Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nose and paranasal sinuses that significantly impactshealth-related quality of life. Nonsteroidal anti-inflammatory drug (NSAID) -exacerbated respiratory disease (N-ERD) affects approximately one fifth of CRSwNP patients. N-ERD and asthma increase the risk of uncontrolled CRSwNP as measured by frequent sinus surgeries and rescue treatment. Compared to non-N-ERD patients, those with N-ERD also have higher risk of asthma exacerbations, severe allergic reactions, and anosmia. Mepolizumab is a humanized monoclonal anti-IL-5 antibody shown to be effective in treating severe eosinophilic asthma and CRSwNP. While evidence suggests that mepolizumab alleviates respiratory symptoms in N-ERD patients, placebo-controlled studies remain limited.

The aim of this prospective randomized, placebo-controlled, multicenter study is to investigate whether mepolizumab reduces polyp size, symptom scores, and exacerbations more than placebo during the 16-week treatment period in patients with uncontrolled CRSwNP, N-ERD and asthma. Additionally, we will examine the effect of mepolizumab on drug dosage and lung and nasal function and evaluate predictive biomarkers.We will recruit 120 patients with N-ERD, nasal polyposis and asthma in three centers in Finland. Patients will be randomized into two 16-week treatment groups in 1:1 ratio (placebo or mepolizumab 100 mg every 4 weeks). The study lasts for 6 months, including recruitment visit 2-4 weeks before randomization. Participants will attend 6 visits, during four of which they will receive a subcutaneous injection of the study product. At each visit, patient-reported outcome tests, clinical examination, airway function tests, and nasal, blood, urine, and stool samples will be conducted.

The efficacy of the 16-week anti-IL-5-treatment in this severe patient group will be analyzed, as well as possible predictive biomarkers.

ClinicalTrials.gov ID NCT04823585. Registered on 28.3.2021.

To investigate the associations between fasting blood glucose (FBG) and type 2 diabetes mellitus (T2DM) and the risk of postoperative CRS recurrence.

A retrospective cohort study was conducted on clinical data of CRS patients who underwent surgery at our center between February 2019 and March 2022 and were followed up until June 2023. All CRS patients were categorized into two subgroups based on the presence of T2DM and postoperative recurrence. The Kaplan-Meier survival curves and binary logistic regression analyses were performed to examine the associations between FBG, T2DM, and the risk of postoperative CRS recurrence.

1163 CRS patients were enrolled, including 134 in the T2DM group and 276 in the recurrent group. The recurrence rate in the T2DM group was significantly higher than that in the non-T2DM group (P < 0.05). T2DM prevalence and FBG levels were higher in the recurrent CRS group than in the non-recurrent CRS group (P < 0.05). The Kaplan-Meier survival curves and unadjusted and adjusted logistic regression models showed that T2DM was an independent risk factor for postoperative CRS recurrence (P < 0.05). Moreover, multivariate logistic regression analysis suggested that FBG, CRS duration, and allergic rhinitis were associated with the risk of postoperative CRS recurrence (P < 0.05).

Elevated FBG levels and accompanying T2DM were associated with an increased risk of postoperative CRS recurrence, which was independent of traditional risk factors. CRS duration and accompanying allergic rhinitis were also proven to be potential risk factors for postoperative CRS recurrence.

Eosinophilic chronic rhinosinusitis (ECRS) is characterized by early, severe olfactory dysfunction and a high recurrence rate, with inadequate treatments. This article aims to elucidate the potential mechanisms by which luteolin may treat olfactory dysfunction in the context of ECRS.

Thirty C57 BL/6 mice were randomly assigned to five groups: a control group and four experimental groups (ECRS, ECRS + Luteolin (Low, Medium, High Dose)). We conducted RNA sequencing, behavioral testing, ELISA, PCR, HE staining, Western blot analysis, and immunofluorescence staining. Additionally, human olfactory epithelial Cells (HOEPCs) were treated with Luteolin, TAK-242, QNZ, and Luteolin + LPS to investigate the underlying mechanisms.

Luteolin significantly reduced IL-4, IL-5, and IL-13 levels in the nasal lavage fluid (NLF) of ECRS mice, improving olfactory function and restoring OMP+ mature and Gap43+ immature olfactory sensory neurons (OSNs). RNA sequencing revealed the involvement of the TLR4/NF-κB pathway in ECRS-related olfactory dysfunction and luteolin's therapeutic effects. Luteolin reduced TLR4+ cells, P65 nuclear translocation, and decreased protein levels of IL-1β, TLR4, MyD88, p-P65, P65, and p-P38. The treatment also lowered OSNs cell apoptosis by decreasing the levels of cleaved caspase-3 and caspase-9 levels, and increasing Bcl-2 protein. Antioxidant enzymes SOD, CAT, and GSH-Px were elevated, while MDA levels decreased. In ECRS HOEPCs, luteolin's anti-apoptotic effects on OSNs were reversed by LPS-induced TLR4/NF-κB activation.

Luteolin ameliorates olfactory dysfunction associated with ECRS by modulating the TLR4/NF-κB signaling pathway. This modulation results in a reduction of TH2-type inflammation, oxidative stress, and apoptosis in OSNs.

To compare the efficacy and adverse events of different oral corticosteroids (OCSs) withdrawal methods for chronic rhinosinusitis with nasal polyp after endoscopic sinus surgery (ESS).

This was a randomized prospective study conducted from Oct 2019 to Jan, 2021. 35 patients who underwent ESS were randomly divided into 2 groups. Regular group (n = 18) received 0.4mg/kg/day of methylprednisolone orally for 10 days, tapering group (n = 17) received 0.4mg/kg/day of methylprednisolone orally for 7 days, followed by progressive reduction of 8 mg of methylprednisolone per week for 3 weeks. The visual analogue scale (VAS) score, the Lund-Kennedy endoscopy (LKE) score, and the E score were assessed preoperatively and at half and 1, 2, and 12 months postoperatively. Statistical analyses were performed using SPSS.

There was no statistical difference in the baseline characteristics between the 2 groups. The postoperative VAS scores and LKE scores of patients were significantly improved from those preoperatively (P-values < 0.05). There was no statistical difference in the LKE score, E score, and VAS score between the 2 groups both preoperatively and postoperatively (P-values > 0.05). There was no statistical difference in adverse events between the 2 groups (P-values > 0.05).

The combination of OCSs and ESS can improve the clinical symptoms of patients and the recovery of nasal mucosa. There was no difference between the 2 drug withdrawal methods in efficacy and adverse events. Drug withdrawal gradually is more complicated therefore, in clinical practice, OCSs withdrawal directly would be the better option for patients.

