Sleep disturbance in adults with chronic pruritic dermatoses is associated with increased C-reactive protein levels.

BACKGROUND: Pruritus is a common symptom that can significantly reduce quality of life through sleep disruption. OBJECTIVE: To examine features of disturbed sleep in patients with chronic pruritic dermatoses and test the hypothesis that systemic inflammation may serve as a biomarker for impaired sleep in these patients. METHODS: Cross-sectional analysis of the National Health and Nutrition Examination Survey investigating systemic inflammation using C-reactive protein (CRP) levels. Logistic regression was used to compare patients with and without sleep disturbances, adjusting for demographics (model 1) and medical comorbidities (model 2). RESULTS: Chronic pruritic dermatoses were associated with multiple sleep disturbances, including nighttime awakenings (model 1: odds ratio [OR], 1.646; 95% confidence interval [CI], 1.031-2.627; model 2: OR, 1.329; 95% CI, 0.888-1.989) and early morning awakening (model 1: OR, 1.669, 95% CI, 1.118-2.493; model 2: OR, 1.582; 95% CI, 1.008-2.481). Mean CRP levels were 52.8% higher among patients with pruritic dermatoses reporting trouble sleeping compared with those who did not (0.663 vs 0.434 mg/dL; P = .034). Trouble sleeping was also positively correlated with CRP levels (ß = 0.142, P = .025). LIMITATIONS: Potential recall bias among participants. CONCLUSIONS: In addition to confirming sleep disturbances with pruritic dermatoses, we found these disturbances are more likely to present with elevated CRP levels. Clinicians should consider the potential risk for sleep-related and cardiac comorbidities in patients diagnosed with itchy skin conditions.

Sleep and pain: recent insights, mechanisms, and future directions in the investigation of this relationship.

Sleep disturbances and chronic pain are considered public health concerns. They are frequently associated, and the direction of its relationship and possible mechanisms underlying it are frequently debated. The exploration of the sleep-pain association is of great clinical interest to explore in order to steer potential therapeutic avenues, accommodate the patient's experience, and adapt the common practice of health professionals. In this review, the direction between sleep-pain in adult and pediatric populations will be discussed. Moreover, the possible mechanisms contributing to this relationship as endogenous pain modulation, inflammation, affect, mood and other states, the role of different endogenous substances (dopamine, orexin, melatonin, vitamin D) as well as other lesser known such as cyclic alternating pattern among others, will be explored. Finally, directions for future studies on this area will be discussed, opening up to the addition of tools such as brain imaging (e.g., fMRI), electrophysiology and non-invasive brain stimulation techniques. Such resources paired with artificial intelligence are key to personalized medicine management for patients facing pain and sleep interacting conditions.

House Dust Mite Related Allergic Rhinitis and REM Sleep Disturbances.

PURPOSE: Sleep disturbances are common in patients with allergic rhinitis (AR). Perennial allergens like house dust mites (HDM) are difficult to avoid and have nocturnal impacts on the respiratory system and Quality of Life (QOL). The Rapid Eye Movement (REM) sleep stage is associated with memory, cognition, dreams, and overall restfulness, which can be impaired in AR patients with Sleep Disordered Breathing (SDB) even when normal all-night apnea-hypopnea (AHI) or respiratory disturbance (RDI) indices are noted on polysomnography (PSG). We hypothesized that AR HDM allergen positive patients would show REM-specific SDB reflected in their objectively elevated REM-RDI values. MATERIALS AND METHODS: This retrospective analysis of 100 patients included 47 with HDM positive allergy testing. All patients underwent PSG testing calculating the RDI during REM. Multivariate logistic regression models evaluated relationships between allergic statuses and sleep parameters while controlling for potential confounders. RESULTS: Compared with allergy negative patients, HDM allergen positive patients were significantly more likely (OR 4.29, 95%CI 1.26-14.62) to have a REM-RDI in the moderate/severe range (≥15 events/h). CONCLUSIONS: Our study highlighted the significance of respiratory allergies to HDM in patients with SDB. We revealed a significant relationship between HDM allergen positivity and SDB characterized by elevated REM-RDI regardless of all-night AHI, RDI, or REM-AHI values. Clinical implications of knowing about disturbed REM and/or HDM allergenicity include better preparation, treatment, outcomes, and QOL for allergic, SDB, and upper airway surgery patients.

