Blood eosinophilia and a higher ethmoid sinus/maxillary sinus score ratio predict new-onset asthma in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUD: Presently, the impact of Chronic rhinosinusitis with nasal polyps (CRSwNP) on asthma onset is unknown. AIMS: To evaluate the role of CRSwNP in asthma onset. MATERIALS AND METHODS: A total of 3107 CRSwNP patients were retrospectively screened from 1 January 2018, to 31 May 2021; 624 patients were enrolled. Clinical data regarding nasal symptoms, Lund-Mackay scores, blood eosinophil percentage, and onset of asthma were analyzed. Patients were divided into different groups according to past history of nasal polyps, Lund-Mackay score, and the extent of blood eosinophilia. Asthma-free rates between these subgroups were analyzed by Kaplan-Meier curves and Cox regression models. RESULTS: The prevalence of asthma was 10.90% in patients with CRSwNP, and new-onset asthma occurred in 3.14% of these patients. Higher Lund-Mackay scores for ethmoid sinus and maxillary sinus (E/M) and blood eosinophil percentages were two independent risk factors for new-onset asthma, with hazard ratios of 1.267 (95%CI, 1.155-1.390) and 1.224 (95%CI, 1.054-1.422), respectively. CRSwNP patients with an E/M ratio > 2.33 or a blood Eos percentage > 5.5% were at risk for asthma onset. CONCLUSIONS AND SIGNIFICANCE: Blood eosinophilia and a higher E/M score ratio were associated with new-onset asthma in patients with CRSwNP.

[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

The IL-31/CysLT2R axis is associated with itching in patients with allergic rhinitis.

BACKGROUND: Itching is a troublesome symptom that disturbs patients with allergic rhinitis (AR). The molecular mechanisms underlying itching in AR need to be further illuminated. The aim of this study was to investigate the role of epithelial cell-derived interleukin-31 (IL-31) in nasal itching in AR. METHODS: A total of 33 patients and 20 healthy control subjects were enrolled in this prospective study. The disease severity of patients with AR was assessed by the total visual analog scale score. The levels of IL-31, cysteinyl leukotriene receptor 1 (CysLT1R), and CysLT2R in the nasal brush specimens from the enrolled subjects were measured by quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining. The expression of CysLT2R in a human nasal epithelial cell line (HNEpC) was assessed by immunofluorescence staining. RESULTS: Compared with the control subjects, the protein and mRNA levels of IL-31 and CysLT2R were significantly increased in patients with AR. Higher levels of IL-31 and CysLT2R in nasal epithelial cells were associated with itching but not nasal congestion, rhinorrhea, or sneezing in AR. A significant relationship was found between IL-31 and CysLT2R in nasal epithelial cells, with a correlation coefficient of 0.93. Furthermore, RT-PCR and immunofluorescence staining revealed that IL-31 directly induced CysLT2R expression in HNEpCs. Nasal steroid treatment inhibited IL-31 and CysLT2R expression in 13 patients with AR in vivo. CONCLUSIONS: Nasal epithelial cell-derived IL-31 might be associated with itching symptoms via CysLT2R in AR.

Prognostic factors for post-operative outcomes in chronic rhinosinusitis with nasal polyps: a systematic review.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high recurrence rate after surgery despite the availability of medical treatments. Multiple clinical and biological factors have been associated with poor post-operative outcomes in patients with CRSwNP. However, these factors and their prognostic values have not yet been extensively summarized. AREAS COVERED: This systematic review included 49 cohort studies exploring the prognostic factors for post-operative outcomes in CRSwNP. A total of 7802 subjects and 174 factors were included. All investigated factors were classified into three categories according to their predictive value and evidence quality, of which 26 factors were considered plausible for post-operative outcome prediction. Previous nasal surgery, ethmoid-to-maxillary (E/M) ratio, fractional exhaled nitric oxide, tissue eosinophil count or percentage, tissue neutrophil count, tissue IL-5, tissue eosinophil cationic protein, and CLC or IgE in nasal secretion provided more reliable information for prognosis in at least two studies. EXPERT OPINION: Exploring predictors through noninvasive or minimally invasive methods for specimen collection is recommended for future work. Models combining multiple factors must be established, as no single factor is effective for the whole population.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

M2 Macrophages Upregulated by Allergen Exposure in Seasonal Allergic Rhinitis.

