Publications by authors named "De Yun Wang"

216 Publications

Management of acute upper respiratory tract infection: the role of early intervention.

Expert Rev Respir Med 2021 Oct 19:1-7. Epub 2021 Oct 19.

Personal Health Care, Procter & Gamble International Operations SA Singapore Branch, Singapore.

Introduction: Upper respiratory tract infection (URTI) is an illness caused by an acute infection by viruses or bacteria of the nose, sinuses, pharynx, and larynx. Most URTIs are short, mild, and self-limiting, but some can lead to serious complications, resulting in heavy social and economic burden on individuals and society.

Areas Covered: This article presents the management guidelines and consensus established through the Delphi method during an expert roundtable conducted in November 2020 and results of a targeted literature review.

Expert Opinion: The current acute URTI management strategies aim toward symptom alleviation and prevention of URTI virus transmission. The effectiveness of these strategies is highly increased with early intervention, administered prior to the peaking of viral shedding. This reduces the chances of developing a full-blown acute URTI, decreases symptom severity, and reduces viral transmission. Mucoadhesive gel nasal sprays have shown promising results for early intervention of acute URTI. They act by creating a barrier that can trap virus particles, thereby preventing invasion of the mucosa by the virus. Additionally, they deliver broad spectrum activity that is effective against a wide variety of pathogens that cause acute URTI. Acute URTI warrants greater attention and proactive management in reducing its burden.
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http://dx.doi.org/10.1080/17476348.2021.1988569DOI Listing
October 2021

Understanding neutralising antibodies against SARS-CoV-2 and their implications in clinical practice.

Mil Med Res 2021 08 31;8(1):47. Epub 2021 Aug 31.

Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.

SARS-CoV-2 is a newly identified member of the coronavirus family that has caused the Coronavirus disease 2019 (COVID-19) pandemic. This rapidly evolving and unrelenting SARS-CoV-2 has disrupted the lives and livelihoods of millions worldwide. As of 23 August 2021, a total of 211,373,303 COVID-19 cases have been confirmed globally with a death toll of 4,424,341. A strong understanding of the infection pathway of SARS-CoV-2, and how our immune system responds to the virus is highly pertinent for guiding the development and improvement of effective treatments. In this review, we discuss the current understanding of neutralising antibodies (NAbs) and their implications in clinical practice. The aspects include the pathophysiology of the immune response, particularly humoral adaptive immunity and the roles of NAbs from B cells in infection clearance. We summarise the onset and persistence of IgA, IgM and IgG antibodies, and we explore their roles in neutralising SARS-CoV-2, their persistence in convalescent individuals, and in reinfection. Furthermore, we also review the applications of neutralising antibodies in the clinical setting-from predictors of disease severity to serological testing to vaccinations, and finally in therapeutics such as convalescent plasma infusion.
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http://dx.doi.org/10.1186/s40779-021-00342-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405719PMC
August 2021

Overexpression of Neutrophil MMP-9 and HIF-1α May Contribute to the Finger-Like Projections Formation and Histo-Pathogenesis in Nasal Inverted Papilloma.

J Inflamm Res 2021 6;14:2979-2991. Epub 2021 Jul 6.

Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

Background: Nasal inverted papilloma (NIP) is defined based on its histological characteristic of inverted epithelium growth into the stroma. The inversion can result in epithelial growth in the underlying connective tissue stroma when the basement membrane completely separates from the epithelial layer. To date, such inversion mechanism underlying NIP's pathological phenomenon is unknown. Therefore, we hypothesized that mediators and soluble proteins released by neutrophils, the most predominant infiltrating cells in NIP, is vital in causing the epithelial changes and pathogenesis of NIP.

Methods: We collected 37 NIP tissues from patients who underwent surgical removal of NIP and performed hematoxylin-eosin (HE), immunohistochemical, and immunofluorescence staining to analyze in-depth the basic characteristics of NIP, including detecting the expression and distribution of MMPs and associated factors in NIP. Western blotting and quantitative real-time PCR were further performed to analyze the protein and mRNA expression levels of specific factors including MMPs, HIF-1α, and tissue inhibitors of metalloproteinases (TIMPs).

Results: We observed finger-like projections that insert into the epithelium in NIP tissue as its main characteristics. The projections contain fibroblasts, extracellular matrix, capillaries, and infiltrating inflammatory cells. We found abundant neutrophils clustered at the finger-like projection of NIP, and also noted MMP-1 and MMP-9 were up-regulated in NIP (p<0.05), whereas TIMP-1/3 was decreased. The expression level of HIF-1α was also found to be increased in NIP tissue. We further showed that MMP-9 and HIF-1α were mainly expressed by neutrophils and were predominantly observed in the finger-like projections that contribute to the NIP pathology.

