Asia-Pacific survey of physicians' perceptions and managements of chronic rhinosinusitis.

BACKGROUND: The diagnosis and management of patients with chronic rhinosinusitis (CRS) may vary between otolaryngologists and allergists. Moreover, the adherence of different practitioners to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 guideline recommendations has not been previously ascertained in Asia-Pacific regions. OBJECTIVE: Different specialists' perceptions and managements of CRS in Asia-Pacific regions were assessed in an attempt to gauge these practices against EPOS 2020 guidelines. METHODS: A transregional, cross-sectional survey was conducted to assess otolaryngologists' and allergists' perceptions and managements of CRS with regard to diagnosis, management and adherence to EPOS 2020 guidelines. RESULTS: Sixteen physicians in Asia-Pacific regions responded to the questionnaire. A total of 71.4% of otolaryngologists preferred to diagnose CRS with a combination of positive nasal symptoms and nasal endoscopy plus sinus CT, whereas 22.2% of allergists took such criterion to diagnose CRS. Compared to allergists, otolaryngologists more often considered the endotype classification (85.8% versus 55.5%). For the preferred first-line treatment, in addition to intranasal corticosteroids recommended by all respondents, 66.7% of allergists preferred antihistamines, whereas 71.4% of otolaryngologists preferred nasal saline irrigation. Regarding the proper timing of surgery, 71.5% of otolaryngologists reported 8-12 weeks of treatment after the initiation of medication, while more than half of the allergists recommended 4-6 weeks of medical treatment. CONCLUSIONS: This survey shows that variable perceptions and practices for CRS may exist between physicians with different specialties and highlights the need for increased communication and awareness between otolaryngologists and allergists to improve the diagnosis and treatment of CRS.

Clinical characteristics and aspirin desensitization in Thai patients with a suggestive history of NSAID-exacerbated respiratory disease.

BACKGROUND: Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is characterized by the triad of chronic rhinosinusitis with nasal polyp, asthma, and aspirin (ASA) or NSAID hypersensitivity. Previous study of NERD has rarely been reported in Asian population. OBJECTIVE: To investigate the clinical characteristics and outcomes of aspirin desensitization (ASAD) in Thai NERD. METHODS: This retrospective chart review included patients with a suggestive history of NERD with or without ASAD from the Adult Allergy Clinic of Siriraj Hospital (Bangkok, Thailand) during January 2008 to December 2018. RESULTS: Ten NERD patients were recruited. The median age of onset was 30 years. Comorbid atopic diseases were found in 4 patients. Asthma control level was step 3 of the Global Initiative for Asthma (GINA) guideline or greater in all patients. Five patients had reactions to more than one NSAIDs. Ibuprofen was the most common culprit agent. Reactions frequently involved the respiratory and cutaneous systems. Four patients underwent ASAD followed by ingestion of ASA 300-600 mg daily. One patient discontinued ASA after taking ASA 600 mg daily for 3 months due to severe gastrointestinal side effect. The remaining three patients successfully continued ASA 300 mg daily as maintenance to control sino-nasal inflammation and to prevent recurrence of nasal polyp. None of the 4 patients required sinus surgery revision. CONCLUSIONS: NERD is a difficult-to-treat disease with unique clinical characteristics. ASAD followed by a maintenance dose of ASA 300 mg daily was found to be effective and well-tolerated in most patients.

The international sinonasal microbiome study: A multicentre, multinational characterization of sinonasal bacterial ecology.

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.

Endotyping of Chronic Rhinosinusitis With and Without Polyp Using Transcription Factor Analysis.