INTRODUCTION: Macrophages play a central role in balancing the immune response by switching phenotypes between the M1 and M2 profiles according to a delicate equilibrium. Based on a previous clinical trial (NCT03649139), this study aimed to evaluate the change in M2 macrophages during pollen exposure in seasonal allergic rhinitis (SAR). METHODS: Nasal symptom scores were recorded. Peripheral M2 macrophages were investigated according to cell surface markers, and M2-associated cytokine/chemokine release in serum and nasal secretion were assessed. In vitro pollen stimulation tests were performed, and polarized macrophage subsets were analyzed by flow cytometry. RESULTS: Compared to baseline, the percentage of peripheral CD163+ M2 macrophages in CD14+ monocytes increased during the pollen season (p < 0.001) and at the end of treatment (p = 0.004) in the SLIT group. The percentage of CD206+CD86- M2 cells in M2 macrophages during the pollen season was higher than that at baseline and at the end of SLIT. On the other hand, the percentage of CD206-CD86+ M2 cells in M2 macrophages significantly increased at the end of treatment in the SLIT group compared to baseline (p = 0.049), the peak pollen period (p = 0.017), and the placebo group (p = 0.0023). M2-associated chemokines CCL26 and YKL-40 were significantly increased during the pollen season in the SLIT group and remained higher at the end of SLIT than at baseline. Correspondingly, in vitro study demonstrated that Artemisia annua promoted M2 macrophage polarization in pollen-induced AR patients. CONCLUSION: Significant M2 macrophage polarization was promoted when patients with SAR were exposed to the allergen, either naturally exposed in pollen seasons or subjectively continuously exposed during the course of SLIT.

Investigation of the Value of T 2 Mapping in the Prediction of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVES: Patients with eosinophilic chronic rhinosinusitis with nasal polyps (eosCRSwNP) usually have more extensive sinus disease, severe symptoms, and poorer disease control compared with patients with non-eosCRSwNP. Separating these entities will be crucial for patient management. The purpose of this study is to investigate T 1, T 2 , and apparent diffusion coefficient (ADC) values of the nasal polyps in patients with CRSwNP and evaluate the usefulness of these parameters for differentiating these diseases. METHODS: Sinonasal magnetic resonance imaging was performed in 36 patients with eosCRSwNP and 20 patients with non-eosCRSwNP (including T 1 mapping, T 2 mapping, and diffusion-weighted imaging) before surgery. The T 1 , T 2 , and ADC values were calculated and correlated with pathologically assessed inflammatory cells of nasal polyps. RESULTS: Significant higher T 2 value, higher eosinophil count, and lower lymphocyte count of the nasal polyps were observed in eosCRSwNP than those in non-eosCRSwNP. There was no significant difference in T 1 or ADC values between the 2 groups. T 2 value was correlated with eosinophil count and lymphocyte count in CRSwNP. The area under the curve of T 2 value for predicting eosCRSwNP was 0.78 with 89.9% sensitivity and 60.0% specificity. CONCLUSION: T 2 value is a promising imaging biomarker for predicting eosCRSwNP. It can help to distinguish eosCRSwNP from non-eosCRSwNP.

Analysis of nasal resistance regulation mechanism during postural changes in patients with obstructive sleep apnea by measuring heart rate variability.

