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Importance: Positive airway pressure (PAP) is the first-line treatment for obstructive sleep apnea (OSA), but evidence on its beneficial effect on major adverse cardiovascular events (MACE) and mortality prevention is limited., Objective: To determine whether PAP initiation and utilization are associated with lower mortality and incidence of MACE among older adults with OSA living in the central US., Design, Setting, and Participants: This retrospective clinical cohort study included Medicare beneficiaries with 2 or more distinct OSA claims identified from multistate, statewide, multiyear (2011-2020) Medicare fee-for-service claims data. Individuals were followed up until death or censoring on December 31, 2020. Analyses were performed between December 2021 and December 2023., Exposures: Evidence of PAP initiation and utilization based on PAP claims after OSA diagnosis., Main Outcomes and Measures: All-cause mortality and MACE, 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 were used to estimate treatment effect sizes controlling for sociodemographic and clinical factors., Results: Among 888 835 beneficiaries with OSA included in the analyses (median [IQR] age, 73 [69-78] years; 390 598 women [43.9%]; 8115 Asian [0.9%], 47 122 Black [5.3%], and 760 324 White [85.5%] participants; median [IQR] follow-up, 3.1 [1.5-5.1] years), those with evidence of PAP initiation (290 015 [32.6%]) had significantly lower all-cause mortality (hazard ratio [HR], 0.53; 95% CI, 0.52-0.54) and MACE incidence risk (HR, 0.90; 95% CI, 0.89-0.91). Higher quartiles (Q) of annual PAP claims were progressively associated with lower mortality (Q2 HR, 0.84; 95% CI, 0.81-0.87; Q3 HR, 0.76; 95% CI, 0.74-0.79; Q4 HR, 0.74; 95% CI, 0.72-0.77) and MACE incidence risk (Q2 HR, 0.92; 95% CI, 0.89-0.95; Q3 HR, 0.89; 95% CI, 0.86-0.91; Q4 HR, 0.87; 95% CI, 0.85-0.90)., Conclusions and Relevance: In this cohort study of Medicare beneficiaries with OSA, PAP utilization was associated with lower all-cause mortality and MACE incidence. Results might inform trials assessing the importance of OSA therapy toward minimizing cardiovascular risk and mortality in older adults.

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., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

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., (© 2022 American Academy of Sleep Medicine.)

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., (© 2022. The Author(s).)

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.

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., (© 2022 American Academy of Sleep Medicine.)

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., Competing Interests: Conflict of interest: K.M. Sundar attended one advisory board for Merck in August 2020 ($1175.00), was a site principal investigator (PI) for a study on iVAPS validation of an expiratory positive airway pressure algorithm funded by Resmed Inc., received nonfinancial support for a study on sham continuous positive airway pressure in chronic cough from Respironics Inc., and was a site PI for VOLCANO-2 funded by NeRRe Therapeutics Inc., outside the submitted work. Conflict of interest: A.C. Stark has nothing to disclose. Conflict of interest: N. Hu has nothing to disclose. Conflict of interest: J. Barkmeier-Kraemer has nothing to disclose., (©The authors 2021.)

Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). The pathophysiology of thrombosis in these disorders remains unclear, and we hypothesized that upregulation of thrombotic, inflammatory, and hypoxia-inducible factor (HIF)-regulated genes may play a role in it. We performed unbiased RNA sequencing in granulocytes and platelets of PV patients and found differential expression of several thrombotic, inflammatory, and HIF-regulated genes. The expression of many of these genes positively correlated with JAK2 expression and JAK2V617F allelic burden. We then validated these findings by quantitative polymerase chain reaction analyses of selected gene transcripts in a larger number of PV and ET granulocytes and platelets (58 patients) and in 28 controls, and we compared these findings in patients with and without thrombosis. The study included 29 females and 29 males; of these, 28 had a history of thrombosis. We found that transcripts of several selected genes were upregulated in patients with PV or ET compared with controls. In granulocytes, the expression levels of F3, SELP, VEGFA, and SLC2A1 were significantly higher in patients with a history of thrombosis compared with those who did not have thrombosis. Patients with a history of thrombosis have significantly higher expression of IL1RAP (P < .05) in platelets compared with those without thrombosis. Our study confirms the presence of a thrombo-inflammatory state and augmented HIF activity in PV and ET and its role in thrombosis. These data may provide the background for targeted therapies in PV and ET.