Inflammation of the nose and paranasal sinus or rhinosinusitis (RS) is a significant global health problem that is both very common and very costly to treat. Previous reports reveal variability in histology and mechanism of inflammation in patients with chronic rhinosinusitis with and without polyp (CRScNP and CRSsNP, respectively). There are various methods and hypothesis that try to explain this variability. Accordingly, the aim of this study was to investigate the incidence of each type of sinonasal inflammation among patients diagnosed with CRScNP or CRSsNP using transcription factor analysis (TFA). This study included mucosa specimens from nose/paranasal sinuses from patients with chronic rhinitis (CR), CRSsNP, or CRScNP that were obtained at the Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during the June 2009 to May 2012 study period. TFA was employed to measure the following transcription factors: T-box transcription factor (T-bet) for Th1, GATA binding protein 3 (GATA-3) for Th2, retinoic acid-related orphan receptor C (RORC) for Th17, and forkhead box P3 (FOXP3) for Treg. Forty-one subjects (22 males, 19 females) were enrolled, with a mean age of 45.93 ± 13 years. Twenty-six patients were diagnosed with CRScNP, 7 with CRSsNP, and 8 with CR (controls). The majority of CRScNP specimens (76.9%) had eosinophil count greater than 100 cells/high-power field (HPF). Mean eosinophil count was 930.08 ± 1,399 cells/HPF (range: 17-5,570). Th2 transcription factor (GATA-3) was statistically significantly higher in the CRScNP group than in the CRS and control groups (p < 0.001); whereas, Treg transcription factor (FOXP3) was statistically significantly lower in the CRScNP group than in the CRSsNP and control groups (p < 0.001). The transcription factors for Th1 and Th17 (T-bet and RORC, respectively) were not significantly different among the three groups. The result of transcription factor analysis revealed hyperfunction of Th2 in patients with CRScNP, which might result in hypereosinophilic infliltration in the polyps. One explanation for this finding is the decreased activity of Treg. Although environment-host interaction is the most probable hypothesis, the etiology of aberrant adaptive immunity needs to be elucidated.

A randomized study of temperature-controlled versus bipolar radiofrequency for inferior turbinate reduction.

UNLABELLED: The objective of this study is to compare outcomes of temperature-controlled radiofrequency (TCRF) and bipolar radiofrequency (BRF) for inferior turbinate reduction in patients with chronic rhinitis (CR). This was a prospective, randomized non-inferiority trial. Eighty-four adult patients with CR refractory to medication were randomized into two intervention groups: TCRF(42) or BRF(42). Primary outcomes consisted of patient-orientated visual analog scale (VAS; 0-10) of nasal obstruction at 4th postoperative week. Secondary subjective outcomes included VAS of nasal discharge, sneezing, hyposmia, and postnasal drip. Objective outcomes included crusting, mucociliary transportation time, minimal cross-sectional area, total nasal volume, and nasal airway resistance performed by blind assessors before and at 4th postoperative week and 1-year follow-up. Baseline and perioperative data showed no statistically significant difference between both groups, except for longer operative time in TCRF (481.5 ± 36.2 vs. 37.1 ± 3.0 s, p < 0.001) and slightly more crusts in BRF group (p = 0.04). Both intention-to-treat and per-protocol analyses, TCRF(39) versus BRF(41), revealed no significant difference among subjective and objective outcomes between two groups at 4th postoperative week. The 95% confidence intervals of mean differences of VAS scores of all subjective symptoms were within defined margin (-1.5 to 1.5), except for nasal discharge. At 1-year follow-up, there was still no significant difference in the outcomes. Minimal pain and minor bleeding without serious adverse effects from both interventions were reported. Both BRF and TCRF resulted in similar short-term outcomes, while less operative time was found in BRF group. Further studies, particularly, on cost-effectiveness should be conducted for better treatment selection. LEVEL OF EVIDENCE: 1b.

The relationship between allergic rhinitis and viral infections.

PURPOSE OF REVIEW: Viral airway inflammation is one of the most common respiratory conditions. The clinical symptoms of viral rhinitis, especially watery rhinorrhea and nasal congestion, may be similar to the symptoms of allergic rhinitis. Both conditions affect considerable numbers of patients and can lead to many upper airway consequences, especially secondary bacterial infection. Viral infection can also lead to lower respiratory traction conditions such as bronchitis, bronchiolitis, pneumonia and, especially, asthma. This article will review the existing scientific literature examining the linkage and relationship between viral infection and allergic airway disease. RECENT FINDINGS: The relationship between viral and allergic airway inflammation can be discussed in terms of the influence of pathogenesis from one condition to the other. Recently, many studies show how early infection can decrease the chance of allergic development. However, there is some evidence demonstrating that viral infection can deteriorate the clinical symptoms of airway allergy. SUMMARY: Viral infection can affect the immune system and allergy as both 'enhancing effect' and 'protective effect'. The influential factors depend on the virulence of the viral strain, the innate immune system and the environmental conditions.

Inflammatory patterns in upper airway disease in the same geographical area may change over time.

