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Chronic Rhinosinusitis and Sleep: A Contemporary Review
Abstract
Patients with chronic rhinosinusitis (CRS) exhibit centrally mediated behavioral changes commonly referred to as "sickness behavior." Sleep alteration is a component of sickness behavior which is estimated to affect up to 70 million patients annually. Patients with CRS have poor sleep quality, and little is known about the underlying etiology and pathophysiology. This narrative review aims to further organize and present the current knowledge associating sleep and CRS.
A literature search was conducted of the OVID MEDLINE database using key search words including: "chronic rhinosinusitis," "sleep," "sleep disorders," and "sleep dysfunction." Additional keywords "nasal obstruction," "nasal polyp," and "fatigue" were identified and used to further delineate relevant articles.
The articles that specifically addressed sleep and CRS were dissected and presented as follows: (1) chronic rhinosinusitis and sleep; (2) chronic rhinosinusitis and fatigue; (3) chronic rhinosinusitis, nasal obstruction, and sleep; and (4) pathophysiology of sleep in chronic rhinosinusitis (cytokines in both sleep and chronic rhinosinusitis and their association to the neuroimmune biology of chronic rhinosinusitis).
Patients with CRS have sleep dysfunction that is associated with their disease severity and overall quality of life. The etiology of sleep dysfunction in CRS is most likely multifactorial. Increasing evidence suggests sleep dysfunction in patients with CRS is partly due to the inflammatory disease process, and sleep physiology in patients with CRS may be actively regulated by the inflammatory component of the disease.
... Chronic rhinosinusitis (CRS) is a highly prevalent condition, affecting approximately 7% to 14% of the North American population [1]. Its impact is significant, as it is linked to reduced quality of life (QoL) [2], impaired sleep [3], and fatigue [4]. ...
... CRS encompasses a variety of conditions and can be further categorized according to its phenotype into cases which present nasal polyps (CRSwNP) and cases which do not (CRSsNP) [3], each one being managed differently. ...
... Both manifestations are usually treated with intranasal corticosteroids (INCS), which exert an anti-inflammatory effect by reducing airway inflammatory cell infiltration by eosinophils, mast cells, and T-lymphocytes, and suppressing production of adhesion molecules and pro-inflammatory genes and mediators, such as NF-κB [3]. ...
Chronic rhinosinusitis (CRS) is a highly prevalent condition. CRS is usually managed with intranasal corticosteroids, useful both before as well as after endoscopic sinus surgery (ESS). However, the greatest drawback of these low-volume sprays is the inadequate delivery into the paranasal sinuses, even after ESS. Recent studies have shown that high-volume steroid nasal rinse (HSNR) has a significantly better penetration of the paranasal sinuses. The purpose of this state-of-the-art review is to systematically overview the current literature about the role of nasal rinses with steroids in CRS. Four authors examined four databases (Embase, Pubmed, Scielo, Cochrane). This review identified 23 studies answering 5 research questions. It included 1182 participants, 722 cases, and 460 controls. Available evidence suggests a potential positive effect of HSNR, which seems to be higher in CRS with nasal polyps. More well-designed studies are needed in order to obtain solid conclusions. The evidence is solid regarding the safety of this treatment modality in the short and long-term. We expect that this lack of severe negative effects will facilitate the acceptance of this treatment modality and the development of future studies.
... The pathophysiology of sleep impairment in CRS remains highly plausible and could be related to many factors including nasal obstruction, depression, sex, pain, and direct neural signaling or by systemic or local neural-immune signaling through proinflammatory somnogenic cytokines [3]. ...
... Consistent poor sleep can have staggering impacts on an individual's performance, overall QOL, and even mortality [3]. ...
... People who suffer from sleep apnea may experience short, infrequent or even interrupted breathing during sleep, causing them to wake up to start normal respiration again. As a result, this condition is also associated with health deficits related to impaired sleep quality [3]. ...
Background
Chronic sinusitis is one of the most prevalent chronic illnesses affecting persons of all age groups. It is an inflammatory process that involves the paranasal sinuses and persists for 12 weeks or longer.
Purpose
The aim of this study was to investigate the effect of chronic rhinosinusitis (CRS) on sleep-disordered breathing.
Patients and methods
This study was conducted prospectively during the period spanning from June 2017 to June 2018 on 100 patients with CRS who attended to the ENT Departments of El-Maadi Armed Forces Medical Complex, Kobry El-Kobba Armed Forces Medical Complex, and El-Demerdash Hospitals. An additional 10 control patients were included in the study. All these patients gave informed consent to participate in this study.
Results
As regards apnea–hypopnea index, a comparative study between preoperative and postoperative measurements revealed a nonsignificant difference ( P >0.05). As regards snore index and snore episodic measurements, the comparative study between preoperative and postoperative measurements revealed a highly significant decrease ( P <0.01). As regards sleep efficiency and minimal and basal oxygen saturation measurements, the comparative study between preoperative and postoperative measurements revealed a highly significant increase ( P <0.05).
Conclusion
Surgery decreased snoring and Epworth Sleepiness Scale scores, increased sleep efficiency and minimal and basal oxygen saturation measurements without changes in the apnea–hypopnea index, and improved sleep quality.
... 12 In addition to depression, sinusitis and AR have also been linked to sleep disturbances and insomnia. [13][14][15][16] A concurrent diagnosis of a mood disorder has been associated with an increase in morbidity and mortality. 17,18 For instance, in patients who had undergone coronary artery bypass surgery, depression was linked to significantly higher mortality rates. ...
... 10,18 Mood disorders have a significant impact on the quality of life of patients, but there is little data on the association of depression and sinonasal inflammation on a national level across the United States. [2][3][4][5][6][7][8][9][10][11][13][14][15]20 This study examines the relationship between sinonasal inflammation and depression symptoms in the United States at a population level by utilizing the National Health Interview Survey. Additionally, this study will also investigate the association between sleep and work days lost with AR and sinusitis. ...
... 14,23,24 Of note, IL-1 and IL-6 are both upregulated in sinusitis, and may possibly contribute to the pathophysiology of sinusitis's positive association with depression. 13,25,26 The physiologic response is complemented by the social limitations the symptoms of sinonasal inflammation impose. Chronic rhinorrhea, sneezing, purulent discharge, or vocal congestion create difficulties in social interaction. ...
Objective
Examine the relationship between depression symptoms and sinonasal inflammatory diseases, and investigate health disparities associated with allergic rhinitis (AR) and sinusitis in the United States.
Study Design
Cross‐sectional analysis of 2014 National Health Interview Survey (NHIS) data.
Methods
Adult cases of AR and sinusitis were extracted from the 2014 NHIS in addition to demographic, socioeconomic, and related depressive symptom data. The dataset was analyzed with chi‐square, t‐tests, and multivariate regression.
Results
There were 19.1 ± 1.1 million adult AR cases and 29.4 ± 1.4 million adult sinusitis cases. Of these, 20.6% and 22.0% reported depression symptoms in the past 12 months for those with AR or sinusitis, respectively. Both diseases were also associated with significantly fewer mean hours of sleep a night (AR: 7.02 vs. 7.14, P < 0.01; Sinusitis: 6.98 vs. 7.14, P < 0.01) and greater mean days of work missed (AR: 4.60 vs. 3.62, P < 0.01; Sinusitis: 5.87 vs. 3.41; P < 0.01). On multivariate analysis, the prevalence of AR and sinusitis was significantly higher among men, Caucasians, older adults, the more educated, and adults with depression symptoms. Only the prevalence of sinusitis varied depending on income and geography.
Conclusion
Allergic rhinitis and sinusitis are associated with an increased likelihood of depressive symptoms, shorter sleep duration, and more workdays lost. The prevalence of both are influenced by age, sex, race/ethnicity, and education level. Targeted initiatives should be developed to address these health disparities and comorbidities associated with inflammatory sinonasal disease.
Level of Evidence
4.
... Our results are also consistent with recent literature showing that individuals with CRS complain of poor sleep and demonstrate poor QOL related to sleep disruption [11,37,38]. However, these studies did not control for OSA severity or sleep duration. ...
... However, the relationship of CRS to poor sleep remained even after controlling for sleep duration. We have shown a relationship of CRS to level of WTC exposure [5], and chronic inflammation has also been shown to be part of CRS; it is possible that systemic mediators of inflammation such as cytokines contribute to sleep disruption [37,39]. ...
Background: World Trade Center (WTC) dust-exposed subjects have multiple comorbidities that affect sleep. These include obstructive sleep apnea (OSA), chronic rhinosinusitis (CRS), gastroesophageal-reflux disorder (GERD) and post-traumatic stress disorder (PTSD). We examined the impact of these conditions to sleep-related outcomes. Methods: Demographics, co-morbidities and symptoms were obtained from 626 WTC (109F/517M), 33–87years, BMI = 29.96 ± 5.53 kg/m2) subjects. OSA diagnosis was from a 2-night home sleep test (ARESTM). Subjective sleep quality, sleep-related quality of life (QOL, Functional Outcomes of Sleep Questionnaire), excessive daytime sleepiness (Epworth Sleepiness Scale), sleep duration and sleep onset and maintenance complaints were assessed. Results: Poor sleep quality and complaints were reported by 19–70% of subjects and average sleep duration was 6.4 h. 74.8% of subjects had OSA. OSA diagnosis/severity was not associated with any sleep-related outcomes. Sleep duration was lower in subjects with all conditions (p < 0.05) except OSA. CRS was a significant risk factor for poor sleep-related QOL, sleepiness, sleep quality and insomnia; PTSD for poor sleep-related QOL and insomnia; GERD for poor sleep quality. These associations remained significant after adjustment for, age, BMI, gender, sleep duration and other comorbidities. Conclusions: Sleep complaints are common and related to several health conditions seen in WTC responders. Initial interventions in symptomatic patients with both OSA and comorbid conditions may need to be directed at sleep duration, insomnia or the comorbid condition itself, in combination with intervention for OSA.
... It was suggested that pro-inflammatory cytokines, hormones, and bacterial cell wall products influence the structural sleeping patterns (such as IL-Iβ, tumor necrosis factor-α (TNF-α), and growth hormone releasing hormone (GHRH) for non rapid eye movement sleep, and Nitric Oxide and prolactin for regulating rapid eye movement sleep (5) . On the other hand, nasal obstruction plays an important role in sleep-disordered breathing. ...
... Correlations between symptom scores and their impact on (2) . The mechanism of sleep disorders in patients with NP seems multifactorial (5) . It may be due to mechanical blockage by the polyps and reduced cross-section area by nasal inflammatory mucosa leading to the increase of the upper airway resistance, and/or to the systemic diffusion of pro-inflammatory cytokines. ...
Background:
Patients with nasal polyposis (NP) complain of several sinonasal symptoms that impact their sleep and quality of life. However, data on sleep disorders related to NP symptoms, before and after surgery, is poor. The aim of the present study was to analyze sleep complaints related to each NP symptom, before and after surgery, using the Dynachron questionnaire.
Methodology:
63 patients operated for NP were included in this prospective study. They filled the DyNaChron questionnaire one day before surgery (V0), 6 weeks (V1) and 7 months (V2) after surgery. The self-ratings (0-10 point visual analog scale) of nasal obstruction, anterior rhinorrhea, postnasal discharge, cough and 5 items related to sleep disturbances, due to each symptom of chronic nasal dysfunction, were extracted from the questionnaire and analyzed.
Results:
There was significant improvement of symptoms and symptom-related sleep disturbance scores at V1 and V2 compared to baseline scores. Before surgery, moderate/severe sleep disorders that patients attributed to nasal obstruction (the patient thinks it is due to nasal obstruction rather than a clinical test to show nasal obstruction) or anterior rhinorrhea were reported in two thirds of patients, postnasal discharge in one half, and chronic cough in one third. After surgery, less than 10% of patients reported moderate/severe sleep disorders at V1. There was a mild increase of patients who rated moderate/severe sleep disorders at V2 in comparison to V1. The correlation between scores of nasal obstruction and its impacts on sleep quality was weak before surgery and strong afterwards.
Conclusion:
Nasalization improved sleep quality significantly at 6 weeks and at 7 months after surgery. However, there was a mild increase of complaints related to postnasal discharge and cough at 7 months after surgery.
... Apart from sinonasal symptoms, CRSwNP is associated with an increased risk of asthma, otitis media, depression and social dysfunction (6). Similarly important is the extensively studied association between CRSwNP and sleep disturbance, which is linked to cardiovascular and cerebrovascular disease and reduced quality of life for both the patient and their partner (7)(8)(9). The impact of CRSwNP on quality of life (QoL) has been observed to be equivalent to other chronic conditions such as chronic obstructive pulmonary disease (COPD), congestive heart failure, and diabetes (10,11). ...
Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic inflammatory disease of the nose and paranasal sinus cavities that significantly affects well-being and social function, particularly in young adults and middle-aged populations. CRSwNP is a common health condition in the Western world, with an estimated prevalence of 3%. Despite worldwide evidence-based treatment guidelines such as the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) chronic rhinosinusitis (CRS) pocket guide, a significant number of patients remain undiagnosed and/or uncontrolled with repeated oral corticosteroids (OCS) treatments and/or (multiple) endoscopic sinus surgeries (ESS).
... The increased nasal airway resistance has been associated with sleep-disordered breathing by Jiang and coworkers [33]. Other mechanisms of sleep disorder in CRS include efferent and afferent neural signaling and brain-immune signaling through immune mediators [34]. The less severe inflammation of anterior ethmoid sinuses comparing posterior ethmoid sinuses was associated with less pre-ESS snoring in our results. ...
Purposes
In patients with chronic rhinosinusitis (CRS), we assessed quality of life (QOL) of chronic rhinosinusitis (CRS) patients with different self-reported snoring frequencies after endoscopic sinus surgery (ESS), and explored factors associated with pre-ESS snoring and post-ESS snoring reduction.
Methods
This prospective cohort study was conducted in a tertiary referral center in Chengdu, China. Adult patients with medically recalcitrant CRS receiving initial ESS were engaged. Self-reported snoring was measured at baseline and 3-year follow-up, along with Sino-Nasal Outcome Test-22 and snoring visual analog scale assessment. Mouth breathing (MB), demographics, behavior, comorbidity factors, and objective CRS severity were considered.
Results
In 210 patients who completed this study, 63 (30%) patients reported pre-ESS habitual snoring, and post-operative habitual snoring was observed in 52 (25%) patients. The presence of self-reported snoring was correlated with worse CRS QOL at baseline and 3-year follow-up. Obesity (odds ratio [OR] = 4.30; 95% confidence interval [CI], 1.64–11.28; p < 0.01) and posterior-to-anterior ethmoid sinus ratio greater than one (PE/AE, OR = 0.32; 95% CI, 0.10–0.99; p = 0.05) were associated with pre-ESS snoring in univariable and multivariable analysis. The post-operative reduction of snoring frequency was related with patient age over 65 (OR = 11.55; 95%CI, 1.35–98.79; p = 0.03) and bilateral opacification in the Lund-Mackay system (OR = 8.04; 95%CI, 1.24–51.90; p = 0.03) in multivariable analysis. Pre-operative snoring and MB were associated with increased risk of post-operative snoring (p < 0.01 for each comparison).
Conclusions
Post-ESS, self-reported snoring was associated with worse CRS QOL. Obesity and PE/AE > 1 were risk factors of pre-operative snoring. Advanced age and bilateral opacification were associated with greater improvement of snoring after ESS.
... About 4.5 to 12% of population suffer from CRS [2] . Moreover, CRS has been shown to have negative impacts on sinonasal symptoms, sleep, mood, and lower airway function, quality of life and work productivity [3][4][5][6][7][8] . CT is the investigation of choice for the evaluation of patients with CRS. ...
... Sleep quality is commonly impaired in patients with chronic rhinosinusitis (CRS) and patient-reported sleep quality is significantly improved after treatment with dupilumab therapy [1]. Nasal blockage may be the cause for poor sleep quality in CRS patients, but other factors have also been suggested, e.g., influence of inflammatory cytokines on the central nervous system [2]. Nasal resistance may be raised by mucosal congestion or/and nasal polyposis in CRS patients, thereby producing a more negative inspiratory swing in pharyngeal intraluminal pressure. ...
