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Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) primarily displays type 2 inflammation, characterized by the activation of interleukin (IL)-4, IL-5, and IL-13 in the pathway. The purpose of this study is to determine the efficacy and safety of dupilumab (an IL-4 antagonist) in treating CRSwNP., Methods: A detailed search was performed in PubMed, Embase and the Cochrane Library databases. All published English-language randomized controlled trials (RCTs) that employed dupilumab to treat CRSwNP in adult patients (≥18 years old) were considered., Results: Three RCTs and 25 studies with 784 individuals were included. The use of dupilumab revealed improvement in polyp size (MD -1.80; 95% CI -2.25 to -1.36), Lund-Mackay score (MD -7.01, 95% CI -9.64 to -4.38), congestion (MD -0.86, 95% CI -0.99 to -0.73), smell (MD 10.83, 95% CI 9.59 to 12.08) and health-related quality of life (MD -19.61, 95% CI -22.53 to -16.69). Systemic corticosteroid use (RR 0.28, 95% CI 0.20-0.39) and revision surgery (RR 0.17, 95% CI 0.05-0.52) were reduced. Serious adverse events were reduced in dupilumab group (RR 0.47; 95% CI 0.29 to 0.76) with no change in risk of adverse events (RR 0.98, 95% CI 0.87 to 1.11)., Conclusions: Dupilumab is effective with minimal adverse events., Protocol Registration: www.crd.york.ac.uk/prospero identifier is CRD42023413004.

Nasal Extranodal NK/T Cell Lymphoma is an aggressive tumour affecting the nasal and midline structures, causing surrounding tissue destruction as the result of its progression. The initial presentations are similar to symptoms of benign nasal polyps, such as nasal obstruction, hyposmia and nasal discharge. As the disease progresses, the involvement of the palate, paranasal sinuses, orbit and skin become alarming symptoms. We report a case of a young male with Nasal ENKTL who presented with symptoms similar to acute on chronic rhinosinusitis with orbital complications. The challenges of diagnosing and getting to the correct management pathway are discussed., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Olfactory disorders (OD) are an umbrella term for a diverse group of smell problems. Numerous tests and questionnaires have been formulated to identify and test the severity of smell impairment, which is not readily available or translated for the Malaysian population. This study aimed to translate the Questionnaire for Olfactory Disorders (QOD) and validate and test the reliability of the Malay Questionnaire for Olfactory Disorders (mQOD)., Methods: This cross-sectional study was conducted in two tertiary centres. A forward and backward translation was conducted for the QOD. The translated questionnaire was distributed to subjects with self-reported smell disorders on days 1 and 7. Internal consistency was analysed using Cronbach's alpha and test-retest reliability was tested with an intraclass correlation coefficient. Confirmatory factor analysis was performed to test construct validity., Results: A total of 375 participants were recruited, 52 dropped out and 323 completed the questionnaire a second time. The Cronbach's alpha coefficient was 0.537 for parosmia (P), 0.892 for life quality (LQ), 0.637 for sincerity (S) and 0.865 for visual analogue score (VAS). The intraclass correlation coefficient (ICC) for domain scores was > 0.9, while the ICC for all items was good to excellent. A three-factor model for mQOD showed an acceptable fit with indices chi-square value (CMIN)/degree of freedom (DF) = 3.332, Tucker-Lewis fit index (TLI) = 0.923, comparative fit index (CFI) = 0.939, root mean square error of approximation (RMSEA) = 0.079 and standardised root mean square residual (SRMR) = 0.0574., Conclusion: The mQOD is a valid and reliable tool for assessing OD in patients., Competing Interests: Conflict of Interest: None., (© Penerbit Universiti Sains Malaysia, 2023.)