Conclusion: Upregulation and release of MMP-9 and HIF-1α from infiltrating neutrophils may cause damage to the epithelial basement membrane and epithelial clefts, forming finger-like projections with angiogenesis and fibroblasts insertion, resulting in epithelial growth in the tissue stroma, a typical histo-pathological characteristic in NIP.
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http://dx.doi.org/10.2147/JIR.S312605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275020PMC
July 2021

Clinical-Pathological Correlation of the Pathophysiology and Mechanism of Action of COVID-19 - a Primer for Clinicians.

Curr Allergy Asthma Rep 2021 07 14;21(6):38. Epub 2021 Jul 14.

Department of Otolaryngology, Head & Neck Surgery, National University Health System, Singapore, Singapore.

Purpose Of Review: Increasing knowledge of the pathogenesis of the SARS-CoV-2 infection and the complex interaction between host and viral factors have allowed clinicians to stratify the severity of COVID-19 infection. Epidemiological data has also helped to model viral carriage and infectivity. This review presents a comprehensive summary of the pathophysiology of COVID-19, the mechanisms of action of the SARS-CoV-2 virus, and the correlation with the clinical and biochemical characteristics of the disease.

Recent Findings: ACE2 and TMPRSS2 receptors have emerged as a key player in the mechanism of infection of SARS-CoV-2. Their distribution throughout the body has been shown to impact the organ-specific manifestations of COVID-19. The immune-evasive and subsequently immunoregulative properties of SARS-CoV-2 are also shown to be implicated in disease proliferation and progression. Information gleaned from the virological properties of SARS-CoV-2 is consistent with and reflects the clinical behavior of the COVID-19 infection. Further study of specific clinical phenotypes and severity classes of COVID-19 may assist in the development of targeted therapeutics to halt progression of disease from mild to moderate-severe. As the understanding of the pathophysiology and mechanism of action of SARS-CoV-2 continues to grow, it is our hope that better and more effective treatment options continue to emerge.
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http://dx.doi.org/10.1007/s11882-021-01015-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277568PMC
July 2021

Induction of IL-25 Expression in Human Nasal Polyp Epithelium by Influenza Virus Infection is Abated by Interferon-Alpha Pretreatment.

J Inflamm Res 2021 28;14:2769-2780. Epub 2021 Jun 28.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.

Background: Epithelial cytokines including IL-25, IL-33 and thymic stromal lymphopoietin (TLSP) are recently established as drivers of type 2 chronic inflammatory diseases such as chronic rhinosinusitis with nasal polyps (CRSwNP). Here, we further confirmed the increased expression of IL-25 in CRSwNP and investigated potential contributors of IL-25 in CRSwNP epithelium.

Methods: Sixty CRSwNP, 25 CRSsNP and 15 healthy control tissues were examined for IL-25 expression and for the accompanying type 2 inflammatory cytokines. We then tested different respiratory virus infections on human nasal epithelial cells (hNECs) for their ability to trigger IL-25 expression. In addition, we subjected hNECs generated from CRSwNP tissues to pretreatment with recombinant interferon-alpha (IFN-α) prior to viral infection to evaluate IFN effects on IL-25 induction.

Results: We confirmed that significantly enhanced levels of IL-25 were observed in CRSwNP tissues, and that IL-25 expression correlated with type 2 inflammatory cytokine expression. In vitro, we observed significantly elevated IL-25 in hNECs infected with influenza A virus as early as 24 hours post-infection (hpi), regardless of tissue origin, and IL-25 correlated positively with viral load. While other respiratory viruses exhibited increasing trends of IL-25, these were not significant at the time-points tested. IFN-α treatment of CRSwNP epithelium was found to exert bimodal effects, ie IFN-α treatment alone induced moderate IL-25 expression, whereas IFN-α pretreatment of hNECs before influenza infection significantly diminished IL-25 induction by active influenza virus infection.

Conclusion: We have authenticated the observation of elevated IL-25 in CRSwNP, which is correlated with type 2 inflammatory cytokines. Notably, we identified influenza virus infection as a potential contributor of IL-25 in both control and CRSwNP epithelium during active infection. This IL-25 induction can be abated by IFN-α pretreatment which ameliorated active influenza infection.

Trial Registration: Chictr.org.cn ChiCTR-BON-16010179, Registered 18 December 2016, http://www.chictr.org.cn/showproj.aspx?proj=17331. The authors agree on the sharing of deidentified participant data where it pertains to request directly related to the data in this article when contacted (Haiyu Hong; [email protected]).
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http://dx.doi.org/10.2147/JIR.S304320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254189PMC
June 2021

FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression.

Commun Biol 2021 07 2;4(1):832. Epub 2021 Jul 2.

Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.