Patients with chronic rhinosinusitis (CRS) report improved sleep quality after dupilumab, an anti IL4/13 therapy. Concurrent CRS and obstructive sleep apnea (OSA) cases are not rare, and CRS seemingly raises nasal resistance. Thus, we hypothesized that improved sleep quality by dupilumab therapy in CRS patients might be due to lowered nasal resistance and subsequent improvement of unrecognized comorbid OSA. Patients with concurrent CRS and OSA were recruited. Nasal resistance was measured invasively with transnasal pressure and flow data collected during normal respiration in the supine position. Results from the first five participants did not support our hypothesis. Subjective and objective measures for CRS and nasal resistance values were improved with dupilumab therapy in CRS patients with nasal polyps. However, apnea severity and sleep-related subjective parameters did not change. In the patients with CRS without nasal polyps, no significant changes in either CRS or OSA-related measures were observed.
... However, inflammation has a key role in CRS [6][7][8]. The CRS, if not managed, can cause fatigue and cognitive dysfunction and worsen patients' sleep quality and quality of life [9][10][11][12]. The goals of treatment are to control the infection and reduce the sinus mucosal inflammation [13]. ...
Chronic rhinosinusitis (CRS) is one of the most common conditions all over the world. The purpose of this study was to investigate the effects of low-level laser therapy (LLLT) in patients with CRS. Fourteen adult patients with CRS participated in this single-blind, sham-controlled clinical trial (12 male, mean age 40 years). Patients received five successive sessions of sham laser followed by five successive sessions of real laser after 2 days. Ga-Al-As laser of 830 nm in a continuous mode at a power output of 30 mW and energy dose of 1 J was applied on the cheeks and the forehead for the maxillary and frontal sinuses, respectively. Laser was delivered on six points over each sinus, each point for 33 s. Four measurements were taken. The total symptom score (TSS) was calculated as the primary outcome measure. The effects of LLLT on TSS were evaluated by using repeated measure ANOVA. The percentage improvement of real laser and sham laser was compared by Wilcoxon signed ranked test. Cohen’s d was used to calculate the effect size. Total symptom score significantly improved after real laser (p = 0.015, Cohen’s d = 0.69). The percentage improvement for real laser (34.12 ± 46.43) was significantly better than the sham laser (5.02 ± 37.34, Z = − 2.23, p = 0.026). No significant improvements were observed after sham laser. This study indicates that five-session active LLLT when compared with sham is effective in the treatment of CRS symptoms.
... Gesundheitszustand der CRS-Patienten sind verglichen mit gesunden Kontrollpatienten stark beeinträchtigt [18][19][20][21][22]. Die persistierenden Symptome sorgen beispielsweise für eine reduzierte Schlafqualität, Müdigkeit und vermehrte Depressionen [23][24][25]. ...
Zusammenfassung Hintergrund und Ziele Die chronische Rhinosinusitis (CRS) ist eine komplexe Erkrankung, die klassischerweise phänotypisch nach dem Vorhandensein oder Fehlen nasaler Polypen eingeteilt wird. Tatsächlich präsentiert sich die CRS jedoch weitaus heterogener, sodass eine polypenbasierte Einteilung als nicht mehr ausreichend erscheint. Die aktuelle Forschung fokussiert sich daher auf die Identifizierung der zugrundeliegenden entzündlichen Mechanismen und die Unterscheidung verschiedener Endotypen. Diese Endotypen können durch Biomarker charakterisiert werden. Allerdings haben viele Studien im Bereich der Biomarkerforschung Schwachstellen, wie beispielsweise bei der zu geringen Studienpopulation, der Auswahl der analysierten Biomarker oder der verwendeten Methode. Ziel der vorliegenden Arbeit war es deswegen ein umfassendes Spektrum verschiedener Biomarker im Nasensekret einer Patientenkohorte zu untersuchen. Zunächst wurde die Konzentration der Biomarker im Nasensekret gemessen und deren Expressionsunterschiede in den verschieden Patientengruppen statistisch ausgewertet. Darauf basierend sollten dann die Biomarker klassifiziert werden, die es erlauben, zwischen den Patientengruppen bzw. Phänotypen zu unterscheiden. Außerdem wurde mittels immunhistologischer Färbung die Lokalisation einiger Biomarker im Gewebe nachgewiesen. Methoden Bei einem Patientenkollektiv von insgesamt 158 Patienten, unterteilt in drei Gruppen (Kontrollpatienten mit gesunder Nasenschleimhaut, Patienten mit chronischer Rhinosinusitis ohne Polypen (CRSsNP) und Patienten mit chronischer Rhinosinusitis mit Polypen (CRSwNP)), wurde mittels nichtinvasiver Einlage eines Schwämmchens präoperativ Nasensekret gewonnen. Mit diesem wurde eine Analyse von zwölf Biomarkern, bestehend aus verschiedenen Zytokinen (IFN-γ, IL-4, -5 -17A, -22, IgE) und entzündlichen Proteinen (CST-2, ECP, MMP-9, PAPP-A, Periostin, Serpin E1) durchgeführt. Die Bestimmung der Proteinkonzentrationen erfolgte mittels ELISAs und Luminex-Assays. Für die Klassifikation der Phänotypen wurden verschiedene Algorithmen auf die generierten Daten von der Biomarkeranalyse angewendet. Zusätzlich wurden beispielhaft sechs Biomarker ausgewählt, um Gewebeproben immunhistologisch zu färben. Ergebnisse und Beobachtungen Es konnte gezeigt werden, dass alle zwölf untersuchten Biomarker bei den CRS-Patienten hochreguliert waren, allerdings in unterschiedlichem Ausmaß. Sehr deutlich exprimiert wurden vor allem CST-2, ECP, PAPP-A und Serpin E1. Nur schwach exprimiert wurden dagegen IgE, MMP-9 und Periostin. Allerdings fiel bei den Messungen insgesamt auf, dass der Großteil der Biomarker im Vergleich zu Ergebnissen anderer Studien und zu denen der CRS-Patienten auch bei den gesunden Kontrollpatienten erhöht war. So zeigte die Kontrollgruppe für IL-17A, IgE, ECP, PAPP-A und Serpin E1 die signifikant höchste Expression. Aus diesem Grund wurde der Fokus auf den Vergleich der beiden Phänotpyen CRSsNP und CRSwNP gelegt. Zur Bestimmung des Expressionsmusters der CRSsNP bzw. CRSwNP und der Bestimmung der besten Biomarkerkombination wurden verschiedene Klassifikationsalgorithmen verwendet. Dadurch konnte MMP-9 als geeigneter Biomarker identifiziert werden, wenn nur ein Biomarker verwendet werden soll. Noch genauer wird die Klassifikation jedoch mit einem Set aus Periostin, CST-2 und ECP oder mit einem Set aus Periostin, CST-2, ECP und PAPP-A. Für die CRS-Gruppen stimmten die Erkenntnisse der immunhistologischen Färbungen mit denen der Immunoassays weitgehend überein. Lediglich die erhöhten Konzentrationen der Kontrollgruppe konnten nicht bestätigt werden. Schlussfolgerungen Die deutlich erhöhten Expressionen der Biomarker in der Kontrollgruppe stellen für die vorliegende Arbeit ein neuartiges und ungelöstes Phänomen dar, das trotz intensiver Bemühungen nicht hinreichend aufgeklärt werden konnte. Da auch die bisher veröffentlichte Literatur keine Erklärung liefern konnte, sollten für nachfolgende Forschungsarbeiten die Kriterien der Kontrollgruppe evaluiert werden. Außerdem variieren die Methoden in den bislang veröffentlichten Biomarkeranalysen erheblich, wodurch eine Vergleichbarkeit der Messwerte nur eingeschränkt möglich ist. Zudem sind die Erkenntnisse der vorhandenen Literatur zumindest für einige Biomarker sehr inkonsistent, weswegen weitere prospektive Studien mit derselben Methode zur Validierung nötig sind. Besonders von IFN-γ und IL-22 waren die Ergebnisse sehr unbeständig, sodass deren Nutzen fragwürdig bleibt. Allerdings konnten in dieser Arbeit mit CST-2, ECP, MMP-9, PAPP-A und Periostin Biomarker herausgearbeitet werden, die geeignet sind, um zwischen Phänotypen zu trennen und demzufolge für nachfolgende Studien mit Hinblick auf eine Clusteranalyse zur Endotypisierung verwendet werden können.
... For example, maxillary rhinosinusitis can cause radiating toothache due to irritation of the trigeminal nerve [35]. In addition, inflammatory mediators can be transmitted from the immune system to the brain via afferent autonomic neurotransmission, and directly across the blood-brain barrier and/or through periventricular organs [36]. Kato stated that it is clear that type 2 cytokines, especially IL-5 and IL-13, but possibly also IL-4, play important roles mediating inflammation in ECRS and nasal polyp development [37]. ...
Citation: Kuruma T, Arimoto M, Yo K, Kawade Y, Kondo Y, et al. (2022) Improvement of Eosinophilic Rhinosinusitis Headache after Endoscopic Modified Lothrop Procedure: Case Report and Literature Review. J Surg 7: 1507. Abstract The main symptoms of eosinophilic chronic rhinosinusitis are olfactory disturbances, nasal obstruction and posterior rhinorrhea. chronic rhinosinusitis cases, only few reports have described an association between eosinophilic chronic rhinosinusitis and headache or its improvement with treatment. We experienced a case of a 43-year-old female patient with eosinophilic chronic rhinosinusitis with recurrent severe frontal headache after endoscopic sinus surgery that was relieved after an endoscopic Among modified Lothrop procedure. In refractory eosinophilic chronic rhinosinusitis, there is severe infiltration of eosinophils around the frontal sinus, as well as polyp formation. We believe that endoscopic modified Lothrop procedure, in which the bilateral frontal sinuses are opened widely as a single cavity, is very useful not only for treatment of the headache, but also for the other symptoms associated with refractory eosinophilic chronic rhinosinusitis, such as posterior rhinorrhea, nasal obstruction, olfactory disturbance, etc.
... 3 CRS is also significantly more common in people over 65 years old. 4 Furthermore, rates of nasal polyps have been shown to be significantly higher in elderly patients with CRS. 5 On an individual level, CRS can worsen sleep quality and fatigue. 6 Soler et al found that patients with CRS reported more cognitive dysfunction, and objectively, they had worse response times on computerized testing. 7 Another group led by Soler looked at baseline health state utility values in CRS. ...
The proportion of the population over 65 years old continues to grow. Chronic rhinosinusitis is common in this population and causes a reduction in quality of life and an increase in health care utilization. Diagnosis of chronic rhinosinusitis with nasal polyps follows the same principles for elderly patients as in the general population, but the elderly population presents some diagnostic challenges worth considering. Presbynasalis, the anatomic and functional changes of the nose and paranasal sinuses associated with aging must be accounted for when caring for these patients. In addition, polypharmacy and other medical issues that can cause similar symptoms must be considered. Medical therapy is generally similar to the general population but with additional concerns given the propensity for geriatric patients to be on multiple medications and to suffer from multiple medical issues. Sinus surgery should be considered following the same indications as in the general population. While some authors have found higher complication rates in endoscopic sinus surgery, others have found higher rates of success. As always, the risks of surgery must be considered with the possible benefits on a patient-to-patient basis.
... Indirect costs were estimated as $13 billion USD per 2014 year [3]. Moreover, CRS has been shown to have negative impacts on sinonasal symptoms, sleep, mood and lower airway function, quality of life and work productivity [4,5]. ...
Background: There is a wide range of anatomical variations affecting the nose, paranasal sinuses (PNS). These variations may cause impairment of mucociliary drainage of the PNS resulting in sinusitis. Aim: The aim of this study was to determine the incidence of anatomic variations of the different structures of the nose in a group of patients with chronic rhinosinusitis without nasal polyposis and compare them with cases didn’t have sinusitis. Methods: This case control study included 140 patients who had diagnostic criteria of CRS according to EPOS 2020. Cases were collected from February 2020 to February 2021 from the outpatient clinic of Otorhinolaryngology Department of Tanta University Hospital. Patients were divided into two equal groups: The first group was the study group including 70 patients who had chronic rhinosinusitis as detected by Computed tomography (CT) of paranasal sinuses. The second group was the control group including 70 patients who had normal CT of paranasal sinuses. Results: There was significant relation between the studied anatomical variations and chronic rhinosinusitis for Septal deviation, Haller cells, Supra agger frontal cell and Supra bulla frontal cell. Conclusions: The relation between anatomical variations and sinusitis is not clear till now. Some studies showed statistically significant association between common anatomical variations and the presence of sinusitis while in other studies no statistically significant relationship. In our study there was significant statistical relation between Septal deviation, Haller cells, Supra agger frontal cell and Supra bulla frontal cell and chronic rhinosinusitis.
... 1-7 Patients with CRS experience significant declines in health-related quality of life (HLQOL), with multiple associated comorbidities, including depression, cognitive deficits, and sleep dysfunction. [8][9][10][11][12] The annual expenditure to treat patients with CRS is over $64B and accounts for 3%-5% of the Nanomedicine: Nanotechnology, Biology, and Medicine 38 (2021) 102453 ...
Chronic rhinosinusitis (CRS) is a debilitating inflammatory disorder of the sinonasal mucosa that substantially diminishes patient quality of life. Progress surrounding management of this disease has been crippled by a lack of therapeutic innovation. It has been posited that increased vascularity within the diseased sinuses of patients with CRS may allow for improved systemic drug delivery via nanoscale liposomal carriers. Such a system could enhance drug distribution, accumulation, and retention within the sinuses, ultimately leading to improved patient outcomes. PEGylated liposomes loaded with indocyanine green (ICG) were synthesized, characterized and systemically administered in a mouse model of CRS. Accumulation and retention of ICG in sinonasal tissue was evaluated. Compared to healthy controls, CRS mice showed significant sinonasal tissue accumulation and retention of PEGylated liposomal ICG for up to 21days (p<0.001). Conversely, free ICG was eliminated from the body after 24hours in both groups.
... This result was in line with Nanayakkara who discovered significantly different condition between SNOT-22 score before and after 14 days therapy. [21][22][23] CRS may decrease quality of life as it causes sleep disturbance and may be resolved after medical treatment is given. 24 Local inflammation in CRS may be initiated with the release of IL-6 ultimately in the daytime, therefore causing fatigue, weakness and sleeping disturbance at night. ...
Background: Chronic rhinosinusitis (CRS) is an inflammation of the nasal and paranasal sinuses mucosa, ongoing for more than 12 weeks. Even now it still creates socioeconomic problem in both developed and developing countries. Pharmacotherapy administration is essential for decreasing the severity of symptom, improving quality of life, and decreasing interleukin (IL)-6 level. Objective: To find out the effect of pharmacotherapy on severity of the symptom, quality of life, and IL-6 level. Method: Randomized clinical trial with pre and posttest design, on 20 CRS without polyp patients, divided into two groups based on skin prick test results. Both groups were equally treated with nasal irrigation, nasal corticosteroid, and antibiotic amoxicillin clavulanate for 14 days. All subjects were assessed for Visual Analog Scale (VAS) score, nasoendoscopy (NE) score, Sinonasal Outcome test (SNOT)-22, and IL-6 level. Statistical analysis was performed with Mann Whitney and Wilcoxon methods. Result: There were significant differences in total analysis results on VAS scores, NE scores, SNOT-22, and IL-6 levels in both groups, with values p<0.05. There was improvement in all variables after pharmacotherapy, but there was no significant difference between the case and control groups, with values p>0.05. Conclusion: Pharmacotherapy in both groups resulte’ in reduced severity of symptoms, improved quality of lives, and decreased IL-6 levels.Keywords: Interleukin-6, pharmacotherapy, chronic rhinosinusitis without polyp, quality of life ABSTRAK Latar belakang: Rinosinusitis kronik (RSK) merupakan inflamasi pada mukosa hidung dan sinus paranasal, yang berlangsung selama lebih dari 12 minggu. Hingga saat ini masih memengaruhi sosioekonomi di negara maju maupun negara berkembang. Pemberian farmakoterapi sangat penting untuk memperbaiki derajat gejala, meningkatkan kualitas hidup, dan menurunkan kadar interleukin (IL)-6. Tujuan: Mengetahui pengaruh pemberian farmakoterapi terhadap perbaikan derajat gejala, peningkatan kualitas hidup, dan penurunan kadar IL-6. Metode: Penelitian kuasi eksperimental, label terbuka pra dan pascaterapi, pada 20 penderita RSK tanpa polip, dibagi dua kelompok berdasarkan hasil uji tusuk kulit. Perlakuan pada kedua kelompok sama, diberikan irigasi hidung, kortikosteroid intranasal, dan antibiotik amoksisilin klavulanat selama 14 hari. Penelitian dilakukan dengan menilai skor Visual Analog Scale (VAS) gejala hidung, skor nasoendoskopi (NE), Sinonasal Outcome test (SNOT)-22, dan kadar IL-6. Analisis statistik menggunakan metode Mann Whitney dan Wilcoxon. Hasil: Didapati perbedaan bermakna pada hasil analisis total pada skor VAS gejala hidung, skor NE, SNOT-22, dan kadar IL-6 pada kedua kelompok dengan nilai p<0,05. Didapati perbaikan pada semua variabel setelah 14 hari pemberian medikamentosa maksimal, namun tidak terdapat perbedaan bermakna antara kedua kelompok dengan nilai p>0,05. Kesimpulan: Pemberian farmakoterapi pada kedua kelompok memberikan hasil berupa perbaikan derajat gejala, peningkatan kualitas hidup, dan penurunan kadar IL-6.
