months after starting PAP. Our main outcomes are feasibility and acceptability ratings. Secondary outcomes include comparing We-PAP to IC for PAP adherence, sleep quality (self-report and objective) and cognitive measures. DISCUSSION: We-PAP is the first couples-based transdiagnostic sleep health intervention for patients with OSA and their partners. Results of this study will be used to inform the design of a subsequent fully powered clinical trial. If successful, this intervention could significantly advance current clinical practice in the treatment of OSA and sleep health more comprehensively in older adults. Moreover, this intervention may be useful for improving sleep in other aging populations with multiple sleep and other health problems, including patients with chronic illnesses or those at risk for Alzheimer's disease and their caregivers. TRIAL REGISTRATION: NCT04759157 . Date of registration: February 8, 2021. URL of trial registry record.

OSA and Chronic Respiratory Disease: Mechanisms and Epidemiology.

Obstructive sleep apnea (OSA) is a highly prevalent disorder that has profound implications on the outcomes of patients with chronic lung disease. The hallmark of OSA is a collapse of the oropharynx resulting in a transient reduction in airflow, large intrathoracic pressure swings, and intermittent hypoxia and hypercapnia. The subsequent cytokine-mediated inflammatory cascade, coupled with tractional lung injury, damages the lungs and may worsen several conditions, including chronic obstructive pulmonary disease, asthma, interstitial lung disease, and pulmonary hypertension. Further complicating this is the sleep fragmentation and deterioration of sleep quality that occurs because of OSA, which can compound the fatigue and physical exhaustion often experienced by patients due to their chronic lung disease. For patients with many pulmonary disorders, the available evidence suggests that the prompt recognition and treatment of sleep-disordered breathing improves their quality of life and may also alter the course of their illness. However, more robust studies are needed to truly understand this relationship and the impacts of confounding comorbidities such as obesity and gastroesophageal reflux disease. Clinicians taking care of patients with chronic pulmonary disease should screen and treat patients for OSA, given the complex bidirectional relationship OSA has with chronic lung disease.

Electronic health record-derived outcomes in obstructive sleep apnea managed with positive airway pressure tracking systems.

STUDY OBJECTIVES: To assess the effectiveness of continuous positive airway pressure (CPAP) management guided by CPAP machine downloads in newly diagnosed patients with obstructive sleep apnea (OSA) using electronic health record-derived health care utilization, biometric variables, and laboratory data. METHODS: Electronic health record data of patients seen at the University of Utah Sleep Program from 2012-2015 were reviewed to identify patients with new diagnosis of OSA in whom CPAP adherence and residual apnea-hypopnea index as measured by a positive airway pressure adherence tracking device data for ≥ 1 year were available. Biometric data, laboratory data, and system-wide charges were compared in the 1 year before and after CPAP therapy. Subgroups were divided by whether patients met tracking criteria, mean nightly usage, and OSA severity. RESULTS: 976 consecutive, newly diagnosed participants with OSA (median age 55 years, 56.6% male) met inclusion criteria. There was a mean decrease of systolic blood pressure (BP) of 1.2 mm Hg and diastolic BP of 1.0 mm Hg within a year of initiation of CPAP therapy. BP improvements in the subgroup meeting CPAP tracking targets were 1.36 mmHg (systolic) and 1.37 mmHg (diastolic). No significant change was noted in body mass index, glycated hemoglobin, or serum creatinine values within a year of starting CPAP therapy, and health care utilization increased (mean acute care visits 0.22 per year to 0.53 per year; mean charges of $3,997 per year to $8,986 per year). CONCLUSIONS: An improvement in BP was noted within a year of CPAP therapy in newly diagnosed patients with OSA, with no difference in the magnitude of improvement between those meeting tracking system adherence targets. CITATION: Locke BW, Neill SE, Howe HE, Crotty MC, Kim J, Sundar KM. Electronic health record-derived outcomes in obstructive sleep apnea managed with positive airway pressure tracking systems. J Clin Sleep Med. 2022;18(3):885-894.

Long-Term Treatment Outcomes after Behavioral Speech Therapy for Chronic Refractory Cough.