Sialyl-Lewis x (sLe, CD15s) is a tetra-saccharide on the surface of leukocytes required for E-selectin-mediated rolling, a prerequisite for leukocytes to migrate out of the blood vessels. Here we show using flow cytometry that sLe expression on basophils and mast cell progenitors depends on fucosyltransferase 6 (FUT6). Using genetic association data analysis and qPCR, the cell type-specific defect was associated with single nucleotide polymorphisms (SNPs) in the FUT6 gene region (tagged by rs17855739 and rs778798), affecting coding sequence and/or expression level of the mRNA. Heterozygous individuals with one functional FUT6 gene harbor a mixed population of sLe and sLe basophils, a phenomenon caused by random monoallelic expression (RME). Microfluidic assay demonstrated FUT6-deficient basophils rolling on E-selectin is severely impaired. FUT6 null alleles carriers exhibit elevated blood basophil counts and a reduced itch sensitivity against insect bites. FUT6-deficiency thus dampens the basophil-mediated allergic response in the periphery, evident also in lower IgE titers and reduced eosinophil counts.
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http://dx.doi.org/10.1038/s42003-021-02295-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253766PMC
July 2021

Precision Medicine in Chronic Rhinosinusitis: Where Does Allergy Fit In?

Handb Exp Pharmacol 2021 Jun 4. Epub 2021 Jun 4.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Chronic rhinosinusitis (CRS) is a clinical syndrome stemming from persistent inflammation of the sinonasal mucosa. Phenotypically, it is traditionally and widely described according to the presence or absence of polyps. While this distinction is simple to use, it has little bearing on prognosis and treatment, for CRS is essentially an inflammatory disease resulting from dysregulated interaction between a multitude of host and environmental factors. Allergy is merely one of them and, like many of the proposed aetiologies, has been subject to much debate which will be discussed here. As our understanding of CRS continues to evolve, previous so-called conventional wisdom about phenotypes (e.g. CRS with nasal polyps is associated with Type 2 inflammation) is being challenged, and new phenotypes are also emerging. In addition, there is growing interest in defining the endotypes of CRS to deliver precise and personalised treatment, especially pertaining to the development of biologics for the group of severe, difficult-to-treat CRS patients. A proposed model of precision medicine tailored to management of CRS will also be introduced to readers, which can be continually modified to adapt to new discoveries about this exciting condition.
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http://dx.doi.org/10.1007/164_2021_489DOI Listing
June 2021

Digital CRISPR-based method for the rapid detection and absolute quantification of nucleic acids.

Biomaterials 2021 07 11;274:120876. Epub 2021 May 11.

Critical Analytics for Manufacturing Personalized Medicine Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 138602, Singapore; Institute of Bioengineering and Bioimaging, A*STAR, The Nanos, #04-01, 31, Biopolis Way, 138669, Singapore; Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, 117411, Singapore; Department of Physiology & the Institute for Digital Medicine (WisDM), Yong Loo Lin School of Medicine, MD9-04-11, 2 Medical Drive, 117593, Singapore. Electronic address:

Rapid diagnostics of adventitious agents in biopharmaceutical/cell manufacturing release testing and the fight against viral infection have become critical. Quantitative real-time PCR and CRISPR-based methods rapidly detect DNA/RNA in 1 h but suffer from inter-site variability. Absolute quantification of DNA/RNA by methods such as digital PCR reduce this variability but are currently too slow for wider application. Here, we report a RApid DIgital Crispr Approach (RADICA) for absolute quantification of nucleic acids in 40-60 min. Using SARS-CoV-2 as a proof-of-concept target, RADICA allows for absolute quantification with a linear dynamic range of 0.6-2027 copies/μL (R value > 0.99), high accuracy and low variability, no cross-reactivity to similar targets, and high tolerance to human background DNA. RADICA's versatility is validated against other targets such as Epstein-Barr virus (EBV) from human B cells and patients' serum. RADICA can accurately detect and absolutely quantify EBV DNA with similar dynamic range of 0.5-2100 copies/μL (R value > 0.98) in 1 h without thermal cycling, providing a 4-fold faster alternative to digital PCR-based detection. RADICA therefore enables rapid and sensitive absolute quantification of nucleic acids which can be widely applied across clinical, research, and biomanufacturing areas.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120876DOI Listing
July 2021

Mucus composition abnormalities in sinonasal mucosa of chronic rhinosinusitis with and without nasal polyps.

Inflammation 2021 Oct 17;44(5):1937-1948. Epub 2021 May 17.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Rd, Singapore, 119228, Singapore.