STUDY OBJECTIVES: Changes in nasal resistance (NR) during postural changes are influenced by venous filling pressure and autonomic nervous system mediation, and heart rate variability (HRV) can reflect changes in the autonomic nervous system. This study aimed to explore the regulatory mechanisms of NR in patients with obstructive sleep apnea (OSA) during postural changes. METHODS: Healthy controls (apnea-hypopnea index < 5 events/h) and patients with OSA were recruited. NR and electrocardiogram data were collected in sitting, supine, left-lateral, and right-lateral postures. HRV parameters were obtained by analyzing the electrocardiogram data from each posture. Subgroups were divided according to sitting-supine NR changes, and HRV parameters were compared between different postures and groups/subgroups. RESULTS: In total, 34 healthy controls and 39 patients with OSA (mean apnea-hypopnea index 34.34 ± 22.44 events/h) were recruited. During sitting-supine postural changes, the NR increased in the control group but did not change significantly in the OSA group. None of the autonomic nervous system-related HRV parameters changed significantly. After the groups were divided into NR-elevated and NR-unchanged subgroups, sympathetic activity-related HRV parameters were higher in the NR-unchanged subgroup but only statistically significant in the OSA group. When comparing the left and right postures, there was no significant change in NR; however, the OSA group had lower parasympathetic activity-related HRV parameters when in the right posture. CONCLUSIONS: During postural changes from the sitting to supine positions, the total NR increases, and this increment is smaller in patients with OSA. This is likely due to overregulation of sympathetic activity, which may occur in patients with OSA. CITATION: Shi Y, Lou H, Wang H, et al. Analysis of nasal resistance regulation mechanism during postural changes in obstructive sleep apnea patients by measuring heart rate variability. J Clin Sleep Med. 2023;19(4):643-650.

Influence of postural changes on nasal resistance in patients with obstructive sleep apnea.

OBJECTIVE: Increased nasal resistance (NR) can augment upper airway collapse in patients with obstructive sleep apnea (OSA). Posture change can lead to altered nasal resistance. Our study aimed to investigate the influence of posture changes on NR in patients with OSA. METHODS: Healthy controls without subjective nasal obstruction (apnea-hypopnea index (AHI) < 5 events/h), patients with OSA and subjective nasal obstruction, and patients with OSA and no subjective nasal obstruction were recruited. NR was measured by active anterior rhinomanometry in sitting, supine, left-lateral, and right-lateral postural positions. Total NR and postural change-related NR increments were calculated and compared among groups. RESULTS: In total, 26 healthy controls and 72 patients with OSA (mean AHI 39.7 ± 24.8 events/h) were recruited. Of patients with OSA, 38/72 (53%) had subjective nasal obstruction. Compared with controls, patients with OSA and no subjective nasal obstruction had lower total NR (inspiration, p = 0.037; expiration, p = 0.020) in the supine postural position. There was no difference in sitting, left-lateral, and right-lateral total NR among groups. Total NR was higher in lateral compared to sitting posture in both patients with OSA and in controls. The NR increment for sitting to supine postural change was significantly lower in patients with OSA (inspiration, p = 0.003; expiration, p = 0.005) compared with controls. The change in NR showed no statistically significant difference among groups in supine-left or supine-right postural change. CONCLUSION: Patients with OSA had lower supine total NR and lower total NR increment in the sitting to supine postural change, which may be related to a different posture-related NR regulatory mechanism. This study provides a new exploratory direction for the compensatory mechanism of the upper airway to collapse during sleep.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Vitamin D Improves the Effect of Glucocorticoids on Attenuating Lipopolysaccharide-Induced IL-6 Production via TLR4/NF-κB Pathway in Human Respiratory Epithelial Cells.

