scholarly journals Therapeutic Options for Chronic Rhinosinusitis in N-ERD Patients

2021 ◽  
Vol 2 ◽  
Author(s):  
Rik J. L. van der Lans ◽  
Wytske J. Fokkens ◽  
Sietze Reitsma

Patients with non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) often suffer from chronic rhinosinusitis (CRS) with nasal polyps, a form of primary diffuse Type 2 CRS. Although this disease is also seen in NSAID-tolerant patients, CRS in N-ERD often is more severe and more treatment resistant; local nasal therapy (nasal corticosteroids) and endoscopic sinus surgery are employed like in NSAID-tolerant patients, but with limited and/or short-lived effects. This mini-review gives an overview of the current additional treatment options for CRS in N-ERD. As such diets, aspirin therapy after desensitization, antileukotriene therapy and biologicals are discussed based on the current body of literature. Selecting the right treatment strategy depends on shared-decision making, local availability and cooperation between ENT-surgeons, allergists, and pulmonologists.

2021 ◽  
Vol 70 (2) ◽  
pp. 109-114
Author(s):  
Zuzana Balatková ◽  
Zdeněk Knížek ◽  
Jan Vodička ◽  
Jan Plzák

The aim of this paper is to present an up-to-date information about therapeutical options in chronic rhinosinusitis with nasal polyps. First choice therapy is a long term regular application of intranasal steroids in combination with salinic solution douches. If this treatment is not eff ective enough, then the pulses of systemic steroids are indicated. If the sufficient control of the disease is not achieved, then surgery is a therapeutic choice; it means functional endoscopic sinus surgery in the extent corresponding to the extension of the sinus disease. However, there remains a certain group of patients in whom the results with this treatment are not optimal. The type 2 immunopathological response affects relevantly the course of the disease. Nowadays, the research is done in this field. Specific agents, which are able to block circulating inflammatory mediators or bind receptors for these mediators are developed and studied. The results of the studies having been completed by now are promising. Keywords: biological therapy – chronic rhinosinusitis – nasal polyps – dupilumab – immunoglobulin E – interleukin


2019 ◽  
Vol 20 (21) ◽  
pp. 5461 ◽  
Author(s):  
Martina Mihalj ◽  
Maro Bujak ◽  
Josip Butković ◽  
Željko Zubčić ◽  
Maja Tolušić Levak ◽  
...  

Trefoil family factor (TFF) proteins contribute to antimicrobial defense and the maintenance of sinonasal epithelial barrier integrity. Dysregulation of TFF expression may be involved in the development of chronic inflammation and tissue remodeling characteristically found in chronic rhinosinusitis with nasal polyposis (CRSwNP). Expressions of TFF1 and TFF3 were determined in specimens of middle nasal turbinate (MNT-0), bulla ethmoidalis (BE), and nasal polyps (NP) from CRSwNP patients (n = 29) and inferior nasal turbinate from a group of control patients (underwent nasal septoplasty, n = 25). An additional MNT sample was collected 6 months after functional endoscopic sinus surgery (FESS, MNT-6). TFF1 mRNA levels were significantly reduced in all specimens by approximately three- to five-fold, while TFF3 was increased in MNT-0, as compared with controls. Six months after surgery their levels were reversed to control values. CRSwNP patients with S. epidermidis isolated from sinus swabs showed upregulation of TFF3 in MNT and NP as compared with patients with sterile swabs. Target gene regulation was not affected by the presence of type 2 inflammation in patients with confirmed allergy. Results of this study imply participation of TFFs genes in the development of CRSwNP.


2020 ◽  
Vol 6 (4) ◽  
pp. 00265-2020
Author(s):  
Yoshihiro Kanemitsu ◽  
Kensuke Fukumitsu ◽  
Ryota Kurokawa ◽  
Norihisa Takeda ◽  
Yoshiyuki Ozawa ◽  
...  

