Is generative pre-trained transformer artificial intelligence (Chat-GPT) a reliable tool for guidelines synthesis? A preliminary evaluation for biologic CRSwNP therapy.

INTRODUCTION: Biologic therapies for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) have emerged as an auspicious treatment alternative. However, the ideal patient population, dosage, and treatment duration are yet to be well-defined. Moreover, biologic therapy has disadvantages, such as high costs and limited access. The proposal of a novel Artificial Intelligence (AI) algorithm offers an intriguing solution for optimizing decision-making protocols. METHODS: The AI algorithm was initially programmed to conduct a systematic literature review searching for the current primary guidelines on biologics' clinical efficacy and safety in treating CRSwNP. The review included a total of 12 studies: 6 systematic reviews, 4 expert consensus guidelines, and 2 surveys. Simultaneously, two independent human researchers conducted a literature search to compare the results. Subsequently, the AI was tasked to critically analyze the identified papers, highlighting strengths and weaknesses, thereby creating a decision-making algorithm and pyramid flow chart. RESULTS: The studies evaluated various biologics, including monoclonal antibodies targeting Interleukin-5 (IL-5), IL-4, IL-13, and Immunoglobulin E (IgE), assessing their effectiveness in different patient populations, such as those with comorbid asthma or refractory CRSwNP. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, demonstrated significant improvement in nasal symptoms and quality of life in patients with CRSwNP in several randomized controlled trials and systematic reviews. Similarly, mepolizumab and reslizumab, which target IL-5, have also shown efficacy in reducing nasal polyp burden and improving symptoms in patients with CRSwNP, particularly those with comorbid asthma. However, additional studies are required to confirm the long-term efficacy and safety of these biologics in treating CRSwNP. CONCLUSIONS: Biologic therapies have surfaced as a promising treatment option for patients with severe or refractory CRSwNP; however, the optimal patient population, dosage, and treatment duration are yet to be defined. The application of AI in decision-making protocols and the creation of therapeutic algorithms for biologic drug selection, could offer fascinating future prospects in the management of CRSwNP.

Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses, with a prevalence of approximately 1% to 7%. It is defined by the presence of at least two cardinal symptoms (nasal blockage, obstruction, or congestion; anterior or posterior nasal drainage; facial pain or pressure; and hyposmia) for at least three consecutive months, with objective findings on imaging or nasal endoscopy. CRS can result in significant patient costs and lower quality of life due to severe fatigue, depression, and sometimes reduced cognitive function. The condition is categorized as primary or secondary and with or without nasal polyps. Treatment is directed at reducing symptoms, improving mucus clearance, reducing inflammation, enhancing ciliary function, and removing bacteria and biofilms from the nasal mucosa. First-line treatment comprises nasal saline irrigation and intranasal corticosteroids. Acute exacerbation of CRS is common and is defined as a transient worsening of symptoms. The role of oral antibiotics and oral corticosteroids for acute exacerbations is unclear. Optimal maintenance therapy can help alleviate exacerbations. Patients with refractory CRS that is not responsive to first-line treatment and patients with alarm symptoms should be referred to an otolaryngologist for further evaluation and consideration of surgical management. Identifying patients who have CRS with nasal polyps or comorbid conditions such as atopic dermatitis, asthma, or eosinophilic esophagitis is especially important to ensure they are referred to a specialist for consideration of biologic therapy.

Current and emerging biological therapies for Chronic rhinosinusitis with nasal polyps with type 2 inflammation.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP), especially CRSwNP with type 2 inflammation, remains the most difficult-to-treat subtype with high prevalence worldwide. The emergence of biologics has the potential to fulfill the unmet medical needs of patients with CRSwNP driven by type 2 inflammation. AREAS COVERED: A current review of the literature was performed to overview current and emerging biological therapies in the treatment of CRSwNP. EXPERT OPINION: In an era of precision medicine, biologics have been given expectations to provide customized therapies to patients with CRSwNP, particularly those with refractory CRSwNP. Large clinical trials and real-world experiences are both essential for the application of biologics. Moreover, to make biological therapy more tailored to patients, an in-depth understanding of the different mechanisms of biologics, further elucidating the relationship between biologics and conventional medical and surgical treatments, and identifying predictive biomarkers warrant thorough investigations.