... We also found that sleep disorders can cause anxiety and depression in CRS patients, which is consistent with the conclusions of many studies (6,10,12,36,37) . Earlier studies have found that the proportion of CRS patients with sleep disorders can reach 60-75%, which is much higher than that of the normal population (6,38,39) . The disturbance of CRS to patients' sleep is mainly manifests as difficulties inducing sleep, difficulties maintaining sleep, early morning awakening and excessive daytime sleepiness (39) . ...
Background Patients with chronic rhinosinusitis (CRS) have a high incidence rate of anxiety and depression. However, changes in anxiety and depression with different severities of CRS,and the effects of symptoms and anatomical factors on the anxiety and depression of CRS patients remain unclear.
Methods A total of 112 patients were enrolled in the study. The Sino-Nasal Outcome Test-20 (SNOT-22) score, Lund-Mackay scale and Lund-Kennedy scale were used to assess the severity of CRS, and the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to evaluate anxiety and depression in patients.
Results In the univariate analysis, SNOT-20 scores, nasal symptom scores, facial/ear symptom scores and sleep scores are significantly positively correlated with patients’ GAD-7 scores (all P<0.05); the patients’ SNOT-20 scores, nasal symptom scores, facial/ear symptom scores, sleep scores, and the higher side of the anterior ethmoid sinus and frontal sinus Lund-Mackay scores were significantly positively correlated with the patients’ PHQ-9 scores (all P<0.05). In a multivariate linear regression model, however, none of the covariates were found to be statistically associated with GAD-7. Another multivariate model indicated associations among the SNOT-20 sleep domain scores, the higher side of frontal sinus Lund- Mackay scores and PHQ-9 scores (both P < 0.01).
Conclusions Exacerbated nasal and facial/ear symptoms, sleep dysfunction increase patients’ depression and anxiety. Lesions of the frontal sinus and anterior ethmoid sinus may be related to patients' depression. Treatment should be tailored to patients with these symptoms.
... It is believed that nasal obstruction causes increased airway resistance resulting in the development of OSA. Moreover, it has been suggested that CRS is associated with the release of inflammatory cytokines, which could be involved in the development of OSA [21]. IH, the hallmark feature of OSA, results in preferential activation of inflammatory pathways that may contribute to inflammatory response of the upper airway. ...
Purpose
Intermittent hypoxia (IH) is characterized by hypoxia-reoxygenation, reported to be a critical risk factor for obstructive sleep apnea (OSA). This experiment aimed to evaluate the direct effects of IH on the human nasal mucosa.
Methods
The direct effects of IH on the human nasal mucosa was evaluated by measuring the ciliary beat frequency (CBF) and expression levels of inflammatory cytokines (granulocyte-macrophage colony-stimulating factor, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α). The normoxia group was exposed to a normoxic condition for 72 h. The IH group was exposed to 288 cycles of IH (1 cycle: hypoxia, 5 min; subsequent normoxia, 10 min) for 72 h. CBF was measured using an automated computer-based video image processing technique. Changes in the expression of cytokines were assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR).
Results
The normoxia group revealed a persistent CBF pattern and a physiological range of inflammatory cytokines. However, the IH group showed a cyclic decrease in CBF and increased expression of inflammatory cytokines. Cytotoxicity assay indicated no difference in the survival rates between the two groups.
Conclusions
IH results in increased expression of inflammatory cytokines that adversely affects the mucociliary transport in the upper airway and, consequently, may result in airway inflammation.
... 83 The effect of CRS, if any, on OSA has been theorized to be related to increased nasal airway resistance and sequelae of chronic inflammation. 84 It has also been posited that chronic post-nasal drainage associated with sino-nasal inflammation can induce inflammatory, obstructive changes in the upper airway including the soft palate and uvula. 83 OSA is not known to be as common in adults as in the pediatric population with CF, and CF adults seem to have OSA less frequently than the general population. ...
Sleep‐disordered breathing(SBD) is an under recognized comorbidity in the cystic fibrosis (CF) population across the lifespan. Nocturnal hypoxemia, obstructive sleep apnea (OSA), and nocturnal hypoventilation are respiratory abnormalities that occur commonly during sleep in patients with lung disease, and have deleterious consequences to thequality of life in people with CF. Effective screening for these abnormalities is needed to allow for timely initiation of treatment, which has been reported to be efficacious. Lack of treatment leads to worsened pulmonary, cardiovascular, and metabolic outcomes in patients. In this review, we give an overview of sleep‐disordered breathing for the CF clinician, includingprevalence, treatment, and suggestions for future research. We strongly encourage the CF community to incorporate evaluation for sleep‐disordered breathing in CF clinical careso that outcomes for the subset of the CF patients with comorbid sleep‐disordered breathing improve.
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... 52 The effect of CRS, if any, on OSA has been theorized to be related to increased nasal airway resistance and sequelae of chronic inflammation. 53 It has also been posited that chronic post-nasal drainage associated with sino-nasal inflammation can induce inflammatory, obstructive changes in the upper airway including the soft palate and uvula. 52 OSA is not known to be as common in adults as in the pediatric population with CF. ...
... Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent (1) condition with remarkable impact on quality of life (2,3) . Furthermore, there is a massive burden of costs regarding the necessary consultations and medical treatment (4)(5)(6) of the patients as well as absenteeism associated with the disease. ...
Background: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is still not completely understood. Regarding the pathogenesis an impaired barrier function of the sino-nasal epithelium has been shown in CRS. Intranasal corticosteroids are widely used for treatment and part of current guidelines. This study aims to analyse the influence of corticosteroids on the epithelial integrity in air-liquid-interface (ALI) epithelial cell cultures of patients with CRSwNP.
Methodology: Polyp tissue from 11 patients with CRSwNP undergoing a phenoethmoidectomy was collected. The epithelial cells were cultured in ALI. After differentiation of the cells, the permeability of the cell layer was defined by measuring the transepithelial resistance (TER). Commonly used corticosteroids, Fluticasone & Mometasone) and Azelastine were added and their impact on the TER was documented and compared to the TER of ALI cultures without additives (controls).
Results: After 48 hours, Fluticasone showed a significant increase of the TER. Mometasone and Azelastine had no significant impact on the TER. The paracellular passage of Dextran molecules in ALI cultures showed a negative correlation to the TER. Preoperative in vivo corticosteroid treatment had no effect on the baseline TER. Further analysis of the impact of preoperative corticosteroid treatment showed no effect on polyp size, sense of smell, histopathologic eosinophilic count and allergic sensitization.
Conclusion: Fluticasone shows a direct effect in restoring sino-nasal epithelial barrier in-vitro, even in the absence of inflammatory cells.
... The etiology of sleep dysfunction in CRS is multifactorial. Although CRS patients usually experience nasal obstruction, it has been suggested that CRS is associated with the release of proinflammatory cytokines, which may also result in sleep impairment [5]. ...
Purpose:
Chronic rhinosinusitis (CRS) patients often complain of nasal obstruction, which may cause sleep impairment for them. The goal of this study was to investigate the influence of functional endoscopic sinus surgery (FESS) on sleep related outcomes in CRS patients.
Materials and methods:
CRS patients who received FESS were included in this study. Prior to FESS and 3 months after surgery the patients were asked about the severity of nasal obstruction and completed the 20-item Sinonasal Outcome Test (SNOT-20), along with the Epworth Sleepiness Scale (ESS) questionnaire. Endoscopic examination, acoustic rhinometry, and polysomnography were performed in all patients. They were divided into four groups according to their preoperative apnea hypopnea index (AHI) scores: nonobstructive sleep apnea syndrome (non-OSAS), mild OSAS, moderate OSAS, and severe OSAS.
Results:
A total of 96 subjects completed the study. The scores of the sleep domain of the SNOT-20 and ESS decreased in all of the AHI groups, with the exception of the severe OSAS group, after FESS. A reduction in the AHI of less than 5 was achieved in 9 patients (13.2%) after FESS.
Conclusions:
Our results showed that FESS improved sleep quality in CRS patients, except those with severe OSAS, and a preoperative lower AHI was the only significant predictor of post-FESS OSAS outcome.
... In the present study, the sleep dysfunction of SNOT-22 had not a positive significant impact on the QOL outcomes. Despite, recent studies have focused on the relationship between sleep dysfunction and QOL in CRS [21,22]. DeConde et al., found that the decision to undergo surgical intervention in patients with CRS is best predicted by healthrelated QOL domains pertaining to worse psychological impairment and sleep dysfunction [23]. ...
Objectives
To compare the outcome of patients with unilateral CRSsNP (U CRSsNP) and bilateral CRSsNP (B CRSsNP) undergoing FESS. Also, we evaluate the impact of SNOT-22 domains to predict their quality of life (QOL) outcomes and compare these factors with those of CRSwNP group, published in previous work.
Methods
A prospective cohort study was performed in the hospital 20 August,66 patients who were presented between January 2016 and December 2017 were diagnosed with CRS according to guideline recommendations, and were beforehand refractory to initial medical therapy and elected to FESS. The Sino Nasal Outcome Test-22 (SNOT-22) was used to evaluate QOL.
Results
A higher significant improvement was observed between preoperative and postoperative SNOT-22 scores in U CRSsNP group [37.13 ± 9.307 versus 14.11 ± 8.531] and in B CRSsNP group [41.76 ± 6.949 versus 18.57 ± 8.495]. In the U CRSsNP group, patients having a preoperative SNOT-22 score higher than 20 points attained MCID in 88%. For the other group, patients having preoperative SNOT-22 score superior to 40 points achieved MCID in 66%. A multivariate logistic regression model found preoperative predictors that have impact on QOL outcomes.
Conclusions
Outcomes from this study suggest that patients with U CRSsNP having a preoperative SNOT-22 scores between 10 and 19, and patients with B CRSsNP having a preoperative SNOT-22 scores between 10 and 19 or 20–29 had no chance of achieving an MCID improvement after FESS. Also, preoperative rhinologic symptoms and preoperative psychological dysfunction domains of SNOT-22 are helpful tools to predict improvement after FESS unlike the unilateral character of CRS.
... Patients in the working age group are especially predisposed to the impairment with loss of workplace productivity (1,8). This is due to the detrimental health effects of CRS, which include bodily pain (9), headache (10), nasal dysfunctions (10), poor sleep (11,12), fatigue (10) and acute infections (13). ...
... [1,2,3,4,5] Patients with CRS experience significant declines in quality of life more disabling than other chronic conditions such as coronary heart disease and Parkinson's Disease. [6,7,8,9,10,11] Despite its large impact on society, the pathogenesis of this condition remains unclear, as CRS is complex with multiple etiologies (e.g., allergen, bacterial, viral, or fungal exposure). [12,13,14,15] Regardless of etiology, a seemingly unchecked state of persistent inflammation is common in most patients. ...
LL-37 is an immune peptide that regulates innate and adaptive immune responses in the upper airways. Elevated levels of LL-37 have been linked to cell death and inflammatory diseases, such as chronic rhinosinusitis (CRS). Glycosaminoglycans (GAGs) are polysaccharides that are found on respiratory epithelial cells and serve important roles in mucosal surface repair. Recent findings suggest that a synthetic glycosaminoglycan (GM-0111) can protect against LL-37-induced sinonasal mucosal inflammation and cell death in a murine model of acute RS. Herein, we elucidated the mechanisms by which LL-37 causes sinonasal inflammation and how GM-0111 can prevent these mechanisms. When challenged with LL-37, human nasal epithelial cells (HNEpCs) and mouse macrophages (J774.2) demonstrated increased release of adenosine triphosphate (ATP) and interleukin (IL)-6 and -8, as well as cell death and lysis. These cellular responses were all blocked dose-dependently by pre-treatment with GM-0111. We identified that LL-37-induced cell death is associated with caspase-1 and -8 activation, but not activation of caspase-3/7. These responses were again blocked by GM-0111. Our data suggest that LL-37 causes cellular death of HNEpCs and macrophages through the pro-inflammatory necrotic and/or pyroptotic pathways rather than apoptosis, and that a GM-0111 is capable of inhibiting these pro-inflammatory cellular events.
... Although initially disconcerting that subjects were electing ESS for psychological and sleep dysfunction, outcomes data have shown significant improvement in these subdomains after surgery, and there is emerging evidence on the mechanisms supporting the link between central nervous system dysfunction and chronic inflammation. 22 Further establishing the underlying mechanisms linking sinonasal symptoms and general health-related outcomes may identify important targets for medical therapies. ...
Objective:
Medically refractory chronic rhinosinusitis (CRS) can be managed with appropriate continued medical therapy (CMT) or surgery followed by CMT. Patients who initially elect CMT and do not experience adequate symptom resolution may "cross over" to endoscopic sinus surgery (ESS). Our objective was to identify patient covariates associated with this subset of patients who elect this change in treatment modality.
Study design:
Retrospective analysis of a prospective, multi-center cohort of adult patients with CRS enrolled between March 2011 and June 2015 in academic, tertiary referral clinics.
Methods:
Subjects who initially elected CMT were followed up to 18 months, provided a comprehensive medical history, and completed the 22-item SinoNasal Outcome Test (SNOT-22) at baseline and during 6-month follow-up intervals. Hazard regression modeling was used to identify covariates associated with elective change in treatment modality.
Results:
One hundred seventy-nine subjects were followed for an average 15.1 (standard deviation ± 4.6) months. Subjects who elected ESS (55 of 179) had significantly worse average endoscopy scores and reported worse SNOT-22 sleep dysfunction scores at baseline (P ≤ 0.026). For each single increasing (worsening) point of Lund-Kennedy endoscopy score, the hazard ratio (HR) of crossover increased by ∼6%. Similarly, for every point of worsening in baseline SNOT-22 total score, the hazard of treatment crossover increased by ∼2%. After covariate adjustment, only baseline SNOT-22 sleep dysfunction scores were associated with an increased risk of treatment crossover (HR = 1.07; 95% confidence interval: 1.02-1.11; P = 0.003).
Conclusion:
Baseline total SNOT-22 and endoscopy scores are associated with treatment crossover, but reported sleep dysfunction is the only significant independent predictor of treatment crossover.
Level of evidence:
2c. Laryngoscope, 2017.
... A successful management plan for CRS often requires combinations of both topical and systemic medical therapies, and in select refractory cases, need for adjunctive surgery [3••, 4]. While CRS has been shown to have negative impacts on sinonasal symptoms [5], sleep [6], mood [7], and lower airway function [8], the primary patient-centered clinical endpoints of CRS are reductions in quality of life (QoL) [9] and work productivity [10]. Therefore, CRS not only has large direct treatment-related health care costs but also has substantial indirect costs to society resulting from lost work capabilities [11]. ...
Purpose of review:
The objective of this article is to provide an updated review of the economic burden of chronic rhinosinusitis (CRS) and discuss how both medical and surgical interventions impact direct and indirect costs related to CRS. By understanding the economics of CRS, clinicians may improve the patient-centeredness of their care and help distinguish between low and high value interventions.
