Comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: did dupilumab make a difference?

BACKGROUND: The clinical heterogeneity of chronic rhinosinusitis (CRS) and bronchial asthma is attributable to different underlying inflammatory profiles. However, the similarity between CRS with nasal polyps (CRSwNP) and type-2 asthma pathophysiology speculates that one biological therapy could affect both comorbidities. Despite dupilumab, a monoclonal antibody that targets IL-4α and IL-13 receptors, being used in patients with nasal polyps and severe asthma, real-life data about its efficacy in improving the quality of life and patient symptoms is still lacking. This study's primary objective was to evaluate dupilumab treatment's effect on the frequency of olfactory symptoms and health-related quality of life tests as measured by the Sino-nasal outcome test (SNOT-22) in patients with NP. The secondary objective was the effect of dupilumab on asthma symptom control as measured by the asthma control test (ACT). METHODS: A prospective study was conducted of 166 patients with CRSwNP, with or without asthma. The following variables were collected at baseline and after at least six months of continuous dupilumab therapy; SNOT-22, olfactory symptoms frequency, and ACT score. RESULTS: Asthma prevalence in patients with CRSwNP was high (59.63%), and being female with a history of frequent use of oral corticosteroid (OCS) courses and repeated unsuccessful nasal and para-nasal surgeries for polyposis increased the likelihood of having underlying asthma by 2, 1 and 4 times more, respectively. Additionally, being asthmatic required a longer duration of dupilumab treatment. However, both the health-related quality of life and olfactory symptoms improved equally in both groups. CONCLUSION: Even with associated comorbid asthma in patients with CRSwNP, treatment with dupilumab could improve the quality of life, olfactory symptoms, and asthma symptom control.

Investigating the Relationship between Obstructive Sleep Apnoea, Inflammation and Cardio-Metabolic Diseases.

Obstructive sleep apnoea (OSA) is a prevalent underdiagnosed disorder whose incidence increases with age and weight. Uniquely characterised by frequent breathing interruptions during sleep-known as intermittent hypoxia (IH)-OSA disrupts the circadian rhythm. Patients with OSA have repeated episodes of hypoxia and reoxygenation, leading to systemic consequences. OSA consequences range from apparent symptoms like excessive daytime sleepiness, neurocognitive deterioration and decreased quality of life to pathological complications characterised by elevated biomarkers linked to endocrine-metabolic and cardiovascular changes. OSA is a well-recognized risk factor for cardiovascular and cerebrovascular diseases. Furthermore, OSA is linked to other conditions that worsen cardiovascular outcomes, such as obesity. The relationship between OSA and obesity is complex and reciprocal, involving interaction between biological and lifestyle factors. The pathogenesis of both OSA and obesity involve oxidative stress, inflammation and metabolic dysregulation. The current medical practice uses continuous positive airway pressure (CPAP) as the gold standard tool to manage OSA. It has been shown to improve symptoms and cardiac function, reduce cardiovascular risk and normalise biomarkers. Nonetheless, a full understanding of the factors involved in the deleterious effects of OSA and the best methods to eliminate their occurrence are still poorly understood. In this review, we present the factors and evidence linking OSA to increased risk of cardiovascular conditions.

Increased ANGPTL3, 4 and ANGPTL8/betatrophin expression levels in obesity and T2D.

BACKGROUND: Hypertriglyceridemia is associated with increased risk for cardiovascular diseases and type 2 diabetes (T2D). Angiopoietin like proteins particularly 3, 4 and recently 8 are well established regulators of plasma triglyceride level through regulating the activity of lipoprotein lipase. Plasma level and association between ANGPTL3, 4 and 8 is not well established in human subjects. This study was designed to establish the level of these proteins in plasma and adipose tissues and investigate the association between ANGPTL8 with ANGPTL3 and 4 in T2D and non-diabetics subjects. METHODS: A total of 235 subjects were enrolled in this study, 144 non-diabetics and 91 T2D. ANGPTL 3, 4 and 8 levels were measured in plasma by ELISA and using real time RT-PCR in adipose tissues. RESULTS: In this study, we showed that ANGPTL3, 4 and 8 were higher in T2D subjects. Dividing the non-diabetic subjects according to their BMI showed higher level of ANGPTL3, 4 and 8 in obese subjects compared to non-obese subjects. No significant difference was observed between the T2D subjects. ANGPTL8 was showed positive correlation with ANGPTL3 in the non-diabetic subjects in the non-obese (r = 0.2437, p-Value = 0.0543) and obese subjects (r = 0.418, p-Value = 0.0125). No association was observed in the T2D subjects. On the other hand, ANGPTL4 was positively associated with the obese subjects in both the non-diabetics (r = 0.3322, p-Value = 0.0316) and the obese T2D subjects (r = 0.3161, p-Value = 0.0211). CONCLUSION: In conclusion, our data shows that ANGPTL3, 4 and 8 are increased in obesity and T2D. ANGPTL8 associates with ANGPTL3 in the non-diabetic subjects while it associated more with ANGPTL4 in the obese and T2D subjects. Taken together, this data highlight the role of these proteins in metabolic diseases and how they interact with each other's under different physiological and pathophysiological conditions.