Role of CD23 Activated ERK Signaling Pathway in the Pathogenesis of Eosinophilic Chronic Sinusitis with Nasal Polyps.

Objective: In the context of the rising prevalence of eosinophilic chronic sinusitis accompanied by nasal polyps, this study aims toinvestigate the role of CD23 in the pathogenesis of eosinophilic chronic sinusitis with nasal polyps. Methods: The cross-sectional study was conducted, 75 patients with chronic sinusitis and nasal polyps treated in our hospital from January 2019 to May 2021 were selected, including 40 cases of eosinophilic patients with the average age of 29.92 years and 35 cases of non-eosinophilic patients with the average age of 30.05 years and 30 patients with the average age of 30.14 years who underwent skull base benign tumor resection in our hospital were selected as the control group, the expression of CD23 in polyp tissue was detected by immunohistochemistry, and the expression of CD23, p-ERK and CCL20 in polyp tissue were detected by Western blot. Specifically, tissue samples were processed and subjected to staining using specific antibodies targeting CD23. The stained sections were then visualized under a microscope to determine the expression levels of CD23. CD23, p-ERK, and CCL20 expressions in polyp tissue were evaluated via Western blot. Total protein was extracted, separated on a gel, transferred to a membrane, and probed with specific antibodies. Chemiluminescence allowed visualization and quantification of protein expressions. Results: Immunohistochemistry showed that CD23 expression was high in the eosinophilic group but low in the non-eosinophilic and control groups. The relative expression levels of CD23 protein, p-ERK protein, and CCL20 protein in polyp tissue s of the eosinophilic group were (0.892 ± 0.092), (0.733 ± 0.101) and (0.813 ± 0.106), respectively, which were significantly higher than those in non-eosinophilic group and control group (P < .05). The relative expression levels of CD23 protein, p-ERK protein, and CCL20 protein in the non-eosinophilic group were (0.461 ± 0.087), 0.412 ± 0.096) and (0.424 ± 0.098), which were significantly higher than those in the control group (P < .05). The relative expression level of CD23 protein in the eosinophilic group was positively correlated with the relative expression levels of p-ERK protein and CCL20 protein (P < .05). The Lund-Kennedy score in the eosinophilic group was (6.10 ± 1.01), which was significantly higher than that in the non-eosinophilic group (P < .05). The relative expression level of CD23 protein in the eosinophilic group was positively correlated with Lund-Kennedy score (P < .05). Conclusion: Eosinophilic chronic sinusitis with nasal polyp mucosal tissue CD23 expression is up-regulated, which is positively correlated with the ERK signaling pathway and disease severity. This study provides valuable insights into potential therapeutic targets that could be explored to develop future treatment modalities. The potential clinical significance of the study is to reveal the important role of CD23 in the pathogenesis of chronic sinusitis with nasal polyps. The upward adjustment of CD23 is positively related to the severity of the disease, which provides valuable guidance for future treatment strategies. This discovery may provide new ways for the development of CD23 treatment methods, so as to better control the progress of the disease of eosinophilic chronic sinusitis with nasal polyps. Further research can explore the molecular mechanism of CD23 regulation, further verify the feasibility of CD23 as the treatment target, and evaluate the potential value of CD23 as a prognostic logo.

[Experience of biological therapy in severe forms of chronic rhinosinusitis with nasal polyps in the conditions of regional healthcare]. / Opyt biologicheskoi terapii pri tyazhelykh formakh khronicheskogo polipoznogo rinosinusita v usloviyakh regional'nogo zdravookhraneniya.

Recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) with a predominant Th2 endotype of inflammation, including associated with bronchial asthma and/or allergic rhinitis, aspirin triad, refers to diseases with an insufficient level of control, despite the use of a wide range of options for conservative and surgical treatment. OBJECTIVE: To analyze our own experience, clinical and organizational features of the application of the method of biological therapy in patients with severe forms of recurrent CRSwNP. MATERIAL AND METHODS: 25 patients with severe and moderate forms of CRSwNP were examined, who, in a round-the-clock hospital (model CSG 36.018) was treated with Dupilumab, in the form of subcutaneous injections of 300 mg/2 ml 1 every two weeks. The diagnosis was confirmed on the basis of anamnestic data, SNOT-22 quality of life questionnaires, visual endoscopic examination, evaluation of CT data (Lund-Mackay scale), laboratory data. The effectiveness of treatment was monitored after 16 weeks, based on endoscopic examination data, evaluation of CT and SNOT-22 data. In 3 observations, a study of pathomorphological material for tissue eosinophilia was performed. RESULTS: The duration of the course of treatment ranged from 10 to 56 weeks. The most striking clinical effect was observed for signs such as sense of smell and nasal breathing (in some cases-after the first injection). The degree of regression of polyps according to CT and endoscopic examination was more prolonged in time, the same dynamics was observed in the level of total IgE. In a number of patients, the phenomenon of eosinophilia growth was observed against the background of treatment (with regression of clinical symptoms). Pathomorphological examination confirmed a high level of tissue eosinophilia as one of the fundamental signs of Th2 inflammation. One patient with concomitant chronic tubar dysfunction had an improvement in hearing. All patients with AD noted a subjective improvement in disease control (a decrease in the frequency and severity of choking attacks). The cancellation (break in treatment) of treatment was accompanied by a gradual return of symptoms in all patients at various times. CONCLUSIONS: Patients who have not achieved an acceptable level of control of CRSwNP,that meets the criteria of Th2 inflammation can be considered as candidates for the use of targeted biological therapy. With strict compliance with the selection criteria, there is a good clinical effect, primarily in relation to nasal symptoms (sense of smell and nasal breathing) and improved control of asthma symptoms.

Unified Airway Disease: Medical Management.

Concurrent chronic rhinosinusitis with nasal polyps (CRSwNP) in the upper airway, and asthma in the lower airway, often have a shared underlying pathophysiology, namely type 2 inflammation; hence, the term "unified airway disease." The combination of CRSwNP and asthma is associated with uncontrolled disease. The range of treatment of CRSwNP includes intranasal corticosteroids, nasal saline irrigation, oral corticosteroids, antibiotics, and biologics. A combined clinical algorithm for the management of the upper and lower airways in type 2 inflammation will be beneficial, especially for patients with uncontrolled disease who may benefit from biologics.

Rhinosinusitis: clinical-based phenotyping.

Rhinosinusitis (RS) is a common disease and is currently classified into two main types: acute RS (ARS) and chronic RS (CRS), which in turn includes CRS with or without nasal polyps. Different guidelines consider this classification. However, in clinical practice, other phenotypes exist. The current article would propose new clinical-based phenotyping of RS, including the following clinical phenotypes: simple catarrhal RS, Acute RS, acute bacterial RS, severe (complicated) acute RS, chronic RS, and recurrent chronic RS. Treatment strategy should be tailored considering the clinical phenotype and could include phytomedicines, intranasal non-pharmacological remedies, and local bacteriotherapy. In conclusion, RS requires thorough diagnostic work-up, and the therapeutic approach should be mainly based on appropriate management.

Adverse events of biological therapy in chronic rhinosinusitis with nasal polyps: A systematic review.