Recent findings:
Direct costs related to CRS are primarily driven by outpatient physician visits, prescription medical therapy, and endoscopic sinus surgery (ESS). CRS produces large indirect costs and these costs often vary based on the severity of the patients CRS-specific QoL impairment. The overall direct cost related to CRS is estimated to range between $10 and $13 billion per year in the USA. The overall indirect cost related to CRS-related losses in work productivity is estimated to be in excess of $20 billion per year. In the appropriate patients with refractory CRS, ESS provides significant reductions in both direct and indirect costs; however, continued medical therapy alone may be a high value intervention in select patients who have lower severity in their baseline QoL and work productivity.
... However, RDI focuses mainly on daytime symptoms such as breathing through the nose. Nighttime symptoms and the consequences of a blocked nose and disturbed sleep have not been investigated thoroughly in this patient group (5) . Interestingly, even Hippocrates (6) observed that nasal polyposis was associ- The recruitment was consecutive and only a few patients were missed for inclusion due to clinicians forgetting to include them. ...
Background:
Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) is a chronic disease that has a major impact on generic and disease-specific quality of life. Little is known about the influence of CRSwNP on sleep and what effect surgery for CRSwNP has on sleep quality. The aim of the study was to investigate sleep quality in patients with CRSwNP before and after endoscopic surgery.
Methodology:
Forty-two patients filled out four validated sleep questionnaires and one sino/nasal, disease specific quality of life questionnaire before surgery and three months later. A healthy control group filled out the same questionnaires at baseline and after three months.
Results:
An impact on sleep patterns was found in all sleep questionnaires and surgery clearly improved the quality of sleep. The Sino-nasal outcome test sum score decreased from median 51,5 to 26,5. Epworth sleepiness scale showed a decline in score from score 7.5 to 6.0. Surgery also reduced the risk for obstructive sleep apnoea in 13 patients evaluated by the Berlin Questionnaire and Multivariable Apnea Prediction Index.
Conclusions:
Patients with CRSwNP had impaired sleep quality, daytime sleepiness, nasal patency, and risk for sleep apnea, all of which improved after corrective surgery.
Objectives
To investigate whether hormone replacement therapy (HRT) impacts health care resource utilization in the management of chronic rhinosinusitis (CRS) in older women.
Methods
Using the TriNetX US health record database, women 55 years or older with a diagnosis of CRS were included and followed for 3 years. The cohort was stratified into two groups: women who received HRT at the beginning of the study were compared to women who did not receive HRT. The groups were matched by age, race, ethnicity, history of asthma, and history of nasal polyps. Outcomes included whether the patient underwent endoscopic sinus surgery (ESS) and frequency of antibiotic use. Measures of association, Kaplan–Meier analysis, and cohort descriptive statistics were calculated.
Results
Of the 65,400 women included, the mean age was 66.9 years. 27.0% and 3.6% of patients had a history of asthma or nasal polyps, respectively. Overall, 2.0% of CRS patients underwent ESS, with the HRT group less likely to undergo ESS [OR: 0.28; 95% CI: (0.25–0.32)] compared to patients who did not receive HRT. When stratified by polyp status, HRT patients with nasal polyps had a greater decrease in ESS rates compared to control than HRT patients without nasal polyps. The HRT group had a higher mean number of antibiotic prescriptions compared to the non‐HRT group.
Conclusion
HRT is associated with decreased utilization of ESS to treat CRS, with a greater effect size for ESS among CRSwNP patients. However, HRT was associated with higher antibiotic utilization.
Level of Evidence
Level 3 Laryngoscope , 2024
Background
Chronic rhinosinusitis (CRS) is a common chronic disease that seriously affects patients’ quality of life and imposes a heavy physical and mental burden on patients. There is growing evidence that sleep disorders are strongly associated with patients with CRS. However, there is no systematic evidence to clarify the prevalence and influencing factors of sleep disorders in patients with CRS with nasal polyps (NP) (CRSwNP) and CRS without NP (CRSsNP). For this reason, this study will systematically analyse the prevalence of sleep disorders in patients with CRSwNP and CRSsNP and explore the related influencing factors.
Methods and analysis
We will electronically search PubMed, Web of Science, Embase, Cochrane, Ovid, Scopus, the China National Knowledge Infrastructure, the Wanfang database, the China Biomedical Literature Database and the China Scientific Journals Database from the establishment of the database to September 2023 to collect the prevalence of sleep disorders in patients with CRSwNP or CRSsNP and related studies on factors affecting sleep disorders. Two researchers will independently conduct literature screening and data extraction and evaluate the quality of the included studies using the Newcastle-Ottawa Quality Scale and Agency for Healthcare Research and Quality scales. The extracted data will be meta-analysed using Review Manager 5.3 and Stata 14.0 software, and the quality of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation. Publication bias will be assessed using the funnel plots, Egger’s test and Begg’s test.
Ethics and dissemination
This review will not require ethical approval, as we will only use research data from the published documents. Our final findings will be published in a peer-reviewed, open-access journal for dissemination.
PROSPERO registration number
CRD42023446833.
Objectives:
Approximately 20% of patients with chronic rhinosinusitis (CRS) have comorbid obstructive sleep apnea (OSA). Patients with undiagnosed OSA are at high risk for perioperative complications. The Sinonasal Outcomes Test (SNOT-22) Questionnaire is commonly administered to CRS patients, whereas OSA screening tools are less routinely employed. This study compared SNOT-22 sleep subdomain (Sleep-SNOT) scores among non-OSA CRS versus OSA-CRS patients undergoing ESS, and assessed sensitivity, specificity, and diagnostic accuracy of the Sleep-SNOT for OSA screening.
Methods:
Retrospective review of patients that underwent endoscopic sinus surgery (ESS) for CRS from 2012 to 2021. Patients either carried a reported OSA diagnosis and completed the SNOT-22, or had undocumented OSA status and completed both STOP-BANG and SNOT-22. Demographics, questionnaire scores, and OSA status were collected. A receiver operating characteristic (ROC) curve assessed cutoff scores, sensitivity, and specificity of the Sleep-SNOT for OSA screening.
Results:
Of 600 patients reviewed, 109 were included. 41% had comorbid OSA. OSA patients had a higher BMI (32.1 ± 7.7 vs. 28.35 ± 6.7 kg/m2 ; p = 0.02), Sleep-SNOT (21.96 ± 12.1 vs. 16.8 ± 11.2; p = 0.021) and STOP-BANG (3.1 ± 1.44 vs. 2.06 ± 1.27; p = 0.038) scores. A Sleep-SNOT score of 17.5 had a sensitivity of 68.9%, specificity of 55.7%, and diagnostic accuracy of 63% for OSA detection (p = 0.022).
Conclusions:
Sleep-SNOT scores are greater for CRS-OSA patients. The Sleep-SNOT ROC curve demonstrates a high sensitivity, specificity, and accuracy for OSA screening in CRS patients. A Sleep-SNOT score of ≥17.5 should prompt further OSA evaluation. The Sleep-SNOT may be considered as a surrogate OSA screening tool when other validated tools are not employed.
Level of evidence:
Retrospective chart review, Level 3 Laryngoscope, 2023.
Historically, frontal sinus surgery has evolved from external approaches to endoscopic surgery. Endoscopic intranasal approach has revolutionized frontal sinus surgery and has become the standard approach to frontal sinus disease although open approaches remain relevant in situations of difficult disease or as part of combined approaches. In recent decades, the number of endoscopic surgical procedures performed on the frontal sinus and the associated costs have increased considerably. Some of the more recent medical therapies for the treatment of chronic rhinosinusitis (CRS) are associated with significant costs. We are moving toward precision medicine in which the characteristics of the disease and the expectations of the patient are taken into account to offer the best treatment among the various options. This chapter addresses the epidemiology and socio-economic impact of frontal sinus diseases and frontal sinus surgery.KeywordsFrontal sinusHistoryAnatomySurgeryIndicationsComplicationsEconomic importancePediatrics
Background:
Productivity loss and activity limitations due to chronic rhinosinusitis (CRS) are known to contribute to the significant economic and personal burden of disease. The purpose of this study was to evaluate productivity and activity impairment before and after endoscopic sinus surgery (ESS) for medically refractory CRS.
Methods:
Prospective, multi-institutional, observational cohort study. Patients diagnosed with medically refractory CRS completed the Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire before surgery and approximately 6-months post-procedure. Factors associated with minimal clinical important differences (MCID) for productivity and activity impairment were identified.
Results:
A total of 279 study participants were screened for inclusion, of which 176 (63.1%) with postoperative follow-up were included in the final cohort. Preoperative productivity and activity impairment were described in 63.2% and 69.8% of patients, respectively. Among those patients, postoperative improvement equaling at least one MCID was reported in both productivity (76.1%) and activity (76.4%) impairment. Multivariate regression identified sphenoidotomy (odds ratio [OR] = 4.18, 95% CI:1.03-17.02) as the only factor associated with increased likelihood of productivity improvement, whereas septoplasty during ESS (OR = 8.45, 95% CI:2.33-30.68) and migraine (OR = 0.35; 95% CI:0.12-0.96) were associated with differential odds of activity improvement.
Conclusions:
CRS is associated with a substantial burden on productivity and activity that significantly improves after treatment with ESS. These data may facilitate improved patient counseling and shared-decision making regarding surgical management for CRS. This article is protected by copyright. All rights reserved.
Background
Mental health conditions are common in the United States, and recent efforts have examined the development of mental health conditions among patients with sinusitis.
Objectives
The purpose of this study was to investigate the association between depression, anxiety, and financial hardship among patients with sinusitis.
Methods
Cross-sectional study using the 2018 National Health Interview Survey (NHIS). Data regarding demographics, perceived financial hardship, self-reported depression and anxiety, mental healthcare utilization, and treatment compliance were obtained.
Results
Among patients with sinusitis (N = 28 million adults), 9% reported depression and 24% reported anxiety. Sinusitis patients with depression and anxiety reported an increased severity of financial insecurity (p < 0.001). On multivariable logistic regression, worsening financial insecurity increased the odds of depression and anxiety. Patients reporting the highest financial insecurity severity had the highest odds of depression (OR = 3.88, 95% CI = 3.84–3.93, p < 0.001) and anxiety (OR = 2.09, 95% CI = 2.08–2.10, p < 0.001) among measures of financial stress. Specific financial stressors were independently associated with patient-reported depression and anxiety. Sinusitis patients with increased financial insecurity were more likely to require mental health services and treatment (p < 0.001), but were also more likely to report cost-related treatment noncompliance (p < 0.001) and reduced access to mental healthcare due to costs (p < 0.001).
Conclusion
Perceived financial hardship is associated with self-reported depression and anxiety among patients with sinusitis. Sinusitis patients with financial hardship also face challenges in accessing and maintaining mental health services and treatment due to costs. Understanding the burden of financial insecurity on mental health and access to treatment may improve quality of care through the development of screening tools and individualized treatment strategies.
Background
Dupilumab is a novel monoclonal antibody that recently received FDA approval for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). Endoscopic sinus surgery (ESS) has been the mainstay of treatment for patients refractory to initial medical therapy. Data comparing the cost-effectiveness of these treatments is scarce. The objective of this study is to compare the cost-effectiveness of dupilumab and ESS treatment for patients with CRSwNP refractory to medical therapy.
Methods
A cohort-style Markov decision tree economic evaluation with 10-year time horizon was performed. The two comparative treatment strategies were dupilumab therapy or ESS followed by postoperative maintenance therapy. Patients with response to treatment continued with either maintenance or dupilumab therapy; patients with no response underwent ESS. The primary outcome measure was incremental cost per quality-adjusted life year (QALY) calculated from sino-nasal outcome test (SNOT-22) scores. Sensitivity analyses were performed including discounting scenarios and a probabilistic sensitivity analysis.
Results
The dupilumab strategy cost $195,164 and produced 1.779 QALYs. The ESS strategy cost $20,549 and produced 1.526 QALYs. This implies an incremental cost of $691,691 for dupilumab for every one-unit increase in QALY compared with ESS. Probability sensitivity analysis indicated that ESS was more cost-effective than dupilumab in all iterations.
Conclusions
While dupilumab and ESS may demonstrate similar clinical effectiveness, ESS remains the most cost-effective treatment option and should remain standard of care for CRSwNP patients refractory to medical therapy.
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Zusammenfassung Hintergrund und Ziele Bisherige Studien konnten zeigen, dass sich das olfaktorische Riechvermögen bei Patienten mit chronischer Rhinosinusitis mit Polypenbildung nach einer funktionell endoskopischen Nasennebenhöhlenoperation (FESS) verbessert. Aussagen bezüglich der Veränderung der trigeminalen Sensibilität nach dem Eingriff fehlten jedoch bisher. Das Ziel der vorliegenden Untersuchung war es daher zu untersuchen, inwieweit die operative Therapie mit FESS bei Patienten mit chronischer Rhinosinusitis mit Polypenbildung zu einer Verbesserung des olfaktorischen Riechvermögens und der trigeminalen Sensibilität führt. Außerdem sollten mögliche Zusammenhänge zwischen dem olfaktorischen Riechvermögen und der trigeminalen Sensibilität eruiert und der Einfluss von Alter, Polyposis-Grad und dem subjektiv eingeschätzten Riechvermögen auf die Outcomes evaluiert werden. Methoden In die monozentrische, prospektive Studie wurden 54 Patienten eingeschlossen – 34 Patienten aus der Hals-Nasen-Ohren-Klinik des Universitätsklinikums Erlangen mit Indikation zur FESS aufgrund der Diagnose chronischer Rhinosinusitis mit Polypenbildung und 20 gesunde Kontrollpatienten. Die Patienten beider Studiengruppen wurden im Abstand von drei Monaten hinsichtlich ihres subjektiv eingeschätzten Riechvermögens befragt. Außerdem wurde an beiden Terminen eine ausführliche olfaktorische Riechtestung mittels eines standardisierten SchwelleDiskrimination-Identifikations-Tests (SDI) und eine KohlenstoffdioxidSchwellenbestimmung mittels Trigeminometer zur Prüfung der trigeminalen Sensibilität durchgeführt. Bei den Teilnehmern in der Patientengruppe wurde zudem der Polyposis-Grad erhoben. Die Untersuchungen in der Patientengruppe erfolgten unmittelbar präoperativ und drei Monate postoperativ. Ergebnisse und Beobachtungen In der Patientengruppe zeigte sich postoperativ eine statistisch signifikante Verbesserung des olfaktorischen Riechvermögens sowohl beim subjektiv 2 eingeschätzten Riechempfinden (p = 0,00) als auch beim SDI-Wert (p = 0,001). Der SDI-Wert war in der Kontrollgruppe (35,5 ± 5,1, Range 24-44,3) im Vergleich zur Patientengruppe (23,6 ± 10,7, Range 7-43,5) bereits zu Beginn der Studie signifikant erhöht (p <0,001). Der Vergleich zwischen den beiden Studiengruppen war zu Studienende ebenfalls signifikant (p = 0,003). In der Patientengruppe waren die PräPost-Vergleiche nach FESS für die einzelnen Testkomponenten des SDI-Tests ebenfalls signifikant, während für die Kontrollgruppe keine signifikanten Veränderungen im Beobachtungsintervall festgestellt wurden. Der Vergleich der trigeminalen Sensibilität zwischen den beiden Studiengruppen zu Studienbeginn zeigte mit p = 0,014 einen signifikanten Unterschied. Bei der Untersuchung der trigeminalen Schwelle konnte für die Patientengruppe postoperativ eine Reduktion der durchschnittlichen Reaktionszeit von 966,3 ± 645,2 Millisekunden auf 780,1 ± 629,8 Millisekunden beobachtet werden. Die Veränderung zeigte mit p = 0,071 einen Trend zur Signifikanz, während die Kontrollgruppe kaum Veränderungen aufwies. In der Patientengruppe konnte sowohl für die prä- als auch für postoperative subjektive Einschätzung des Riechvermögens ein starker Zusammenhang festgestellt werden (r = 0,69 und r = 0,72). Außerdem bestand ein p = 0,003 signifikanter, moderater, negativ gerichteter Zusammenhang zwischen PolyposisGrad und SDI-Wert (r = -0,47, p = 0,003). Die Prüfung möglicher Korrelationen zwischen den einzelnen Teilen der Riechtestung und der trigeminalen Sensibilität lieferte entweder keine oder nur schwachen Zusammenhänge in beiden Studiengruppen. Schlussfolgerungen Die Studienergebnisse konnten zeigen, dass die FESS bei Patienten mit chronischer Rhinosinusitis mit Polypenbildung eine maßgebliche Verbesserung von olfaktorischem Riechvermögen, trigeminaler Sensibilität und subjektiv eingeschätztem Riechempfinden bewirkt. Ausgedehntere Polypen hatten eine stärkere negative Auswirkung auf das olfaktorische Riechvermögen als solche mit kleinerem Lund-Kennedy-Score. Da sich das olfaktorische Riechvermögen nicht bei allen Patienten verbessert hat, sollte die Indikation zur Operation stets sorgfältig und unter Berücksichtigung des Patientenalters gestellt werden.