Recurrent infections of the nose, sinuses and ears are common problems for people with primary ciliary dyskinesia. While pulmonary exacerbations in primary ciliary dyskinesia are defined, there is no definition for ear-nose-throat exacerbations, a potential outcome for research and clinical trials.

We set up an expert panel of 24 ear-nose-throat specialists, respiratory physicians, other healthcare professionals and patients to develop consensus definitions of sinonasal and otological exacerbations in children and adults with primary ciliary dyskinesia for research settings. We reviewed the literature and used a modified Delphi approach with four electronic surveys.

Definitions for both sinonasal and otological exacerbations are based on a combination of major and minor criteria, requiring three major or two major and at least two minor criteria each. Major criteria for a sinonasal exacerbation are 1) reported acute increase in nasal discharge or change in colour, 2) reported acute pain or sensitivity in the sinus regions and 3) mucopurulent discharge on examination. Minor criteria include reported symptoms, examination signs, doctor's decision to treat and improvement after at least 14 days. Major criteria for the otological exacerbation are 1) reported acute ear pain or sensitivity, 2) reported acute ear discharge, 3) ear discharge on examination and 4) signs of otitis media in otoscopy. Minor criteria are reported acute hearing problems, signs of acute complication, and doctor's decision to treat.

These definitions might offer a useful outcome measure for primary ciliary dyskinesia research in different settings. They should be validated in future studies and trials together with other potential outcomes, to assess their usability.

TAM receptors (TYRO3, AXL, and MER) play important roles in inflammatory responses, but their effects in chronic rhinosinusitis with nasal polyps (CRSwNP) remain elucidated. We aim to evaluate the values of TAM receptors in disease severity and postoperative recurrence of CRSwNP.

We initially enrolled 160 patients with CRSwNP who were treated with functional endoscopic sinus surgery (FESS) and postoperative recurrence was evaluated during the follow-up period. Circulating TAM receptor levels were detected by enzyme-linked immunosorbent assay (ELISA), and tissue expressions were measured by real-time polymerase chain reaction (RT-PCR) and immunohistochemical (IHC). The relationships between TAM receptor levels and postoperative recurrence were examined.

A total of 150 patients completed the follow-up schedule, 49 patients experienced postoperative recurrence and the remaining 101 patients were non-recurrent. In recurrent CRSwNP patients, serum levels of TAM receptors were increased compared to those in non-recurrent patients and were positively correlated with disease severity scores (P < 0.05). Circulating TYRO3 and MER were identified as potential predictors of postoperative recurrence based on receiver operating characteristics (ROC) and Kaplan-Meier plots (P < 0.05). Furthermore, tissue TAM receptor levels, as determined by both RT-PCR and IHC, were enhanced in the recurrent group than in the non-recurrent group (P < 0.05) and were predictive of postoperative recurrence (P < 0.05). Interestingly, circulating TYRO3 and MER concentrations, as well as tissue TYRO3 expression, were found to be significantly increased in patients who experienced postoperative recurrence (P < 0.05). IHC images from the same patients revealed that TAM expressions were enhanced in the recurrent tissues compared to their baseline tissue levels.

Our laboratory results demonstrated that TAM receptors were increased in recurrent CRSwNP patients and associated with postoperative recurrence. Moreover, the new laboratory findings suggested that measuring circulating levels of TAM receptors might serve as a promising new approach to assess disease progression and predict the risk of postoperative recurrence.

Our previous study revealed that serum amyloid A (SAA) levels in polyp tissues could serve as a biomarker for the prediction of corticosteroid insensitivity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, their association with disease control status in the patients after endoscopic sinus surgery remains to be assessed.

Polyp tissues and control uncinate process mucosa were collected from 48 patients with CRSwNP and 10 healthy control subjects. SAA expression was examined using immunohistochemistry and enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were performed to determine the predictive value of SAA in nasal polyps. The clinical characteristics of 2 CRSwNP subtypes (SAAhigh and SAAlow) were evaluated.

The SAA expression levels in polyp tissues were significantly elevated both in non-eosinophilic and eosinophilic CRSwNP as compared to the healthy controls. In patients with CRSwNP, the tissue SAA level was significantly higher in the disease-controlled patients than those of the partly controlled and uncontrolled. ROC curve analysis revealed that a cut-off value of 114.9 ng/mL for the tissue SAA level predicted the patients with disease-controlled status with 93.33% sensitivity and 63.64% specificity (AUC = .8727, P < .001). Furthermore, The SAAhigh subgroup showed higher tissue eosinophil numbers and percentage of the disease-controlled patients compared to the SAAlow subgroup.

Our findings suggest that measurements of SAA in polyp tissues may provide useful information for evaluating CRSwNP conditions, especially identifying the CRSwNP patients with disease-controlled status after endoscopic sinus surgery.

In her late 50 s, a woman with a medical history of endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) experienced a relapse of nasal polyps, significantly impacting her breathing and sense of smell. She underwent a multifaceted treatment approach, including oral corticosteroids, functional endoscopic sinus surgery, and omalizumab injections. Digital high-speed videomicroscopy (DHSV) revealed only partial improvement in ciliary beat pattern and ciliary beat frequency with oral corticosteroid treatment, while significant improvement in these ciliary parameters was observed with omalizumab injections. Furthermore, administration of omalizumab resulted in a decrease in her SNOT-22 (Sinonasal Outcome Test 22) score. Notably, this case report represents the first study investigating ciliary function using DHSV in a patient treated with omalizumab.

Characterization of inflammation in chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP) is an ongoing research process. To overcome limitations of current cytologic techniques, we investigated whether immunofluorescence multiplex image cytometry could quantify intact neutrophils, eosinophils, and other immune cells in solid upper airway mucosa. We used a four-channel immunofluorescence-microscopy technique for the simultaneous detection of the leukocyte marker CD45, the neutrophil marker myeloperoxidase, two eosinophil markers, i.e., major basic protein and eosinophil peroxidase, and DAPI (4',6-diamidin-2-phenylindole), in formalin-fixed paraffin-embedded upper airway tissue samples of patients with CRSwNP and CRSsNP, as well as of patients free of CRS with inferior turbinate hypertrophy (controls). Image acquisition and analysis were performed with TissueFAXS and StrataQuest (TissueGnostics, Vienna, Austria), respectively. Positive and negative immunostaining were differentiated with a specific fluorescence signal/background signal ratio. Isotype controls were used as negative controls. In six controls, nine patients with CRSsNP, and 11 patients with CRSwNP, the median area scanned and median cell count per patient were 14.2 mm2 and 34,356, respectively. In CRSwNP, the number of eosinophils was three times higher (23%) than that of neutrophils (7%). Three times more immune cells were encountered in CRSwNP (33%) compared to CRSsNP (11%). In controls, inflammation was balanced between the epithelial layer and lamina propria, in contrast to CRS (three times more pronounced inflammation in the lamina propria). The quantification of intact neutrophils, eosinophils, and other immune cells in solid tissue with undisrupted architecture seems feasible with immunofluorescence multiplex image cytometry.