The management of chronic rhinosinusitis with nasal polyps (CRSwNP) is challenging due to disease recurrence and adverse effects. Both surgical and medical treatment modalities impact the quality of patients' lives. Monoclonal antibody treatment has recently been used successfully in CRS with limited reported adverse events. We aimed to review the literature to shed more light on the safety and adverse events associated with the biological therapy of CRSwNP. A comprehensive systematic review was conducted on the safety of different biological treatments when used for managing CRSwNP. We have included 13 studies in the present systematic review, including 12 randomized controlled trials (RCTs) and one cross-sectional study. The total sample size for the included studies was 2282 patients. Six studies investigated the safety and adverse events of dupilumab; three investigated omalizumab, three investigated mepolizumab, and only one investigated reslizumab. Some studies have reported that adverse events were common with these types of drugs. However they were not specific and self-limited. Headaches, injection site reactions, and pharyngitis were the most common adverse events found among the reported adverse events. The Dupilumab trial reported pharyngitis in 225 patients (22.4 %) followed by erythema in 9.4 %, headache in 8.1 %, epistaxis in 5.1 %, and asthma in 1.7 % of patients. Trials which used omalizumab reported headaches, nasal pharyngitis, injection-site reactions to be the most common adverse events with estimated prevalence rates of 8.1 %, 5.9 %, and 5.2 %, respectively. Mepolizumab and reslizumab studies reported that 40 % of patients were complicated by nasal polyps/congestion/pharyngitis/infections, 14 had a headache (15.5 %), two developed asthma (2.2 %), and only one patient (1.1 %) had epistaxis as an adverse event. Although the literature's current investigations indicate the safety of the biologic treatment modalities, further studies are needed as some uncertainty among the trials have been reported.

Updates in biologic therapy for chronic rhinosinusitis with nasal polyps and NSAID-exacerbated respiratory disease.

Chronic rhinosinusitis with nasal polyps (CRSwNP) associated with type 2 inflammation and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) can be difficult to control with standard medical therapy and sinus surgery. In this group, biologicals are potentially promising treatment options. The phase III clinical trials for omalizumab, dupilumab, mepolizumab and benralizumab in CRSwNP have demonstrated favourable outcomes. Moving forward, direct comparisons among biologicals, refining patient selection criteria for specific biologicals, determining optimal treatment duration and monitoring long-term outcomes are areas of emerging interest. This review summarizes the clinical evidence from the recent 2 years on the role of biologicals in severe CRSwNP and N-ERD, and proposes an approach towards decision-making in their use.

Usefulness of bilateral mucoplasty plus reboot surgery in severe type-2 chronic rhinosinusitis with nasal polyps.

BACKGROUND: Although extended endoscopic sinus surgery (ESS) constitutes an alternative approach in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), the surgical techniques proposed so far do not allow for an optimal control of the disease. This study introduces bilateral mucoplasty as a complementary technique to extended ESS such as reboot surgery, analyzing its benefits in healing and quality of life (QoL). METHODS: Patients diagnosed with severe Type-2 CRSwNP were selected for a prospective cohort study in two surgery groups: reboot surgery plus bilateral mucoplasty versus reboot surgery only. In the first group, an autologous endonasal mucosal graft from the nostril floor was placed bilaterally onto the ethmoidal roof. Endoscopic, radiological and QoL outcomes were compared before and one year after surgery between the two groups using Modified Lund Kennedy (LKM), Meltzer and Lund Mackay (LM) scores, and the Sino-Nasal Outcome Test 22 (SNOT-22). RESULTS: 64 patients with homogeneous baseline characteristics were included: 17 patients underwent a reboot surgery plus a bilateral mucoplasty and 47 a reboot surgery only. LKM, Meltzer and SNOT-22 scores showed significant differences before and after surgery in both groups, with higher improvement in the mucoplasty group. A greater mean improvement of 20.5 ± 6.4 points in SNOT-22 change was associated with bilateral mucoplasty. CONCLUSION: Bilateral mucoplasty plus reboot surgery constitutes a useful surgical resource in Type-2 CRSwNP patients, showing improved endoscopic, radiological and QoL outcomes one year after surgery. Further studies are needed to determine their long-term benefits.

Biologic Therapies for Allergic Rhinitis and Nasal Polyposis.