Mucus secretion and its composition are vital in the maintenance of airway health, among which hypoxia-inducible factors (HIFs) are thought to be involved in the regulation of mucin synthesis and regulation. Nasal mucus composition difference between healthy individuals and chronic rhinosinusitis (CRS) patients may contribute to the pathology of chronic nasal diseases, but so far, their role has yet to be completely understood. Nasal biopsy specimens were obtained from 24 healthy subjects and 99 patients with CRS without (CRSsNP, n=36) or with (CRSwNP, n=63) nasal polyps. Immunohistochemical (IHC) and immunofluorescent (IF) staining, quantitative real-time PCR, and western blot were performed to compare the nasal mucus composition between the subjects. Areas of the serous gland and mucous gland were both significantly increased in CRSsNP patients. In CRSwNP patients, a decrease in submucosal gland density and a marked increase in goblet cells were observed. The major gel-forming mucins in the sinonasal mucosa of CRSsNP and CRSwNP are MUC5B and MUC5AC respectively. Mucous cells are found in a higher proportion in both CRSsNP and CRSwNP. The proportion of MUC5AC-positive goblet cells was increased in CRSwNP. The mRNA level of HIF-2α was significantly increased in CRS, and both HIF-1α and HIF-2α were expressed in serous cell but not mucous cell. Over secretion and altered composition of mucus are observed in sinonasal mucosa of CRS, which was mainly associated with glandular hyperplasia in CRSsNP and goblet cell hyperplasia in CRSwNP. Mucus abnormality compromised both non-specific and specific antimicrobial capabilities in the sinonasal mucosa. HIF expression may contribute to differences in mucin synthesis and serous gland regulation, which needs further investigation to understand the pathology of CRS.
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http://dx.doi.org/10.1007/s10753-021-01471-6DOI Listing
October 2021

Highlights in the advances of chronic rhinosinusitis.

Allergy 2021 May 4. Epub 2021 May 4.

Department of Otorhinolaryngology, Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands.

Chronic rhinosinusitis (CRS) is a complex upper airway inflammatory disease with a broad spectrum of clinical variants. As our understanding of the disease pathophysiology evolves, so too does our philosophy towards the approach and management of CRS. Endotyping is gaining favour over phenotype-based classifications, owing to its potential in prognosticating disease severity and delivering precision treatment. Endotyping is especially useful in challenging CRS with nasal polyposis cases, for whom novel treatment options such as biologicals are now available. The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) reflects these changes with updated rhinosinusitis classifications and new integrated care pathways. With the coronavirus disease 2019 (COVID-19) pandemic, physicians and rhinologists have to balance the responsibility of managing their patients' upper airway while adequately protecting themselves from droplet and aerosol transmission. This review summarises the key updates from EPOS2020, endotype-based classification and biomarkers. The role of biologicals in CRS and the lessons we can draw from their use in severe asthma will be examined. Finally, the principles of CRS management during COVID-19 will also be discussed.
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http://dx.doi.org/10.1111/all.14892DOI Listing
May 2021

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

Front Cell Dev Biol 2021 15;9:625251. Epub 2021 Apr 15.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Background: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them.

Methods: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP.

Results: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes.

Conclusion: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.
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http://dx.doi.org/10.3389/fcell.2021.625251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083899PMC
April 2021

Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives.

Allergy 2021 06 4;76(6):1640-1660. Epub 2021 Jun 4.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.
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http://dx.doi.org/10.1111/all.14840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251022PMC
June 2021

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Allergy 2021 10;76(10):2952-2964

Regional Ministry of Health of Andalusia, Seville, Spain.

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
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http://dx.doi.org/10.1111/all.14838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251336PMC
October 2021

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA LEN consensus.

Allergy 2021 08 14;76(8):2354-2366. Epub 2021 May 14.

Division of Allergy, Department of Pediatric Medicine, The Bambino Gesù Children's Research Hospital Holy see, IRCCS, Rome, Italy.

Background: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases.

Methods: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis.

Results: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001).

Conclusions: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
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http://dx.doi.org/10.1111/all.14815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250633PMC
August 2021

Contact-Free Co-Culture Model for the Study of Innate Immune Cell Activation During Respiratory Virus Infection.

J Vis Exp 2021 02 28(168). Epub 2021 Feb 28.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore; NUHS Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore;

The early interactions between the nasal epithelial layer and the innate immune cells during viral infections remains an under-explored area. The significance of innate immunity signaling in viral infections has increased substantially as patients with respiratory infections who exhibit high innate T cell activation show a better disease outcome. Hence, dissecting these early innate immune interactions allows the elucidation of the processes that govern them and may facilitate the development of potential therapeutic targets and strategies for dampening or even preventing early progression of viral infections. This protocol details a versatile model that can be used to study early crosstalk, interactions, and activation of innate immune cells from factors secreted by virally infected airway epithelial cells. Using an H3N2 influenza virus (A/Aichi/2/1968) as the representative virus model, innate cell activation of co-cultured peripheral blood mononuclear cells (PBMCs) has been analyzed using flow cytometry to investigate the subsets of cells that are activated by the soluble factors released from the epithelium in response to the viral infection. The results demonstrate the gating strategy for differentiating the subsets of cells and reveal the clear differences between the activated populations of PBMCs and their crosstalk with the control and infected epithelium. The activated subsets can then be further analyzed to determine their functions as well as molecular changes specific to the cells. Findings from such a crosstalk investigation may uncover factors that are important for the activation of vital innate cell populations, which are beneficial in controlling and suppressing the progression of viral infection. Furthermore, these factors can be universally applied to different viral diseases, especially to newly emerging viruses, to dampen the impact of such viruses when they first circulate in naïve human populations.
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http://dx.doi.org/10.3791/62115DOI Listing
February 2021

Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines.