Increased CD4 counts, pain and depression are correlates of lower sleep quality in treated HIV positive patients with low baseline CD4 counts.

Poor sleep quality leads to increased immune activation and immune activation leads to worse sleep quality. South African HIV positive patients typically have delayed start of treatment, which has been associated with CD4+ effector T cells being more spontaneously activated in chronically treated patients. This cross-sectional study investigated whether subjective sleep quality was associated with CD4+ T lymphocyte reconstitution in treated South African HIV+ patients. One hundred and thirty-nine treated HIV+ patients (109 F, age average (SD) = 43 (9)) were recruited from Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, South Africa. Participants completed questionnaires evaluating their subjective sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth sleepiness scale), pain, and depression severity (Beck Depression Inventory). Univariate and multivariate analyses were run to determine the correlates of sleep quality in this population. Patients had been on antiretroviral treatment for about 4 years and had increased their CD4 counts from a median at baseline of 82 to 467 cells/µL. They had overall poor sleep quality (average (SD) PSQI = 7.7 (±5), 61% reporting PSQI > 5, a marker of lower sleep quality), 41% had clinical depression (average (SD) BDI = 17 (±12)) and 55% reported pain. In two separate multivariate analyses, both the overall CD4 count increase from baseline (p = 0.0006) and higher current CD4 counts (p = 0.0007) were associated with worse sleep quality, when adjusting for depression severity (p < 0.001), daytime sleepiness (p = 0.01) and the presence of pain (p < 0.01). In this cohort of treated South African HIV positive patients, poor sleep quality was associated with higher current CD4 counts, when adjusting for depression severity, daytime sleepiness and pain. Further studies should investigate the temporal relationship between HIV-related poor sleep quality and underlying immune activation.

Relationship between sleep disorders and lymphocyte subsets and cytokines in patients with lung cancer.

This study aimed to investigate the relationship between sleep disorders and lymphocyte subsets and cytokines in patients with lung cancer undergoing radiotherapy, and to establish a theoretical foundation for predicting sleep disorders and preventing interventions in radiotherapy in lung cancer patients. Ninety-two patients with lung cancer requiring radiotherapy were selected as the study subjects. The patients' demographic data and disease-related conditions were investigated. Their quality of sleep was measured before radiotherapy, after two and four weeks of radiotherapy, and at the end of radiotherapy. According to the Pittsburgh Sleep Quality Index Number Table (PSQI), patients with PSQI score> 7 points were put into a sleep disorder group, and patients with PSQI score 0-7 were put into a normal sleep group. Lymphocyte subsets were enumerated and cytokine levels (IL-6, IL-1b) were measured during these four periods. The difference in sleep disorders at four weeks between patients with or without synchronous chemotherapy was statistically significant (P less than 0.05). The levels of lymphocyte subsets in the sleep disorder group and the control sleep group showed no difference in the index of lymphocyte subsets before radiotherapy. In the sleep disorder group, CD4+ cells were lower after two weeks of radiotherapy (P less than 0.05). After four weeks of radiotherapy, CD3+, CD4+, and CD16+56+ subsets were lower (P less than 0.05). At the end of radiotherapy, there was no difference in each index. There was no significant difference in IL-6 levels between the two groups before radiotherapy, after two weeks, or after four weeks (P greater than 0.05). At the end of radiotherapy, IL-6 levels in the sleep disorder group were higher than those in the control sleep group (P less than 0.05). There was no significant difference in IL-1b between the two groups (P greater than 0.05). In conclusion, monitoring of T-lymphocyte subsets and IL-6 levels in patients is enhanced during radiotherapy. Clinically effective programs of radiotherapy for lung cancer improve the body's immune status.

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance.