PURPOSE OF REVIEW: There is an emerging body of research on targeted biologic therapies for the treatment of severe inflammatory nasal disorders, especially chronic rhinosinusitis with nasal polyposis (CRSwNP). This paper will evaluate the efficacy of biologic therapies for severe nasal inflammation by summarizing key preclinical trials of biologics for animal models of allergic rhinitis and the recent phase 2 and 3 clinical trials of biologic therapies for CRSwNP. RECENT FINDINGS: Biologics that target the IL-4 receptor (dupilumab), IgE (omalizumab), and IL-5 (mepolizumab, reslizumab, and benralizumab) in patients with CRSwNP have shown improvement of various metrics including Sino-Nasal Outcome Test (SNOT-22) scores, Nasal Polyp Scores (NPS), Nasal Congestion Scores (NCS), and Lund-Mackay sinus opacification scores. The efficacy demonstrated through the dupilumab phase 3 trials (LIBERTY NP SINUS-24 and SINUS-52) led to approval of the first biologic for the treatment of CRSwNP. Phase 3 trials for omalizumab (POLYP 1 and 2) and mepolizumab (SYNAPSE study) and post hoc analyses of phase 3 asthma studies for reslizumab and benralizumab have also demonstrated positive results for the use of biologics for patients with CRSwNP. Future efficacy studies and risk/benefit and cost analyses of these biologics and other cytokine targets for allergic rhinitis with and without nasal polyposis need to be performed.

Chronic rhinosinusitis with nasal polyposis: the role of personalized and integrated medicine.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a common disorder. From a clinical and immunopathological point of view, different phenotypes and endotypes have been identified. As asthma is frequent comorbidity, biological agents for treating CRSwNP associated with asthma may be an attractive strategy. Biological agents have several mechanisms, such as antagonizing IgE, interleukin (IL) 4, IL-5, and IL-13. However, a workup is mandatory, mainly concerning pheno-endotyping. In this regard, clinical cytological grading (CCG) has been proposed as a useful tool to manage patients with CRSwNP as it allows us to define clinical and immunopathological phenotypes able to identify the ideal candidate for biologics. In particular, the mixed cellular pattern, such as eosinophils and mast cells, could be sensitive to anti-IL-4 agents. There is still a need for well-established indications, criteria of responsiveness, duration, and safety. Moreover, personalized medicine could be opportunely integrated and/or alternated with intranasal corticosteroids to prevent relevant adverse events.

Haemorrhagic nasal polyp mimicking melanoma in an 83-year-old on rivaroxaban.

An 83-year-old woman presented with rapid onset unilateral nasal obstruction after sneezing. She had a history of hypertension and atrial fibrillation, and was on rivaroxaban. Examination revealed a dark red polypoidal lesion completely obstructing the left nostril. She underwent CT and MRI, and proceeded to urgent excision biopsy of the lesion. Intraoperative appearance was in keeping with a haemorrhagic polyp arising from the nasal septum. Histology revealed haematoma within a layer of nasal mucosa. There was no evidence of haemangioma underlying the polyp. Our literature search has identified this case as the first described haemorrhagic polyp of the nasal septum. It is likely that rivaroxaban contributed to the formation of this haemorrhagic polyp, and it is important to differentiate benign haemorrhagic lesions from malignant conditions such as melanoma. Similar cases may become more common in the future as the proportion of the population on anticoagulants increases.

Dupilumab in the treatment of chronic rhinosinusitis with nasal polyposis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) imparts a significant healthcare challenge, resulting in diminished quality of life for patients and high costs with resource utilization for disease management. Understanding of CRSwNP pathophysiology has progressively evolved and the identification of various inflammatory biomarkers has led to the development of monoclonal antibodies that target the underlying mechanisms of inflammation. Dupilumab, which targets IL-4 and IL-13 signaling, serves as a novel agent for CRSwNP treatment. Three clinical trials, NCT01920893, SINUS-24 and SINUS-52, have shown that dupilumab improves both subjective patient-reported outcomes and objective physician-evaluated metrics for CRSwNP. The favorable findings have resulted in approval by the US FDA in June 2019 as the first biologic therapy for CRSwNP.

