Huge Long Standing Staghorn Rhinolith in a Young Adult.

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.

Malaysian Society of Allergy and Immunology Consensus Statement on Sublingual Immunotherapy in Allergic Rhinitis.

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.

Diagnostic value of serum and tissue eosinophil in diagnosis of asthma among patients with chronic rhinosinusitis.

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 × 109/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 × 109/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 × 109/L and tissue eosinophil > 58 per HPF.

Validity and Reliability of the Malay Questionnaire for Olfactory Disorders.

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.

Endoscopic Excision of Frontal Recess Osteoma in a Patient With Nasal Polyposis.

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.

IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma.

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.

Allergic Rhinitis: A Clinical and Pathophysiological Overview.

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.

Zonula occludens-1 expression is reduced in nasal epithelial cells of allergic rhinitis patients.

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.

IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression.

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.

Higher Wheal Sizes of Dermatophagoides farinae Sensitization Exhibit Worse Nasal Symptoms in Allergic Rhinitis Patients.

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.

The Effectiveness of Budesonide Nasal Irrigation in Patients with Allergic Rhinitis.

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.

The prevalence of complementary and alternative medicines (CAM) usage among allergic rhinitis patients in Malaysia.

PURPOSE: We conducted this study to estimate the prevalence of complementary and alternative medicines (CAM) usage among allergic rhinitis (AR) patients in Malaysia and understand the practice of CAM usage among them. We also included a literature review on the commonly used CAM for AR. METHODS: A cross-sectional study which included a questionnaire-based study and information of allergic rhinitis from patient's clinic records. Patients with AR who attended the ORL-HNS department in Hospital Universiti Sains Malaysia and Hospital Sultanah Aminah, Malaysia were enrolled after consented, on a first-come first-serve basis as convenience sampling from July 2020 until February 2021. A pre-tested self-administered, 16-item questionnaire in Malay language was distributed to the participants. The questionnaire consists of a set of 16 questions with subsets to enquire about the sociodemographic data and pattern of usage of CAM and its effectiveness. RESULTS: 372 patients were enrolled in this study consisting of 217 (58.3%) female and 155 (41.7%) male patients. 231 (62.1%) participants had used CAM for AR in the past 10 years. A higher proportion of females (p = 0.015) and those with higher income (p = 0.004) had used CAM. Among the users, 87.9% found CAM to be effective. No differences were found in terms of age (p = 0.888) and education level (p = 0.057) for CAM usage. CONCLUSION: CAM is widely used in Malaysia to alleviate AR symptoms, with a large proportion of users think it is effective. Therefore, more researches should be conducted to provide evidence and guidance to integrate CAM into AR management.

Nasal Epithelial Barrier Integrity and Tight Junctions Disruption in Allergic Rhinitis: Overview and Pathogenic Insights.

Allergic rhinitis (AR) is a common disorder affecting up to 40% of the population worldwide and it usually persists throughout life. Nasal epithelial barrier constitutes the first line of defense against invasion of harmful pathogens or aeroallergens. Cell junctions comprising of tight junctions (TJs), adherens junctions, desmosomes and hemidesmosomes form the nasal epithelial barrier. Impairment of TJ molecules plays causative roles in the pathogenesis of AR. In this review, we describe and discuss the components of TJs and their disruption leading to development of AR, as well as regulation of TJs expression by epigenetic changes, neuro-immune interaction, epithelial-derived cytokines (thymic stromal lymphopoietin, IL-25 and IL-33), T helper 2 (Th2) cytokines (IL-4, IL-5, IL-6 and IL-13) and innate lymphoid cells. These growing evidence support the development of novel therapeutic approaches to restore nasal epithelial TJs expression in AR patients.

Orbital Cellulitis Secondary to Dental Abscess in Children.

Paediatric orbital cellulitis is a potential sight- and life-threatening condition. It is a serious infection in children that can result in significant complications, including blindness, cavernous sinus thrombosis, cerebral venous sinus thrombosis, meningitis, subdural empyema, and brain abscess. Of the patients with orbital cellulitis, 17% died from meningitis, and 20% of the survivors had permanent loss of vision. Therefore, the potential for sight- and life-threatening complications makes prompt diagnosis and early treatment very important. We report here a case of a two-year-old girl who presented with a three-day history of left periorbital swelling, preceded by left upper perioral swelling that extended upward to the left cheek and left lower lid and was associated with low-grade fever. The patient had been admitted and was treated as having left preseptal with facial cellulitis; the patient was started on intravenous amoxicillin/clavulanic acid (200 mg three times per day dose), and chloramphenicol ointment was applied to the periorbital area. On day 3, the condition worsened, and dental examination showed multiple dental caries, upper gum swelling and abscess, and mobility of teeth 61 and 62 (two baby teeth). Contrast-enhanced computed tomography (CECT) of the orbit, paranasal, and brain showed a left periosteal abscess collection extending to the inferomedial region of the orbit. Examination and tooth extraction were performed under general anesthesia. The intraoperative results showed the presence of a left upper gum abscess, which was possibly the primary source of infection. Clinical improvement was observed postoperatively. Orbital cellulitis can be a complication of a dental abscess. This case emphasizes the importance of primary tooth care in children. A lack of care can result in fatal complications.

Reduced occludin and claudin-7 expression is associated with urban locations and exposure to second-hand smoke in allergic rhinitis patients.