A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations. Furthermore, despite evidence that sleep disturbance, which is a core symptom of MDD, is itself associated with alterations in lymphocyte distributions, there is a paucity of studies examining the contribution of sleep disturbance on lymphocyte populations in MDD populations. Here, we measured differences in the percentages of 13 different lymphocytes and 6 different leukocytes in 54 unmedicated MDD patients (partially remitted to moderate) and 56 age and sex-matched healthy controls (HC). The relationship between self-reported sleep disturbance and cell counts was evaluated in the MDD group using the Pittsburgh Sleep Quality Index (PSQI). The MDD group showed a significantly increased percentage of CD127low/CCR4+ Treg cells, and memory Treg cells, as well as a reduction in CD56+CD16- (putative immunoregulatory) NKC counts, the latter, prior to correction for body mass index. There also was a trend for higher effector memory CD8+ cell counts in the MDD group versus the HC group. Further, within the MDD group, self-reported sleep disturbance was associated with an increased percentage of effector memory CD8+ cells but with a lower percentage of CD56+CD16- NKC. These results provide important new insights into the immune pathways involved in MDD, and provide novel evidence that MDD and associated sleep disturbance increase effector memory CD8+ and Treg pathways. Targeting sleep disturbance may have implications as a therapeutic strategy to normalize NKC and memory CD8+ cells in MDD.

Sleep influences the immune response and the rejection process alters sleep pattern: Evidence from a skin allograft model in mice.

INTRODUCTION: Sleep generally regulates immune functions in a supportive manner and can affect parameters that are directly involved in the rejection process. STUDY OBJECTIVES: The first objective was to assess whether sleep deprivation (SD) or sleep restriction (SR) affects the allograft rejection process in mice. The second objective was to investigate whether the rejection process itself modulates the sleep pattern of allografted mice. DESIGN: Adult BALB/c and C57BL/6J male mice were used as the donors and recipients, respectively, except for the syngeneic group (ISOTX), which received skin from mice of the same strain (C57BL/6J). The recipients were randomly assigned to either one of two control groups - TX (allogenic) or ISOTX (syngeneic) - which underwent stereotaxic surgery to enable sleep recording prior to the allograft but were not sleep deprived; one of two paradoxical sleep deprived groups - SDTX and TXSD - which underwent 72h of continuous SD either before or after the allograft respectively, and one of two sleep restricted groups - SRTX and TXSR - which underwent 21h of SD and 3h of sleep for 15days either before or after the allograft respectively. INTERVENTIONS: The skin allograft was inspected daily to determine the survival time, expected as 8.0±0.4days in this transplant model under no treatment. The sleep pattern was controlled throughout the rejection process in the SD and SR groups. Draining lymph nodes, spleen, blood and skin grafts were harvested on the 5th day after transplantation for evaluation of the immune parameters related to allograft rejection. MEASUREMENTS AND RESULTS: In the control groups, we observed a reduction in paradoxical sleep throughout the entire allograft rejection process. Acute and chronic experimental sleep loss in the SD and SR groups produced marked alterations in the immune response. Both SD and SR prolonged allograft survival compared to the non-sleep-deprived group. There were reductions in the following parameters involved in the allograft rejection under sleep loss: CD4+ and CD8+ T cell subpopulations in the peripheral lymph organs and spleen, circulating sIL-2R levels, graft-infiltrating CD4+ T cells and skin allograft global gene expression. CONCLUSIONS: We provide, as far as we are aware, the first evidence in vivo that the immune response can alter the normal sleep pattern, and that sleep loss can conversely affect the immune response related to graft rejection.

Allergic sensitization and objective measures of sleep in urban school-aged children with asthma.