Chronic rhinosinusitis with nasal polyposis: the role of personalized and integrated medicine.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a frequent disorder. From a clinical and an immunopathological point of view, different phenotypes and endotypes have been identified. The frequent comorbidity with asthma allowed to pave the way to the use of biological agents for the treatment of CRSwNP. Biological agents are targeted to antagonize IgE, interleukin (IL) 4, IL-5, and IL-13 at present. However, a correct and appropriate workup is mandatory, mainly concerning the exact definition of the specific pheno-endotype. The preliminary outcomes are promising, even though there is a need for well-established indications, criteria of responsiveness, duration, and safety. On the other hand, this personalized medicine could be fruitfully integrated with gold-standard medications, such as intranasal corticosteroids. As CRSwNP is a chronic disorder, treatment should be long-lasting, so complementary anti-inflammatory treatments could be opportunely integrated and/or alternated to steroids.

Effects of biological therapies on chronic rhinosinusitis in severe asthmatic patients.

OBJECTIVE: The introduction of monoclonal antibody (mAb) therapies represents a promising treatment for refractory chronic rhinosinusitis (CRS). We assessed the effects of selected mAbs (omalizumab, mepolizumab, benralizumab) on CRS in severe asthmatic patients in a real-life setting. METHODS: A prospective observational study on severe asthmatic patients, treated with 3 different mAb (omalizumab, mepolizumab, benralizumab), and comorbid CRS was conducted. All patients were followed for 52 weeks. The degree of nasal control, SinoNasal Outcome Test (SNOT) 22, Nasal Polyp Score (NPS), Lund Kennedy Score (LKS) were collected at baseline and at 52-week. RESULTS: 40 patients (33 with nasal polyps) were studied. 33 patients (82.5%) had uncontrolled nasal disease at baseline, and 15 (37.5%) were uncontrolled after 52 weeks. Significant improvement was observed for SNOT 22 (P < 0.001), SNOT 1-12 (P < 0.001) and degree of nasal control (P < 0.001). Differences in NPS (P = 0.130) and LKS (P = 0.124) were not significant. Net change in the above-mentioned parameters among the three treatment groups was not significantly different. CONCLUSIONS: The study shows an improvement of nasal symptoms after 52 weeks of mAb treatment, which was not associated with significant improvement of endoscopic findings. Larger studies are needed to assess the real-life efficacy of mAbs in CRS.

Association of Chronic Rhinosinusitis With Depression and Anxiety in a Nationwide Insurance Population.

Importance: Chronic rhinosinusitis (CRS) is associated with a decreased quality of life, affecting physical and emotional aspects of daily function, the latter of which could manifest as depression and anxiety. Objective: To evaluate the risk of depression and anxiety in CRS, depending on the CRS phenotype (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]). Design, Setting, and Participants: This retrospective nationwide cohort study used population-based insurance data (consisting of data from approximately 1 million patients). The study population included 16 224 patients with CRS and 32 448 individuals without CRS, with propensity score matching between groups according to sociodemographic factors and enrollment year. Data were collected from January 1, 2002, through December 31, 2013, and analyzed from July 1 through November 15, 2018. Main Outcomes and Measures: Survival analysis, the log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of depression and anxiety for each group. Results: Among the 48 672 individuals included in the study population (58.8% female), the overall incidence of depression during the 11-year follow-up was 1.51-fold higher in the CRS group than in the non-CRS group (24.2 vs 16.0 per 1000 person-years; adjusted HR, 1.54; 95% CI, 1.48-1.61). The incidence of anxiety was also higher in the CRS group than in the comparison group (42.2 vs 27.8 per 1000 person-years; adjusted HR, 1.57; 95% CI, 1.52-1.62). Moreover, the adjusted HRs of developing depression (CRSsNP, 1.61 [95% CI, 1.54-1.69]; CRSwNP, 1.41 [95% CI, 1.32-1.50]) and anxiety (CRSsNP, 1.63 [95% CI, 1.57-1.69]; CRSwNP, 1.45 [95% CI, 1.38-1.52]) were greater in patients with CRSsNP than in those with CRSwNP. Conclusions and Relevance: This observational study suggests that CRS is associated with an increased incidence of depression and anxiety. Specifically, findings from this study found that patients without nasal polyps showed a higher risk of developing depression and anxiety than those with nasal polyps.