Chondroid syringoma of the nose: A rare case report and literature review.

INTRODUCTION AND IMPORTANCE: A chondroid syringoma is an exceptionally rare benign lesion of the sweat glands also known as mixed tumor of the skin (MTS). It can occur in different areas of the head and neck such as the lips, cheek, nose and scalp (Gotoh et al., 2022 [1]). It is usually painless and grows slowly. Based on pathological features it can be differentiated into apocrine or eccrine (Mixed cutaneous tumor: chondroid syringoma a case report, 2019 [2]). CASE PRESENTATION: Our patient presented with a nasal lesion in the left soft triangle, progressively increasing in size. He did not undergo any surgeries to the nose or any history of trauma. Due to the COVID-19 lockdown our patient did not seek early medical advice. In addition, the implementation of facemasks enabled for the concealment of the abnormality, which reduced the need of seeking treatment. CLINICAL DISCUSSION: Chondroid syringoma is a non-ulcerative tumor that grows slowly with an average diameter between 0.5 and 3 cm, however lesions reaching 9 cm have been also seen (Wan et al., 2018 [4]). The mainstay method of management is surgical excision while maintaining the aesthetic appearance of the patient. CONCLUSION: Owing to its rarity, clinical misdiagnosis is common, however absolute diagnosis is achieved by histopathology. This case delineates the rarity of this lesion and the mainstay method of management, which is surgical excision.

Assessment of chronic rhinosinusitis with nasal polyps: Development of the Nasal Polyp Patient Assessment Scoring Sheet tool.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with a wide range of validated subjective and objective assessment tools to assess disease severity. However, a comprehensive and easy-to-use tool that integrates these measures for determining disease severity and response to treatment is still obscure. The objective of this study was to develop a standardized assessment tool that facilitates diagnosis, uniform patient monitoring, and comparison of treatment outcomes between different centers both in routine clinical practice and in research. Methods: To develop this tool, published literature on assessment tools was searched on various databases. A panel of 12 steering committee members conducted an advisory board meeting to review the findings. Specific outcome measures to be included in a comprehensive assessment tool and follow-up sheet were then collated following consensus approval from the panel. The tool was further validated for content and revised with expert recommendations to arrive at the finalized Nasal Polyp Patient Assessment Scoring Sheet (N-PASS) tool. Results: The N-PASS tool was developed by integrating the subjective and objective measures for CRS assessment. Based on expert opinions, N-PASS was revised to be used as an easy-to-use guidance tool that captures patient-reported and physician-assessed components for comprehensively assessing disease status and response to treatment. Conclusion: The N-PASS tool can be used to aid in the diagnosis and management of CRS cases with nasal polyps. The tool would also aid in improved monitoring of patients and pave the way for an international disease registry. Level of evidence: Oxford Level 3.

Management of a pediatric patient with spontaneous cerebrospinal fluid leak in the lateral recess of sphenoid sinus and meningoencephalocele: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Spontaneous cerebrospinal fluid (CSF) leak in the lateral recess of the sphenoid (LRS) sinus in a pediatric population is rare and is surgically challenging to repair. CASE PRESENTATION: We report a case of a 13-year-old girl with hydrocephalus and a ventriculoperitoneal shunt who presented with a two-month history of clear rhinorrhea from the right nostril. Computed tomography (CT) of the head was performed and showed CSF leak through a defect in the lateral recess of the sphenoid sinus. Defect closure was achieved using an endoscopic endonasal approach. CLINICAL DISCUSSION: CSF leak with meningoencephalocele from the sphenoid sinus is amongst the most difficult cases for repair. Yet the successful rate of repair is as high as 90 % if done endoscopically. Moreover, the location of the defect determines the surgical approach. CONCLUSION: Spontaneous CSF rhinorrhea from the lateral recess of the sphenoid (LRS) sinus, although rare, requires prompt diagnosis and treatment, as it may lead to significant mortality and morbidity.