Allergy 2021 08 24;76(8):2337-2353. Epub 2021 Mar 24.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.
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http://dx.doi.org/10.1111/all.14809DOI Listing
August 2021

Design and Multicenter Clinical Validation of a 3-Dimensionally Printed Nasopharyngeal Swab for SARS-CoV-2 Testing.

JAMA Otolaryngol Head Neck Surg 2021 05;147(5):418-425

Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore.

Importance: Three-dimensionally printed nasopharyngeal swabs (3DP swabs) have been used to mitigate swab shortages during the coronavirus disease 2019 (COVID-19) pandemic. Clinical validation for diagnostic accuracy and consistency, as well as patient acceptability, is crucial to evaluate the swab's performance.

Objective: To determine the accuracy and acceptability of the 3DP swab for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Design, Setting, And Participants: A diagnostic study was conducted from May to July 2020 at 2 tertiary care centers in Singapore with different reference swabs (FLOQSwab [COPAN Diagnostics] or Dacron swab [Deltalab]) and swab processing techniques (wet or dry) to evaluate the performance of the 3DP swab compared with traditional, standard-of-care nasopharyngeal swabs used in health care institutions. The participants were patients with COVID-19 in the first 2 weeks of illness and controls with acute respiratory illness with negative test results for SARS-CoV-2. Paired nasopharyngeal swabs were obtained from the same nostril and tested for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction. The sequence of swabs was randomized based on odd and even participant numbers.

Main Outcomes And Measures: Primary outcome measures were overall agreement (OA), positive percentage agreement (PPA), and negative percentage agreement of the 3DP swab compared with reference swabs. Secondary outcome measures were the correlation of cycle threshold (Ct) values of both swabs.

Results: The mean (SD) age of participants was 45.4 (13.1) years, and most participants were men (87 of 89 [97.8%]), in keeping with the epidemiology of the COVID-19 pandemic in Singapore. A total of 79 patients with COVID-19 and 10 controls were recruited. Among the patients with COVID-19, the overall agreement and PPA of the 3DP swab was 91.1% and 93.5%, respectively, compared with reference swabs. The PPA was 100% for patients with COVID-19 who were tested within the first week of illness. All controls tested negative. The reverse-transcriptase polymerase chain reaction Ct values for the ORF1ab and E-gene targets showed a strong correlation (intraclass correlations coefficient, 0.869-0.920) between the 3DP and reference swab on independent testing at each institution despite differences in sample processing. Discordant results for both gene targets were observed only at high Ct values.

Conclusions And Relevance: In this diagnostic study of 79 patients with COVID-19 and 10 controls, the 3DP swab performed accurately and consistently across health care institutions and could help mitigate strained resources in the escalating COVID-19 pandemic.
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http://dx.doi.org/10.1001/jamaoto.2020.5680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893548PMC
May 2021

Self-reported Taste and Smell Disorders in Patients with COVID-19: Distinct Features in China.

Curr Med Sci 2021 Feb 13;41(1):14-23. Epub 2021 Feb 13.

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.
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http://dx.doi.org/10.1007/s11596-021-2312-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881907PMC
February 2021

Chemosensory Dysfunction in Patients with COVID-19: What Do We Learn from the Global Outbreak?

Curr Allergy Asthma Rep 2021 02 3;21(2). Epub 2021 Feb 3.

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China.

Purpose Of Review: Chemosensory dysfunction in the patients with COVID-19 has been reported frequently in the studies from different regions of the world. However, the prevalence of smell and/or taste disorders presents significant ethnic and geographic variability. In addition, the pathogenesis of chemosensory dysfunction remains unclarified.

Recent Findings: This is a narrative review on the recent state of the prevalence, mechanism, and diagnostic and therapeutic strategy of chemosensory dysfunction in COVID-19 patients during the global pandemic. The chemosensory dysfunction was analysis based on recent studies, which either used questionnaires, Likert scales (0-10), or smell tests to estimate the smell and taste dysfunction. The ethnic and geographic difference of the prevalence of smell and/or taste disorders and the potential underlying mechanisms have been discussed. Several suggestions on the diagnosis and treatment of COVID-19 patients with smell and taste disorders were summarized for the physicians. This review provides a comprehensive overview of the current studies regarding the chemosensory dysfunction during the COVID-19 worldwide outbreak.
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http://dx.doi.org/10.1007/s11882-020-00987-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857344PMC
February 2021

Clinical Diagnostic Study of a Novel Injection Molded Swab for SARS-Cov-2 Testing.