Role of Vitamin D and Its Receptors in the Pathophysiology of Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) is a disease that represents a challenging therapeutic problem. Vitamin D and its receptors (VDR) are involved in the regulation of the immune system and may play role in CRS. Objectives of this study were to assess the relationships between the total concentration of vitamin D (25VD3) in sera, vitamin D receptor (VDR) expression, 1α-hydroxylase expression, and clinical data, including age, gender, Sino-Nasal Outcome Test (SNOT-22), computerized tomography (CT) scan, allergy status, and vitamin D supplementation in CRS patients with (CRSwNP) and without nasal polyps (CRSsNP), and in a control group. METHODS: The studied group comprised 52 patients with CRS without nasal polyps (sNP), 55 with CRS with nasal polyps (wNP), and 59 in the control group. The endpoints were determined by appropriate methods. We conducted immunohistochemical staining of gathered tissue from the ostiomeatal complex for determination of VDR and 1α-hydroxylase. Analytical results were compared with clinical data as already noted. RESULTS: A decrease in VDR nuclear staining occurred in CRS patients as compared to controls. Insignificant differences were observed in 1α-hydroxylase, expression in all studied groups, while VDR and cytochrome CYP27B1 protein expression (1α-hydroxylase) correlated with clinical data. CONCLUSIONS: The data provide evidence that indicates that vitamin D and its receptor and enzymes may play a role in CRS.

Biologic Agents for the Treatment of Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis is a complex inflammatory disorder, which is often recalcitrant to medical and surgical management. Recently, biologic agents have been studied as an adjunct treatment for this patient population. OBJECTIVE: The purpose of this study is to examine the role of biologic agents for chronic rhinosinusitis patients by reviewing literature and clinical trials. METHODS: A comprehensive review of literature and clinical trials-both recently completed and ongoing-was undertaken to examine up-to-date evidence of current biologic therapy and its role in chronic rhinosinusitis patients-including anti-IgE, anti-IL-4, anti-IL-5, anti-IL-13, and GATA-3 DNAzyme. RESULTS: Specific biologic agents discussed include omalizumab, reslizumab, mepolizumab, benralizumab, dupilumab, and Hgd40/SB010. Risks, side effects, and administration information are also reviewed. An algorithm for the use of biologics in patients with chronic rhinosinusitis with nasal polyposis is proposed. CONCLUSION: These treatments have promising results and may prove to be an important adjunct for patients with recalcitrant sinus disease.

Biotherapeutics in Chronic Rhinosinusitis with and without Nasal Polyps.

In western countries, 85% of chronic rhinosinusitis with nasal polyp disease reveals a type 2 inflammatory pattern with expression of IL-4, -5, and -13 as well as increased concentrations of IgE, whereas chronic rhinosinusitis without nasal polyps merely expresses these biomarkers. The degree of type 2 inflammation furthermore is associated with disease severity, asthma comorbidity, and recurrence of disease after surgery. Therefore, these biomarkers also form the targets for innovative therapeutic approaches such as monoclonal antibodies directed against IgE, IL-5, and IL-4 receptor alpha, blocking the activity of IL-4 and -13. Having demonstrated efficacy in severe asthma, the antibodies have been tested in proof-of-concept studies in patients with nasal polyposis with or without asthma, and have demonstrated their potential to reduce nasal and sinus nasal polyp burden monitored by nasal endoscopy and computed tomography scanning, and to improve typical symptoms. No biomarkers have been identified to select subjects for therapy, to predict response to a specific drug, or to monitor treatment success, which is best documented by nasal polyp score and symptoms. Phase 3 studies are currently in preparation or running, which aim to demonstrate efficacy in larger patient populations and to achieve registration for the indication nasal polyps.