There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy.

Chronic rhino sinusitis (CRS) is a common disease. Maxillary sinusitis not cured by the medicines was addressed by the open surgical procedure namely Caldwell Luc operation. Thereafter introduction of nasal endoscopes in 1970's led to the minimally invasive surgery FESS which preserved the physiology of the nose and sinuses. In the year 2002 balloon sinuplasty was introduced in the western world and subsequently in India. Due to various logistics it was not performed and reintroduced in the year 2015 in India. It can be termed as micro minimally invasive surgery wherein anatomy as well as physiology of the nose and sinuses were preserved in cases of medically non responsive mild to moderate sinusitis. 20 cases were selected for exclusive balloon sinuplasty of maxillary sinus. Balloon sinuplasty is a relatively new procedure which can be termed as micro minimally invasive surgery addressing the CRS without the traditional forms for surgery like incision, cutting or microdebriding. The principle is causing microfractures by inflating the sinus opening and thus facilitating the drainage of the sinus contents. No immediate or late post operative complications were noted. Sinus patency 6 months later was present in 90% of the cases. Balloon sinuplasty is an excellent procedure for medically nonresponsive CRS without polyposis. The success rate is spectacular matching the FESS with almost no immediate post operative and late complication. The recurrence rate of sinusitis is low. We conclude that balloon sinuplasty is a micro invasive procedure which saves operating time, time of hospital stay of the patient and delivers excellent result with almost no complications. We hope it could be incorporated as a routine surgery for mild to moderate sinusitis not responding to medicines.

Hypoxia-inducible factor 1α (HIF1α) and Tet methylcytosine dioxygenase 2 (TET2) have been reported to mediate nasal polypogenesis through the epithelial-to-mesenchymal transition (EMT). Additionally, HIF1α can regulate the expression and function of TET2. However, the precise mechanism of how TET2 regulates the EMT through HIF1α mediation in nasal epithelial cells is still poorly understood.

Nasal tissue samples were collected from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. The expression of HIF1α and TET2 was detected using Western blotting and immunohistochemistry. EMT markers (E-cadherin and vimentin) were also evaluated by immunohistochemistry. Primary human nasal epithelial cells (hNECs) were stimulated with CoCl2 to mimic hypoxia. Vitamin C (VC), a TET2 non-specific activator, and small interfering RNA (siRNA) transfection of TET2 were used to further determine the role of TET2 in hypoxia-induced EMT. Finally, reactive oxygen species (ROS) and Nrf2 were measured to explore the downstream consequences of TET2 in hypoxic hNECs.

TET2 levels were lower in the nasal epithelium of CRSwNP patients and were positively correlated with E-cadherin but negatively correlated with vimentin in CRS. However, HIF1α exhibited the opposite pattern and was negatively correlated with TET2 expression. CoCl2-simulated hypoxia led to EMT and increased HIF1α in hNECs in vitro, with simultaneous downregulation of TET2 expression. Addition of VC activated TET2 expression in hNECs, but inhibited EMT and HIF1α expression. Furthermore, siRNA knockdown of TET2 contributed to the EMT in CoCl2-simulated hNECs despite the addition of VC. Finally, TET2 regulated the EMT in hypoxic hNECs through Nrf2 expression and ROS generation.

TET2 was negatively correlated with HIF1α and EMT in vivo. TET2 was downregulated by HIF1α, resulting in the EMT in CoCl2-hypoxic hNECs via regulation of oxidative stress in vitro. Hence, TET2 might provide a new therapeutic approach for CRSwNP.

To confirm the relevance of upper and lower airway inflammation in eosinophilic chronic rhinosinusitis (ECRS), the effects of endoscopic sinus surgery (ESS) on lower airway functions and inflammation need to be examined in ECRS patients.

Chronic rhinosinusitis patients with nasal polyps (25 non-ECRS, 28 ECRS) were enrolled. The 12 patients in the ECRS group had comorbid asthma, in contrast to none in the non-ECRS group. We divided ECRS patients into 2 groups of ECRS with and without asthma. Clinical markers, including fraction of exhaled nitric oxide (FeNO), respiratory functions, and the Asthma Control Test (ACT) questionnaire, were investigated before and after ESS.

The FeNO levels in the ECRS with asthma group decreased after ESS. The mean FeNO levels in this group were 56.3 ppb before ESS and 24.9, 25.1, 25.0, and 15.5 ppb 1, 2, 3, and 4 months, respectively, after ESS. The mean forced expiratory rates in 1 second before and after ESS were 67.6% and 73.0%, respectively. The mean maximal expiratory flow rates at 50% of the vital capacity before and after ESS were 45.8% and 58.0%, respectively. Significant differences were observed in respiratory functions before and after ESS. The mean ACT scores in the ECRS with asthma group before and after ESS were 17.5 and 23.5, respectively. The ACT scores were significantly higher after than before ESS.

The present results indicate that ECRS and bronchial asthma are common eosinophilic airway inflammatory diseases, and ESS for eosinophilic sinusitis may improve lower airway function.

To observe the efficacy and safety of postoperative long-term low-dose oral administration of clarithromycin in patients with refractory chronic rhinosinusitis (RCRS), to explore the characteristics of postoperative microbiota in the nasal cavity in patients with RCRS, and to compare the differences and changes in microbiota in the nasal cavity before and after medication.

This was a prospective, self-controlled study. Eighteen patients with RCRS who had persistent symptoms after endoscopic sinus surgery and standard therapy with normal immunoglobulin E and eosinophil level were included. Low dose (250 mg, once daily) clarithromycin was orally administrated for 12 weeks. Symptom severity and endoscopic findings were evaluated before, after 4 weeks, and 12 weeks of treatment, and nasal cavity microbiota was analyzed simultaneously.

A total of 18 patients with RCRS were enrolled and 17 patients completed the study. Four weeks after oral administration of clarithromycin, significant improvement was observed in subjective symptoms including nasal congestion, rhinorrhea, postnasal drip, and general discomfort, as well as endoscopic findings including general surgical cavity condition, rhinedema, and rhinorrhea (P < .05). After continuous treatment to the 12th week, symptoms showed significant improvement compared with baseline, and endoscopic score showed significant improvement compared with both baseline and 4 weeks after treatment. Analysis of middle nasal meatus flora revealed a significant decrease of Streptococcus pneumoniae after 12 weeks of clarithromycin treatment (P < .05), while the richness, composition, and diversity were similar before and after treatment. Patients enrolled experienced no adverse drug reaction or allergic reaction, nor clinical significant liver function impairment observed.

Postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS can improve the clinical symptoms and facilitate the mucosal epithelialization, with good tolerance and safety. The efficacy of clarithromycin in patients with RCRS may be related to its regulatory effect on nasal cavity microbiota.

To determine age-related risk factors for chronic rhinosinusitis (CRS) with asthma.

Data were obtained from a national survey of non-hospitalized civilians conducted by the Korean Center for Disease Control and Prevention. CRS diagnosis was based on the guidelines of the European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Asthma was judged based on whether the patient had been diagnosed with asthma in the past. Of the 45,811 survey participants, 26,335 were included in the cross-sectional study. Participants included in the study were divided into the control, CRS, and CRS with asthma groups. Age-related risk factors were analyzed in patients aged < 60 or > 60 years. Univariate logistic analyses were performed to evaluate the relationship between groups. Risk factors included age, sex, household income, residence, education level, occupation, and body mass index (BMI).

Education level (Odds Ratio [OR]: 0.342, P = .0003), BMI (OR: 1.09, P = .0082), and total IgE (TIgE) levels (OR: 5.582, P = .003) were significantly different between the control and the CRS with asthma group. Education level (OR: 0.478, P = .0016) and TIgE levels (OR: 4, P = .0218) were significantly different between the CRS and CRS with asthma groups under 60 years of age. BMI (OR: 1.087, P = .0443; OR: 1.104, P = .0224) showed a significant difference between all three groups with age > 60 years.

Progression to CRS with asthma is influenced by education level, occupation, and TIgE levels in patients under 60 years of age. BMI was the only influencing factor associated with the progression to CRS with asthma in those aged > 60 years.

To analyze the oxidative stress status and its association with tissue neutrophilia and oral steroid response in chronic rhinosinusitis with nasal polyps (CRSwNP) patients.

The levels of total oxidant status (TOS) were detected in the sinonasal tissues by using specific assay kits. Tissue neutrophil was examined by immunohistochemical staining, and oxidant status index (OSI) was evaluated in polyps tissues, and the messenger RNA (mRNA) levels of superoxide dismutase 2 (SOD2), aldehyde dehydrogenase 1 (ALDH1A1), and microsomal glutathione S-transferase 1 (MGST1) were examined using quantitative real-time polymerase chain reaction in the sinonasal tissues. The receiver operating characteristics (ROCs) curve of ALDH1A1, MGST1, and SOD2 mRNA levels were evaluated to determine the steroid response of CRSwNP patients.

The levels of TOS and OSI were significantly higher in CRSwNP and CRSsNP than in normal controls, and OSI in polyps tissues was positively associated with tissue neutrophilia and poor steroid response. The ALDH1A1, MGST1, and SOD2 mRNA levels showed comparable accuracy as predictors of poor steroid response indicated by the area under the curve.

These findings provided evidence that the increased level of oxidative stress contributes to enhanced tissue neutrophilia and poor steroid response in CRSwNP patients.

Chronic rhinosinusitis with nasal polyps (CRSwNPs) remains a major challenge due to its high recurrence rate after endoscopic sinus surgery (ESS). We aimed to investigate the risk factors of recurrence among patients who underwent ESS for Chronic rhinosinusitis (CRS).

Prospective cohort study including 391 cases in a single institution receiving ESS were included for analysis from 2014 and 2017. Baseline characteristics including rectal Staphylococcus aureus (S aureus) carriage in patients receiving ESS for CRSwNPs. The primary outcome was the recurrence of CRSwNPs. Multivariate regression model was established to identify independently predictive factors for recurrence.

Overall, 142 (36.3%) cases with recurrence within 2 years after ESS were observed in this study. After variable selection, multivariate regression model consisted of 4 variables including asthma (odds ratio [OR] = 3.41; P < .001), nonsteroidal anti-inflammatory drug allergy (OR = 2.27; P = .005), previous ESS (OR = 3.64; P < .001), and preoperative carriage of S aureus in rectum (OR = 2.34; P = .001).

Based on our results, surgeons could predict certain groups of patients who are at high risk for recurrence after ESS. Rectal carriage of S aureus is more statistically related to the recurrence of CRSwNP after ESS compared with skin and nasal carriage.

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.

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.

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.

Chronic rhinosinusitis (CRS) is a relatively common inflammatory disease of the nasal and paranasal sinus mucosa. Several epidemiological studies have established an association between particulate matter (PM) and CRS. Based on those data, PM has emerged as an important environmental factor in the development of CRS. Recent research has investigated the mechanisms and treatment options for CRS caused by PM through cellular experimentation. Therefore, the authors would like to explain the definition of PM, present research investigating the relationship between PM and CRS, and summarize the involved mechanisms reported to date.

Maxillary sinus floor elevation, via the lateral approach, is one of the most predictable bone augmentation procedures performed in implant dentistry. but both intra- and postoperative complications can occur, and some of them are severe. Our aim is as follows: To review the pertinent literature on the topic, especially assessing the risk factors related to complications. To give clinical recommendations to minimize intra- and postoperative complications with the ultimate scope of improving the standard of clinical care and patient safety.

Although it has been postulated that tobacco use, as well as other environmental exposures, may contribute to chronic rhinosinusitis (CRS), the data remain limited. Here, we utilised a large state population database to assess the association between tobacco use and CRS prevalence among patients undergoing endoscopic sinus surgery (ESS).

Employing a case-control study design, the Utah Population Database was queried for patients age >18 with a diagnosis of CRS and tobacco use who underwent ESS between 1996 and 2018. Smoking status was compared between patients with CRS (n = 34 350) and random population controls matched 5:1 on sex, birth year, birthplace, time residing in Utah, and pedigree (i.e., familial) information (n = 166 020). Conditional logistic regression models were used for comparisons between CRS patients and their matched controls. All analyses were repeated, additionally adjusting for race, ethnicity, tobacco use, asthma history, and interaction between tobacco use and asthma history.

A total of 200 370 patients were included in the final analysis. Patients with CRS were significantly more likely to demonstrate a history of tobacco use than controls (19.6% vs. 15.0%; p < .001), with an adjusted odds ratio (aOR) of 1.42, 95% confidence interval 1.37-1.47; p < .001. More patients with CRS and comorbid asthma used tobacco (19.5%) than controls with asthma (15.0%; p < .001).

History of tobacco use may portend increased risk for the development of CRS among patients undergoing ESS compared to healthy controls.