Infect Dis Ther 2021 Jun 11;10(2):1015-1022. Epub 2021 Jan 11.

Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore, Singapore.

Introduction: The gold standard for COVID-19 diagnosis is currently a real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2. This is most commonly performed on respiratory secretions obtained via a nasopharyngeal swab. Due to supply chain limitations and high demand worldwide because of the COVID-19 pandemic, access to commercial nasopharyngeal swabs has not been assured. 3D printing methods have been used to meet the shortfall. For longer-term considerations, 3D printing may not compare well with injection molding as a production method due to the challenging scalability and greater production costs of 3D printing.

Methods: To secure sufficient nasopharyngeal swab availability for our national healthcare system, we designed a novel injection molded nasopharyngeal swab (the IM2 swab). We performed a clinical diagnostic study comparing the IM2 swab to the Copan FLOQSwab. Forty patients with a known diagnosis of COVID-19 and 10 healthy controls were recruited. Paired nasopharyngeal swabs were obtained from the same nostril of each participant and tested for SARS-CoV-2 by RT-PCR.

Results: When compared to the Copan FLOQswab, results from the IM2 swab displayed excellent overall agreement and positive percent agreement of 96.0% and 94.9%, respectively. There was no significant difference in mean RT-PCR cycle threshold values for the ORF1ab (28.05 vs. 28.03, p = 0.97) and E-gene (29.72 vs. 29.37, p = 0.64) targets, respectively. We did not observe any significant adverse events and there was no significant difference in patient-reported pain.

Conclusion: In summary, the IM2 nasopharyngeal swab is a clinically safe, highly accurate option to commercial nasopharyngeal swabs.
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http://dx.doi.org/10.1007/s40121-020-00391-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799401PMC
June 2021

Host Antiviral Response Suppresses Ciliogenesis and Motile Ciliary Functions in the Nasal Epithelium.

Front Cell Dev Biol 2020 21;8:581340. Epub 2020 Dec 21.

Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Background: Respiratory viral infections are one of the main drivers of development and exacerbation for chronic airway inflammatory diseases. Increased viral susceptibility and impaired mucociliary clearance are often associated with chronic airway inflammatory diseases and served as risk factors of exacerbations. However, the links between viral susceptibility, viral clearance, and impaired mucociliary functions are unclear. Therefore, the objective of this study is to provide the insights into the effects of improper clearance of respiratory viruses from the epithelium following infection, and their resulting persistent activation of antiviral response, on mucociliary functions.

Methods: In order to investigate the effects of persistent antiviral responses triggered by viral components from improper clearance on cilia formation and function, we established an air-liquid interface (ALI) culture of human nasal epithelial cells (hNECs) and used Poly(I:C) as a surrogate of viral components to simulate their effects toward re-epithelization and mucociliary functions of the nasal epithelium following damages from a viral infection.

Results: Through previous and current viral infection expression data, we found that respiratory viral infection of hNECs downregulated motile cilia gene expression. We then further tested the effects of antiviral response activation on the differentiation of hNECs using Poly(I:C) stimulation on differentiating human nasal epithelial stem/progenitor cells (hNESPCs). Using this model, we observed reduced ciliated cell differentiation compared to goblet cells, reduced protein and mRNA in ciliogenesis-associated markers, and increased mis-assembly and mis-localization of ciliary protein DNAH5 following treatment with 25 μg/ml Poly(I:C) in differentiating hNECs. Additionally, the cilia length and ciliary beat frequency (CBF) were also decreased, which suggest impairment of ciliary function as well.

Conclusion: Our results suggest that the impairments of ciliogenesis and ciliary function in hNECs may be triggered by specific expression of host antiviral response genes during re-epithelization of the nasal epithelium following viral infection. This event may in turn drive the development and exacerbation of chronic airway inflammatory diseases.
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http://dx.doi.org/10.3389/fcell.2020.581340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779769PMC
December 2020

Next-Generation Allergic Rhinitis Care in Singapore: 2019 ARIA Care Pathways.

Ann Acad Med Singap 2020 11;49(11):885-896

Department of Otolaryngology, Head and Neck Surgery, Sengkang General Hospital, Singapore.