BACKGROUND: Allergic sensitization is associated with increased child asthma morbidity and decreased pulmonary function. Nocturnal symptoms and/or awakenings typically are measured by self-report from diary data, whereas objective assessments of sleep in child asthma studies are lacking. OBJECTIVE: To investigate the association between increased allergic sensitization (number of positive allergy test results measured by skin prick test or specific immunoglobulin E) and sleep outcomes (sleep efficiency, sleep duration, and mean number of awakenings measured by actigraphy) in urban schoolchildren with persistent asthma. METHODS: One hundred ninety-six children with persistent asthma (7-9 years old) attending public school in 1 of 4 large urban school districts completed allergy testing during a study clinic visit. Forced expiratory volume in 1 second was monitored at home using a handheld spirometer. Sleep outcomes were measured with a wrist Actiwatch during a 1-month period in the fall and winter seasons. RESULTS: Number of positive allergy test results significantly predicted mean sleep efficiency (P = .02), such that children with more positive test results experienced less efficient sleep. Number of positive allergy test results significantly predicted mean number of night awakenings (P = .05), such that children with more positive allergy test results experienced more night awakenings. Variability in forced expiratory volume in 1 second was a significant moderator in the association between number of positive allergy test results and variability in sleep efficiency (P = .04). Racial and ethnic differences in allergic sensitization and sleep outcomes were found between African Americans and Latinos. CONCLUSION: More positive allergy test results were associated with poorer sleep outcomes measured objectively in this sample of urban children. Implications for environmental control interventions and asthma treatments in different racial and ethnic groups are discussed.

Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome.

We aimed to study serum cytokine levels in 11 electrical status epilepticus in sleep (ESES) patients and 20 healthy control children. Patients showed significantly higher levels of interleukin (IL)-1α, IL-6, IL-10, chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C motif) ligand (CXCL)8/IL-8 than controls, while macrophage migration inhibitory factor (MIF) and CCL3 were significantly lower. Follow-up analyses in five patients revealed a significant decrease of IL-6 levels after immunomodulating treatment. IL-6 changes were accompanied by clear improvement of electroencephalography (EEG) patterns and neuropsychological evaluation. We hypothesize that IL-6 correlates with disease activity and immunomodulating treatment efficacy.

Effects of treatment with etanercept versus methotrexate on sleep quality, fatigue and selected immune parameters in patients with active rheumatoid arthritis.

OBJECTIVES: To compare sleep quality, disease activity and patient-reported outcomes such as fatigue and immune parameters in patients with rheumatoid arthritis treated with etanercept (ETA) or methotrexate (MTX). METHODS: Of 36 patients (28-joint Disease Activity Score, DAS28CRP≥3.2) in this 16-week (w), open, prospective study, 19 (11 women) received MTX 12.5-17 mg/w, and 17 (14 women) received ETA 25 mg x 2/w, alone or in combination with MTX. Clinical (DAS28CRP, visual analogue scale), laboratory (C-reactive protein [CRP]), sleep (polysomnography), functional (Multidimensional Fatigue Inventory; Health Assessment Questionnaire-Disability Index (HAQ-DI); 36-item Short-Form Health Survey (SF-36), immunological (humoral/cellular) and neuroendocrine (hormonal) parameters were recorded at baseline (BL), w8 and w16. RESULTS: BL characteristics did not differ significantly between the ETA and MTX groups except disease duration: mean age (years): 48.6±8.8 vs. 49.4±16.6; mean disease duration (months): 19.6±46.3 vs. 81.2±79.2; and DAS28CRP: 4.4±0.9 vs. 4.4±1.7, respectively. DAS28CRP, SF-36, and HAQ-DI improved significantly in both groups from BL to w16 (p≤0.05). The DAS28CRP improvements at w16 (mean changes -1.8 in the ETA group, and -1.4 in MTX group), were not statistically significant from each other. The absolute values of sleep efficiency, total sleep time, and stage 2 sleep duration increased significantly in the ETA group, but no significant changes were reported in the MTX group. CONCLUSIONS: Both therapies improved disease activity, CRP, SF-36 and HAQ-DI, with faster, more pronounced changes in DAS28CRP in the ETA group, which alone had significantly improved sleep parameters.

Clinical, autoimmune, and psychiatric parameters correlate with sleep disturbance in patients with systemic sclerosis and rheumatoid arthritis.