BACKGROUND: Glucocorticoid (GC) resistance results in unsatisfactory outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Previous studies have shown that calcitriol, the active form of vitamin D, alone or in combination with corticosteroids, exerts crucial immunomodulatory effects on inflammatory responses. However, whether vitamin D can improve the effect of GCs to attenuate inflammation in the epithelium of CRSwNP remains unclear. METHODS: A human bronchial epithelial cell line (Beas-2B) and primary human nasal epithelial cells (HNECs) obtained from 10 patients with CRSwNP were exposed to lipopolysaccharide (LPS) for 24 h to establish an inflammation model. LPS-stimulated HNECs and Beas-2B cells were treated with/without dexamethasone in the presence or absence of calcitriol pretreatment for 24 h. The expression levels of interleukin-6 (IL-6) mRNA and protein were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Toll-like receptor 4 (TLR4)/NF-κB pathway related markers were examined by western blotting. One-way ANOVA or the Kruskal-Wallis test with post hoc analysis were used for multiple comparisons among groups. RESULTS: The production of IL-6 in Beas-2B cells and primary HNECs after LPS stimulation was significantly increased, which could be inhibited by dexamethasone or calcitriol alone. However, significant inhibition of IL-6 production was observed in the calcitriol plus dexamethasone group. Further analysis showed that calcitriol could enhance the effect of dexamethasone in inhibiting LPS-induced overexpression of TLR4, Myd88, and phosphorylation of p65. CONCLUSION: Our findings demonstrated that vitamin D could improve the effect of GCs to alleviate the level of IL-6 induced by LPS via the TLR4/NF-κB pathway in human respiratory epithelial cells.

Comparison of Different Biologics for Treating Chronic Rhinosinusitis With Nasal Polyps: A Network Analysis.

BACKGROUND: Several promising clinical trials have demonstrated the effects of type 2 biologics compared with placebos in chronic rhinosinusitis with nasal polyps (CRSwNP). However, there are no head-to-head randomized controlled trials (RCTs) between the biologics. OBJECTIVE: To compare the efficacy and safety of different biologics used for the treatment of CRSwNP. METHODS: We systematically identified RCTs investigating the effects of biologics for CRSwNP. Primary outcomes were nasal polyp score (NPS), nasal congestion severity, and serious adverse events. Secondary outcomes included the 22-item Sino-Nasal Outcome Test (SNOT-22) score, loss of smell severity, the University of Pennsylvania Smell Identification Test score, and the Lund-Mackay computed tomography score. Bucher indirect treatment comparison (ITC) was used to compare the outcome parameters. RESULTS: Seven RCTs (Bachert 2017, OSTRO, POLYP 1, POLYP 2, SINUS-24, SINUS-52, and SYNAPSE) involving 1913 patients and 4 biologics (benralizumab, dupilumab, mepolizumab, and omalizumab) were included for ITC. Dupilumab presented better effects in decreasing NPS and nasal congestion severity compared with the other 3 biologics at 24 weeks of the treatment and at the end of follow-up (more than 48 weeks). Benralizumab was the least effective in reducing nasal congestion severity and SNOT-22 score at 24 weeks. No significant differences were observed between the effects of the other biologics. CONCLUSION: Our current findings suggest that dupilumab exhibits the best efficacy and safety for the treatment of CRSwNP.

Hexamerin-2 Protein of Locust as a Novel Allergen in Occupational Allergy.

BACKGROUND: Occupational exposure to locusts induces a high prevalence of allergic sensitization. However, knowledge on occupational locust allergens remains unclear. OBJECTIVE: This study aimed to identify the allergens from locusts causing occupational allergies. METHODS: We conducted a survey of 57 persons exposed to locusts using questionnaires and immunological tests for occupational allergies in long-term locust laboratories. The major allergen was identified by immunoblotting and analysed by mass spectrometry. The allergenicity of the allergen was assessed by sIgE detection, immunoblotting and ELISA inhibition assays. RESULTS: The survey indicated that the frequency of locust occupational allergies was 40.4% among subjects exposed to locust. The symptoms in most males were allergic rhinitis, while females showed higher prevalence of atopic dermatitis. Occupational exposure increased the allergy risk. The recombinant hexamerin-2 protein possesses high allergenicity in the allergic exposure group. Hexamerin-2 protein can inhibit IgE reactivity with locust protein extracts by approximately 60%. The potential for cross-reactivity with cockroaches was indicated by sequence alignment of hexamerin-2 protein and allergens of cockroaches. CONCLUSION: The hexamerin-2 protein of locusts as an important allergen was identified. Therefore, occupational exposure is an important risk factor for locust allergy.