Background: Chronic rhinosinusitis (CRS) is one of the most common chronic inflammatory diseases of sinonasal mucosa. Asthma among CRS patients is often underdiagnosed which makes the management of CRS more challenging. Therefore, using serum and tissue eosinophil as an indicator and predictor of asthma in CRS patients is vital for further preventing recurrent and increasing the effectiveness of treatment for CRS., Objective: To determine the association and diagnostic ability of serum and tissue eosinophils in the diagnosis of asthma among CRS patients., Methods: A cross-sectional study was conducted involving 24 CRS patients with asthma and without asthma, respectively, from the Otorhinolaryngology clinic of two tertiary hospitals located on the East Coast of Peninsular Malaysia. Serum and tissue eosinophils (obtained from nasal polyp) levels between both groups were compared. Association between serum and tissue eosinophils with asthma was evaluated using logistic regression analysis, adjusting for important sociodemographic characteristics. The diagnostic ability of serum and tissue eosinophil was then evaluated by assessing the receiver operating characteristic curve., Results: A total of 48 CRS patients with a mean [SD] age of 47.50 [14.99] years were included. Patients with asthma had significantly higher serum [0.48 vs 0.35 × 10 9 /L] and tissue eosinophil [100 vs 8.5 per HPF] levels. Tissue eosinophils were found to be an independent predictor of asthma with adjusted OR 1.05, p < 0.001, after adjusting for age and serum eosinophils. The area under the receiver operating characteristic curve for serum eosinophil was 69.0%. At optimal cut-off value (0.375 × 10 9 /L), the sensitivity and specificity for serum eosinophil was 75.0% and 70.8%. The area under the receiver operating characteristic curve for tissue eosinophil was 93.4%. At the optimal cut-off value (58.0 per HPF), the sensitivity and specificity for tissue eosinophils were 79.2% and 91.7%, respectively., Conclusion: This study indicates a significantly higher level of serum and tissue eosinophils in CRS with asthma. However, there was no correlation between serum and tissue eosinophils in both group. Based on this study, the CRS patient needs to be screened for asthma if the level of serum eosinophil is > 0.375 × 10 9 /L and tissue eosinophil > 58 per HPF., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rhinolith is an uncommon condition that usually happens due to mineralisation of calcium and magnesium salts over a retained foreign body inside the nasal cavity for long period of time. Here we report one such case of a 33-year-old lady who presented to us with long standing intermittent epistaxis and on examination rhinolith was discovered., Competing Interests: Conflict of InterestThe authors shared no conflicts of interest in regards of the research and publication of this article., (© Association of Otolaryngologists of India 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Allergic rhinitis (AR) is an IgE-mediated inflammatory disease of the upper airway. AR affects the patients' quality of life, is a known risk factor for asthma and a socio-economic burden. Allergen-specific immunotherapy (AIT), comprising sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT), involves administering increasing doses of the causative allergen to induce clinical and immunologic tolerance to the allergens. It is the only currently available treatment for AR that has been proven to induce disease-modifying effects (i.e., long-term remission of allergic symptoms or potential prevention of asthma and new sensitizations). Although AIT is conventionally recommended for patients who are non-responsive to symptom-relieving pharmacotherapy, it is presently recommended as a first-line treatment for patients with moderate to severe AR who prefer a treatment with the potential for long-term remission. In light of the relatively recent implementation of AIT in Malaysia, guidelines on its appropriate indication and application are important to attain optimal outcomes. This consensus statement was developed by an expert group formed by the Malaysian Society of Allergy and Immunology to provide evidence-based recommendations for the practice of AIT in Malaysia. Patient and product selection, choice of AIT, and strategy towards an effective treatment outcome in AIT are presented.

Paranasal sinus (PNS) osteomas are benign growths that are usually asymptomatic and often discovered incidentally upon imaging. Nasal polyps, on the other hand, are relatively commoner than osteomas. With the adoption of endoscopic technology in the otorhinolaryngology (ORL) field, surgeons are shifting toward less invasive surgical methods in managing such cases. We present a case of a 23-year-old male who had chronic rhinosinusitis with nasal polyps. A computed tomography (CT) done as part of his preoperative planning revealed findings suggestive of nasal polyps with left frontal recess osteoma. Both pathologies were removed successfully via an endoscopic endonasal approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Gima et al.)