Expert Opinion on Biological Treatment of Chronic Rhinosinusitis with Nasal Polyps in the Gulf Region.

Chronic rhinosinusitis (CRS) is defined as the inflammation of nose and paranasal sinuses, affecting the patients' quality of life and productivity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a principal clinical entity confirmed by the existence of chronic sinonasal inflammation and is characterized by anterior or posterior rhinorrhea, nasal congestion, hyposmia and/or facial pressure or facial pain. Several epidemiologic studies have revealed wide variations in the incidence of CRS among regions globally ranging from 4.6% to 12%. The Gulf countries are also witnessing an unprecedented burden of CRSwNP. According to the current clinical guidelines, glucocorticosteroids and antibiotics are the principal pharmacotherapeutic approaches. Endoscopic sinus surgery is recommended for those who have failed maximal pharmacotherapy. Recently, biologics are considered as an alternative best approach due to the complications associated with medical therapy and surgery. However, precise data on the clinical position of biologic agents in the management of CRSwNP in the Gulf region is not available. The present review article addresses the current diagnostic and management approaches for CRSwNP and also emphasizes the role of emerging biologics in the current treatment strategies for CRSwNP in the Gulf region. Further, a consensus protocol was convened to rationalize the guideline recommendations, strategize the best practices with biologics, and develop clinical practice guidelines for all primary-care specialists in the Gulf region. The consensus-based report will be a useful reference tool for primary-care physicians in primary-healthcare settings, regarding the appropriate time for the initiation of biological treatment in the Gulf region.

Increased plasma ANGPTL7 levels with increased obstructive sleep apnea severity.

Background: Weight-loss surgery is one of the recommended methods for treating obstructive sleep apnea (OSA) in obese patients. While weight reduction is critical to relieve symptoms of OSA, the biochemical factors involved in post-surgery improvement are still unknown. We aimed to explore the link between ANGPTL7 and OSA in patients with different OSA severity. Furthermore, we examined the effect of treating OSA with bariatric surgery on ANGPTL7 level. Methods: We quantified levels of circulating ANGPTL7 in fasting plasma and adipose tissue samples of 88 participants before and after bariatric surgery. Confocal microscopy analyses were also performed to assess the ANGPTL7 expression in subcutaneous white adipose tissue biopsies obtained from people with moderate-to-severe OSA compared to those with none or mild OSA. The study involved 57 individuals with none or mild OSA and 31 patients with moderate-to-severe OSA. Results: Levels of circulating ANGPTL7 were significantly higher in people with moderate-to-severe OSA (1440 ± 1310 pg/ml) compared to the none or mild OSA group (734 ± 904 pg/ml, p = 0.01). The increase in ANGPTL7 correlated significantly and positively with the apnea-hypopnea index (AHI, r = .226, p = .037), and AHI-supine (r = .266, p = .019) in participants with moderate-to-severe OSA. Multivariate logistic regression analysis demonstrated an association between ANGPTL7 and OSA severity (log2 ANGPTL7; OR =1.24, p = 0.024). ANGPTL7 levels exhibited significant positive correlations with the levels of TG and oxLDL (p-value = 0.002 and 0.01 respectively). Bariatric surgery reduced the levels of both ANGPTL7 and AHI significantly. Conclusion: Here we report significantly increased levels of ANGPTL7 both in the circulation and in adipose tissue of patients with OSA, which concurred with increased inflammation and OSA severity. Levels of ANGPTL7 decreased significantly as OSA showed a significant improvement post-surgery supporting a potential role for ANGPTL7 in either OSA progression or a role in an OSA-related mechanism.

Prevalence, Risk Factors, and Comorbidities of Obstructive Sleep Apnea Risk Among a Working Population in Kuwait: A Cross-Sectional Study.