Introduction: Commensal bacteria have always played a significant role in the maintenance of health and disease but are being unravelled only recently. Studies suggest that the nasal microbiome has a significant role in the development of various disease conditions. Search engines were used for searching articles having a nasal microbiome and disease correlation. In olfactory dysfunction, dysbiosis of the microbiome may have a significant role to play in the pathogenesis. The nasal microbiome influences the phenotype of CRS and is also capable of modulating the immune response and plays a role in polyp formation. Microbiome dysbiosis has a pivotal role in the development of Allergic Rhinitis; but, yet known how is this role played. The nasal microbiome has a close association with the severity and phenotype of asthma. They contribute significantly to the onset, severity, and development of asthma. The nasal microbiome has a significant impact on the immunity and protection of its host. The nasal microbiome has been a stimulus in the development of Otitis Media and its manifestations. Studies suggest that the resident nasal microbiome is responsible for the initiation of neurodegenerative diseases like Parkinson's Disease.Materials and Methods: Literature search from PubMed, Medline, and Google with the Mesh terms: nasal microbiome AND diseases. Conclusion: With increasing evidence on the role of the nasal microbiome on various diseases, it would be interesting to see how this microbiome can be modulated by pro/pre/post biotics to prevent a disease or the severity of illness.

Background: The aim of the study was to evaluate the ear in otologically asymptomatic patients of chronic rhinosinusitis and summarize the otological and audiological findings. Methods: This is a cross sectional study conducted in the Department of Otorhinolaryngology - Head & Neck Surgery, Jaipur Golden Hospital, New Delhi, from January 2019 to October 2019. 80 cases aged between 15 and 55 years with Chronic rhinosinusitis were included in the study. Detailed clinical examination and history was carried out followed by Diagnostic nasal endoscopy and Otoendoscopy. All the data collected was statistically analyzed. Results: In patients of Chronic rhinosinusitis, Nasal obstruction was the most common complaint. Out of 80 patients 47 had abnormal Tympanic Membrane finding in one or the other ear, among them Tympanosclerotic patch was the most common finding. Co-relation between Diagnostic nasal endoscopy in right and left ipsilateral nasal cavity and tympanic membrane showed statistically significant association between nasal polyp and presence of abnormal tympanic membrane. Statistically significant association between duration of chronic rhinosinusitis and presence of abnormal tympanic membrane finding on otoendoscopy was found. Conclusion: chronic rhinosinusitis affects the ears slowly and silently. Hence, the ears should always be proactively evaluated in every patient of chronic rhinosinusitis to diagnose inevident disease in ears and if necessary, initiate timely preventive and therapeutic intervention.

Adult and pediatric patients with chronic rhinosinusitis (CRS) may have differing philosophies in therapeutic management. Few studies have examined sinonasal tissue-level comparisons of these groups. This study examines histopathologic differences between children and adults with CRS, with the goal of understanding disease pathogenesis and optimizing medical management for both populations.

In a retrospective cohort of CRS patients who underwent functional endoscopic sinus surgery (FESS), demographic factors, pertinent comorbidities, and a structured histopathologic report of 13 variables were compared across pediatric and adult CRS patients with and without nasal polyps (pCRSwNP, pCRSsNP, aCRSwNP, aCRSsNP, respectively).

A total of 378 adult (181 aCRSsNP, 197 aCRSwNP) and 50 pediatric (28 pCRSsNP, 22 pCRSwNP) patients were analyzed. Significantly more children compared with adults had a comorbid asthma diagnosis (64.5% vs. 37.2%, p = 0.003). Adults with CRS exhibited significantly more tissue neutrophilia (28.9% vs. 12.0%, p = 0.006), basement membrane thickening (70.3% vs. 44.0%, p < 0.001), subepithelial edema (61% vs. 30.0%, p < 0.001), squamous metaplasia (22.0% vs. 4.0%, p < 0.001), and eosinophil aggregates (22.8% vs. 4.0%, p < 0.001) than children with CRS. The majority (66.5%) of adult CRS patients exhibited a lymphoplasmacytic-predominant inflammatory background, whereas the majority (57.8%) of children with CRS exhibited a lymphocyte-predominant inflammatory background.

Sinonasal tissue of adult and pediatric CRS patients demonstrates clear histopathologic differences. Our findings provide insight into differing pathophysiology, which may enable optimization of targeted therapies for patients in each of these unique clinical groups.

Dupilumab was the first biologic approved to treat chronic rhinosinusitis with nasal polyps (CRSwNP). While the risk of adverse events in phase-III clinical trials was low, dupilumab-associated adverse reactions (DAR) with real-world use is unknown and potentially under-reported. We aimed to evaluate DAR for CRSwNP treatment (CRSwNP-tx) using the FDA Adverse Event Reporting System (FAERS).

Retrospective database study.

FAERS was queried for DAR from 2019Q1 to 2021Q2. Individual DAR (iDAR) were categorized and quantitatively compared between treatment groups (CRSwNP, asthma, atopic dermatitis). Zero-truncated Poisson regression was modeled to predict the number of iDAR, and logistic regression was modeled to predict serious DARs.

There were 15,411 DAR observations; 911 for CRSwNP-tx, of which 121 (13.3%) had serious reactions and 3 died. Common CRSwNP-tx iDAR were dermatologic (13.9%), generalized (13.3%), and injection-site (10.8%) symptoms. The number of CRSwNP-tx iDAR was 2.99 [2.81, 3.17], compared to 3.44 [3.32, 3.56] for asthma and 3.18 [3.13, 3.24] for atopic dermatitis (Kruskal-Wallis test, P < .001). For CRSwNP-tx, iDAR reported-risk-ratio was 0.84 [0.77, 0.92] among men and 1.12 [1.04, 1.22] among older adults (>50). Serious DAR reported-odds-ratio was 1.37 [0.91, 2.04] among men and 1.39 [0.93, 2.08] among older adults.

While there are limitations with FAERS, this analysis suggests CRSwNP-tx is associated with fewer iDAR compared with other treatment indications. More iDAR are experienced among women and older adults, but men tend to have more serious DAR.

3 Laryngoscope, 132:2307-2313, 2022.

Treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) includes endoscopic sinus surgery and topic and/or systemic corticosteroids, which have only temporary effects. The development of biologic therapies has provided a new treatment paradigm for CRSwNP. Dupilumab is the only biological approved in Italy for CRSwNP, but its efficacy in a real-life context is still scarce.

We carried out a monocentric prospective study at our institution with a 6-month follow-up on patients administered biweekly 300 mg dupilumab therapy for CRSwNP, prescribed according to EPOS 2020 criteria. Patients were evaluated at baseline and every 2 months.

Median values at baseline and 6 months were, respectively, 3/12 and 8/12 for the Brief Smell Identification Test (p = 0.005), 5/8 and 2/8 for the Nasal Polyp Score (p < 0.001), 10/20 and 6/20 for the Lund-Kennedy score (p < 0.001), 65/110 and 14/110 for the Sinonasal Outcome Test (p < 0.001), and 15/25 and 23/25 for the Asthma Control Test score (p = 0.009). Adverse events were mild, consisting mainly in discomfort at the site of injection. Four patients developed asymptomatic hypereosinophilia. The treatment was not discontinued in any patient.