Allergic rhinitis (AR) is a common disorder of the upper airway, while asthma is a disease affecting the lower airway and both diseases are usually comorbid. Interleukin (IL)-4 and IL-13 are critical cytokines in the induction of the pathogenic Th2 responses in AR and asthma. Targeting the IL-4/IL-13 axis at various levels of its signaling pathway has emerged as promising targeted therapy in both AR and asthma patient populations. In this review, we discuss the biological characteristics of IL-4 and IL-13, their signaling pathways, and therapeutic antibodies against each cytokine as well as their receptors. In particular, the pleiotropic roles of IL-4 and IL-13 in orchestrating Th2 responses in AR and asthma patients indicate that dual IL-4/IL-13 blockade is a promising therapeutic strategy for both diseases., Competing Interests: The authors declare there are no competing interests., (©2022 Nur Husna et al.)

Allergic rhinitis (AR) is a common allergic disease characterized by disruption of nasal epithelial barrier. In this study, we investigated the mRNA expression of zonula occludens-1 ( ZO-1 ), ZO-2 and ZO-3 and histone deacetylase 1 ( HDAC1 ) and HDAC2 in AR patients compared to healthy controls. RNA samples were extracted from nasal epithelial cells of house dust mites (HDMs)-sensitized AR patients and healthy controls ( n  = 28 in each group). The RNAs were reverse transcribed into cDNAs for measurement of ZO-1 , ZO-2 , ZO-3 , HDAC1 and HDAC2 expression levels by quantitative PCR. The mRNA expression of ZO-1 was significantly decreased in AR patients compared to healthy controls ( p  = 0.010). No significant difference was observed in the expression levels of ZO-2 , ZO-3 , HDAC1 and HDAC2 in AR patients compared to healthy controls. We found significant associations of higher HDAC2 levels in AR patients with lower frequency of changing bedsheet ( p  = 0.043) and with AR patients sensitized to Dermatophagoides farinae ( p  = 0.041). Higher expression of ZO-2 was observed in AR patients who had pets ( p  = 0.007). In conclusion, our data indicated that ZO-1 expression was lower in AR patients contributing to decreased integrity of nasal epithelial barrier integrity, and HDAC2 may be involved in the pathogenesis of the disease., Competing Interests: The authors declare there are no competing interests., (©2022 Siti Sarah et al.)

Allergic rhinitis (AR) represents a global health concern where it affects approximately 400 million people worldwide. The prevalence of AR has increased over the years along with increased urbanization and environmental pollutants thought to be some of the leading causes of the disease. Understanding the pathophysiology of AR is crucial in the development of novel therapies to treat this incurable disease that often comorbids with other airway diseases. Hence in this mini review, we summarize the well-established yet vital aspects of AR. These include the epidemiology, clinical and laboratory diagnostic criteria, AR in pediatrics, pathophysiology of AR, Th2 responses in the disease, as well as pharmacological and immunomodulating therapies for AR patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nur Husna, Tan, Md Shukri, Mohd Ashari and Wong.)

