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Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon disorder of adult smokers associated with a significant morbidity. Arising from the aberrant accumulation of Langerhans and other immune cells, PLCH tends to cause a relatively isolated pulmonary involvement as compared to other forms of Langerhans cell (LC) and histiocytic disorders. Increased knowledge of cytokine triggers, dendritic cell trafficking, and clonality of LC populations in PLCH have resulted in an improved understanding of the pathobiology of PLCH. High-resolution CT (HRCT) of the chest has led to better appreciation of nodular and cystic radiographic abnormalities characteristic of the disease. Correlation of HRCT abnormalities with lung pathologic changes has led to an improved comprehension of clinical evolution of PLCH. Current clinical predictors for PLCH outcomes remain poor, although long-term follow-up and radiologic monitoring may help to define disease progression. This review discusses advances in PLCH emphasizing the etiopathologic bases of the disease and currently available radiologic modalities for monitoring disease progression. [ABSTRACT FROM AUTHOR]

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.

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., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: K. M. S. reports a relationship with Hypnoscure LLC that includes board membership; and has served as past consultant for Merck Inc. and ResMed Inc. M. J. M. reports a relationship with Janssen Pharmaceuticals Inc. that includes speaking and lecture fees. None declared (A. S.)., (Published by Elsevier Inc.)

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., Competing Interests: Disclosure B.W. Locke. receives research funding from the American Thoracic Society ASPIRE Fellowship and the National Institutes of Health under the Ruth L. Kirschstein National Research Service Award 5T32HL105321 J.P. Brown. no conflicts of interest. K.M. Sundar is co-founder of Hypnoscure LLC—a software application for population management of sleep apnea through the University of Utah Technology Commercialization Office., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Disclosures K.M. Sundar has served as consultant in the past for Merck Inc. He is a cofounder of Hypnoscure LLC (software for population management of sleep apnea) in conjuction with the University of Utah Technology Commercialization Office. A.C. Stark has no conflicts to disclose. P. Dicpinigaitis serves as a consultant to Bellus, Chiesi, GSK, Merck, Trevi., (Published by Elsevier Inc.)

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, M age = 56 ± 13) and 49 (57%) were in the NAS group (36 females, M age = 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.

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., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Vagal nerve stimulators (VNS), which have been approved for management of refractory epilepsy and depression, induce unique disturbances of breathing during sleep (SDB VNS ) 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 SDB VNS 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 (AHI AASM ) with three novel scoring criteria for hypopnea according to degree of oxygen desaturation associated with VNS events: AHI VNS0 (none required); AHI VNS2 (2% required); and AHI VNS3 (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/m 2 . AHI AASM measured ≥ 15/hour in 7 (26.9%) subjects versus 21 (80.8%) by AHI VNS0 ; 15 (70.0%) by AHI VNS2 ; and 5 (19.2%) by AHI VNS3 . Clinically significant hypoxemia was not present. The mean time SpO 2 <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 AHI VNS0 was 27.7/hour with a lowest AHI VNS0 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., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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.)

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.

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.)

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., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

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.)

Background: An association between chronic cough and obstructive sleep apnea (OSA) has been reported in prior studies with resolution or improvement in cough after continuous positive airway pressure (CPAP) therapy. Controlled studies of the benefit of CPAP on cough-quality of life measures have not been conducted., Research Question: Does CPAP therapy for OSA improve cough in patients with chronic unexplained cough?, Study Design and Methods: Patients with unexplained chronic cough (> 2 months duration of cough) and OSA were randomized to receive either CPAP or sham CPAP therapy for 6 weeks. The primary end point was the change in health status assessed with the Leicester Cough Questionnaire (LCQ) in patients treated with CPAP vs. sham CPAP. Secondary end points were changes in exhaled breath condensate markers of airway inflammation (interleukin-6, nitrite/nitrates, hydrogen peroxide and 8-isoprostanes)., Results: A total of 22 patients with chronic unexplained cough and OSA were randomized of whom18 completed 6 weeks of treatments with either CPAP or sham CPAP. The CPAP vs. sham CPAP-treated group were comparable in terms of sex distribution, body mass index, and OSA severity. Following CPAP therapy, there was a significantly greater improvement in total LCQ scores as compared to those treated with sham therapy (ANCOVA p value 0.016). No significant differences were noted in the exhaled breath condensate marker changes between CPAP-treated vs. sham CPAP-treated groups., Conclusion: Treatment of comorbid OSA in patients with chronic cough improved cough quality of life measures following treatment of OSA with CPAP in this pilot study. Larger studies to understand this association and unravel mechanisms of CPAP benefit in chronic cough need to be undertaken. Clinical Trial Registration NCT03172130.