INTRODUCTION: Current literature reveals that up to 88% of individuals undergoing behavioral speech therapy (BST) for chronic refractory cough (CRC) demonstrate benefit at 4-8 weeks post-treatment. However, investigations of BST are confounded by overlapping use of neuromodulators, missing follow-up data, and an absence of long-term outcomes. This study investigated treatment outcomes beyond 6 months in individuals diagnosed with CRC, and whose treatment outcomes were clinically undocumented. METHODS: Participants with CRC 6 months or greater beyond treatment completion were recruited. Participants completed a post-treatment Leicester Cough Questionnaire (LCQ) and a telephone interview. Demographic data, cough characteristics, treatment adherence, BST outcomes, and pre- and post-treatment LCQ scores were evaluated. RESULTS: 80 individuals met inclusion criteria and 29 consented to participate. Of these, 27 were recommended BST. The majority were female (19/27) with average age of 58 years (SD = 12). Mean cough duration was 60 months (SD = 98) and mean post-BST duration was 20 months (SD = 9). A significant increase in pre- to post-treatment LCQ scores occurred [4.4 (SD = 4.2)] (p < 0.0001). CONCLUSION: This study addressed long-term BST benefit for CRC and demonstrated a significant improvement in long-term post-treatment LCQ total scores more than a year after BST for CRC. More than half of participants indicated improvement or elimination of their cough. These findings further support the benefit of BST for CRC. Future research should consider patient perspectives about treatment outcomes given that 44% of participants reported no benefit from BST.

Is laryngeal hypersensitivity the basis of unexplained or refractory chronic cough?

Refractory chronic cough (RCC) and unexplained chronic cough (UCC) are common problems seen in primary care and subspecialty clinics. The role of cough hypersensitivity and laryngeal dysfunction in contributing to the persistence of cough in RCC/UCC is not well recognised. Data of patients with RCC and UCC evaluated in 2019 by an interdisciplinary cough clinic led by a pulmonologist and speech-language pathology team was reviewed. Patients completed validated questionnaires including the Leicester cough questionnaire (LCQ), voice handicap index (VHI) and dyspnoea index (DI) questionnaire at initial encounter. Presence of cough hypersensitivity was based upon a history of allotussia and hypertussia. Laryngeal dysfunction was diagnosed in those with a history of laryngeal paresthesias, throat clearing, voice abnormalities, upper airway dyspnoea and documentation of functional or anatomic laryngeal abnormalities on nasoendoscopy. Of the 60 UCC/RCC patients analysed, 75% of patients were female and 85% were over 40 years of age. Cough hypersensitivity was documented in all patients and multiple cough triggers occurred in 75% of patients. 95%, 50% and 25% of patients reported laryngeal paresthesias, voice abnormalities and upper airway dyspnoea, respectively. Significant associations between LCQ and VHI and DI scores occurred when adjusting for age, sex, ethnicity and body mass index. Laryngeal functional abnormalities were documented on 44 out of 60 patients on nasoendoscopy. Hypertussia, allotussia and laryngeal dysfunction are common in patients with RCC and UCC. Evaluation of UCC and RCC can delineate laryngeal hypersensitivity and allows appropriate treatment to be directed at this phenotype.

Evaluation and Management of Adults with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea syndrome (OSAS) is a common and underdiagnosed medical condition characterized by recurrent sleep-dependent pauses and reductions in airflow. While a narrow, collapsible oropharynx plays a central role in the pathophysiology of OSAS, there are other equally important nonanatomic factors including sleep-stage dependent muscle tone, arousal threshold, and loop gain that drive obstructive apneas and hypopneas. Through mechanisms of intermittent hypoxemia, arousal-related sleep fragmentation, and intrathoracic pressure changes, OSAS impacts multiple organ systems. Risk factors for OSAS include obesity, male sex, age, specific craniofacial features, and ethnicity. The prevalence of OSAS is rising due to increasing obesity rates and improved sensitivity in the tools used for diagnosis. Validated questionnaires have an important but limited role in the identification of patients that would benefit from formal testing for OSA. While an in-laboratory polysomnography remains the gold standard for diagnosis, the widespread availability and accuracy of home sleep apnea testing modalities increase access and ease of OSAS diagnosis for many patients. In adults, the most common treatment involves the application of positive airway pressure (PAP), but compliance continues to be a challenge. Alternative treatments including mandibular advancement device, hypoglossal nerve stimulator, positional therapies, and surgical options coupled with weight loss and exercise offer possibilities of an individualized personal approach to OSAS. Treatment of symptomatic patients with OSAS has been found to be beneficial with regard to sleep-related quality of life, sleepiness, and motor vehicle accidents. The benefit of treating asymptomatic OSA patients, particularly with regard to cardiovascular outcomes, is controversial and more data are needed.