Dupilumab was confirmed to be an effective and safe treatment for CRSwNP, as previously seen in registrational studies.

ELOM-080 is a phytomedicine approved for the treatment of acute and chronic inflammatory diseases of the respiratory tract, sinusitis, and bronchitis in particular. This prospective, randomized, placebo-controlled, double-blind clinical trial was conducted to assess efficacy and safety of ELOM-080 in the treatment of acute viral rhinosinusitis (AVRS).

Patients with AVRS received oral treatment (4 × 1 capsule per day) with either ELOM-080 or matching placebo. Primary endpoints were the change in major symptom score (MSS) after 7 and 14 days of treatment assessed by the investigator (MSS_INV ). Secondary endpoints were changes in MSS assessed by the patients (MSS_PAT ), olfactory function (12-item Sniffin' Sticks), 20-Item Sino-Nasal Outcome Test (SNOT-20 GAV; German adapted version), influence of treatment on viral load, and safety.

Four hundred and sixty-three patients were randomized. At day 4, subjective burden of disease (MSS) was significantly ameliorated compared to placebo (p = 0.012). During the first treatment week MSS scores improved about 1 day earlier, and 3 days earlier in the second week. Effect with ELOM-080 on mean MSS_INV was statistically significantly superior to placebo at visit 3 (p = 0.016) and visit 4 (p = 0.014). In chemosensory testing identification scores improved comparably in both treatments. The improvement of the SNOT-20 GAV was more pronounced in ELOM-080 patients. Treatment with ELOM-080 indicated a potential for decreasing viral load. Both treatments were well tolerated.

ELOM-080 improves the burden of AVRS significantly in comparison to placebo, remission of symptoms occurred 3 days earlier. The results confirm the efficacy and safety of ELOM-080 for treatment of AVRS.

1 Laryngoscope, 2022.

Chronic rhinosinusitis (CRS) is a chronic inflammatory process of nasal mucosa and paranasal sinuses, lasting more than 12 weeks, without complete resolution of symptoms. CRS is treated medically, followed by Endoscopic sinus surgery (ESS) if necessary, and supplemented by post-operative topical treatment with highly variable clinical outcomes. However, till date there is no consensus on the composition and duration of maximal medical treatment. Despite proven role of topical steroids, the mode of delivery, dose and duration of topical intranasal corticosteroids still remains debatable. Studies found that high volume sinonasal irrigation (> 50 ml) using budesonide is most efficient method but still there is not sufficient data to prove this and results are variable with multiple modifiable factors therefore, this study has been conducted. (1) To determine the difference in mean decrease in Lund-Kennedy endoscopic scores and SNOT-22 scores among post ESS patients with high volume budesonide nasal irrigation nasal cavity and control nasal cavity of chronic rhinosinusitis patients. (2) To determine safety by measuring serum cortisol levels and intra ocular pressure. This is hospital based interventional, randomised, double blind, control trial study. A total of 66 patients of CRS with previous failed medical therapy were included. Same patients nasal cavities were divided into control and case nasal cavities, to avoid demographic bias. All subjects had a baseline SNOT-22 scores (Sino Nasal Outcome Test scores), Lund Kennedy endoscopy score, NCCT PNS score. All patients were undergone ESS procedure. After nasal pack removal, nasal cavities were randomly assigned 1:1 to receive normal saline irrigation (control group) or 1 mg of budesonide irrigation (case group) for transnasal irrigation twice daily for 12 weeks. A total of 66 patients with 132 nasal cavities were included in the study. Out of which 16 were female and 50 were male with mean age 33 year and mean duration of symptoms was 38.19 months. Mean duration of follow up was for 3 months. Mean decrement in SNOT-22 score in control nasal cavity from 52.54(16.309) to 30.06 (18.16) and in endoscopic score from 6.53 (1.33) to 3.93 (1.6) which is statically significant (p value < 0.05) in both scores. Mean decrement in SNOT-22 score in case nasal cavity from 53.73 (15.75) to 21.15 (13.52) and in endoscopic score from 6.74 (1.8) to 2.77 (1.4) which is statically significant (p value < 0.05) in both scores. Decrement in SNOT-22 scores and endoscopy scores in case nasal cavity in comparision to control nasal cavity were compared by student 't' test and found to be statically significant (p value equals to 0.0001). In subjective outcomes 57.57% shows total improvement in control nasal cavities while 72.73% case nasal cavities shows total improvement. Our study shows high volume budesonide irrigation is safe and superior over normal saline irrigation and results were statistically comparable. Still further studies with larger sample size and longer duration of irrigation needed.Based on available evidence, high volume budesonide irrigation is statically safe and superior over normal saline irrigation.

Chronic rhinosinusitis (CRS) significantly affect the quality of life (QoL) of patients. The study was conducted in CRS patients who were treated with functional endoscopic sinus surgery (FESS) after failure of medical treatment to analyze clinical outcome using prospectively collected data through a symptom-based rhinosinusitis outcome measure, the Sino-nasal Outcome Test-22 (SNOT-22). The aim of the study was to evaluate and compare the QoL in patients of chronic rhinosinusitis pre-operative and after FESS by SNOT-22. The prospective study was conducted on 40 patients of chronic rhinosinusitis with or without nasal polyposis. Demographic, clinical, diagnostic nasal endoscopy and radiological findings were recorded. Visual analogue scoring and SNOT-22 questionnaire scoring were done preoperatively and at 3rd and 6th months post-operatively. These scores were compared and a value of p < 0.01 was considered statistical significant. Nasal obstruction (80%) was the most commonly reported disabling condition followed by rhinorrhea (75%), facial pain-pressure (72.5%), headache and sneezing. The mean preoperative nasal endoscopy score was 8.08 ± 3.65. The mean preoperative Lund Mackay CT scan score was 11.725 ± 3.64. The mean preoperative SNOT-22 score was 46.25 ± 20.44. After FESS, nasal discharge was improved in 86% patients. Average VAS scores showed significant postoperative improvement at 6 months (p < 0.01). The mean postoperative diagnostic nasal endoscopy score improved to 2.80 ± 1.64 at 6 months (p < 0.01). The mean postoperative SNOT-22 scores decreased at postoperative follow up visits at 3 and 6 months to 14.58 ± 4.90 at 3 months and 22.38 ±7.93 at 6 months (p < 0.01). CRS patient refractory to medical treatment showed statistical significant improvement after FESS. The SNOT-22 scoring was easy to use scoring used for QoL assessment showed significant improvement after FESS.

Histopathology of nasal polyps contains rich prognostic information, which is difficult to objectively extract. In the present study, we aimed to develop a prognostic indicator of patient outcomes by analyzing scanned conventional haematoxylin and eosin (H&E) -stained slides alone using deep learning.