Objective: Obstructive sleep apnea (OSA), a serious respiratory disorder, confers increased risk of cardiovascular disease and mortality. Adherence to the standard and effective treatment, continuous positive airway pressure (CPAP), is often poor. Personal relationships can influence adherence, but some forms of partner involvement (e.g., support, encouragement) have positive effects on CPAP adherence, whereas others (e.g., criticism, blame) are counterproductive. In the former, constructive partner efforts may enhance a patient's sense of autonomy, an important foundation for self-care. The present study examined how patients' perceptions of autonomy support from an intimate partner predict adherence to CPAP, and whether it is an independent predictor, relative to generally positive partner behavior (i.e., partner responsiveness) and partner negativity (i.e., negative social control)., Method: Ninety-two married or cohabiting OSA patients (mean age 49.7 years) completed measures of perceived partner autonomy support, responsiveness, and negative social control at Days 14 and 60 of CPAP treatment. Objective daily CPAP machine adherence data were collected for 60 days., Results: Perceived partner autonomy support predicted more minutes of CPAP used per night and increasing CPAP use over time. These effects were independent of the significant adverse effects of partner negative social control and the more limited beneficial effects of partner responsiveness., Conclusion: The study findings establish perceived partner autonomy support as an interpersonal predictor of adherence that is independent of negative social control and perceived partner responsiveness, and may inform psychosocial interventions for CPAP adherence and more general couple approaches to chronic illness management. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

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 and Objective: Patients with chronic respiratory failure are increasingly managed with domiciliary non-invasive ventilation (NIV). There may be limited ability to provide NIV titration for these complex patients, and ventilatory requirements and upper airway support needs may change over time. Therefore, an automatically adjusting expiratory positive airway pressure (AutoEPAP) algorithm may offer advantages over manually adjusted EPAP for treating these patients. This study compared 4% oxygen desaturation index (ODI4%) values during the use of an AutoEPAP algorithm versus manual EPAP titration with the intelligent volume-assured pressure support (iVAPS) algorithm., Methods: This prospective, single-blind, randomized, crossover study was conducted at six US sites. Patients with chronic respiratory failure (neuromuscular disease, chronic obstructive pulmonary disease, obesity hypoventilation and other aetiologies) and an apnoea-hypopnoea index of >5/h who were already established NIV users underwent a single night of NIV with the iVAPS manual EPAP and iVAPS AutoEPAP in the sleep laboratory in random order., Results: A total of 38 patients constituted the study population. Mean ODI4% was statistically non-inferior with AutoEPAP versus manual EPAP (P < 0.0001). There was no difference in the effect on ODI4% across respiratory failure subgroups. Ventilation parameters and gas exchange were similar with either NIV mode, indicating equally effective treatment of respiratory failure. Sleep parameters were improved during AutoEPAP versus manual EPAP., Conclusion: A single night of NIV using the iVAPS with AutoEPAP algorithm was non-inferior to a single night of iVAPS with manual EPAP titration in patients with respiratory failure., Clinical Trial Registration: NCT02683772 at clinicaltrials.gov., (© 2019 Asian Pacific Society of Respirology.)

Objective: Obstructive sleep apnea (OSA) is characterized by frequent interruptions in breathing related to upper airway collapse during sleep and may adversely affect phonatory function. This study aimed to: (1) establish the prevalence, risks, and quality of life burden of voice disorders in OSA and (2) explore the relation between voice disorders and positive airway pressure (PAP) therapy., Study Design: Cross-sectional, descriptive epidemiology study., Methods: Analyses were based on 94 individuals with OSA (53 men, 41 women; mean age = 54.7 ± 12.8 years) who completed a telephone interview., Results: Twenty-eight percent of participants reported having a current voice disorder. Of those with a current voice disorder, 83% had experienced symptoms for at least a year, and 58% had symptoms for at least 4 years. The prevalence of a current voice disorder was greater in women than men (44% vs 15%, P = .0020) but did not vary significantly across different age groups, body mass index (BMI), apnea/hypopnea index (AHI) severity, or medical history. After adjusting for sex, consistent use of PAP therapy (with humidification) was associated with (1) lower occurrence of voice disorders in women (Mantel-Haenszel [MH] χ 2 P = .0195), (2) reduced snoring severity accompanied by fewer voice disorders in men (MH χ 2 P = .0101), and (3) fewer reports of acid reflux as a possible trigger for voice problems (MH χ 2 P = .0226). Patients with OSA who also had a current voice disorder experienced lower overall quality of life compared to those without., Conclusions: Chronic, longstanding voice disorders are common in women with OSA and produce significant adverse effects on quality of life. Nightly PAP use (with humidification) was associated with fewer voice symptoms and reduced severity of snoring and acid reflux as possible contributors. Further research is necessary to better understand the origin of these voice disorders in OSA and their potential response to treatment.