OBJECTIVES: Sleep disturbance is an important contributor to poor quality of life in rheumatic disorders. This study aims to test whether clinical, autoimmune and psychological factors are associated with sleep disturbance in systemic sclerosis (SSc) compared to rheumatoid arthritis (RA) patients and controls. METHODS: 101 female subjects (SSc=33, RA=34, healthy controls=34) participated in this observational, cross-sectional, parallel group study. Sleep disturbance was assessed with the Pittsburgh Sleep Quality Index (PSQI). Other assessments included the visual analogue scale (VAS) for pain, 36-item Short-Form Health Survey (SF-36), Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Clinical parameters, therapeutic regimen, and serologic status were recorded. RESULTS: In SSc patients, PSQI scores were higher than in RA patients and controls. Linear regression analysis showed that in SSc patients PSQI scores was associated with BDI, disease duration, modified Rodnan skin score and VAS, while DAS28 and BDI were associated with PSQI scores in RA patients. Anti-Scl70 and ANA positive SSc patients showed higher PSQI scores compared to those ANA positive only, while no differences were observed in RA patients classified according to rheumatoid factor positivity. SSc patients treated with immunosuppressants had lower PSQI scores compared to those not on therapy, whereas only corticosteroid treatment was significantly associated with higher PSQI scores in RA patients. RA patients with disease activity higher than moderate (DAS28≥3.2) had higher PSQI scores than those with lower than moderate (DAS28<3.2). CONCLUSIONS: Longitudinal studies are needed to identify disease-specific patterns associated with sleep disturbances and the influence on sleep function induced by immunosuppressive therapy among rheumatic patients.

Association between sleep quality and inflammatory complement components in collegiate males.

BACKGROUND: An accumulating amount of evidence has linked humoral mediators of inflammation with sleep measures. Nevertheless, important details of this association, in particular the role of the complement components in the context of chronic sleep attributes, have remained largely uncharacterized. MATERIALS AND METHODS: Fifty university students (age, 23.3 ± 3.8 years; BMI, 23.7 ± 2.9 kg/m(2)) completed the study. Four dichotomized sleep measures assessed by the Pittsburgh Sleep Quality Index (PSQI) were used in association analysis using binary logistic regression with complement component 3, 4, and complement factor I (CFI). The sleep measures were defined as sleep quality (good sleep/poor sleep; PSQI ≤5/PSQI >5), bedtime (early/late; before 00:00 h/after 0:00 h), sleep duration (short/normal ≤6 h/>6 h), and sleep onset latency (normal/disturbed; 0-1 score/2-3 score on the PSQI component of sleep latency). RESULTS: The complement component 4 was associated with sleep quality (unadjusted, OR = 1.025, p < 0.05; adjusted for age, OR = 1.025, p < 0.05; adjusted for BMI, OR = 1.027, p < 0.05) and sleep duration (unadjusted, OR = 1.041, p < 0.01; adjusted for age, OR = 1.041, p < 0.01; adjusted for BMI, OR = 1.046, p < 0.01). CFI was associated with bedtime (unadjusted, OR = 0.737, p < 0.01; adjusted for age, OR = 0.717, p < 0.01; adjusted for BMI, OR = 0.677, p < 0.01) and with sleep duration (unadjusted, OR = 0.796, p < 0.05; adjusted for age, OR = 0.796, p < 0.05). CONCLUSION: The findings indicate the importance of the role of complement components in the dynamics of sleep. Therefore, sleep should be assessed in conditions where complement components are affected.

Nocturnal eczema: Review of sleep and circadian rhythms in children with atopic dermatitis and future research directions.

Children with atopic dermatitis (AD) experience significant sleep disruption, and clinically, the disease is noted to worsen in a circadian manner at night. Epidemiologic findings highlight many negative consequences of AD, such as impaired linear growth, which is uniquely related to disturbed sleep. Clinical guidelines currently recommend assessing sleep in patients with AD as a crucial parameter of disease control with appropriate treatment. In this review we describe our current understanding of the roles of sleep cycles and circadian rhythms in the nighttime exacerbation of AD (nocturnal eczema). We present a schematic to explain the mechanism of nocturnal eczema. Treatment options for sleep disturbance and future directions for research are discussed in the context of AD.

Therapeutic implications of the choroid plexus-cerebrospinal fluid interface in neuropsychiatric disorders.