An interpretable supervised deep learning model was developed using 185 H&E-stained whole-slide images (WSIs) of nasal polyps, each from a patient randomly selected from the pool of 232 patients who underwent endoscopic sinus surgery at the First Affiliated Hospital of Sun Yat-sen University (internal cohort). We internally validated the model on a holdout dataset from the internal cohort (47 H&E-stained WSIs) and externally validated the model on 122 H&E-stained WSIs from the Seventh Affiliated Hospital of Sun Yat-sen University and the University of Hong Kong-Shenzhen Hospital (external cohort). A poor prognosis score (PPS) was established to evaluate patient outcomes, and then risk activation mapping was applied to visualize the histopathological features underlying PPS.

The model yielded a patient-level sensitivity of 79.5%, and specificity of 92.3%, with areas under the receiver operating characteristic curve of 0.943, on the multi-center external cohort. The predictive ability of PPS was superior to that of conventional tissue eosinophil number. Notably, eosinophil infiltration, goblet cell hyperplasia, glandular hyperplasia, squamous metaplasia, and fibrin deposition were identified as the main underlying features of PPS.

Our deep learning model is an effective method for decoding pathological images of nasal polyps, providing a valuable solution for disease prognosis prediction and precise patient treatment. This article is protected by copyright. All rights reserved.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease of the upper airways. AZD1981 is a selective antagonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 and other type 2 cells, including innate lymphoid cells type 2, eosinophils, and basophils.

To evaluate the efficacy of AZD1981 in reducing nasal polyp size when added to intranasal corticosteroids in adult patients with CRSwNP.

Eighty-one subjects (18-70 years of age) with CRSwNP were recruited and screened for trial eligibility from allergy and otolaryngology clinics from a single tertiary care site between June 2016 and August 2019. Eligible patients were randomized in a double-blind fashion to receive either AZD1981 (n = 22) or placebo (n = 21) orally three times a day for 12 weeks, added to intranasal corticosteroids. The primary endpoint was a change in nasal polyp score (NPS) at 12 weeks. Secondary endpoints included improvement in sinus computed tomography using Lund Mackay scoring, symptoms using visual analog scale, quality of life using Sino Nasal Outcome Test-22, and the Brief Smell Identification Test.

Forty-three patients met the inclusion criteria and were enrolled. At 12 weeks, there was no difference in NPS change in the AZD1981 arm (mean 0, standard error 0.34, n = 15) compared with placebo (mean 0.20, standard error 0.36, n = 17); mean difference -0.20 (95% confidence interval: -1.21, 0.81; p = .69). No significant differences were observed for Lund Mackay score, symptoms, quality of life, or smell test. AZD1981 was well tolerated except for one case of hypersensitivity reaction.

In patients with CRSwNP, the addition of AZD1981 to intranasal corticosteroids did not change nasal polyp size, radiographic scores, symptoms, or disease-specific quality of life.

Dysosmia could alter dietary quality through mechanisms including changes in appetite, food choice, and subsequent nutritional intake. However, there are few studies that directly assess olfactory performance and dietary quality. In this pilot study, we aimed to measure dietary quality in patients with dysosmia compared with controls with normosmia.

Community-dwelling adults prospectively underwent olfactory testing using the Sniffin' Sticks test from which composite threshold, discrimination, and identification (TDI) scores were used to identify patients with dysosmia (TDI <31) and controls with normosmia (TDI ≥31). Participants completed the Diet History Questionnaire III (DHQ III), a standardized and validated tool for nutritional assessment developed by the National Institutes of Health. The Healthy Eating Index (HEI) was calculated to determine compliance with the US Dietary Guidelines for Americans.

Sixty patients were enrolled, including 29 patients with dysosmia and 31 controls with normosmia with no difference in age or sex among groups. A significant correlation between TDI score and HEI component score was seen for protein (r = 0.256; p = 0.048), dairy (r = 0.285; p = 0.027), and saturated fat (r = -0.262; p = 0.043) scores. Compared with controls with normosmia, patients with dysosmia were found to have less total protein and total dairy intake, as well as less total saturated fat intake.

This study found significantly altered nutritional quality in patients with reduced olfactory function, including decreased intake of protein, dairy, and saturated fats. These findings are relevant given the high prevalence of dysosmia in the aging population and previous studies showing associations with mortality.

Endoscopic sinus surgery (ESS) is a current procedure for treating patients with chronic rhinosinusitis (CRS). Image-guided surgery (IGS) for ESS may help reduce complications and improve precision. However, it is uncertain in which cases IGS is beneficial. This work aims to compare ESS with and without IGS in patients with CRS.

PubMed, Embase, Scopus, Web of Science, Scielo, Cochrane Central Register of Controlled Trials, CINAHL, LILACS and Clinicaltrials.gov will be searched for reported clinical trials comparing the quality of life and perioperative outcomes of ESS with and without navigation. The search is planned for 20 April 2022. Three independent authors will select eligible articles and extract their data. The risk of bias will be assessed using the Cochrane Handbook for Systematic Reviews of Interventions. The Grading of Recommendation Assessment, Development and Evaluation method will evaluate the strength of the evidence. Data synthesis will be performed using the Review Manager software V.5.4.1. To assess heterogeneity, I² statistics will be computed. Additionally, meta-analysis will be performed if the included studies are sufficiently homogenous.

This study reviews published data, and thus it is not necessary to obtain ethical approval. The findings of this systematic review will be published in a peer-reviewed journal.

CRD42020214791.

Open and closed sinus lifting procedures are predictable methods to augment the bone needed for appropriate implant placement in the posterior maxilla in cases where available bone is limited. However, these techniques may give rise to complications and associated comorbidities. In the case of open sinus lifting, perforation of the Schneiderian membrane during osteotomy is the most common complication, with an incidence rate of around 20%-25%. Apart from those complications associated with oral surgery in general (such as swelling or hematoma), there are specific complications of open sinus lifting procedures that may arise less frequently (chronic rhinosinusitis, hemorrhage, or ostium blockage by overfilling) but which may nevertheless compromise the viability of the graft and/or the implants and cause substantial discomfort to the patient. Closed sinus lifting is a less invasive approach that allows transcrestal placement of the implants in cases where there is sufficient residual bone height. However, it may also be associated with specific complications, including membrane perforation, benign paroxysmal positional vertigo, and implant displacement to the sinus cavity. New technologies have been proposed to reduce these complications and comorbidities associated with conventional sinus lifting procedures, such as the use of piezoelectric devices and hydraulic sinus lift or reamer burs. The evidence supporting their effectiveness and safety, however, is still lacking. A detailed medical history together with a thorough radiographic and clinical examination are essential prior to any kind of bone regenerative augmentation involving the maxillary sinus. Moreover, it is recommended to employ the most appropriate surgical technique for the specific characteristics of the case and, at the same time, accommodating the experience and skills of the surgeon.