Objective:
Chronic rhinosinusitis (CRS) with nasal polyp (wNP) is a more severe inflammatory form of CRS that often coexists with obstructive sleep apnea (OSA). However, little is known the relationship between OSA and immunologic profile on patients with CRSwNP. We aimed to investigate the immune profile of patients with CRSwNP according to OSA severity.
Methods:
This study included 63 patients with CRSwNP and nine control subjects. Protein levels of inflammatory mediators were determined using multiplex immunoassay. All patients underwent standard polysomnography.
Results:
We found that, in patients with eosinophilic CRSwNP (ECRSwNP), IL-6 and CXCL-1 (type 1 immune-related markers) were upregulated in cases of moderate-to-severe OSA. Additionally, IL-4, IL-13, CCL-11, CCL-24 (type 2 immune-related markers), and IL-17A (type 3 immune-related marker) were increased in patients with moderate-to-severe OSA. Though there were no significant differences in type 1, 2, or 3 immune-related markers among patients with non-eosinophilic CRSwNP (NECRSwNP) according to the severity of OSA, TGF--β expression was increased in those with moderate-to-severe OSA. Furthermore, in ECRSwNP with moderate-to-severe OSA, associations were detected between serum markers and some upregulated inflammatory markers.
Conclusion:
Our findings revealed that OSA may increase the heterogeneity of immune profiles (types 1, 2, and 3) in patients with ECRSwNP but not in those with NECRSwNP.
Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document.
Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.
Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided.
Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS.
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Background
Chronic rhinosinusitis (CRS) is associated with sleep dysfunction, but the underlying pathophysiology is poorly understood. The purpose of this study was to determine if mucosal eosinophilia or neutrophilia were associated with sleep dysfunction severity or altered the improvement in sleep dysfunction following functional endoscopic sinus surgery (FESS).
Methods
A total of 104 patients with medically refractory CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP), completed the Pittsburgh Sleep Quality Index (PSQI) before and after FESS. Anterior ethmoid mucosa was collected during FESS and densest infiltrates of eosinophilia and neutrophilia per high‐power field (HPF) were determined by microscopy. Eosinophilic (>10 eosinophils/HPF) and neutrophilic (>4 neutrophils/HPF) CRS were then compared to preoperative and postoperative PSQI measures.
Results
Of 104 study participants, 88 (85%) reported preoperative PSQI scores consistent with “poor sleep,” (PSQI total > 5). The cohort overall demonstrated significant improvement in poor sleep (65%; χ² = 12.03; p < 0.001) 16.8 ± 5.0 months after FESS. Regardless of nasal polyposis, neither eosinophilic nor neutrophilic CRS was associated with differences in mean postoperative PSQI improvement. However, in patients with neutrophilic CRSsNP, there was a significant relationship between severity of neutrophilia and improvement in sleep latency (R = –0.798, p = 0.003) and sleep efficacy (R = –0.777, p = 0.005).
Conclusion
Chronic inflammation has been hypothesized to play a pathophysiologic role in sleep dysfunction associated with CRS. This study suggests that in patients with medically refractory CRS, evidence of mucosal eosinophilia and neutrophilia lack strong associations with patient‐reported sleep dysfunction or improvements in sleep quality after FESS, overall. However, neutrophilia may impact sleep latency and efficacy in patients with CRSsNP.
Historically, osteopathic principles have focused on the appropriate drainage of cranial structures to relieve symptoms of rhinitis, which include nasal congestion, anterior/posterior rhinorrhea, sneezing, and itching. Allergic rhinitis is primarily an aberrant immunologic reaction caused by cytokines secreted from lymphocytes that traverse the lymphatic pathway throughout the body. Several studies have documented that, when manipulated, the lymphatic system enhanced the motion of these lymphocytes to important immune structures in both human and animal models. Additionally, modulation of both sympathetic and parasympathetic outflow has been found either to inhibit or enhance secretion and/or drainage of important allergic sites. Osteopathic approaches to rhinitis play an effective role in the comprehensive management of rhinitis, and techniques based on these approaches are therapeutic options for rhinitis. This article provides an up-to-date literature review about the management of rhinitis using the 5 models of osteopathic medicine: biomechanical, respiratory-circulatory, metabolic, neurologic, and behavioral.
Assessment of the nose is critical in evaluating obstructive sleep apnea (OSA) because the nose plays an important role in the physiology of sleep by regulating nasal airway resistance and stimulating ventilation. Nasal obstruction is common in sleep apnea, contributes to OSA, and interferes with tolerance of OSA treatment with continuous positive airway pressure (CPAP) or oral appliances. Medical treatment of nasal obstruction and rhinitis with nasal corticosteroid sprays is associated with improved OSA severity and sleep symptoms. Surgery for nasal obstruction, including septoplasty, turbinate reduction, rhinoplasty, and sinus surgery, improves OSA-related quality-of-life measures and CPAP tolerance.
Allergic disease can have profound influence on sleep through several anatomical and physiological mechanisms. When medical therapies fail to adequately alleviate symptoms, surgery can play a role in improving sleep quality. Here we describe the treatment modalities available to address the allergic patient that presents with complaints of sleep disturbance and discuss relevant literature for these interventions.
Atopic dermatitis, or eczema, is chronic inflammatory pruritic skin disorder, affecting both children and adults. Patients with atopic dermatitis often experience sleep disturbance, especially during flares of their skin disease. Sleep disturbances in atopic dermatitis range from difficulty falling asleep, shorter sleep duration, nighttime awakenings, and daytime sleepiness and fatigue. In addition, atopic dermatitis has also been associated with parasomnias and sleep-related breathing disorders. In children with atopic dermatitis, sleep disturbance may extend from the child to adult caregiver. The effects of sleep disruption in this setting are widespread including increased risk of mood disorders, impaired ability to perform activities of daily living, and decreased quality of life.
Objective: Facial pain associated with temporomandibular disorder (TMD) is considered a component of Costen’s syndrome. However, prior to the current study, no previous clinical and radiographic studies have addressed facial pain in patients with TMD.
Methods: The study included 212 patients with chronic facial pain examined in an otolaryngology clinic. These were stratified into 132 patients with TMD and 80 patients without TMD. Clinical and radiographic findings were documented in both groups.
Results: Forty-eight patients in the TMD group had normal endoscopic findings and clear CT scans and had their facial pain directly attributable to TMD.
Conclusion: In patients presenting with facial pain, where nasal endoscopy reveals no abnormality, TMD should be specifically addressed, especially if CT scans of the paranasal sinuses are clear.
Objective
Up to 75% of patients with chronic rhinosinusitis (CRS) suffer with poor sleep quality and reduced quality of life. Endoscopic sinus surgery has demonstrated encouraging results in improving sleep function. The aim of this systematic review is to assess the change in sleep quality after surgery for CRS.
Data Sources
PubMed, Web of Science, EMBASE.
Review Methods
An electronic search was conducted with the keywords “sinusitis” or “rhinosinusitis” and “sleep.” Studies were included only when adults underwent endoscopic sinus surgery and were evaluated pre- and postoperatively by the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), the Apnea-Hypopnea Index (AHI), the sleep domain of Sino-Nasal Outcome Test–22, or the sleep domain of Rhinosinusitis Disability Index.
Results
The database search yielded 1939 studies, of which 7 remained after dual-investigator screening. The standardized mean differences (95% CI) for the ESS, PSQI, and AHI were −0.94 (−1.63 to −0.26), −0.80 (−1.46 to −0.14), and −0.20 (−0.32 to −0.07), indicating large, moderate to large, and small improvements, respectively. All analyses displayed high heterogeneity ( I ² = 95%-99%).
Conclusion
Sleep quality, as measured by the ESS and PSQI surveys, shows substantial improvement after surgery for CRS, with smaller improvement seen for AHI. Generalizability of our results is limited by high heterogeneity among studies and by broad confidence intervals that cannot exclude small to trivial changes. The findings of this meta-analysis provide insight into the effect of CRS-related endoscopic sinus surgery on sleep quality, which should guide future research direction and counseling of patients in the clinical setting.
Background:
Chronic rhinosinusitis (CRS) is a highly prevalent inflammatory condition, with significant effects on morbidity and quality of life. Given that other chronic inflammatory conditions have been associated with increased mortality risk, we sought to evaluate the relationship between mortality and CRS including the influence of asthma. Our objective was to determine if CRS, with or without asthma, is associated with altered risk of mortality.
Methods:
Using a statewide population database, we retrospectively identified 27,005 patients diagnosed with CRS between 1996 and 2012, and 134,440 unaffected controls matched 5:1 on birth year and sex. Risk of mortality was determined from Cox models and Kaplan-Meier curves were used to compare survival.
Results:
A significant interaction between CRS and asthma status was observed in which CRS appeared to confer a protective effect in asthma patients. Asthma, when present, increased mortality in CRS-negative controls (p-interaction < 0.0001). Independent of asthma status, CRS patients exhibited a decreased mortality risk (hazard ratio [HR] = 0.80; 95% confidence interval [CI], 0.74 to 0.85) compared to controls. However, in patients diagnosed at or before the median age of CRS onset (42 years) independent of asthma status, survival was not improved (HR = 0.98; 95% CI, 0.81 to 1.18). Risk of mortality was greater in CRS with nasal polyps (n = 1643) compared to 25,362 polyp-negative CRS patients (HR = 1.38; 95% CI, 1.09 to 1.77).
Conclusion:
CRS was associated with lower risk of mortality compared to controls, and appeared to mitigate increased mortality from asthma. We posit that better survival conferred by CRS may be secondary to treatment. However, the etiology of this relationship and the effect of CRS treatment on mortality are unknown.
Objective: Previous studies have found that excessive daytime sleepiness (EDS) is a more common problem in asthmatic subjects than in the general population. The aim of this study was to investigate whether the prevalence of EDS is increased in asthmatic subjects and, if so, to analyse the occurrence of potential risk factors for EDS in asthmatics.
Methods: Cross-sectional epidemiological study. In 2008, a postal questionnaire was sent out to a random sample of 45,000 individuals aged 16–75 years in four Swedish cities.
Results: Of the 25,160 persons who participated, 7.3% were defined as having asthma. The prevalence of EDS was significantly higher in asthmatic subjects (42.1% vs 28.5%, p<0.001) compared with non-asthmatic subjects. Asthma was an independent risk factor for EDS (adjusted OR 1.29) and the risk of having EDS increased with asthma severity. Risk factors for EDS in subjects with asthma included insomnia (OR, 3.87; 95% CI, 3.10–4.84), chronic rhinosinusitis (OR, 2.00; 95% CI, 1.53–2.62), current smoking (OR, 1.60; 95% CI, 1.15–2.22) and obesity (OR, 1.53; 95% CI, 1.09–2.13).
Conclusions: EDS is a common problem among subjects with asthma. Asthma is an independent risk factor for having EDS. Furthermore, subjects with asthma often have other risk factors for EDS, many of them potentially modifiable.
Although the somnogenic actions of interferon-α (IFNα) and IFNβ have been reported, the sleep effects of IFNγ remained unknown. Thus, we investigated the effects of intracerebroventricular injection of human IFNγ on sleep in rabbits. IFNγ dose-dependently increased nonrapid eye movement sleep (NREMS), electroencephalographic slow wave activity and brain temperature (Tbr). These effects were markedly attenuated after the heat treatment of IFNγ. IFNγ suppressed rapid eye movement sleep if given during the light period, but not if given at dark onset. Although a tumor necrosis factor receptor fragment did not affect any sleep parameters when given at dark onset, it significantly attenuated IFNγ-induced NREMS and Tbr. These data suggest that IFNγ may be involved in the sleep responses during infection. Further, IFNγ may have a synergistic interaction with intrinsic TNFα in the brain.
Tumor necrosis factor (TNF) is a well characterized sleep- regulatory substance. To study receptor mechanisms for the sleep-promoting effects of TNF, sleep patterns were determined in control and TNF 55 kDa receptor knock-out (TNFR-KO) mice with a B6 3 129 background after intraperitoneal injections of saline or murine TNFa. The TNFR-KO mice had significantly less baseline sleep than the controls. TNFa dose-dependently increased non-rapid eye movement sleep (NREMS) in the con- trols but did not influence sleep in TNFR-KO mice. Although TNFR-KO mice failed to respond to TNFa, they had an increase in NREMS and a decrease in rapid eye movement sleep after interleukin-1b treatment. These results indicate that TNFa af- fects sleep via the 55 kDa receptor and provide further evi- dence that TNFa is involved in physiological sleep regulation. Current results also extend the list of species to mice in which TNFa and interleukin-1b are somnogenic.
Study objectives:
Sleep loss triggers changes in inflammatory signaling pathways in the brain and periphery. The mechanisms that underlie these changes are ill-defined. The Toll-like receptor 4 (TLR4) activates inflammatory signaling cascades in response to endogenous and pathogen-associated ligands known to be elevated in association with sleep loss. TLR4 is therefore a possible mediator of some of the inflammation-related effects of sleep loss. Here we describe the baseline electroencephalographic sleep phenotype and the biochemical and electroencephalographic responses to sleep loss in TLR4-deficient mice.
Design, measurements and results:
TLR4-deficient mice and wild type controls were subjected to electroencephalographic and electromyographic recordings during spontaneous sleep/wake cycles and during and after sleep restriction sessions of 3, 6, and 24-h duration, during which sleep was disrupted by an automated sleep restriction system. Relative to wild type control mice, TLR4-deficient mice exhibited an increase in the duration of the primary daily waking bout occurring at dark onset in a light/dark cycle. The amount of time spent in non-rapid eye movement sleep by TLR4-deficient mice was reduced in proportion to increased wakefulness in the hours immediately after dark onset. Subsequent to sleep restriction, EEG measures of increased sleep drive were attenuated in TLR4-deficient mice relative to wild-type mice. TLR4 was enriched 10-fold in brain cells positive for the cell surface marker CD11b (cells of the monocyte lineage) relative to CD11b-negative cells in wild type mouse brains. To assess whether this population was affected selectively by TLR4 knockout, flow cytometry was used to count F4/80- and CD45-positive cells in the brains of sleep deprived and time of day control mice. While wild-type mice exhibited a significant reduction in the number of CD11b-positive cells in the brain after 24-h sleep restriction, TLR4-deficient mice did not.
Conclusion:
These data demonstrate that innate immune signaling pathways active in the monocyte lineage, including presumably microglia, detect and mediate in part the cerebral reaction to sleep loss.
This prospective, randomized, and controlled study examined the effects of tumor necrosis factor soluble receptor type I (sTNFRI, a TNF-α antagonist) on experimentally induced rhinosinusitis in rats. The experimental groups received an instillation of lipopolysaccharide (LPS) plus an intramuscular injection of amoxicillin/clavulanate (antibiotic group), an instillation of sTNFRI (sTNFRI group), an instillation of sTNFRI and an injection of amoxicillin/clavulanate (sTNFRI/antibiotic group), or no additional treatment (LPS group). Histopathological changes were determined using hematoxylin-eosin and periodic acid-Schiff (PAS) staining. Leakage of exudate was determined using fluorescence microscopy. Vascular permeability was measured using the Evans blue dye technique. Expression of MUC5AC was measured using reverse transcriptase PCR. The sTNFRI, antibiotic, and sTNFRI/antibiotic groups had significantly less capillary permeability, mucosal edema, PAS staining, and expression of MUC5AC than the LPS group. There were no differences in capillary permeability, mucosal edema, PAS staining, and MUC5AC expression between the sTNFRI and sTNFRI/antibiotic groups. The antibiotic group had PAS staining similar to that of the sTNFRI and sTNFRI/antibiotic groups but had a greater increase in capillary permeability, mucosal edema, and MUC5AC expression. This study shows that sTNFRI reduces inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats.