Allergic rhinitis (AR) is prevalent in Singapore, with a significant disease burden. Afflicting up to 13% of the population, AR impairs quality of life, leads to reduced work productivity and is an independent risk factor for asthma. In the last 2 decades, local studies have identified patient and physician behaviours leading to suboptimal control of the disease. Yet, there is an overall lack of attention to address this important health issue. Allergic Rhinitis and its Impact on Asthma (ARIA) is a European organisation aimed at implementing evidence-based management for AR worldwide. Recent focus in Europe has been directed towards empowering patients for self-management, exploring the complementary role of mobile health, and establishing healthcare system-based integrated care pathways. Consolidation of these ongoing efforts has led to the release of the 2019 ARIA care pathways. This review summarises the ARIA update with particular emphasis on the current status of adult AR in Singapore. In addition, we identify unmet needs and future opportunities for research and clinical care of AR in the local context.
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November 2020

Primary care management of allergic rhinitis: a cross-sectional study in four ASEAN countries.

Multidiscip Respir Med 2020 Jan 11;15(1):726. Epub 2020 Dec 11.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Background: In primary care, general practitioners (GPs) and pharmacists are tasked with the frontline responsibility of identifying and managing allergic rhinitis (AR) patients. There are currently no consolidated data on current treatment practices, patient compliance, and usage of guidelines within Southeast Asian Nations (ASEAN). Objective: To assess the attitudes and practices on AR of GPs and pharmacists in 4 ASEAN countries (Philippines, Indonesia, Thailand, and Malaysia).

Methods: A cross-sectional survey of 329 GPs and 548 pharmacists was conducted from May to November 2019. Participants answered a questionnaire focused on their i) current practice in the management of AR, ii) views on patient compliance, iii) understanding and usage of guidelines.

Results: Clinical history was the most preferred method to diagnose AR by 95.4% of GPs and 58.8% of pharmacists. Second-generation antihistamines were the most widely available treatment option in GP clinics and pharmacies (94.8% and 97.2%) and correspondingly the most preferred treatment for both mild (90.3%, 76.8%) to moderatesevere rhinitis (90.3%, 78.6%) by GPs and pharmacists, respectively. Loratadine was ranked as the most preferred 2 generation antihistamines (GP vs pharmacists: 55.3% vs 58.9%). More than 90% of GPs and pharmacists ranked length and efficacy of treatment as important factors that increase patient compliance. Awareness of the ARIA guidelines was high among GPs (80%) and lower among pharmacists (48.4%). However, only 63.3% of GPs and 48.2% of pharmacists knew how to identify AR patients.

Conclusions: The survey in the 4 ASEAN countries has identified a need to strengthen the awareness and use of ARIA guidelines among the primary care practitioners. Adherence to ARIA guidelines, choosing the appropriate treatment option and prioritizing factors that increases patient compliance may contribute to better management outcomes of AR at the primary care practice.
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http://dx.doi.org/10.4081/mrm.2020.726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750812PMC
January 2020

Defective STING expression potentiates IL-13 signaling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps.

J Allergy Clin Immunol 2021 05 17;147(5):1692-1703. Epub 2020 Dec 17.

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown.

Objective: Our aim was to explore the expression, regulation, and function of STING in CRSwNP.

Methods: STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B in vitro.

Results: STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13-induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP.

Conclusions: Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP.
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http://dx.doi.org/10.1016/j.jaci.2020.12.623DOI Listing
May 2021

Leukotriene A Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy.

Front Immunol 2020 24;11:559746. Epub 2020 Nov 24.

Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Background: Allergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs.

Methods: pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders.

Results: specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A hydrolase (LTAH) was consistent with the proteomics data. The LTAH level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTAH generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTAH might be a potential biomarker for predicting the efficiency of AIT.

Conclusion: Serum LTAH may be a potential biomarker for early prediction of an effective AIT.
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http://dx.doi.org/10.3389/fimmu.2020.559746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732448PMC
May 2021

Role of microRNAs in inflammatory upper airway diseases.

Allergy 2021 07 26;76(7):1967-1980. Epub 2020 Dec 26.

INGENIO, Immunoal·lèrgia Respiratòria Clínica i Experimental (IRCE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.

MicroRNAs (miRNAs) are a conserved family of small endogenous noncoding RNA molecules that modulate post-transcriptional gene expression in physiological and pathological processes. miRNAs can silence target mRNAs through degradation or inhibition of translation, showing their pivotal role in the pathogenesis of many human diseases. miRNAs play a role in regulating immune functions and inflammation and are implicated in controlling the development and activation of T and B cells. Inflammatory chronic upper airway diseases, such as rhinitis and rhinosinusitis, are spread all over the world and characterized by an exaggerated inflammation involving a complex interaction between immune and resident cells. Until now and despite allergy, little is known about their etiology and the processes implicated in the immune response and tuning inflammation of these diseases. This review highlights the knowledge of the current literature about miRNAs in inflammatory chronic upper airways diseases and how this may be exploited in the development of new clinical and therapeutic strategies.
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http://dx.doi.org/10.1111/all.14706DOI Listing
July 2021

Role of yes-associated protein in interleukin-13 induced nasal remodeling of chronic rhinosinusitis with nasal polyps.