The choroid plexus (CP) comprises an epithelial monolayer that forms an important physical, enzymatic and immunologic barrier, called the blood-cerebrospinal fluid barrier (BCSFB). It is a highly vascularized organ located in the brain ventricles that is key in maintaining brain homeostasis as it produces cerebrospinal fluid (CSF) and has other important secretory functions. Furthermore, the CP-CSF interface plays a putative role in neurogenesis and has been implicated in neuropsychiatric diseases such as the neurodevelopmental disorders schizophrenia and autism. A role for this CNS border was also implicated in sleep disturbances and chronic and/or severe stress, which are risk factors for the development of neuropsychiatric conditions. Understanding the mechanisms by which disturbance of the homeostasis at the CP-CSF interface is involved in these different chronic low-grade inflammatory diseases can give new insights into therapeutic strategies. Hence, this review discusses the different roles that have been suggested so far for the CP in these neuropsychiatric disorders, with special attention to potential therapeutic applications.

Psychological Aspects of Cardiac Care and Rehabilitation: Time to Wake Up to Sleep?

Psychological and psychosocial factors have long been linked to cardiovascular disease. These psychosocial factors, including low socioeconomic status, social support/isolation, stress and distress, personality, and sleep disturbance increase risk of cardiovascular events and negatively impact quality of life. These factors may have direct effects on cardiovascular disease via immune or neuroendocrine pathways, or more indirect effects, by, for example, limiting adherence to recommended therapies and cardiac rehabilitation. Most psychosocial risk factors can be assessed relatively easily using standardised tools. Sleep disturbance, in particular, is gaining evidence for its importance and may be crucial to address. While the management of certain psychosocial risk factors is an ethical requirement for care and improves quality of life, unfortunately there is little evidence that such strategies impact on 'hard' endpoints such as recurrent myocardial infarction. A comprehensive biopsychosocial approach to management of these psychosocial factors is required to maximise the benefits patients derive from cardiac care.

[Fibromyalgia syndrome: A disease of the small nerve fibers?]. / Fibromyalgiesyndrom : Eine Erkrankung der kleinen Nervenfasern?

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and additional associated symptoms, such as fatigue, sleep disturbances and depressive moods. The pathophysiology of pain in FMS is unclear. In recent years, an involvement of the thinly myelinated A-delta and the unmyelinated C-nerve fibers has been reported in FMS patients. Independent research groups published consistent objective and multidimensional findings of damage to these small nerve fibers, such as disturbances of fiber function, electrical properties and morphological changes. All these alterations are not specific for FMS; however, they were described for the first time in subgroups of FMS patients. While the reasons for this small fiber pathology and its contribution to FMS pain are still unclear, a new research field has now been opened that will focus on uncovering the underlying pathophysiology. This review article summarizes these new findings and discusses the significance for the understanding of FMS.

Sleep duration, C-reactive protein and risk of incident coronary heart disease--results from the Framingham Offspring Study.

BACKGROUND: Both sleep-duration and C-reactive protein (CRP) are useful predictors of coronary heart disease (CHD). The increased CRP level is associated with the unusual sleep-duration. However, it is unclear whether CRP impacts the CHD risk prediction of sleep-duration. METHODS AND RESULTS: A total of 3381 individuals from the Framingham Offspring Study, aged 30+, CHD-free, and without missing measurement of CRP and sleep-duration and being followed to the end of 2007 were included in this analysis. Hazards ratio (HR) from the Cox regression models was used to evaluate the strength of association between the sleep-duration, CRP levels, and risk of incident CHD. Compared to sleep-duration 7-8 h (n = 2512) after adjusting for age and gender, the HR (95% CL) of incident CHD were 1.42 (1.15, 1.76, p < 0.005) for sleep-duration ≤6 h (n = 588) and 1.23 (0.90, 1.70, p < 0.2) for sleep-duration ≥9 h (n = 281), respectively. A further adjustment for other covariates including CRP did not change the CHD risk association. When subjects were categorized into 9 groups by sleep-duration (≤6, 7-8, and ≥9 h) and CRP levels (<1, 1-3, and ≥3 mg/L), and compared to those whose sleep-duration was 7-8 h and CRP levels were <1 mg/L, the HRs of CHD were similar for sleep-duration in ≤6 h or ≥9 h categories regardless of their CRP levels. The increased CRP levels, however, did show an increased risk for CHD when sleep-duration was 7-8 h CONCLUSION: The levels of CRP do not significantly attenuate the association between sleep duration and incident CHD.