The breakdown of nasal epithelial barrier occurs in allergic rhinitis (AR) patients. Impairment of cell junction molecules including tight junctions (TJs) and desmosomes plays causative roles in the pathogenesis of AR. In this study, we investigated the transcript expression levels of TJs including occludin (OCLN), claudin-3 and -7 (CLDN3 and CLDN7), desmoglein 3 (DSG3) and thymic stromal lymphopoietin (TSLP) in AR patients (n = 30) and non-allergic controls (n = 30). Nasal epithelial cells of non-allergic controls and AR patients were collected to examine their mRNA expression levels, and to correlate with clinico-demographical and environmental parameters. We demonstrated that the expression of OCLN (p = 0.009), CLDN3 (p = 0.032) or CLDN7 (p = 0.004) transcript was significantly lower in AR patients compared with non-allergic controls. No significant difference was observed in the expression of DSG3 (p = 0.750) or TSLP (p = 0.991) transcript in AR patients compared with non-allergic controls. A significant association between urban locations and lower OCLN expression (p = 0.010), or exposure to second-hand smoke with lower CLDN7 expression (p = 0.042) was found in AR patients. Interestingly, none of the TJs expression was significantly associated with having pets, frequency of changing bedsheet and housekeeping. These results suggest that defective nasal epithelial barrier in AR patients is attributable to reduced expression of OCLN and CLDN7 associated with urban locations and exposure to second-hand smoke, supporting recent findings that air pollution represents one of the causes of AR.

Knowledge, Attitude, and Practice of Intranasal Corticosteroid in Allergic Rhinitis Patients: Development of a New Questionnaire.

OBJECTIVES: The knowledge gap and attitude of allergic rhinitis (AR) patients using intranasal corticosteroid (INCS) led to the poor outcome of their disease. We aimed to develop and validate a new questionnaire to assess the knowledge, attitude, and practice (KAP) of AR patients that can be used to assess and understand the factors affecting compliance of INCS. METHODS: The questionnaire comprised development and validation stages. A self-administered questionnaire was developed after a comprehensive literature review. It was subjected to content and face validity before a revised final version was drafted. Exploratory factor analysis was used to assess the validity of the questionnaire. Cronbach's alpha was used to verify internal consistency. RESULTS: The development phase resulted in a questionnaire consisting of 14 items. Explanatory factor analysis revealed four factors associated with KAP. The four factors were extracted, and 12 items were kept. The factors were attitude domain with four items (factor 1), practice domain with four items (factor 2), and knowledge domain with four items (factor 3 has two items, and factor 4 has two items). The Cronbach's alpha of the four factors ranged from 0.614 to 0.809. The final questionnaire consists of 3 domains with 12 items (the knowledge domain with four questions; the attitude domain with four questions; the practice domain with four questions) and was valid and reliable. CONCLUSIONS: The newly developed questionnaire has adequate validity and reliability. It is a useful tool to improve the treatment of AR patients by understanding the factors affecting their compliance.

Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis.

Allergic rhinitis (AR) is a common disease affecting 400 million of the population worldwide. Nasal epithelial cells form a barrier against the invasion of environmental pathogens. These nasal epithelial cells are connected together by tight junction (TJ) proteins including zonula occludens-1 (ZO-1), ZO-2 and ZO-3. Impairment of ZO proteins are observed in AR patients whereby dysfunction of ZOs allows allergens to pass the nasal passage into the subepithelium causing AR development. In this review, we discuss ZO proteins and their impairment leading to AR, regulation of their expression by Th1 cytokines (i.e., IL-2, TNF-α and IFN-γ), Th2 cytokines (i.e., IL-4 and IL-13) and histone deacetylases (i.e., HDAC1 and HDAC2). These findings are pivotal for future development of targeted therapies by restoring ZO protein expression and improving nasal epithelial barrier integrity in AR patients.

Association of IL-1 gene polymorphisms with chronic rhinosinusitis with and without nasal polyp.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common and complex chronic inflammatory disease of sinonasal mucosa. Even though the pathogenesis of CRS is multifactorial and still unclear, the role of cytokines especially interleukin-1 (IL-1) is being investigated worldwide in different population because of varying results obtained. OBJECTIVE: To study the association of IL-1 (A and B) gene polymorphisms with chronic rhinosinusitis with nasal polyp (CRSwNP) and without nasal polyp (CRSsNP), and other factors related. METHODS: This is a case-controlled study which include a total of 138 subjects recruited from Otorhinolaryngology-Head and Neck Surgery clinic in Hospital Universiti Sains Malaysia. Genotyping of the IL-1A (+4845G, +4845T) and IL-1B (-511C, -511T) were performed with restriction fragment length polymorphism analysis. RESULTS: There was a statistical significant association between IL-1B (-511C, -511T) polymorphism with CRSwNP and CRSsNP (p < 0.001). The CT genotype of IL-1B was markedly increased in CRSwNP subjects (52.2%). However, there was no significant association found between IL-1A (+4845G, +4845T) with CRSwNP and CRSsNP (p = 0.093). No association was found in factors related to CRS, which included asthma, atopy, allergy, aspirin sensitivity, and family history of nasal polyp (p value of 0.382, 0.382, 0.144, >0.95, and 0.254, respectively). CONCLUSION: This study indicates an association of IL-1B (-511C, -511T) polymorphism with CRSwNP and CRSsNP in our population, hence there is a possibility of IL-1B involvement in modulating pathogenesis of CRS. There was no significant association of IL-1A (+4845G, +4845T) polymorphism with CRSwNP and CRSsNP, and other factors related.