The IL-4/IL-13 axis is involved in the pathogenesis of allergic rhinitis (AR). In this study, we investigated the serum cytokines levels of IL-4, IL-5, IL-6, and IL-13 in AR patients, and the transcript expression levels of their receptors ( i.e. IL4R , IL5RA , IL6R, and IL13RA1 ) in nasal epithelial cells of AR patients versus non-allergic controls. Nasal epithelial cells and blood samples of non-allergic controls ( n = 30) and AR patients ( n = 30) were collected to examine mRNA expression and serum cytokines levels, respectively. Bioinformatics analyses of IL-4/IL-13 receptor heterodimer association with tight junction (TJ) and JAK/STAT signaling genes were conducted in a gene expression profiling (GEP) dataset (GSE44037) of AR patients ( n = 12) and healthy controls ( n = 6). Serum IL-4, IL-5, IL-6 or IL-13 levels, and IL13RA1 transcript expression were significantly higher in AR patients compared with non-allergic controls. IL-4 and IL-13 serum levels were positively correlated with IL13RA1 expression in AR patients but not in non-allergic controls. In the GEP dataset (GSE44037), six TJ ( CLDN4 , CLDN7 , CLDN12 , CLDN15 , TJP1 , and TJP2 ) genes' expressions were negatively correlated, respectively, with IL-4Rα/IL-13Rα1 heterodimeric receptor expression in AR patients and not in control samples. These six TJ genes contributed to the significant enrichment of tight junction Gene Ontology (GO ID: 0070160). Lastly, STATs DNA binding motif analysis showed that each of these TJ genes contains STATs binding consensus sequence within intronic and intergenic regions. Our results suggest that increased IL-4/IL-13 serum cytokines levels may contribute to decreased TJs expression via IL-4Rα/IL-13Rα1 heterodimeric receptor in nasal epithelium of AR patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nur Husna, Md Shukri, Tuan Sharif, Tan, Mohd Ashari and Wong.)

Allergic rhinitis (AR) is a global health burden and it manifests in both nasal and non-nasal symptoms. Skin prick test (SPT) is a routine procedure to diagnose AR sensitized to common allergens including house dust mites (HDMs). The degree of sensitivity of a patient toward allergens is determined by the size of the wheal formed by SPT procedure. SPT wheal sizes are influenced by recent anti-histamine usage, however it remains unclear if SPT wheal sizes are also influenced by other factors. In this study, we set out to investigate the association between SPT wheal sizes with the demographical, clinical and environmental characteristics, as well as nasal and non-nasal symptoms severity scores, of AR patients ( n = 30) sensitized to common HDMs (i.e., Dermatophagoides pteronyssinus, Dermatophagoides farinae , and Blomia tropicalis ). We showed that SPT wheal sizes of HDM allergens were not associated with clinical, demographical and environmental characteristics examined. Nonetheless, significant correlations were observed between SPT wheal sizes of D. farinae sensitization with worse severity scores of all five nasal symptoms examined (i.e., sneezing, runny nose, itchy nose, congestion and postnasal drip) and four of the six non-nasal symptoms examined (i.e., throat symptoms, ear symptoms, headache and mental function). Such relationships were not observed in SPT wheal sizes of D. pteronyssinus and B. tropicalis sensitization. We suggest that increased SPT wheal sizes for D. farinae sensitization may predict the likelihood of more severe nasal and, to a lesser extent, non-nasal manifestations in AR patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nur Husna, Md Shukri, Tan, Mohd Ashari and Wong.)

Background: Allergic rhinitis (AR) is a long-standing disease and has been shown to cause significant impairment in patients' quality of life. Saline nasal irrigation is a proven adjunct in the treatment of AR. The addition of steroid to the saline solution can provide local steroid effect and increase the effectiveness of this technique. Our study aimed to determine the effectiveness of budesonide nasal irrigation as an adjunct to the treatment of AR, compared with saline nasal irrigation., Methods: This was a randomised controlled study involving 99 patients diagnosed with AR, half of whom were treated with saline nasal irrigation and the other half with budesonide nasal irrigation. Parameters measured include the Sino-Nasal Outcome Test (SNOT-22) questionnaire, endoscopic nasal examination findings and blood eosinophil count., Results: Patients treated with budesonide nasal irrigation had significant improvement in total SNOT-22 score ( P < 0.001) and improvement in the endoscopic nasal examination findings, such as nasal mucosa oedema and secretions ( P < 0.001). However, there was no significant improvement of blood eosinophil count in patients treated with either budesonide or saline nasal irrigation., Conclusion: Budesonide nasal irrigation is effective as an adjunct in the treatment of AR., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2022.)