Background: Chronic cough patients are rendered therapies for gastro-esophageal reflux (GERD), upper airway cough syndrome (UACS) and cough-variant asthma (CVA) with varying benefit. Idiopathic or unexplained cough has emerged as an important clinical entity in both primary care and subspecialty clinics. Recent evidence points to a link between chronic cough and untreated obstructive sleep apnea (OSA)., Methods: A prospective observational study was done to evaluate the effect of OSA therapy in patients with chronic cough. Patients enrolled into the study underwent questionnaires to evaluate for GERD, UACS and CVA along with screening questionnaires for OSA and daytime sleepiness. The Leicester cough questionnaire (LCQ) was done at baseline and during serial visits to evaluate cough intensity and was used as the primary outcome measure of the effect of CPAP therapy on chronic cough., Results: Out of 37 patients enrolled into the study, only 28 patients had follow up LCQ scores available and therefore underwent analysis. 22/28 patients were suspected to have OSA based on abnormal STOP-BANG screening questionnaire scores and overnight oximetry abnormalities. Of these 19/28 patients had overnight attended polysomnography with definitive diagnosis of OSA yielding a 68% prevalence of OSA in our chronic cough population. Chronic cough patients treated for OSA tended to be older with a significantly higher BMI than chronic cough patients without OSA. Significant improvement of LCQ scores occurred with CPAP therapy for OSA in chronic cough patients., Conclusion: OSA is significantly prevalent in chronic cough patients. Subjects with chronic cough and OSA tend to be older and obese. Treatment of OSA in chronic cough patients yields significant improvement in their health status.

Sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis. This review explores the basis for sepsis related immune dysfunction and discusses its clinical implications for the treating intensivist. Recent trends indicate that a significant proportion of septic patients succumb to the complications of secondary infections and chronic critical care illness from the initial bout of sepsis. Therefore care-givers in the ICU need to be aware of the impediments posed by sepsis-related immune dysfunction that can impair recovery in patients with sepsis and contribute to sepsis-related mortality.

Chronic cough is defined as cough lasting more than 2 months. Common causes for chronic cough in nonsmokers with normal chest radiographs and pulmonary functions include gastroesophageal reflux disease (GERD), cough-variant asthma (CVA), and upper airway cough syndrome (UACS). Current guidelines recommend diagnosing the etiology of chronic cough based upon the results of therapy for suspected GERD, CVA, and UACS. Despite following current recommendations for diagnosis and treatment, the cause for a significant proportion of chronic cough remains unexplained.Recent reports indicate the resolution of chronic cough following treatment of concomitantly diagnosed obstructive sleep apnea (OSA). Whether this represents a co-occurrence of two commonly prevalent disorders or a pathophysiologic relationship between OSA and cough remains unknown. This review offers insights into a pathophysiologic link between OSA and the commonly purported etiologies for cough, namely, GERD, UACS, and CVA. In addition, evidence for a relationship between airway inflammation that can trigger or perpetuate cough and OSA is discussed. This review explores mechanisms by which nocturnal continuous positive airway therapy resolves cough by improving underlying airway inflammation secondary to OSA and impacts upon GERD, CVA, and UACS.