Effects of Acute Alcohol Intake on Nasal Patency.

BACKGROUND: Acute alcohol intake may influence nasal patency; however, there is lack of objective evidence. OBJECTIVE: The aim of this study was to evaluate the effects of acute alcohol intake on nasal patency employing both subjective and objective measures. METHODS: A total of 31 participants were classified into 2 groups of non-heavy drinkers (n = 17) and heavy drinkers (n = 14). Both groups consumed wine in 1 h and were assessed for subjective nasal symptoms and objective nasal patency, using rhinomanometry and acoustic rhinometry, at baseline and at 0.5, 2, and 6 h post-alcohol consumption. RESULTS: Alcohol consumption significantly increased nasal obstruction from baseline values in both heavy and non-heavy drinking groups. Total nasal volume (TNV) and the minimal cross-sectional area (MCA) were significantly decreased and nasal airway resistance (NAR) significantly increased from baseline values by 2 h post-alcohol consumption for both heavy and non-heavy drinking groups (P < .05). Significant differences were found in TNV, MCA, and NAR between baseline and post-drinking in allergic rhinitis subjects; with no significant differences in MCA and NAR in subjects without allergic rhinitis. Pulse rate (PR) and temperature (T) were elevated, and blood pressure (BP) was decreased after alcohol consumption (P < .05). Blood alcohol concentration (BAC) was not significantly correlated with nasal patency with regard to any subjective or objective measurement. CONCLUSION: Acute alcohol consumption may impair nasal patency, independent of the amount consumed. Individuals with allergic rhinitis may be more prone to nasal obstruction after alcohol consumption than those without allergic rhinitis.

[Neuroimmunomodulation in allergic rhinitis].

The role of neuroimmunomodulation in allergic diseases is a research hotspot in recent years. Allergic rhinitis（AR） is caused by overactive immune response to a foreign antigen in nasal mucosa. Immune cells release inflammatory mediators（including histamine, cytokines and neurotrophins）, which directly activate peripheral neurons to mediate nasal congestion, itching, sneezing, and other hyperresponsive symptoms. Upon activation, these peripheral neurons release neurotransmitters （including acetylcholine and norepinephrine） and neuropeptides（including calcitonin gene-related peptide, substance P and vasoactive intestinal peptide） that directly act on immune cells to drive allergic inflammation. Neuro-immune signaling may play a significant role in the pathophysiology of AR. Therefore, a better understanding of these cellular and molecular neuro-immune interactions may inspire the discovery of new targets and novel therapies.

Antihistamine premedication improves safety and efficacy of allergen immunotherapy.

BACKGROUND: Allergen immunotherapy (AIT)-associated adverse events are a major concern for safety and efficacy of AIT. Presently, there is no consensus to whether antihistamine premedication could improve such conditions. OBJECTIVE: To identify the superiority of antihistamine pretreatment in AIT. METHODS: A comprehensive literature search for randomized controlled trials reporting the effects of antihistamine premedication on safety and efficacy of AIT was performed in MEDLINE, Embase, and Cochrane Library databases. Safety was evaluated according to the number of patients reporting systemic adverse reactions (SARs, the primary outcome) and efficacy according to the number of patients achieving target maintenance dose (TMD) and sustained unresponsiveness to allergen. RESULTS: A total of 11 randomized controlled trials (including 609 patients) satisfied the inclusion criteria for the meta-analysis. All premedication protocols were temporary. Pooled analysis revealed that compared with control patients, significantly fewer antihistamine-pretreated patients reported total and moderate-to-severe SARs (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.23-0.56; P < .05 and OR, 0.20; 95% CI, 0.06-0.74; P < .05, respectively) and total and moderate-to-severe SAR episodes (OR, 0.42; 95% CI, 0.34-0.53; P < .05 and OR, 0.09; 95% CI, 0.01-0.50; P < .05, respectively). Similarly, antihistamine pretreatment significantly increased the number of patients achieving TMD (OR, 2.94; 95% CI, 1.72-5.03; P < .05), but not sustained unresponsiveness (OR, 1.65; 95% CI, 0.77-3.54; P = 0.2), compared with the control group. Subgroup analysis according to different allergens and dose-escalating approaches also displayed superiority of antihistamine pretreatment than control. CONCLUSION: Antihistamine premedication can markedly improve safety and efficacy of AIT by reducing frequency and severity of SAR and increasing TMD.