Chronic cough is increasingly being recognized as a process that has multiple initiating and perpetuating triggers. Obstructive sleep apnea has recently emerged as a possible disease that can lead to chronic cough. This review details the available clinical evidence that links these two disparate diseases and explores mechanistic bases of their relationship.

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.

Background: A number of different modalities have been employed in addition to conventional ventilation to improve oxygenation in patients with severe 2009 pandemic influenza A (H1N1) pneumonia. Outcomes with ventilatory and rescue therapies for H1N1 influenza-related acute respiratory distress syndrome (ARDS) have been varied. A single intensive care unit (ICU) experience with management of laboratory-confirmed 2009 pandemic influenza A (H1N1) ARDS with a combination of proning and airway pressure release ventilation (APRV) is described., Methods: A retrospective review of medical records of ICU patients seen at Utah Valley Regional Medical Center during the first and second waves of the H1N1 influenza pandemic was done., Results: Fourteen ICU patients were managed with invasive ventilation for 2009 pandemic influenza A (H1N1)-related ARDS. Hypoxemia refractory to conventional ventilation was noted in 11 of 14 patients despite application of APRV. Following proning in patients on APRV, improvement of hypoxemia and hemodynamic status was achieved. Only 2 of 11 patients on APRV and proning required continuous dialysis. Mortality in intubated patients receiving a combination of proning and APRV was 27.3% (3/11) with 2 of these dying during the first wave of the H1N1 influenza pandemic. In all, 3 of 11 patients on proning and APRV underwent tracheostomy, with 2 of these undergoing tube thoracostomy. ARDSnet fluid-conservative protocol was safely tolerated in 8 of 11 of the intubated patients following initiation of proning and APRV., Conclusions: Proning in combination with APRV provides improvement of hypoxemia with limitation of end-organ dysfunction and thereby facilitates recovery from severe 2009 pandemic influenza A (H1N1).

Objective: Ventilator-associated pneumonia (VAP) is associated with significant morbidity and mortality. Measures to reduce the incidence of VAP have resulted in institutions reporting a zero or near-zero VAP rates. The implications of zero VAP rates are unclear. This study was done to compare outcomes between two intensive care units (ICU) with one of them reporting a zero VAP rate., Design, Setting and Patients: This study retrospectively compared VAP rates between two ICUs: Utah Valley Regional Medical Center (UVRMC) with 25 ICU beds and American Fork Hospital (AFH) with 9 ICU beds. Both facilities are under the same management and attended by a single group of intensivists. Both ICUs have similar nursing and respiratory staffing patterns. Both ICUs use the same intensive care program for reduction of VAP rates. ICU outcomes between AFH (reporting zero VAP rate) and UVRMC (VAP rate of 2.41/1000 ventilator days) were compared for the years 2007-2008., Measurements and Main Results: UVRMC VAP rates during 2007 and 2008 were 2.31/1000 ventilator days and 2.5/1000 ventilator days respectively compared to a zero VAP rate at AFH. The total days of ventilation, mean days of ventilation per patient and mean duration of ICU stay per patient was higher in the UVRMC group as compared to AFH ICU group. There was no significant difference in mean age and APACHE II score between ICU patients at UVRMC and AFH. There was no statistical difference in rates of VAP and mortality between UVRMC and AFH., Conclusions: During comparisons of VAP rate between institutions, a zero VAP rate needs to be considered in the context of overall ventilator days, mean durations of ventilator stay and ICU mortality., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

A 74-year-old woman presented with a 2-day history of cough, dyspnea and wheezing following aspiration of a tetracycline tablet. She developed a left lower lobe pneumonitis, and bronchoscopy revealed left main bronchus narrowing and exudate. The course of this patient is discussed in reference to the available literature on toxic aspirations., (Copyright 2001 S. Karger AG, Basel)

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