Interleukin-1 beta (IL-1 beta) is a well characterized sleep regulatory substance. To study receptor mechanisms for the sleep-promoting effects of IL-1 beta, sleep patterns were determined in control and IL-1 type I receptor knockout (IL-1RI KO) mice with a B6x129 background after intraperitoneal injections of saline or murine recombinant IL-1 beta. The IL-1RI KO mice had slightly but significantly less sleep during the dark period compared with the controls. IL-1 beta dose dependently increased non-rapid eye movement sleep (NREMS) and suppressed rapid eye movement sleep (REMS) in the controls. The IL-1RI KO mice did not respond to IL-1 beta. In contrast, the IL-1RI KO mice increased NREMS and decreased REMS after administration of tumor necrosis factor-alpha (TNF-alpha), another well characterized sleep-promoting substance. These results 1) provide further evidence that IL-1 beta is involved in sleep regulation, 2) indicate that the effects of IL-1 beta on sleep are mediated by the type I receptor, and 3) suggest that TNF-alpha is capable of inducing sleep without the involvement of IL-1.
To determine whether variations in gene expression exist at multiple subsites along the sinonasal tract in patients with chronic sinusitis with polyps and in healthy controls.
Prospective, controlled study.
Academic medical center.
Tissue expression levels of 5 genes, previously found to be characteristic of ethmoid polyps, were measured using real-time quantitative polymerase chain reaction in 100 sinonasal tissue samples. Specimens harvested from 5 regions--the ethmoid sinus, septum, inferior turbinate, middle turbinate, and lateral nasal wall--in 10 patients with chronic sinusitis and ethmoid polyps were compared to tissue from similar regions in 10 control patients without sinusitis. Western blot analysis was performed to validate differential gene expression at the protein level.
Gene expression levels of ethmoid polyps differed significantly from those of healthy ethmoid mucosa, as well as tissue from 4 surrounding anatomical sites in both patients with chronic sinusitis and controls. Alterations specific to the polyp tissue included downregulated genes, prolactin-induced protein (fold change 377.2 ± 169.0, P < .0001), and zinc α2-glycoprotein (fold change 72.1 ± 26.5, P < .0001), as well as upregulated genes, met proto-oncogene (fold change 2.5 ± 0.7, P = .029), and periostin (fold change 7.5 ± 3.4, P = .003). No significant differences in gene expression was found for neurabin 2 (fold change 1.0, P = .99).
The transcriptional pattern of ethmoid polyps appears to be unique compared with other subsites in the sinonasal cavity of patients with chronic sinusitis. Care must be taken when collecting specimens for molecular studies of the sinonasal tract to differentiate polyp from nonpolyp tissue in chronic sinusitis.
Hepatocyte growth factor (HGF) is a growth factor thought to attenuate Th2-driven eosinophilic airway inflammatory responses. Increased expression of HGF and its receptor c-Met in nasal polyps suggests a role in disease pathogenesis. The effect of HGF on human sinonasal epithelial cell (SNEC) responses to Th2 inflammatory cytokines in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been explored.
SNECs isolated from patients with CRSwNP and control subjects were grown in cell culture at the air-liquid interface. The Th2 cytokine IL-13 was applied for 24 hours in the presence or absence of HGF. Eotaxin-3 and c-Met expression was assessed using real-time PCR, immunohistochemistry, and flow cytometry.
SNECs obtained from both CRSwNP and control subjects showed markedly increased expression of eotaxin-3 after exposure to IL-13. HGF significantly blocked IL-13-induced expression of eotaxin-3 in control SNECs, but not in SNECs derived from CRSwNP subjects.
SNECs are active participants in sinonasal mucosal immunity, expressing inflammatory mediators in response to potential pathogens and endogenous cytokines. Although Th2 cytokines can elicit expression of proeosinophilic mediators by SNECs, HGF appears to have a down-regulating effect on this response. In patients with CRSwNP, SNECs are resistant to this attenuation, showing continued IL-13-induced eotaxin-3 expression despite HGF treatment. Abnormalities in the regulation of epithelial cell responses to endogenous cytokines and growth factors may contribute to the persistent eosinophilic inflammatory state in CRSwNP.
Chronic daytime fatigue and excessive daytime sleepiness (EDS) are potentially invalidating and also common complaints in primary care and general neurological practice. The lack of distinction in the clinical use of terms like fatigue and sleepiness is an important issue. Although these semiological concepts present fundamental differences from physiological and pathological points of view, general medical literature still often confuses both symptoms. The objective of the present review is to contribute to the clinical distinction between fatigue and sleepiness and describe available measurement tools and respective treatment options. We found that sleepiness and fatigue both present with semiological multidimensionality and clinical complexity. Although relating to different underlying concepts, they can show overlapping features and several clinical conditions can present with both complaints simultaneously. Existing specific assessment tools are sometimes underutilised, causing EDS and fatigue to continue to be confounded. The blurring contributions of several studies are mainly due to the fact that typically only one of these two clinical dimensions is investigated. Despite consensus on objective sleepiness measures, simple and validated objective fatigue assessments are generally lacking and seem elusive. Causal and symptomatic treatment options exist predominantly for sleepiness-associated conditions. Although comprehension of sleepiness and its underlying physiology has seemed to improve over time, descriptions of common pathways of fatigue remain relatively incomplete. Clinical research and practice should systematically investigate both conditions with adequate measurement tools. Behavioural medicine is certainly underestimated, especially in the management of chronic daytime fatigue.
Clinical practice related to sleep problems and sleep disorders has been expanding rapidly in the last few years, but scientific research is not keeping pace. Sleep apnea, insomnia, and restless legs syndrome are three examples of very common disorders for which we have little biological information. This new book cuts across a variety of medical disciplines such as neurology, pulmonology, pediatrics, internal medicine, psychiatry, psychology, otolaryngology, and nursing, as well as other medical practices with an interest in the management of sleep pathology. This area of research is not limited to very young and old patients-sleep disorders reach across all ages and ethnicities. Sleep Disorders and Sleep Deprivation presents a structured analysis that explores the following: Improving awareness among the general public and health care professionals. Increasing investment in interdisciplinary somnology and sleep medicine research training and mentoring activities. Validating and developing new and existing technologies for diagnosis and treatment. This book will be of interest to those looking to learn more about the enormous public health burden of sleep disorders and sleep deprivation and the strikingly limited capacity of the health care enterprise to identify and treat the majority of individuals suffering from sleep problems. © 2006 by the National Academy of Sciences. All rights reserved.
Human interleukin 1 beta (IL-1 beta) is synthesized as an inactive precursor that is cleaved by IL-1 converting enzyme (ICE) between Asp116 and Ala117 to form COOH-terminal mature IL-1 beta and NH2-terminal IL-1 beta propeptide. Little is known about the fate of the NH2-terminal cleavage product. In this study, human recombinant (hr)IL-1 beta propeptide (amino acids 2-116) was produced and used to prepare specific antibodies which do not recognize mature human IL-1 beta. These anti-propeptide antibodies were used for immunoprecipitation of biosynthetically labeled proteins from lipopolysaccharide-stimulated human monocytes. Analysis of immunoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography revealed that these antibodies recognize precursor IL-1 beta and two unique proteins: one migrating at 17.5 kD and one at 14 kD. The larger of these two proteins has a migration nearly identical to that of the recombinant IL-1 beta propeptide, and most likely represents naturally derived propeptide. The protein migrating at 14 kD may result from a second cleavage by ICE, between Asp27 and Gly28. These proteins accumulate intracellularly and extracellularly during pulse-chase experiments, and therefore represent stable products of precursor IL-1 beta cleavage.
While nasal mucosal stimulation in animals has been reported to produce central apneas and while nasal packing in humans is known to produce sleep-disordered breathing, it is controversial whether intranasal obstruction in humans produces predominantly central or obstructive apnea. To answer this question, we studied eight normal men by having them sleep in random order with their nose open or occluded with petrolatum gauze. Esophageal pressure was measured to detect respiratory effort, and standard techniques were used to monitor and score the stages of sleep. Intranasal occlusion increased both the number of apneas plus hypopneas per hour of sleep and the minutes of obstructive events per hour of sleep (p<0.05). The minutes of central events per hour of sleep also increased significantly but not to the degree that occurred with obstructive events. Nasal obstruction produced no immediate changes in pulmonary function. The subject with the highest resistance measured through the mouth with the pulse flow method had the most apneas following nasal occlusion. We conclude that intranasal obstruction produces predominantly obstructive apneas and hypopneas during sleep.
Sleep disturbance, reduced quality-of-life (QOL), and other components of "sickness behavior" in patients with chronic rhinosinusitis (CRS) are poorly understood. These complex changes in central behavior are due to the effects of immune mediators acting in the brain. We hypothesized that immune mediators that have been associated with CRS are also associated with sickness behavior, somnifacient complaints, and CRS disease specific QOL.
Twenty patients with CRS were prospectively enrolled and completed the Pittsburgh Sleep Quality Index (PSQI), disease-specific QOL, and olfactory instruments. Ethmoid mucosa was obtained and RT-PCR was performed for the cytokines IL-4,-13, and transforming growth factor-beta (TGF-β). Average change in crossover threshold was calculated and differences in gene expression were correlated with sleep quality, CRS specific QOL and disease severity.
Patients with CRS reported overall poor sleep quality and poor CRS specific QOL with significant correlations between them. Increased expression of TGF-β (r=-0.443;p=0.050) and IL-4 (r=-0.548;p=0.012) correlated with sleep dysfunction while IL-13 expression was linearly associated with worse sleep quality (PSQI scores r=-0.417;p=0.075). IL-4 and TGF-β expression was not associated with CRS disease severity or QOL, while significantly higher levels of IL-13 expression correlated with worse CRS disease severity and QOL.
Patients with CRS exhibited behavioral changes commonly referred to as sickness behavior which include poor sleep quality and reduced QOL. The up-regulation of IL-4 and TGF-β may contribute to inflammatory brain-mediated effects on sleep quality, while IL-13 may be a pleiotropic signaling molecule influencing sleep, QOL, and CRS disease severity.
NA/2b.
From cats prepared for chronic pollygraphic recording of sleep patterns, records were obtained for 8 hr, after (1) intracerebroventricular (i.c.v.) injection of artificial cerebrospinal fluid (aCSF), day 1; (2) i.c.v. injection of interleukin-1 (Il-1), day 2; and (3) injection of aCSF, day 3. Three doses of Il-1 were tested. The dose of 40 nmol totally inhibited sleep, whereas the dose of 10 nmol slightly prolonged sleep. The dose of 20 nmol of Il-1 elicited sleep and a body temperature increase. Total sleep (TS) time was significantly increased, due mainly to the significant increase in non-REM (NREM) sleep as compared to control day 1. REM sleep was also increased, but this increase did not reach statistical significance. Wakefulness (W) was significantly reduced. At this time cats were febrile. On day 3, a further significant increase in TS occurred. NREM was significantly increased compared with day 1, whereas the increase in REM sleep was significant compared to both day 1 and day 2. At this time body temperature was normal. The increase in REM sleep on days 2 and 3 resulted entirely from the significant increase in the number of REM periods. The results show that Il-1 at a dose of 20 nmol has sleep-promoting effects on NREM and REM sleep concomitant with pyrogenic effects. These two responses differed in their time courses and were not correlated (correlation coefficients were all nonsignificant).
To evaluate sleep quality in patients with chronic rhinosinusitis (CRS) using a validated outcome measure and to compare measures of CRS disease severity with sleep dysfunction.
Cross-sectional evaluation of a multi-center cohort.
According to the 2007 Adult Sinusitis Guidelines, patients with CRS were prospectively enrolled from four academic, tertiary care centers across North America. Each subject completed the Pittsburgh Sleep Quality Index (PSQI) instrument, in addition to CRS-specific measures of quality-of-life (QOL), endoscopy, computed tomography (CT), and olfaction. Patient demographics, comorbid conditions, and clinical measures of disease severity were compared between patients with "good" (PSQI; ≤5) and "poor" (PSQI; > 5) sleep quality.
Patients (n = 268) reported a mean PSQI score of 9.4 (range: 0-21). Seventy-five percent of patients reported PSQI scores above the traditional cutoff, indicating poor sleep quality. Patients with poor sleep quality were found to have significantly worse QOL scores on both the Rhinosinusitis Disability Index (P < 0.001) and 22-item Sinonasal Outcome Test (P < 0.001). No significant differences in average endoscopy, CT, or olfactory function scores were found between patients with good or poor sleep quality. Tobacco smokers reported worse average PSQI total scores compared to nonsmokers (P = 0.030). Patients reporting poor sleep were more likely to have a history of depression, even after controlling for gender (P = 0.020).
The majority of patients with CRS have a poor quality of sleep, as measured by the PSQI survey. Poor sleep quality is significantly associated with CRS-specific QOL, gender, comorbid depression, and tobacco use, but not CT score or endoscopy grade.
2b. Laryngoscope, 2013.
Exogenous interleukin-1 (IL-1), applied intraventricularly, has been reported to enhance slow wave sleep. Here, we demonstrate that endogenous interleukin-1-like activity and IL-1β of the cat CSF increases during sleep in comparison to wake.
TUMOR necrosis factor-alpha (TNF alpha) is thought to play a physiological role in the brain. These studies were performed to determine whether a diurnal rhythm of TNF alpha exist in the rat brain. Samples were collected from hippocampus, hypothalamus, cerebral cortex, cerebellum, pens and midbrain at light onset and at 6 h intervals thereafter over a day. A TNF alpha bioassay was used to measure TNF alpha in each area. TNF alpha was highest at light onset in the hypothalamus, hippocampus and cerebral cortex. Levels at light onset were about 10-fold greater than minimal night-time levels. Changes in TNF alpha activity in other brain areas were also evident, but smaller. These results support the hypothesis that TNF alpha has physiological roles in the brain.
Proinflammatory cytokines, including interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are involved in sleep regulation. IL-10 is an anti-inflammatory cytokine that inhibits proinflammatory cytokine production. We hypothesized that IL-10 could attenuate sleep. Thirty-one male rabbits were used. Three doses of IL-10 (5 ng, 50 ng, and 250 ng) were injected intracerebroventricularly during the rest (light) period. One dose of IL-10 (250, ng) was injected during the active (dark) cycle. Appropriate time-matched control injections of saline were given to the same rabbits on different days. The two highest doses of IL-10 significantly inhibited spontaneous nonrapid eye movement sleep if IL-10 was given during the light cycle. The highest dose of IL-10 (250 ng) also significantly decreased rapid eye movement sleep. IL-10 administered at dark onset had no effect on sleep. The sleep inhibitory properties of IL-10 provide additional evidence for the hypothesis that a br;tin cytokine network is involved in regulation of physiologic sleep.
Although it is well established that the cytokines tumor necrosis factor (TNF) and interleukin (IL)-1 regulate sleep, there is no direct evidence implicating IL-6 in the regulation/modulation of sleep. We tested the hypotheses that central administration of rat recombinant IL-6 increases non-rapid eye movements (NREM) sleep of rats, and that central administration of anti-IL-6 antibodies reduces NREM sleep. Effective doses of IL-6 (100 and 500 ng) initially enhance NREM sleep, after which NREM sleep may be suppressed. IL-6 induces febrile responses at doses lower (50 ng) than those required to alter sleep. Rapid eye movements (REM) sleep is not altered by the doses of IL-6 tested. Central administration of monoclonal or polyclonal anti-rat IL-6 antibodies does not alter any of the parameters determined in this study. Collectively, these results support the hypothesis that IL-6 possesses sleep modulatory properties. However, this cytokine may not be involved in the regulation of spontaneous sleep in healthy animals because antagonizing the IL-6 system using antibodies does not alter sleep. The interpretation of these data is consistent with those of previous studies demonstrating correlations between increased IL-6 and excessive daytime sleepiness during some pathophysiological conditions.