BackgroundSensitisation to moulds and Staphylococcus aureus enterotoxins (SEs) is associated with the pathophysiology of both asthma and chronic rhinosinusitis (CRS). The purpose of this study was to clarify the contribution of sensitisation to these allergens to Type 2 inflammation in the blood, nose and the lower airways, and clinical outcomes in CRS patients.MethodsWe prospectively enrolled 56 CRS patients who underwent endoscopic sinus surgery (ESS) (20 with comorbid asthma) and 28 healthy controls between October 2015 and December 2017. CRS patients were followed up for 12 months after surgery. Type 2 inflammation-related biomarkers were analysed using blood, resected tissue samples and sputum. 10 allergens including Alternaria, Aspergillus and SEs were measured. Type 2 inflammation-related biomarkers and clinical outcomes were compared in the stratification with the presence or absence of allergen sensitisation.ResultsSensitisation rate to moulds and SEs in asthmatic patients was increased when changing the cut-off value of specific IgE titre from 0.35 UA·mL−1 to 0.10 UA·mL−1 (1.7- and 4.5-fold, respectively). Moulds and SEs affected the prevalence of asthma and eosinophilic CRS by interacting with each other. All Type 2 inflammation-related biomarkers except for eosinophils in sinus tissue were significantly higher in patients with mould or SE (mould/SE) sensitisation (≥0.10 UA·mL−1) (n=19) than in those without (n=37) and healthy subjects (all p<0.05). Meanwhile, mould/SE sensitisation did not affect longitudinal changes in clinical outcomes after ESS. Changes in serum mould/SE-IgE levels after ESS remained unclear.ConclusionMould/SE sensitisation (≥0.10 UA·mL−1) may affect the development of Type 2 inflammation and clinical outcomes in CRS patients.


Medicina ◽  
2019 ◽  
Vol 55 (4) ◽  
pp. 95 ◽  
Author(s):  
Sinead Ahern ◽  
Anders Cervin

Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory condition of the paranasal sinuses and nasal passage. It is characterized as inflammation of the sinonasal passage, presenting with two or more symptoms (nasal blockage, secretions, facial pain and headaches) for more than 12 weeks consecutively. The disease is phenotypically differentiated based on the presence of nasal polyps; CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Traditionally, CRSwNP has been associated with a type 2 inflammatory profile, while CRSsNP has been associated with a type 1 inflammatory profile. Extensive work in characterizing the inflammatory profiles of CRS patients has challenged this dichotomy, with great variation both between and within populations described. Recent efforts of endotyping CRS based on underlying pathophysiology have further highlighted the heterogeneity of the disease, revealing mixed inflammatory profiles coordinated by a number of inflammatory cell types. This review will highlight the current understanding of inflammation in CRS, and discuss the importance and impact of refining this understanding in the development of appropriate treatment options for CRS sufferers.


Author(s):  
Andrew Thamboo ◽  
S. Kilty ◽  
I. Witterick ◽  
Y. Chan ◽  
C. J. Chin ◽  
...  

Abstract Background Recent evidence suggests that biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of chronic rhinosinusitis with nasal polyposis (CRSwNP). There remains a population in CRSwNP that despite medical therapy and endoscopic sinus surgery have persistent signs and symptoms of disease. Therefore, biologics, monoclonal antibody agents, could be beneficial therapeutic treatments for these patients. There have been eight randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL-5R, IL-33, and immunoglobulin (Ig)E. However, there are no formal recommendations for the optimal use of biologics in managing Chronic Rhinosinusitis (CRS) within the Canadian health care environment. Methods A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. 17 fellowship trained rhinologists across Canada evaluated the 28 original statements on a scale of 1–10 and provided comments. A rating within 1–3 indicated disagreement, 8–10 demonstrated agreement and 4–7 represented being neutral towards a statement. All ratings were quantitively reviewed by mean, median, mode, range and standard deviation. Consensus was defined by removing the highest and lowest of the scores and using the “3 point relaxed system”. Results After three rounds, a total of 11 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with CRS. Conclusion This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of patients with CRS, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years. Graphical abstract


2020 ◽  
pp. 1-4
Author(s):  
Charles S. Ebert Jr. ◽  
Adam J. Kimple ◽  
Adam M. Zanation ◽  
Brian D. Thorp ◽  
Charles S. Ebert Jr. ◽  
...  