Background: Recent reports suggest an association between unexplained chronic cough and obstructive sleep apnea (OSA). Current guidelines provide an empiric integrative approach to the management of chronic cough, particularly for etiologies of gastroesophageal reflux (GERD), upper airway cough syndrome (UACS) and cough variant asthma (CVA) but do not provide any recommendations regarding testing for OSA. This study was done to evaluate the prevalence of OSA in patients referred for chronic cough and examine the impact of treating OSA in resolution of chronic cough., Methods: A retrospective review of chronic cough patients seen over a four-year period in a community-based pulmonary practice was done. Patients with abnormal chest radiographs, abnormal pulmonary function tests, history of known parenchymal lung disease, and inadequate followup were excluded. Clinical data, treatments provided and degree of resolution of cough was evaluated based on chart review. Specifically, diagnostic testing for OSA and impact of management of OSA on chronic cough was assessed., Results: 75 patients with isolated chronic cough were identified. 44/75 had single etiologies for cough (GERD 37%, UACS 12%, CVA 8%). 31/75 had multiple etiologies for their chronic cough (GERD-UACS 31%, GERD-CVA 5%, UACS-CVA 3%, GERD-UACS-CVA 3%). 31% patients underwent further diagnostic testing to evaluate for UACS, GERD and CVA. Specific testing for OSA was carried out in 38/75 (51%) patients and 33/75 (44%) were found to have obstructive sleep apnea. 93% of the patients that had interventions to optimize their sleep-disordered breathing had improvement in their cough., Conclusions: OSA is a common finding in patients with chronic cough, even when another cause of cough has been identified. CPAP therapy in combination with other specific therapy for cough leads to a reduction in cough severity. Sleep apnea evaluation and therapy needs to considered early during the management of chronic cough and as a part of the diagnostic workup for chronic cough.

Background: Herpes simplex-1 virus (HSV-1) reactivation in the respiratory tract is common in intensive care unit (ICU) patients. However, susceptible ICU populations are poorly defined. Clinical recognition of HSV infection of the respiratory tract is difficult and the impact of such reactivation is not understood., Materials and Methods: A retrospective analysis of HSV-1 positive patients encountered over a 5-year period at a multispecialty ICU was carried out. HSV-1 was identified in respiratory secretions using a qualitative polymerase chain reaction (PCR) technique. Patient charts were reviewed for clinical features that would typify HSV-1 respiratory involvement, and the morbidity and mortality risks found with HSV-1 respiratory involvement., Results: A review of 48 HSV-1 positive ICU patients showed that patients reactivating HSV in the respiratory tract fell into one of the three categories: (1) septic elderly patients with and without ARDS, (2) immunosuppressed patients, especially those receiving high-dose steroids, and (3) post-thoracotomy patients. Abnormalities suggestive of HSV-1 reactivation in the respiratory tract included, haemorrhagic or excessive respiratory secretions, concomitant orofacial herpes (42%), and bronchoscopic abnormalities (hemorrhagic ulcers and mucosal friability) (83%). Twenty eight percent of the HSV-1 infected patients experienced postextubation stridor. HSV-1 reactivation was associated with extended ventilator stays, significant mortality (42%), and ventilator-associated pneumonias (52%)., Conclusions: Identification of susceptible populations and definition of clinical features of HSV-1 related respiratory disease can enable diagnosis of HSV-1 infection in ICU patients. Although detection by a PCR technique can rapidly diagnose HSV-1 reactivation, prospective studies are required to clarify HSV disease versus mere shedding, and understand the impact of HSV-1 reactivation in hospitalized patients.

It has been hypothesized that O(2) sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O(2) sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plethysmography was used to study unanesthetized, unrestrained mice. When exposed to an acute hypoxic stimulus, gp91(phox)-null mutant and wild-type mice increased their minute ventilation by similar amounts. In contrast, p47(phox)-null mutant mice demonstrated increases in minute ventilation in response to hypoxia that exceeded that of their wild-type counterparts: 98.0 +/- 18.0 vs. 20.0 +/- 13.0% (n = 11, P = 0.003). In vitro recordings of carotid sinus nerve (CSN) activity demonstrated that resting (basal) neural activity was marginally elevated in p47(phox)-null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5-fold greater in p47(phox)-null mutant than in wild-type mice: 109.61 +/- 13.29 vs. 72.54 +/- 7.65 impulses/s (n = 8 and 7, respectively, P = 0.026). Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was approximately 58% larger in p47(phox)-null mutant mice. Quantities of EPO mRNA in kidney were similar in gp91(phox)- and p47(phox)-null mutant mice and their respective wild-type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the previous observation that absence of the gp91(phox) component of the phagocytic NADPH oxidase does not alter the O(2)-sensing mechanism of the carotid body. However, absence of the p47(phox) component significantly potentiates ventilatory and chemoreceptor responses to hypoxia. O(2) sensing in EPO-producing cells of the kidney appears to be independent of the gp91(phox) and p47(phox) components of the phagocytic NADPH oxidase.

The author presents in this article the ayurvedic explanation for the genesis of degenerative diseases.