Neutrophilic asthma is characterised by increased rhinosinusitis with sleep disturbance and GERD.

BACKGROUND: Asthma is a heterogeneous inflammatory disease and eosinophilic, non-eosinophilic and neutrophilic forms are recognised. While clinically similar to eosinophilic asthma, patients with non-eosinophilic asthma have different responses to treatment and little is known about the triggers of symptoms and inflammation. OBJECTIVE: This study sought to characterise asthma control, exacerbation frequency and potential triggers of non-eosinophilic and specifically neutrophilic asthma such as infection, gastroesophageal reflux disease, and rhinosinusitis. METHODS: Adults with asthma (n=65; doctor's diagnosis plus demonstrated response to bronchodilator and/or airways hyperresponsiveness to hypertonic saline) were recruited from the Respiratory and Sleep Medicine Ambulatory Care Service at John Hunter Hospital, NSW, Australia. Questionnaires were administered to assess gastroesophageal reflux disease, rhinosinusitis and asthma control. A sputum induction was performed and sputum was processed for assessment of inflammatory cells, infection, and lipid laden macrophages (Oil Red O). RESULTS: Participants with neutrophilic asthma (n=11, 23%) had a higher frequency of primary care doctor visits for asthma exacerbations and a high prevalence (> 70%) of chest infections in the previous 12 months. There was also an increased prevalence of rhinosinusitis (64%) and increased symptoms of gastroesophageal reflux disease compared to those with eosinophilic asthma. CONCLUSIONS: The clinical pattern of neutrophilic asthma is different from paucigranulocytic and eosinophilic asthma with evidence of abnormal upper airways responses. Specific and targeted treatment of these airway problems may assist in the control and management of neutrophilic asthma.

Elucidating sleep disorders: a comprehensive bioinformatics analysis of functional gene sets and hub genes.

Background: Sleep disorders (SD) are known to have a profound impact on human health and quality of life although their exact pathogenic mechanisms remain poorly understood. Methods: The study first accessed SD datasets from the GEO and identified DEGs. These DEGs were then subjected to gene set enrichment analysis. Several advanced techniques, including the RF, SVM-RFE, PPI networks, and LASSO methodologies, were utilized to identify hub genes closely associated with SD. Additionally, the ssGSEA approach was employed to analyze immune cell infiltration and functional gene set scores in SD. DEGs were also scrutinized in relation to miRNA, and the DGIdb database was used to explore potential pharmacological treatments for SD. Furthermore, in an SD murine model, the expression levels of these hub genes were confirmed through RT-qPCR and Western Blot analyses. Results: The findings of the study indicate that DEGs are significantly enriched in functions and pathways related to immune cell activity, stress response, and neural system regulation. The analysis of immunoinfiltration demonstrated a marked elevation in the levels of Activated CD4+ T cells and CD8+ T cells in the SD cohort, accompanied by a notable rise in Central memory CD4 T cells, Central memory CD8 T cells, and Natural killer T cells. Using machine learning algorithms, the study also identified hub genes closely associated with SD, including IPO9, RAP2A, DDX17, MBNL2, PIK3AP1, and ZNF385A. Based on these genes, an SD diagnostic model was constructed and its efficacy validated across multiple datasets. In the SD murine model, the mRNA and protein expressions of these 6 hub genes were found to be consistent with the results of the bioinformatics analysis. Conclusion: In conclusion, this study identified 6 genes closely linked to SD, which may play pivotal roles in neural system development, the immune microenvironment, and inflammatory responses. Additionally, the key gene-based SD diagnostic model constructed in this study, validated on multiple datasets showed a high degree of reliability and accuracy, predicting its wide potential for clinical applications. However, limited by the range of data sources and sample size, this may affect the generalizability of the results.