Background: Implantation of sinus stents and spacers can be used as adjuvant management to maintain patency of sinuses after endoscopic sinus surgery for chronic rhinosinusitis. These implants are typically removed several weeks after surgery. We present two cases of different patients who were initially treated by different physicians and were found to have retained sinus spacers in their paranasal sinuses 6-10 years after implantation. Case Presentation: Case 1: A 40-year-old male with chronic rhinosinusitis and history of balloon sinuplasty six years prior presented with worsening symptoms of chronic rhinosinusitis refractory to medical management. He underwent revision functional endoscopic sinus surgery and was found to have retained sinus implants in the left and right frontal sinus recesses. Case 2: A 48-year-old female with long-standing chronic rhinosinusitis refractory to medical management presented after two prior sinus surgeries most recently 10 years ago. She underwent revision functional endoscopic surgery and was found to have a retained sinus implant from prior surgery in the right frontal recess outflow tract embedded within scar tissue and reactive hyperostosis. Foreign bodies from both patients were removed without complication and patients were healing appropriately in the post-operative period. Conclusions: While sinus stents and spacers can help with post-operative scarring, leaving then unmonitored and in place will eventually result in them becoming a nidus for scarring and infection. It is critical that patients are aware of any foreign bodies we place, if they need scheduled removal or routine observation, and what symptoms may indicate that they are causing a problem.


2018 ◽  
Vol 33 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Nuray Bayar Muluk ◽  
Cemal Cingi ◽  
Glenis K. Scadding ◽  
Guy Scadding

Objectives We reviewed the phenotyping and endotyping of chronic rhinosinusitis (CRS) and treatment options. Methods We searched PubMed, Google, Google Scholar, and the Proquest Central Database of the Kırıkkale University Library. Results Phenotypes are observable properties of an organism produced by the environment acting upon the genotype, that is, patients with a particular disorder are subgrouped according to common characteristics. Currently, CRS is usually phenotyped as being with (CRSwNP) or without (CRSsNP) nasal polyps. However, this is not immutable as some individuals progress from nonpolyp to polypoid CRS over time. Phenotypes of CRS are also based on inflammatory patterns, generally CRSwNP is eosinophilic, CRSsNP neutrophilic; but there is a spectrum, rather than a clear-cut division into 2 types. An endotype is a subtype of a condition defined by a distinct functional or pathobiological mechanism. Endotypes of CRS can be (1) nontype Th2, (2) moderate type Th2, and (3) severe type Th2 immune reactions, based on cytokines and mediators such as IL4, 5, 13. CRS endotyping can also include a (1) type 2 cytokine-based approach, (2) eosinophil-mediated approach, (3) immunoglobulin E-based approach, and (4) cysteinyl leukotriene-based approach. Subdivisions of CRSwNP can be made into nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergic fungal sinusitis, and eosinophil pauci-granulomatous arteritis by testing. General treatment for all CRS is nasal douching. The place of surgery needs careful reconsideration. Endotype-directed therapies include glucocorticosteroids, antibiotics, aspirin, antifungals, anticytokines, and immunoglobulin replacement. The recognition of united airways and the co-occurrence of CRSwNPs and severe asthma should lead to common endotyping of both upper and lower airways in order to better direct therapy. Conclusion Endotyping can allow for the identification of groups of patients with CRS with a high likelihood of successful treatment, such as patients with a moderate type 2 immune reaction or those with acquired immune deficiency.


PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Jane A. Pinaire ◽  
Anne Reifel-Miller

The increasing prevalence of obesity is a fundamental contributor to the growing prevalence of the metabolic syndrome. Rexinoids, a class of compounds that selectively bind and activate RXR, are being studied as a potential option for the treatment of metabolic syndrome. These compounds have glucose-lowering, insulin-sensitizing, and antiobesity effects in animal models of insulin resistance and type 2 diabetes. However, undesirable side effects such as hypertriglyceridemia and suppression of the thyroid hormone axis also occur. This review examines and compares the effects of four RXR-selective ligands: LGD1069, LG100268, AGN194204, and LG101506, a selective RXR modulator. Similar to selective modulators of other nuclear receptors such as the estrogen receptor (SERMs), LG101506 binding to RXR selectively maintains the desirable characteristic effects of rexinoids while minimizing the undesirable effects. These recent findings suggest that, with continued research efforts, RXR-specific ligands with improved pharmacological profiles may eventually be available as additional treatment options for the current epidemic of obesity, insulin resistance, type 2 diabetes, and all of the associated metabolic sequelae.


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