BACKGROUND: Inflammatory patterns of nasal polyps (NPs) may vary. Changes over time have not been investigated so far. This study was designed to evaluate the inflammatory patterns of NPs in Thailand at two time points 12 years apart, explore differences in Staphylococcus aureus (SA) mucosal carriage rates over time, and the latter's relationship with the inflammatory patterns. METHODS: Formalin-fixed nasal tissue was obtained from 89 (47 in 1999 and 42 in 2011) patients suffering from chronic rhinosinusitis with NPs (CRSwNPs). Tissues were evaluated for eosinophils, neutrophils, IgE(+) cells, IgE and macrophage mannose receptors, interleukin (IL)-5 and IL-17 cytokine profile, and the presence of SA, using automated immunohistochemistry and peptide nucleic acid-fluorescence in situ hybridization. RESULTS: We found a significant increase in the absolute values of eosinophils and IgE(+) cells in the 2011 CRSwNP tissue series compared with 1999 and a significant but smaller increase in neutrophils. Semiquantitative evaluation revealed significantly higher mean values of positive cells for all studied inflammatory markers in the 2011 group of patients, except for the high-affinity IgE receptor. This "eosinophilic shift" of inflammation was accompanied by higher SA carriage, as well as higher frequencies of SA invasion (54.8% versus 10.6%; p < 0.001) in the 2011 compared with 1999 subjects. Patients with asthma were more likely to have higher SA carriage rates compared with nonasthmatic patients. CONCLUSION: There was a shift from predominantly neutrophilic to eosinophilic CRSwNPs in Thai patients within 12 years, with an increase in various inflammatory markers including IgE, which is associated with an increase in intramucosal presence of SA.

Staphylococcus aureus superantigens and their role in eosinophilic nasal polyp disease.

Nasal polyposis is a chronic disease of the upper airways which adversely affects the quality of life of patients. Its pathophysiology is still unclear. Recently, several studies have shown different inflammatory pathways which relate to both innate and adaptive immune responses. Moreover, different phenotypes may exist in different ethnic groups of patients. This article will review recent data regarding the type of inflammation, cytokine profiles, involvement of macrophages and dendritic cells, and the impact of various organisms (especially Staphylococcus aureus and its superantigens) and their association with lower airway disease (especially asthma).

A randomized, prospective, double-blind study of the efficacy of dexpanthenol nasal spray on the postoperative treatment of patients with chronic rhinosinusitis after endoscopic sinus surgery.

OBJECTIVE: To assess the efficacy of dexpanthenol nasal spray compared with normal saline spray in the postoperative treatment of patients with chronic rhinosinusitis (CRS) who underwent endoscopic sinus surgery (ESS). MATERIALS AND METHOD: A prospective, randomized controlled study was conducted in CRS patients who underwent ESS. The enrolled patients had never been operated intranasally. These patients received either dexpanthenol or normal saline nasal spray intranasally four times a day for six weeks post-operatively. RESULTS: Fifty CRS patients were recruited in the present study. Age ranged from 23 to 63 years (means 43.4 +/- 11.2 years). Forty-four percent of patients were diagnosed as CRS without nasal polyps (NP) (CRSs NP) and 56% were CRS with NP (CRSw NP). Twenty-five cases were randomly assigned to use dexpanthenol nasal spray whereas the other 25 cases used normal saline nasal spray. The preoperative severity of CRS, determined by the computerized tomography (CT) scan scoring system of Lund-McKay was 13.9 +/- 6.2 in the dexpanthenol group and 13.6 +/- 6.9 in the normal saline group, which were not statistically different (p > 0.05). The endoscopic scoring was 10.2 +/- 2 in the dexpanthenol group and 10.7 +/- 3 in the normal saline group, which were not statistically different (p > 0.05). The mucociliary transit time improvement (time difference between pre- and post-treatment by nasal spray) was 8.4 +/- 3.3 minutes in the dexpanthenol group and 1.7 +/- 1.2 minutes in the normal saline group, which were statistically different (p < 0.05). CONCLUSION: The majority of the postoperative symptom scores and all of the endoscopic scores of the dexpanthenol group were not statistically different from those of the normal saline group. However, dexpanthenol nasal spray has superior efficacy compared with normal saline nasal spray on improvement of mucociliary clearance and nasal discharge in the postoperative care of CRS patients after ESS.

Quantification of Der f 1 in houses of patients allergic to house dust mite, Dermatophagoides farinae, using a locally produced detection reagents.