Background: Obstructive sleep apnea (OSA) affects a considerable proportion of adults globally and is associated with elevated morbidity and mortality. Given the lack of epidemiologic data on the burden of OSA in Kuwait, this study sought to estimate its prevalence, associated risk factors, and comorbid conditions among a working population in Kuwait. Methods: This was a cross-sectional study of a sample of working adults (n = 651) from public institutions in Kuwait. High/low risk for OSA was ascertained according to the Berlin Questionnaire criteria. Participants self-reported their coexisting health conditions. Associations were assessed using Poisson regression with robust variance estimation; adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were estimated. Results: Overall, 20.0% (130/651) of participants were classified as being at high risk for OSA, with more male than female subjects being at high risk (24.0% [56/233] vs. 17.7% [74/418], P = 0.053), though this difference did not gain statistical significance. Moreover, a high risk for OSA was more common among older and obese subjects. Factors associated with increased prevalence of a high risk for OSA included current smoking status (aPR = 1.58, 95% CI: 1.02-2.06), longer hours spent watching television (1.76, 1.10-2.81), and lower self-perceived physical health (2.11, 1.15-3.87). However, decreasing trends in the prevalence of high risk for OSA were observed with frequent engagement in vigorous physical activity and longer nightly sleep duration. Compared to those at a low risk for OSA, the subjects at high risk for OSA were more likely to have insomnia disorder (2.83, 1.81-4.41), diabetes (1.94, 1.15-3.27), hypertension (3.00, 1.75-5.16), and depression (4.47, 1.80-11.08). Conclusion: This study estimated that 1/5 of working adults in Kuwait were at high risk for OSA, and the prevalence varied according to personal characteristics and lifestyle factors. Also, a high risk for OSA classification was associated with multiple comorbid health conditions.

The Rise of IGFBP4 in People with Obstructive Sleep Apnea and Multilevel Sleep Surgery Recovers Its Basal Levels.

IGFBP4 is the smallest member of the insulin-like growth factor binding protein family (IGFBP). It is a hepatic protein that plays a role in modulating the activity and bioavailability of IGF-I. The expression of IGFBP4 was found to increase under conditions of hypoxia. Obstructive sleep apnea (OSA) is a common disorder, characterized by cyclic episodes of intermittent hypoxia and fragmented sleep. Our aim was to quantify levels of circulating IGFBP1, IGFBP2, IGFBP3, IGFBP4, and IGFBP7 in fasting plasma samples of 69 Kuwaiti participants and explore its correlation with indices of OSA. The quantification was performed using multiplexing assay. The study involved 28 controls and 41 patients with OSA. Levels of circulating IGFBP4 were significantly higher in people with OSA (289.74 ± 23.30 ng/ml) compared to the control group (217.60 ± 21.74 ng/ml, p = 0.028). The increase in IGFBP4 correlated significantly and positively with AHI (r = .574, p = .01) and AI (r = .794, p = .001) in people with moderate and severe OSA. There was a significant decline in circulating IGFBP4 after 3 months of surgery (225.89 ± 18.16 ng/ml, p = 0.012). This was accompanied by a prominent improvement in OSA (AHI 8.97 ± 2.37 events/h, p = 0.001). In this study, our data showed a significant increase in circulating IGFBP4 in people with OSA. We also report a significant positive correlation between IGFBP4 and indices of OSA at baseline, which suggests IGFBP4 as a potential diagnostic biomarker for OSA. There was a significant improvement in OSA after 3 months of surgical intervention, which concurred with a significant decline in IGFBP4 levels. Altogether, the detected change suggests a potential link between IGFBP4 and OSA or an OSA-related factor, whereby OSA might play a role in triggering the induction of IGFBP4 expression.

Robust Antibody Levels in Both Diabetic and Non-Diabetic Individuals After BNT162b2 mRNA COVID-19 Vaccination.