Allergy 2021 02 1;76(2):600-604. Epub 2021 Jan 1.

Department of Otorhinolaryngology-Head and Neck Surgery, Department of Allergy, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

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http://dx.doi.org/10.1111/all.14699DOI Listing
February 2021

Assessment of perception, attitude, and practice of primary care practitioners towards allergic rhinitis practice guidelines: Development and validation of a new questionnaire.

World Allergy Organ J 2020 Dec 18;13(12):100482. Epub 2020 Nov 18.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.

Background: Primary care practitioners (PCPs), being the front liners, play an important role in treating allergic rhinitis (AR). As there is no proper tool to assess their perception, attitude, and practice in utilizing the guidelines, we aimed to develop and validate a new questionnaire for such purpose.

Methods: The development phase consists of both literature and expert panel review. The validation phase consists of content validity, face validity, and construct validity. Cronbach's alpha was used to verify internal consistency. The development phase produced a questionnaire with 3 domains: perception, attitude, and practice consisting of 60 items (PAP-PCP questionnaire). Item response theory analysis for perception demonstrated the difficulty and discrimination values were acceptable except for 3 items. Exploratory factor analysis for attitude and practice domains showed the psychometric properties were good except for 3 items in practice domain. Experts judgement was used to decide on the final selection of questionnaire which consists of 59 items.

Results: The final validated questionnaire has 3 domains with 59 items. All domains had Cronbach's alpha above 0.65 which was reliable. 302 physicians completed the questionnaire. 98% PCPs diagnosed AR based on clinical history. Although, majority agree AR guidelines is useful (67%), they had difficulty in using it to classify AR (54.9%) and determine AR severity (73.9%). Oral anti-histamines (first and second generation) were the most prescribed (>75%) followed by intranasal corticosteroids (59%) and combined intranasal corticosteroid and oral anti-histamine (51%). Majority agreed that treatment efficacy (81.8%), adverse effects (83.8%), fear of adverse effects (73.5%), route of administration (69.4%), dosing frequency (72.5%), taste (64.6%) and cost (73.5%) affect treatment compliance.

Conclusions: The newly developed and validated questionnaire is a promising instrument in understanding the treatment gap in AR. Although further testing and refinement are needed, it provides an initial means for evaluating knowledge and understanding of PCPs in treating AR.
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http://dx.doi.org/10.1016/j.waojou.2020.100482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689322PMC
December 2020

Infection of human Nasal Epithelial Cells with SARS-CoV-2 and a 382-nt deletion isolate lacking ORF8 reveals similar viral kinetics and host transcriptional profiles.

PLoS Pathog 2020 12 7;16(12):e1009130. Epub 2020 Dec 7.

Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.

The novel coronavirus SARS-CoV-2 is the causative agent of Coronavirus Disease 2019 (COVID-19), a global healthcare and economic catastrophe. Understanding of the host immune response to SARS-CoV-2 is still in its infancy. A 382-nt deletion strain lacking ORF8 (Δ382 herein) was isolated in Singapore in March 2020. Infection with Δ382 was associated with less severe disease in patients, compared to infection with wild-type SARS-CoV-2. Here, we established Nasal Epithelial cells (NECs) differentiated from healthy nasal-tissue derived stem cells as a suitable model for the ex-vivo study of SARS-CoV-2 mediated pathogenesis. Infection of NECs with either SARS-CoV-2 or Δ382 resulted in virus particles released exclusively from the apical side, with similar replication kinetics. Screening of a panel of 49 cytokines for basolateral secretion from infected NECs identified CXCL10 as the only cytokine significantly induced upon infection, at comparable levels in both wild-type and Δ382 infected cells. Transcriptome analysis revealed the temporal up-regulation of distinct gene subsets during infection, with anti-viral signaling pathways only detected at late time-points (72 hours post-infection, hpi). This immune response to SARS-CoV-2 was significantly attenuated when compared to infection with an influenza strain, H3N2, which elicited an inflammatory response within 8 hpi, and a greater magnitude of anti-viral gene up-regulation at late time-points. Remarkably, Δ382 induced a host transcriptional response nearly identical to that of wild-type SARS-CoV-2 at every post-infection time-point examined. In accordance with previous results, Δ382 infected cells showed an absence of transcripts mapping to ORF8, and conserved expression of other SARS-CoV-2 genes. Our findings shed light on the airway epithelial response to SARS-CoV-2 infection, and demonstrate a non-essential role for ORF8 in modulating host gene expression and cytokine production from infected cells.
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http://dx.doi.org/10.1371/journal.ppat.1009130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746279PMC
December 2020
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