Background
Recruitment of macrophages is crucial to the pathogenesis of the nasal polyp (NP) because this disease is believed to be inflammation related. Information regarding the expression of C-C chemokine ligand 2 (CCL2), an essential modulator of monocyte chemotaxis in nasal polyp fibroblasts (NPFs), remains unavailable. In this study, the effects of tumor necrosis factor (TNF)-α on CCL2 expression in NPFs and the signaling pathway involved were investigated.
Methods
Primary cultures of NPFs were established from NPs. The expressions of CCL2, c-Fos, and c-Jun mRNAs in NPF after TNF-α stimulation were detected by Northern blot. Western blot was used to examine the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Activator protein (AP) 1/DNA interactions were evaluated by electrophoretic mobility shift assay (EMSA).
Results
Northern blot showed that TNF-α stimulated CCL2 gene expression in NPFs. Significant increase of B-Raf, phosphorated MAPK including mitogen-activated ERK-activate kinase (MEK)1/2, extracellular signal-related kinase 1/2, and p38 were detected by Western blot. c-Fos and c-Jun mRNAs were induced by TNF-α, and PD98059 (MEK inhibitor) and SB203580 (p38 inhibitor) abolished the up-regulation of c-Fos. EMSA revealed that TNF-α increased AP-1/DNA binding, and PD98059 and SB203580 attenuated this reaction, possibly via reducing c-Fos synthesis. PD98059 and curcumin (AP-1 inhibitor) markedly suppressed the TNF-α–induced CCL2 expression, whereas the effect of SB203580 was less noted.
Conclusion
TNF-α induces CCL2 transcription in NPFs. B-Raf/MEK/ERK signaling cascade and to a less extent the p38 pathway are responsible for c-Fos activation and the subsequent AP-1/DNA interaction leading to CCL2 expression.
Recently the role of various cytokines in the pathogenesis of chronic rhinosinusitis has come under investigation. Various studies have reported increased levels of interleukin-3, interleukin-4, interleukin-5, interleukin-13, and granulocyte macrophage-colony stimulating factor in the sinonasal mucosa of patients with chronic rhinosinusitis. The present study investigated the levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1 beta), interleukin-5 (IL-5), interleukin-6 (IL-6), interleukin-8 (IL-8), and turner necrosis factor-alpha (TNF-alpha), in the sinonasal mucosa of patients with chronic rhinosinusitis, and evaluated the response of these cytokines to oral corticosteroids. Chronic rhinosinusitis subjects (n = 15) and control subjects (n = 9) underwent ent nasal endoscopy and biopsy of the sinonasal mucosa. Chronic rhinosinusitis subjects were subsequently tr treated with a 10-day tapering dose of prednisone followed by a second sinonasal endoscopic exam and biopsy. Mucosal biopsy specimens were immunostained for IL-I beta, IL-5, IL-6, IL-8, and TNF-a. In chronic rhinosinusitis subjects, mucosal levels of IL-1 beta IL,-6 IL-8, and TNF-alpha were significantly elevated when compared with control subjects, and levels of IL-5 demonstrated a strong trend toward elevation. In posttreatment chronic rhinosinusitis subjects, levels of IL-6 were significantly decreased when compared with pretreatment levels, and TNF-alpha levels demonstrated a significant trend coward reduction. These findings support the hypothesis that the inflammatory response in chronic rhinosinusitis is associated with elevated levels of pro-inflammatory cytokines, and suggest that oral corticosteroids may evert a benefic beneficial effect by significantly reducing the levels of IL-6 and TNF-alpha.
Background: Urinary leukotriene E4 (LTE4) is a marker of the body's production of cysteinyl LTs, important mediators of airway inflammation. The role of the latter in nocturnal asthma is a topic of increasing interest.
Objective: This investigation was aimed at determining whether nighttime attacks are associated with increased release of LTs, expressed by urinary LTE4, and the relationship between the two phenomena.
Methods: Three groups were studied: group A, seven control subjects; group B, nine asthmatic patients without nocturnal attacks; and group C, nine asthmatic patients with a comparable daytine FEV1 but who were experiencing nocturnal exacerbations (morning dips in peak expiratory flow >20%). Urine was collected over 24 hours in three samples (9:00 am to 3:00 pm; 3:00 pm to 9:00 pm; and 9:00 pm to 9:00 am). LTE4 was measured by high-performance liquid chromatography and radioimmunoassay and expressed as nanograms per millimole of creatinine.
Results: No significant differences between urinary LTE4 were noticed within groups A and B. Conversely, in group C urinary LTE4 at night (geometric mean with 95% confidence interval: 35.16 with 28.77–42.85) was significantly higher than that of the other samples (respectively 23.12 with 17.78–30.06, p<0.05; and 25.18 with 21.03–30.13, p<0.02); it was also significantly higher than in all the samples of other groups. A significant (p<0.02) linear correlation was observed between morning dip in peak expiratory flow and the log urinary LTE4 in the nocturnal sample.
Conclusion: These results indicate the role of LTs in nocturnal asthma and suggest that urinary LTE4 may be a useful marker of this condition.
Nasal obstruction frequently has been associated with sleep-disordered breathing as a potential etiologic factor. Nasal obstruction results in pathologic changes in airflow velocity and resistance. Experimentally produced nasal obstruction increases resistance and leads to sleep-disordered breathing events, including apnea, hypopnea, and snoring. Clinical research examining the correlation between nasal obstruction and sleep-disordered breathing is limited, especially in regard to patients with conditions that increase nasal resistance, such as rhinitis and sinusitis. To further identify risk factors for sleep-disordered breathing, the role of chronic and acute nasal congestion was investigated in a population-based sample. Data on nasal congestion history and sleep problems were obtained by questionnaire (n = 4927) and by objective in-laboratory measurement (n = 911). Participants who often or almost always experienced nighttime symptoms of rhinitis (5 or more nights a month) were significantly (p < 0.0001) more likely to report habitual snoring (3 to 7 nights a week), chronic excessive daytime sleepiness, or chronic nonrestorative sleep than were those who rarely or never had symptoms. Habitual snorers had significantly (p< 0.02) lower air flow than nonsnorers, although a linear relation between decreased airflow and sleep-disordered breathing severity did not exist. Participants who reported nasal congestion due to allergy were 1.8 times more likely to have moderate to severe sleep-disordered breathing than were those without nasal congestion due to allergy. Men and women with nasal obstruction, especially chronic nighttime symptoms of rhinitis, are significantly more likely to be habitual snorers, and a proportion also may have frequent episodes of apnea and hypopnea, indicative of severe sleep-disordered breathing. Because allergic rhinitis is a common cause of nasal obstruction and it is a modifiable risk factor, further study of this association is warranted. (J Allergy Clin Immunol 1997;99:S757-62.)
Background:
Interleukin-18 (IL-18) is a member of the IL-1 cytokine family that affects chronic inflammation. We sought to characterize IL-18 expression and investigate its release during chronic rhinosinusitis (CRS).
Methods:
The expression of IL-18 in nasal polyps (NPs) and uncinate tissues (UTs) from both CRS and non-CRS patients was examined via immunohistochemistry. After culturing dispersed NP cells (DNPCs) with or without various stimulations, IL-18 levels were measured in the culture supernatants. Furthermore, the effect of IL-18 neutralization on staphylococcus enterotoxin B (SEB)-induced cytokine production was also examined.
Results:
Similar expression of IL-18 in the epithelial layers was observed between the NPs and UTs. However, there was a significantly higher number of IL-18(+) cells in the lamina propria from NPs compared to UTs without CRS. This increased number was significantly correlated with the radiological severity of sinusitis and local eosinophilia. After the dispersion, IL-18 was spontaneously released by NP cells in a phase-dependent manner. While SEB, fungal antigens, and TLR agonists did not enhance the release, exposure to protease or one cycle of a freeze-and-thaw treatment did induce release of IL-18 from rested DNPCs. In addition, neutralization of IL-18 significantly suppressed SEB-induced IL-5, IL-13, and IFN-γ, but not IL-17A production.
Conclusions:
These results suggest that the pro-inflammatory effect of IL-18 released by danger signals may be involved in the pathogenesis of CRS, which includes eosinophilic inflammation and NP formation, via the augmentation of both Th2- and Th1-associated cytokine production.
Sleep is integral to the health and well-being of all people. Sleep disorders are on the rise and affect millions of people in America. Misconceptions about sleep are prevalent, and the negative effects of poor sleep on society are underrepresented. The goal of this study is to investigate and report the effects of poor sleep on society. Information is obtained through a systematic review of current literature, including journal articles, books, and reports. Multiple themes emerged from the literature review relative to poor sleep and societal impacts. These themes include major disasters related to insufficient sleep, performance and productivity, stress, drowsy driving, substance use and abuse, mortality and morbidity, overall health and wellbeing, effects on healthcare systems, and economic costs. Poor sleep decreases human productivity and performance, and increases mortality and morbidity. The National Sleep Foundation estimates that poor sleep costs America billions of dollars each year and greatly compromises public safety and health. Possible solutions to the Nation's sleep problem may begin with promoting education and awareness of sleep disorders and their negative societal impact, research in sleep medicine, as well as public education about healthy sleep. The beginnings of these solutions lie in the hands of healthcare workers and educational institutions. Interventions in the form of questionnaires have been validated as effective in determining a person's risk of sleep apnea. The STOP-BANG questionnaire is one such intervention that may be useful by allied health professionals to assist in patient screening of sleep apnea.
In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-α, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.
Sickness behavior refers to a coordinated set of behavioral changes that develop in sick individuals during the course of an infection. At the molecular level, these changes are due to the brain effects of proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFα). Peripherally released cytokines act on the brain via a fast transmission pathway involving primary afferent nerves innervating the bodily site of inflammation and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffusing into the brain parenchyma by volume transmission. At the behavioral level, sickness behavior appears to be the expression of a central motivational state that reorganizes the organism priorities to cope with infectious pathogens. There is evidence that the sickness motivational state can interact with other motivational states and respond to nonimmune stimuli probably by way of sensitization and/or classical conditioning. However, the mechanisms that are involved in plasticity of the sickness motivational state are not yet understood.
Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3. Immune dysfunction in CFS, with predominance of so-called T-helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T-helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.
Transforming growth factor-β1 (TGF-β1) plays a key role in the tissue remodeling processes involved in chronic rhinosinusitis (CRS), with the biological functions of secreted TGF-β1 regulated by multiple proteins. Among these regulators, latency-associated peptide and latent TGF-β-binding protein inhibit TGF-β1 function, whereas different proteases and integrins activate it. Progress in understanding the factors responsible for the bioactivity and expression of TGF-β1 has revealed that the dysregulation of TGF-β1 activation and expression is closely associated with the chronic respiratory inflammatory diseases involved in CRS. This review of the regulation of TGF-β1 activation and expression provides insight into the mechanism responsible for the different CRS subtypes, which will help further the investigation of novel therapy targets for the treatment of CRS.
We propose that sleep begins within small groups of highly interconnected neurons and is characterized by altered input → output (i→0) relationships for any specific neuronal group. Further, experimental findings suggest that growth factors, released locally in response to neuronal activity, and acting in paracrine and autocrine fashions, induce the altered i→0 relationships. These growth factors also act to provide the structural basis for synapses. Thus, we envision that sleep mechanisms (neural use-dependent induction of growth factors and their subsequent effects on i→0 relationships) cannot be separated from sleep function (growth factor-induced synaptic sculpturing). This mechanism/firnction is envisioned to take place in all areas of the brain, including sleep regulatory circuits as well as throughout the cortex. Finally, the “sleep” of neuronal groups (altered i→o relationships) is coordinated by the known sleep regulatory circuits and activational-projection systems in the brain. The theory extends and integrates existing sleep theories to cover a broader range of phenomena.
Descriptions of rhinosinusitis (RS) patients and evaluation of treatment effectiveness are currently hindered by the lack of a valid measure of health status and quality of life. The RSOM contains 31 RS-specific items (e.g., runny nose, cough, facial pain/pressure), grouped into 7 domains (nasal, eye, sleep, ear, and general symptoms; practical problems, and emotional consequences), and was created from discussions with RS patients. Two categorical rating scales were selected for patients to indicate the Magnitude and Importance of each item. The RSOM score is calculated as the sum of the Magnitude X Importance scores. The goal of this project was to validate the RSOM-31. In 142 patients who completed the RSOM, the average age was 45 and there were 86 women. The average total RSOM score was 5.8 (0.8—15.1 = good—bad). The domains most affected were sleep (7.7), general problems (6.4), nasal (6.3), and emotional (6.2). The RSOM score correlated significantly with an overall global quality of life question (r = 0.36); and the Vitality (r = 0.50), General Health (r = 0.47), Social Functioning (r = 0.46), and Role-Physical (r = 0.41) sub-scales of the Medical Outcomes Study Short Form 36. The average total RSOM score decreased over time (indicating improvement) and was correlated with the patient's assessment of their response to treatment (F Value 6.49; P < 0.0001). This study demonstrates that the 31-item RSOM is a valid measure of RS health status and quality of life.
Impaired insulin action in the brain represents an early step in the progression toward type 2 diabetes, and elevated levels of saturated free fatty acids are known to impair insulin action in prediabetic subjects. One potential mediator that links fatty acids to inflammation and insulin resistance is the Toll-like receptor (TLR) family. Therefore, C3H/HeJ/TLR2-KO (TLR2/4-deficient) mice were fed a high-fat diet (HFD), and insulin action in the brain as well as cortical and locomotor activity was analyzed by using telemetric implants. TLR2/4-deficient mice were protected from HFD-induced glucose intolerance and insulin resistance in the brain and displayed an improvement in cortical and locomotor activity that was not observed in C3H/HeJ mice. Sleep recordings revealed a 42% increase in rapid eye movement sleep in the deficient mice during daytime, and these mice spent 41% more time awake during the night period. Treatment of control mice with a neutralizing IL-6 antibody improved insulin action in the brain as well as cortical activity and diminished osteopontin protein to levels of the TLR2/4-deficient mice. Together, our data suggest that the lack of functional TLR2/4 protects mice from a fat-mediated impairment in insulin action, brain activity, locomotion, and sleep architecture by an IL-6/osteopontin-dependent mechanism.
Sleep is impaired in allergic rhinitis (AR) patients, with subsequent effects on daytime performance and health-related quality of life (QOL). Sleep quality in AR has rarely been considered through validated tools and consensus classifications.
To evaluate sleep quality and daytime somnolence in AR patients, and to estimate its relationship to disease severity according to Allergic Rhinitis and Its Impact on Asthma (ARIA) conventional and modified classifications, as well as in terms of QOL and comorbidities.
Allergic rhinitis adult patients were evaluated through a prospective, observational, multicentre survey in Spain. Symptoms were assessed using the Total Symptoms Score (TSS), specific QOL by the Rhinitis Quality of Life Questionnaire (RQLQ), sleep quality by Pittsburgh scale, and diurnal somnolence by a scale based on Epworth's, all recorded in a unique visit.
A total of 2275 patients were included. According to ARIA criteria, 50.2% had persistent and 49.8% intermittent rhinitis, whereas 87.6% were classified as moderate-severe and 12.4% as mild; 52.8% had poor sleep quality, with a global median score for Pittsburgh scale of 6 (normal < 5) and 21.1% suffered from excessive diurnal somnolence. Correlation between Pittsburgh scale and RQLQ was moderate (r = 0.54). Among symptoms, nasal obstruction and concomitant asthma mainly, contributed to bad sleep quality. In a logistic regression model, moderate-severe rhinitis and nasal obstruction were all associated with a worse sleep quality.
Sleep quality is altered in AR patients. Sleep quality was worse in moderate-severe, and particularly in severe AR. Nasal obstruction and RQLQ deterioration are associated with a poorer sleep quality. Sleep impairment is common in allergic rhinitis, particularly in more severe forms. Nasal obstruction and concomitant asthma should be considered as contributing factors.
This is a large epidemiological survey of patients with allergic rhinitis showing a strong relationship between disease severity, as assessed by a consensus classification, and sleep impairment, as measured by a validated sleep quality tool.
Biofilms might play a potential role in the pathogenesis and high recurrence rate of chronic rhinosinusitis with nasal polyposis (CRSwNP). Biofilm persistence has been thought to correlate with epithelial damage, subepithelial inflammatory cell infiltration, and tumor necrosis factor-α receptor (TNFR) expression in CRSwNP.
Case-control experimental study.