The emergence of effective vaccines for COVID-19 has been welcomed by the world with great optimism. Given their increased susceptibility to COVID-19, the question arises whether individuals with type-2 diabetes mellitus (T2DM) and other metabolic conditions can respond effectively to the mRNA-based vaccine. We aimed to evaluate the levels of anti-SARS-CoV-2 IgG and neutralizing antibodies in people with T2DM and/or other metabolic risk factors (hypertension and obesity) compared to those without. This study included 262 people (81 diabetic and 181 non-diabetic persons) that took two doses of BNT162b2 (Pfizer-BioNTech) mRNA vaccine. Both T2DM and non-diabetic individuals had a robust response to vaccination as demonstrated by their high antibody titers. However, both SARS-CoV-2 IgG and neutralizing antibodies titers were lower in people with T2DM. The mean ( ± 1 standard deviation) levels were 154 ± 49.1 vs. 138 ± 59.4 BAU/ml for IgG and 87.1 ± 11.6 vs. 79.7 ± 19.5% for neutralizing antibodies in individuals without diabetes compared to those with T2DM, respectively. In a multiple linear regression adjusted for individual characteristics, comorbidities, previous COVID-19 infection, and duration since second vaccine dose, diabetics had 13.86 BAU/ml (95% CI: 27.08 to 0.64 BAU/ml, p=0.041) less IgG antibodies and 4.42% (95% CI: 8.53 to 0.32%, p=0.036) fewer neutralizing antibodies than non-diabetics. Hypertension and obesity did not show significant changes in antibody titers. Taken together, both type-2 diabetic and non-diabetic individuals elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine; nonetheless, lower levels were seen in people with diabetes. Continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity. Nonetheless, it is important that people get their COVID-19 vaccination especially people with diabetes.

Previous COVID-19 Infection and Antibody Levels After Vaccination.

Background: The emergence of new COVID-19 variants of concern coupled with a global inequity in vaccine access and distribution has prompted many public health authorities to circumvent the vaccine shortages by altering vaccination protocols and prioritizing persons at high risk. Individuals with previous COVID-19 infection may not have been prioritized due to existing humoral immunity. Objective: We aimed to study the association between previous COVID-19 infection and antibody levels after COVID-19 vaccination. Methods: A serological analysis to measure SARS-CoV-2 immunoglobulin (Ig)G, IgA, and neutralizing antibodies was performed on individuals who received one or two doses of either BNT162b2 or ChAdOx1 vaccines in Kuwait. A Student t-test was performed and followed by generalized linear regression models adjusted for individual characteristics and comorbidities were fitted to compare the average levels of IgG and neutralizing antibodies between vaccinated individuals with and without previous COVID-19 infection. Results: A total of 1,025 individuals were recruited. The mean levels of IgG, IgA, and neutralizing antibodies were higher in vaccinated subjects with previous COVID-19 infections than in those without previous infection. Regression analysis showed a steeper slope of decline for IgG and neutralizing antibodies in vaccinated individuals without previous COVID-19 infection compared to those with previous COVID-19 infection. Conclusion: Previous COVID-19 infection appeared to elicit robust and sustained levels of SARS-CoV-2 antibodies in vaccinated individuals. Given the inconsistent supply of COVID-19 vaccines in many countries due to inequities in global distribution, our results suggest that even greater efforts should be made to vaccinate more people, especially individuals without previous COVID-19 infection.

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery.

BACKGROUND: Obstructive sleep apnea (OSA) is caused by partial or complete obstruction of the upper airways. Corrective surgeries aim at removing obstructions in the nasopharynx, oropharynx, and hypopharynx. OSA is associated with an increased risk of various metabolic diseases. Our objective was to evaluate the effect of surgery on the plasma metabolome. METHODS: This study included 39 OSA patients who underwent Multilevel Sleep Surgery (MLS). Clinical and anthropometric measures were taken at baseline and five months after surgery. RESULTS: The mean Apnea-Hypopnea Index (AHI) significantly dropped from 22.0 ± 18.5 events/hour to 8.97 ± 9.57 events/hour (p-Value < 0.001). Epworth's sleepiness Score (ESS) dropped from 12.8 ± 6.23 to 2.95 ± 2.40 (p-Value < 0.001), indicating the success of the surgery in treating OSA. Plasma levels of metabolites, phosphocholines (PC) PC.41.5, PC.42.3, ceremide (Cer) Cer.44.0, and triglyceride (TG) TG.53.6, TG.55.6 and TG.56.8 were decreased (p-Value < 0.05), whereas lysophosphatidylcholines (LPC) 20.0 and PC.39.3 were increased (p-Value < 0.05) after surgery. CONCLUSION: This study highlights the success of MLS in treating OSA. Treatment of OSA resulted in an improvement of the metabolic status that was characterized by decreased TG, PCs, and Cer metabolites after surgery, indicating that the success of the surgery positively impacted the metabolic status of these patients.