Clinical trials of biologics to treat chronic rhinosinusitis with nasal polyposis (CRSwNP) have evaluated objective outcomes (e.g., University of Pennsylvania Smell Identification Test [UPSIT], nasal polyps score [NPS], and computed tomography Lund-Mackay score [CT-LMK]) and patient-reported symptoms (e.g., nasal congestion/obstruction [NC], loss of smell [LoS], and total symptom score [TSS]). We estimated anchor-based thresholds for clinically meaningful change in objective and patient-reported outcomes in patients with CRSwNP using data from LIBERTY NP SINUS-24 and SINUS-52 trials (NCT02912468; NCT02898454).

Target patient-reported outcomes were NC, LoS, and TSS; target objective outcomes were UPSIT, NPS, and CT-LMK. Anchor measures were the 22-item sinonasal outcome test (SNOT-22) rhinologic symptoms domain and total score and rhinosinusitis visual analog scale (VAS). The appropriateness of each anchor measure was evaluated by reviewing correlations between change in anchor measures and target outcomes and descriptive scores on target outcomes by levels of change in the anchor measure. Established thresholds for anchor measures (3.8 points for SNOT-22 rhinologic symptoms, 8.9 points for SNOT-22 total, 1-category improvement for rhinosinusitis VAS) were used to estimate clinically meaningful score changes for each target outcome.

Based on correlations between change in anchor measures and target outcomes, SNOT-22 rhinologic symptoms domain was deemed the most appropriate anchor measure. Using this anchor measure, thresholds for clinically meaningful within-patient change were NC: 1 point; LoS: 1 point; TSS: 3 points; UPSIT: 8 points; NPS: 1 point; and CT-LMK: 5 points.

These thresholds support interpretation of efficacy results for target outcomes in CRSwNP trials.

2 Laryngoscope, 132:265-271, 2022.

To elucidate whether chronic rhinosinusitis (CRS), usually an inflammatory-mediated rather than infectious process, is a risk factor for extracranial and intracranial complications after elective endoscopic transsphenoidal surgery (ETSS).

A single-center retrospective cohort study of consecutive patients who underwent ETSS between January 2015 and July 2019 was performed, which included chart review and computed tomography assessment. CRS was defined by symptomatology and concurrent endoscopic or radiographic findings.

Of 292 subjects, 11% (n = 33) met criteria for CRS. Median difference in Lund-Mackay scores between the CRS and non-CRS groups was 3.0 (95% CI 2.0-4.0). Complications included acute rhinosinusitis requiring antibiotics (23%, 68/292), epistaxis (10%, 28/292), meningitis (1%, 3/292), cerebrospinal fluid (CSF) leak (7%, 20/292), revision sinonasal procedures (10%, 28/292), and frequent in-office debridement (13%, 39/292). CRS was strongly associated with postoperative acute rhinosinusitis (aRR 1.85, 95% CI 1.18-2.90) and frequent debridement (aRR 1.96, 95% CI 1.00-3.83). Conversely, CRS was not associated with epistaxis (aRR 1.52, 95% CI 0.62-3.72), postoperative CSF leak (aRR 0.91, 95% CI 0.24-3.44), or additional sinonasal procedures (aRR 0.70, 95% CI 0.21-2.29). The rate of meningitis was not significantly higher in the CRS cohort (difference 2.2%, 95% CI -1.0% to 14.5%).

CRS was a strong risk factor for acute rhinosinusitis and need for frequent in-office debridement after ETSS. It was not associated with other postoperative complications including epistaxis, CSF leak, or revision sinonasal procedures. CRS patients had a slightly higher rate of meningitis, which is likely not clinically meaningful.

Due to the high recurrence rate and the variety of complex pathogenesis mechanisms, chronic rhinosinusitis with nasal polyps is difficult to treat. In addition, the disease reduces the quality of life of patients and carries a large financial burden on the healthcare system, therefore, a personalized approach to the treatment of this pathology is becoming popular today. In order to determine which drug route would be most rational for a particular patient, key concepts such as phenotyping, endotyping and genotyping of chronic rhinosinusitis with nasal polyps were introduced. This approach has expanded the understanding of the etiological aspects of the disease and the pathogenetic mechanisms of the formation of nasal polyps. In this regard, immunotherapy of chronic rhinosinusitis with nasal polyps began to develop, consisting in the use of monoclonal antibodies to the substrates of the immune system, which are key figures in the development of certain types of inflammatory reactions of the mucous membrane of the nasal cavity and paranasal sinuses. The use of biological agents represents the first steps in targeted therapy, which is a transition to personalized treatment of patients with chronic rhinosinusitis with nasal polyps. Further studies in the field of immunological mechanisms of the formation of various phenotypes of chronic rhinosinusitis with nasal polyps from the standpoint of proteinomics, transcriptomics and epigenetics give hope for the development of a new drug-based treatment for this disease, which can significantly reduce the need for surgical treatment of patients with this pathology.

Diesel exhaust particles (DEPs) are associated with the prevalence and exacerbation of allergic respiratory diseases, including allergic rhinitis and allergic asthma. However, DEP-induced mechanistic pathways promoting upper airway disease and their clinical implications remain unclear.

We sought to investigate the mechanisms by which DEP exposure contributes to nasal polyposis using human-derived epithelial cells and a murine nasal polyp (NP) model.

Gene set enrichment and weighted gene coexpression network analyses were performed. Cytotoxicity, epithelial-to-mesenchymal transition (EMT) markers, and nasal polyposis were assessed. Effects of DEP exposure on EMT were determined using epithelial cells from normal people or patients with chronic rhinosinusitis with or without NPs. BALB/c mice were exposed to DEP through either a nose-only exposure system or nasal instillation, with or without house dust mite, followed by zinc finger E-box-binding homeobox (ZEB)2 small hairpin RNA delivery.

Bioinformatics analyses revealed that DEP exposure triggered EMT features in airway epithelial cells. Similarly, DEP-exposed human nasal epithelial cells exhibited EMT characteristics, which were dependent on ZEB2 expression. Human nasal epithelial cells derived from patients with chronic rhinosinusitis presented more prominent EMT features after DEP treatment, when compared with those from control subjects and patients with NPs. Coexposure to DEP and house dust mite synergistically increased the number of NPs, epithelial disruptions, and ZEB2 expression. Most importantly, ZEB2 inhibition prevented DEP-induced EMT, thereby alleviating NP formation in mice.

Our data show that DEP facilitated NP formation, possibly via the promotion of ZEB2-induced EMT. ZEB2 may be a therapeutic target for DEP-induced epithelial damage and related airway diseases, including NPs.