A total of 36 patients with CRSwNP undergoing endoscopic sinus surgery were analyzed. The negative control group consisted of eight patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa samples applied as negative controls were processed by hematoxylin-eosin (HE) and Gram staining and TNFR-I and TNFR-II-specific immunofluorescent assay.
Biofilm was detected in 29 of 36 patients with CRSwNP and in none of the eight negative controls. Staining by HE showed strong correlation with the results of Gram staining protocol. In the biofilm-positive cases, TNFR-I and TNFR-II displayed homogeneous pattern of significantly increased epithelial expression compared to the biofilm-negative nasal polyps. In cases of biofilm absence, the expression pattern of TNF-α receptors was characterized by increased TNFR-II-specific immunoreaction. It was found that biofilm detectability corresponded to the integrity of nasal epithelium and to the dominant inflammatory cell type of the subepithelial layer.
Persisting biofilms might increase the epithelial sensitivity against TNF-α that result in epithelium destruction. Coexistence of biofilms and increased TNFR expression might explain the inflammatory mucosal changes, functional disorders, and therapy resistance featuring CRSwNP.
Prostaglandin (PG) D2 is the most potent endogenous sleep-promoting substance. PGD2 is produced by lipocalin-type PGD synthase localized in the leptomeninges, choroid plexus, and oligodendrocytes in the brain, and is secreted into the cerebrospinal fluid as a sleep hormone. PGD2 stimulates DP1 receptors localized in the leptomeninges under the basal forebrain and the hypothalamus. As a consequence, adenosine is released as a paracrine sleep-promoting molecule to activate adenosine A2A receptor-expressing sleep-promoting neurons and to inhibit adenosine A1 receptor-possessing arousal neurons. PGD2 activates a center of non-rapid eye movement (NREM) sleep regulation in the ventrolateral preoptic area, probably mediated by adenosine signaling, which activation inhibits the histaminergic arousal center in the tuberomammillary nucleus via descending GABAergic and galaninergic projections. The administration of a lipocalin-type PGD synthase inhibitor (SeCl4), DP1 antagonist (ONO-4127Na) or adenosine A2A receptor antagonist (caffeine) suppresses both NREM and rapid eye movement (REM) sleep, indicating that the PGD2-adenosine system is crucial for the maintenance of physiological sleep.
There has been little investigation of fatigue, a common symptom in inflammatory bowel disease (IBD). The aim of this study was to evaluate fatigue more comprehensively, considering relationships with psychological and biological factors simultaneously in a population-based IBD community sample.
Manitoba IBD Cohort Study participants (n = 318; 51% Crohn's disease [CD]) were assessed by survey, interview, and blood sample. Fatigue, sleep quality, daytime drowsiness, stress, psychological distress, and quality of life were measured with validated scales. Hemoglobin (Hg) and C-reactive protein (CRP) levels were also obtained. Differences were tested across disease activity and disease subtype.
Elevated CRP was found for 23% of the sample and 12% were anemic; 46% had active disease. Overall, 72% of those with active and 30% with inactive disease reached clinical thresholds for fatigue (Multidimensional Fatigue Inventory; P < 0.001); 77% and 49% of those with active or inactive disease, respectively, experienced poor sleep (P < 0.001). There were few differences between those with CD and ulcerative colitis (UC) on the factors assessed, except for higher CRP levels in CD (mean 8.8 versus 5.3, P < 0.02). Multiple logistic regression analyses found that elevated fatigue was associated with active disease (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.2-7.8), poor sleep quality (OR 4.0, 95% CI 1.9-8.6), and perceived stress (OR 4.2, 95% CI 2.2-8.1), but not with hours of sleep, Hg, or CRP.
Fatigue and poor sleep are not only highly prevalent in active disease, but both are still significant concerns for many with inactive disease. Psychological factors are associated with fatigue in IBD in addition to disease and sleep considerations.
Nasal surgery is commonly involved in surgical treatment for obstructive sleep apnea (OSA). The aim of this study was to investigate the outcomes of nasal surgery for OSA using evidence-based methodology.
The MedLine database (1999∼2009) was searched for original articles published in peer-reviewed journals concerning nasal surgery for snoring/sleep apnea. Data extracted from these articles were reviewed and analyzed using meta-analysis technology.
Thirteen articles were critically appraised. Two studies provided control groups and 11 articles (84.6%) consisted of prospective noncontrolled clinical trials (level II in evidence strength). The weighted mean apnea/hypopnea index measured by polysomnography in nine studies decreased from 35.2 ± 22.6 to 33.5 ± 23.8 event/hour after nasal surgery (overall, p = 0.69). The pooled success rate of nasal surgery in treating OSA was 16.7%. Epworth Sleepiness Scale scores in eight studies decreased from 10.6 ± 3.9 to 7.1 ± 3.7 (overall, p <0.001). Nasal surgery for snoring assessed by individual questionnaires and visual analog scale reported significant improvement (p < 0.05).
The critical literature appraisal and meta-analyses show that nasal surgery can effectively reduce daytime sleepiness and snoring. However, the efficacy of nasal surgery in treating OSA is limited.
Recruitment of macrophages is crucial to the pathogenesis of the nasal polyp (NP) because this disease is believed to be inflammation related. Information regarding the expression of C-C chemokine ligand 2 (CCL2), an essential modulator of monocyte chemotaxis in nasal polyp fibroblasts (NPFs), remains unavailable. In this study, the effects of tumor necrosis factor (TNF)-a on CCL2 expression in NPFs and the signaling pathway involved were investigated.
Primary cultures of NPFs were established from NPs. The expressions of CCL2, c-Fos, and c-Jun mRNAs in NPF after TNF-a stimulation were detected by Northern blot. Western blot was used to examine the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Activator protein (AP) 1/DNA interactions were evaluated by electrophoretic mobility shift assay (EMSA).
Northern blot showed that TNF-alpha stimulated CCL2 gene expression in NPFs. Significant increase of B-Raf, phosphorated MAPK including mitogen-activated ERK-activate kinase (MEK)1/2, extracellular signal-related kinase 1/2, and p38 were detected by Western blot. c-Fos and c-Jun mRNAs were induced by TNF-alpha, and PD98059 (MEK inhibitor) and SB203580 (p38 inhibitor) abolished the up-regulation of c-Fos. EMSA revealed that TNF-a increased AP-1/DNA binding, and PD98059 and SB203580 attenuated this reaction, possibly via reducing c-Fos synthesis. PD98059 and curcunmin (AP-1 inhibitor) markedly suppressed the TNF-alpha-induced CCL2 expression, whereas the effect of SB203580 was less noted.
TNF-alpha induces CCL2 transcription in NPFs. B-Raf/MEK/ERK signaling cascade and to a less extent the p38 pathway are responsible for c-Fos activation and the subsequent AP-1/DNA interaction leading to CCL2 expression.
Nitric oxide (NO), is a biological messenger molecule and a component of innate immunity, with important roles in the regulation of inflammation and in defense against bacterial biofilms. Polymorphisms in genes regulating NO production have the potential for a role in the development of chronic rhinosinusitis (CRS). The purpose of this study was to determine whether polymorphisms in genes regulating NO synthesis are associated with CRS.
An established population of 206 individuals with severe CRS and 196 postal code-matched controls was previously screened using a pooling genome-wide associations study to estimate allelic frequency. Genes regulating NO synthesis with a maximal probability of association were identified. High-probability single nucleotide polymorphisms SNPs from the NO synthase (NOS1) and its ligand NOS1 adaptor protein (NOS1AP) genes were retained for individual genotyping. PLINK software was used to determine association.
Sixteen SNPs were genotyped successfully with a genotype distribution in agreement with Hardy-Weinberg equilibrium. Two SNPs for NOS1 (rs1483757 and rs9658281) were significantly associated with CRS, with a protective effect. The severe subphenotype showed stronger associations. Subgroup analysis for the presence of nasal polyps, origin, and gender did not influence strength of associations.
These data suggest that polymorphisms in the NOS1 gene may play a role in the susceptibility to develop CRS. Study findings apply to patients with severe CRS, unresponsive to surgery.
Individuals with underlying inflammation present with a high prevalence of non-specific co-morbid symptoms including sleep disturbance and fatigue. However, the association between cellular expression of proinflammatory cytokines, alterations of sleep depth and daytime fatigue has not been concurrently examined. In healthy adults (24-61 years old), evening levels of monocyte intracellular proinflammatory cytokine production were assessed prior to evaluation of polysomnographic sleep and measures of fatigue the following day. Stimulated monocyte production of interleukin-6 (IL-6), but not tumor necrosis factor α (TNF-α), was negatively associated with slow wave sleep (ΔR²=.17, p=.029). In contrast, stimulated monocyte production of IL-6 was positively associated with rapid-eye movement (REM) sleep duration during the first sleep cycle (ΔR²=.26, p<.01). Moreover, evening stimulated production of IL-6 was associated with fatigue the following day (ΔR²=.17, p=.05). Mediation analyses showed that slow wave sleep, but not REM sleep duration, mediated the relationship between evening levels of IL-6 production and daytime fatigue. These results indicate that increases in stimulated monocyte production of IL-6 may be associated with decreases in slow wave sleep and increases in REM sleep duration. Relative loss of slow wave sleep may be one pathway through which cellular inflammation leads to daytime fatigue.
Most patients with chronic rhinosinusitis seek medical treatment when the burden of symptoms negatively impacts their quality of life. The degree to which quality of life improves after sinus surgery is a critical indicator of surgical success. This article reviews quality of life outcomes after functional endoscopic sinus surgery, including relevant clinical factors, weaknesses in the current literature, and future research directions.
The lack of distinction in the clinical use of terms like fatigue and sleepiness is an important issue. While both fatigue and sleepiness can potentially be associated with nonrestorative sleep (NRS) complaints, their relationships are still poorly described. We propose to use Rasch analysis-based methods to study the interrelations of fatigue, sleepiness and NRS.
150 subjects (mean age = 39.3 years, range = 18-65) from a community sample underwent a structured computer-assisted web interview. We assessed demographic data, sleep habits, and subjective fatigue with the Fatigue Severity Scale (FSS), global and situational sleepiness with the Epworth Sleepiness (ESS) and the Stanford Sleepiness Scales, respectively, and affective symptoms with the Hospital Anxiety and Depression Scale. Dimensionality, measurement invariance and common person equating were investigated to study the FSS, ESS and their relations to NRS.
NRS was linked to shorter habitual sleep duration and to higher scores on psychometric scales. Both sleepiness and daytime fatigue were positively correlated to each other and to the intensity of affective symptoms. Rasch analyses showed both the ESS and FSS to measure unidimensional concepts of sleepiness and fatigue, respectively. In contrast to the FSS, the ESS only showed partial invariance to an NRS complaint. Common person equating suggests that, despite similar Rasch-derived agreeability scores, fatigue and sleepiness (as measured by the FSS and ESS) nevertheless designate distinct constructs.
NRS complaints can simultaneously present with higher daytime fatigue and sleepiness levels but the associative relationships between fatigue and sleepiness remain relatively unaffected by NRS. Although participants might not present adequate differentiation, fatigue and sleepiness seem to relate to different underlying concepts.
To replicate and extend recent findings in a Turkish population of associations between chronic rhinosinusitis (CRS) with nasal polyposis and single-nucleotide polymorphisms (SNPs) in the IL1A (rs17561 and Ser114Ala), IL1B (rs16944), and TNF (rs361525 and rs1800629) genes.
In a case-control replication study, DNA samples were obtained from 206 patients with severe CRS (cases) and from 196 postal code-matched controls. For IL1A and TNF, the 3 reported SNPs were complemented with tagging SNPs using an International HapMap genotyping data set to ensure complete genetic coverage. For IL1B, only the single reported SNP was assessed. A total of 24 SNPs (7 in IL1A, 1 in IL1B, and 16 in TNF) were individually genotyped. The PLINK software package was used to perform genetic association tests.
Academic research.
Canadian population of individuals with severe CRS.
Allelic differences between cases and controls.
Significant allelic differences between cases and controls were obtained for IL1A rs17561 (odds ratio [OR], 1.48; P = .02). The following 3 additional SNPs in this gene were associated with CRS: rs2856838 (OR, 0.63; P = .003), rs2048874 (OR, 0.57; P = .01), and rs1800587 (OR, 1.49; P = .02). These 3 SNPs remained significant after correction for multiple testing. No association was found with IL1B or TNF.
We replicated the previously reported association between the IL1A polymorphism and severe CRS and identified 3 potential new associations in the same gene. This further supports the potential contribution of IL1A to the development of CRS. We were unable to replicate previous reports of associations with IL1B or TNF.
Allergic rhinitis (AR) has been found to impact the daily activities of allergic patients. This includes the effects on sleep and chronic fatigue. The effect of AR on sexual function has not been well studied. The purpose of this study was to assess the impact of AR on sexual function, sleep, and fatigue. The Rhinosinusitis Disability Index (RSDI) is a quality of life (QOL), validated outcomes tool that assesses how AR affects QOL. Specific questions address the adverse consequence on sexual function, sleep, and fatigue. Four subsets of patient with AR who completed the RSDI were evaluated for the specific questions as well as the physical, emotional, functional, and total scores. The scores were compared with a cohort of normal subjects, patients with a diffuse group of rhinologic disorders, and patients scheduled for septal surgery (non-AR patients). Patients with AR had significantly higher (worse) sexual and sleep RSDI scores than the non-AR patients and normal subjects. Although the AR subjects also had significantly higher fatigue RSDI scores than the normal subjects, there was no significant difference between the AR and non-AR patients' fatigue scores. Non-AR patients had significantly higher sexual, sleep, and fatigue RSDI scores than the normal subjects. AR has a significant negative impact on sexual function and can result in sleep disturbances and fatigue as measured by the RSDI.
Factors conferring susceptibility to chronic rhinosinusitis remain unknown. However, advances in genomics offer powerful tools to explore this disorder. Tumour necrosis factor (TNF) is a crucial proinflammatory cytokine that exerts inflammatory and immunomodulatory activities important in host defense. Our objective was to determine whether polymorphisms in genes in the TNF superfamily (TNF, TNF-alpha-induced protein 3, TNF-alpha-induced protein 6) were associated with chronic rhinosinusitis.
Deoxyribonucleic acid (DNA) extracted from a population of 206 patients with severe chronic rhinosinusitis and 196 postal code-matched controls was used. Three candidate genes related to the TNF inflammatory pathway were assessed. For each gene, an informative set of single nucleotide polymorphisms was genotyped.
Thirty-five single nucleotide polymorphisms were genotyped. Two polymorphisms located within the TNF-alpha-induced protein 3 gene (TNFAIP3) reached the nominal p value threshold (p < .05) for association with chronic rhinosinusitis. However, none of these polymorphisms resist multiple testing adjustments.
Our data suggest that two polymorphisms in TNFAIP3 are weakly associated with severe chronic rhinosinusitis but do not support an association with genetic variants in TNF or TNF-alpha-induced protein 6. Although these results do not support correction for multiple testing and have to be validated in a second population, they nevertheless suggest that further studies of the role of TNFAIP3 in the pathogenesis of disease are warranted.
The aim of this study was to investigate the effect of endoscopic sinus surgery on sleep quality in a patient group who has chronic nasal obstruction resulting from nasal polyposis.
Twenty-seven patients with nasal polyposis, filling at least 50% of each nasal passage, were enrolled in the study. Assessment of nasal patency was determined by nasal endoscopy and acoustic rhinometry. All patients underwent endoscopic sinus surgery with polypectomy. Sleep quality was evaluated, using visual analog scale, Epworth sleepiness scale, and polysomnography before and 3 months after the surgery.
Nasal resistance decreased significantly after the surgery (P < 0.01). Snoring scores were significantly improved postoperatively (P < 0.01) and completely disappeared in 9 of 27 patients. A significant improvement occurred in mean daytime sleepiness scores in the postoperative period (4.14) as compared with the preoperative values (9.44; P < 0.01). There was no significant difference between preoperative (6.85) and postoperative (5.53) mean values of apnea-hypopnea index (P = 0.55).
Endoscopic sinus surgery with polypectomy significantly improves sleep quality, including snoring and daytime sleepiness in patients with chronic nasal obstruction due to nasal polyposis. However, it has a limited benefit on apnea-hypopnea index scores.