BACKGROUND: House dust mite (HDM) allergen quantification in house dust samples before and after the allergen elimination is one means of convincing the target population about the health benefits of allergen removal from their environment. OBJECTIVE: To produce local reagents for quantification of Der f 1 (major allergen of Dermatophagoides farinae) in dust samples from houses of HDM allergic Thai patients. METHODS: Recombinant Der f 1 was used for immunization of a BALB/c mouse for hybridoma production. Polyclonal antibody (PAb) to whole body extract of D. farinae was prepared from an immunized rabbit. A sandwich ELISA (MAb-allergen-PAb) was used, in comparison with the commercialized reagents (Indoor Biotechnology, UK), to quantify Der f 1 in dust samples. RESULTS: Two hybridoma clones, Dfl-1 and Dfl-2, were established. Their secreted MAbs (MAbDfl-1 and MAbDfl-2, respectively) bound to the homologous antigen as well as native Der f 1 and a crude extract of D. farinae. Epitopes of MAbDfI-1 and MAbDfl-2 were located at amino acid residues 206NSQHYGISNYCQ217 and 283DYW---NSWD-WGDSG298 of Der f 1. MAbDf-1 had higher affinity to Der f 1 than the MAbDfl-2. A sandwich ELISA (MAbDfl-1-allergen-PAb) and commercialized reagents (MAbl-allergen-MAb2 sandwich ELISA) were used in comparison for quantification of Der f 1 in 42 dust samples collected from bedrooms and living rooms of 21 houses of the HDM allergic patients. All of the 42 dust samples measured by both ELISAs had the Der f 1 levels higher than 2 mg per gram of fine dust which is the HDM allergy sensitizing level. In addition, Der f 1 levels in 41 samples (except 1 sample from a living room) measured by the MAbDfI-1-PAb and MAbl-MAb2 sandwich ELISAs were higher than 10 mg per g of dust which is the morbidity level of HDM allergen. The local sandwich ELISA showed a high coefficient correlation (r = 0.91) in measuring known amounts of recombinant and native Der f 1. The results indicate that the reagents produced in the present study can be used for measuring the environmental levels of HDM Der f 1. The assay can also be used for standardization of the HDM extract for monitoring patient's allergenic status or for immunotherapeutic purpose.

Enhanced susceptibility of nasal polyp tissues to avian and human influenza viruses.

BACKGROUND: Influenza viruses bind and infect respiratory epithelial cells through sialic acid on cell surface. Differential preference to sialic acid types contributes to host- and tissue-tropism of avian and seasonal influenza viruses. Although the highly pathogenic avian influenza virus H5N1 can infect and cause severe diseases in humans, it is not efficient in infecting human upper respiratory tract. This is because of the scarcity of its receptor, α2,3-linked sialic acid, in human upper airway. Expression of sialic acid can be influenced by various factors including inflammatory process. Allergic rhinitis and nasal polyp are common inflammatory conditions of nasal mucosa and may affect expression of the sialic acid and susceptibility to influenza infection. METHODOLOGY/PRINCIPAL FINDING: To test this hypothesis, we detected α2,3- and α2,6-linked sialic acid in human nasal polyp and normal nasal mucosal tissues by lectin staining and infected explants of those tissues with avian influenza viruses H5N1 and seasonal influenza viruses. We show here that mucosal surface of nasal polyp expressed higher level of α2,3- and α2,6-linked sialic acid than normal nasal mucosa. Accordingly, both H5N1 avian influenza viruses and seasonal influenza viruses replicated more efficiently in nasal polyp tissues explants. CONCLUSIONS/SIGNIFICANCE: Our data suggest a role of nasal inflammatory conditions in susceptibility to influenza infection, especially by avian influenza viruses, which is generally inefficient in infecting human upper airway. The increased receptor expression may contribute to increased susceptibility in some individuals. This may contribute to the gradual adaptation of the virus to human population.

Superantigens.

Superantigens (SAgs) are derived from diverse sources, including bacteria, viruses, and human hepatic tissue. SAgs initially cause lymphocyte activation but then result in clonal deletion and anergy, leading to immune tolerance. They can also act as superallergens by stimulating a broad spectrum of mast cells and basophils in patients with allergic conditions. The newly described staphylococcal SAg-like proteins subvert innate immune function by several mechanisms, which are distinct from SAgs' effects on lymphocytes and other acquired immune processes. There is mounting evidence to suggest that SAgs play a role in the pathophysiology of inflammatory airway disease. The pathophysiologic role of SAg-like proteins awaits clarification.