Evidence of Possible Irritable Larynx Syndrome in Obstructive Sleep Apnea: An Epidemiologic Approach.

OBJECTIVE: "Irritable larynx syndrome" (ILS) often refers to a constellation of laryngeal-based symptoms including chronic cough (CC), diurnal dyspnea, and dysphonia. In patients with OSA, we examined: (1) the frequency, severity, comorbidity, risks and triggers of each problem, (2) whether these symptoms were compatible with stereotypic ILS and (3) the role of CPAP in their expression. STUDY DESIGN: Cross-sectional, descriptive epidemiology study. SETTING: Sleep-Wake Center at University of Utah Health Care, Salt Lake City, UT. SUBJECTS AND METHODS: Ninety-four individuals with OSA (53 men, 41 women; mean age 54.7 ± 12.8 yrs.) underwent an extensive telephone interview that addressed study objectives. RESULTS: Long-term CC, daytime breathing and voice problems were common, especially among women despite less severe OSA. Women, more than men, reported all three chronic conditions alone or in combination: CC (44% vs 11.3%), diurnal dyspnea (41.5% vs 13.2%) and voice disorders (41.5% vs 13.2%). Symptoms were not associated with age, BMI or Apnea Hypopnea Index after adjusting for sex. Although evidence supporting stereotypic ILS symptomatology was inconsistent, those participants with a voice disorder were 3.3 (95% CI = 1.8-6.0) times more likely to report CC and 2.4 (95% CI = 1.3-4.4) times more likely to experience diurnal dyspnea. Esophageal reflux, post-nasal drip, and frequent sinus infections were significantly associated with all three conditions. Triggers that provoked or made symptoms worse varied by condition and sex. Nightly, humidified CPAP use was associated with fewer symptoms overall and improved quality of life. CONCLUSIONS: Symptoms suggestive of possible ILS are common in OSA, especially among women, and lessened by nightly CPAP use.

Association between Obstructive Sleep Apnea and Exfoliation Syndrome: The Utah Project on Exfoliation Syndrome.

PURPOSE: Exfoliation syndrome (XFS), the most common recognizable cause of open-angle glaucoma worldwide, is a systemic disorder with genetic predisposition due to variations in lysyl oxidase-like 1 (LOXL1) function, leading to altered elastin matrices in ocular and systemic tissues. Obstructive sleep apnea (OSA) is a highly prevalent disorder also involving elastic tissue dysfunction and is associated with glaucoma. Because of the similarities between the disorders, we sought to uncover any relationship in the prevalence of these diagnoses. DESIGN: Case-control, retrospective cohort study. PARTICIPANTS: A cohort of 81 735 patients diagnosed with OSA at ages 50 to 90 years was identified from medical records from 1996 to 2017 in the Utah Population Database. Case subjects were matched to random controls on sex and birth year in a 4:1 ratio. METHODS: International Classification of Diseases, Ninth Revision (ICD-9) codes or their Tenth Revision equivalent were used to define a diagnosis of OSA (ICD-9 327.23) and a diagnosis of XFS (ICD-9 365.52 and 366.11). Conditional logistic regression odds ratios (ORs) accounting for individual matching on sex and birth year were used to estimate the risk of XFS in patients with OSA. Models included adjustment for race, obesity, tobacco use, hypertension (HTN), atrial fibrillation (AF), and chronic obstructive pulmonary disease (COPD). MAIN OUTCOME MEASURE: Whether patients with OSA have an increased risk of diagnosis of XFS compared with controls without OSA. RESULTS: There was an increased risk of an XFS diagnosis in patients with OSA compared with non-OSA controls (OR, 1.27; 95% confidence interval [CI], 1.02-1.59; P = 0.03). In a stratification of patients by HTN diagnosis history, patients with OSA and HTN exhibited an increased risk of XFS compared with non-OSA controls with HTN (OR, 2.67; 95% CI, 2.06-3.46; P < 0.0001). CONCLUSIONS: Patients with OSA may be at an increased risk of XFS compared with patients without OSA, particularly in patients with a history of HTN.