Reduced Expression of Antimicrobial Protein Secretory Leukoprotease Inhibitor and Clusterin in Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Antimicrobial peptides and proteins (AMPs) constitute the first line of defense against pathogenic microorganisms in the airway. The association between AMPs and chronic rhinosinusitis with nasal polyps (CRSwNP) requires further investigations. This study is aimed at investigating the expression and regulation of major dysregulated AMPs in the nasal mucosa of CRSwNP. METHODS: The expression of AMPs was analyzed in nasal tissue from patients with eosinophilic (E) CRSwNP and nonECRSwNP and healthy subjects using RNA sequencing. The 10 most abundant AMPs expressed differentially in CRSwNP patients were verified by real-time PCR, and of these, the expression and regulation of secretory leukoprotease inhibitor (SLPI) and clusterin (CLU) were investigated further. RESULTS: The 10 most abundant AMPs expressed differentially in CRSwNP compared to healthy control, regardless of subtypes, included BPIFA1, BPIFB1, BPIFB2, CLU, LTF, LYZ, and SLPI, which were downregulated, and S100A8, S100A9, and HIST1H2BC, which were upregulated. ELISA and immunofluorescence confirmed the decreased expression of SLPI and CLU levels in CRSwNP. SLPI is expressed in both nasal epithelial cells and glandular cells, whereas CLU is mainly expressed in glandular cells. AB/PAS staining further demonstrated that both SLPI and CLU were mainly produced by mucous cells in submucosal glands. Furthermore, the numbers of submucosal glands were significantly decreased in nasal polyp tissue of CRSwNP compared to nasal tissue of controls. SLPI was downregulated by TGF-ß1 and IL-4 in cultured nasal tissues in vitro, while CLU expression was inhibited by TGF-ß1. Glucocorticoid treatment for 2 weeks significantly increased the expression of all downregulated AMPs, but not LYZ. Additionally, budesonide significantly increased the expression of SLPI and CLU in cultured nasal tissues. CONCLUSION: The expression of major antimicrobial proteins is significantly decreased in nasal tissue of CRSwNP. The expression of SLPI and CLU is correlated with the numbers of submucosal glands and regulated by inflammatory cytokines and glucocorticoids.

Chinese expert recommendation on transnasal corticosteroid nebulization for the treatment of chronic rhinosinusitis 2021.

Corticosteroids are efficacious in treating chronic rhinosinusitis (CRS), but concerns on the potential side effects remain, especially for long-term usage of systemic corticosteroids. Accumulated evidence shows that transnasal nebulization may be a reasonable solution in balancing both efficacy and safety. However, no consensus or guideline has been formulated on the use of steroid transnasal nebulization in treating CRS. The consensus is achieved through literature review and exchange of Chinese experts in Group of Otorhinolaryngology and Ophthalmology, Chinese Society of Allergy (CSA). This document covers the development, equipment, pharmacological mechanism, and evidence-based efficacy and safety, as well as the special concern of the application of steroid transnasal nebulization during the coronavirus disease (COVID-19) pandemic. The expert consensus clarifies the application of steroid transnasal nebulization in treating CRS and common comorbidities during the perioperative and postoperative periods.