Olfaction in nasal polyp patients after Reboot surgery: an endotype-based prospective study

Gomes, Sara Costa; Delemarre, Tim; Holtappels, Gabriële; Zele, Thibaut Van; Derycke, Lara; Bonne, Ellen; Eeckels, Anne-Sophie; Zhang, Nan; Voegels, Richard Louis; Bachert, Claus

doi:10.1007/s00405-022-07813-w

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…Similarly, increased levels of type-2 cytokines, 29 and in particular IL-5 in the olfactory tissues have been found to be associated with decreased olfaction and taste in CRSwNP. 30 Although complete removal of diseased mucosa through "reboot" surgery has been shown to provide durable olfaction at 12 months, this aggressive surgery must be balanced by the potential risk of scarring and subsequent loss of olfactory epithelia. 30 There have been two reported studies that evaluated outcomes for FESS against published biologic trials.…”

Section: Discussionmentioning

confidence: 99%

“…30 Although complete removal of diseased mucosa through "reboot" surgery has been shown to provide durable olfaction at 12 months, this aggressive surgery must be balanced by the potential risk of scarring and subsequent loss of olfactory epithelia. 30 There have been two reported studies that evaluated outcomes for FESS against published biologic trials. Dharmarajan et al compared the outcomes of FESS to dupilumab in a retrospective, matched group of 54 patients in each group at 6-and 12 months.…”

Section: Discussionmentioning

confidence: 99%

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A pilot prospective longitudinal study comparing dupilumab to surgery in CRSwNP

Chang

Narendran

Samargandy

et al. 2023

Preprint

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Background: To date, there have not been any direct comparative studies assessing clinical outcomes in CRSwNP between biologic and surgical therapies. Objective: To directly compare the effect of dupilumab to FESS using subjective and objective outcomes of CRSwNP patients in a prospective longitudinal study. Methods: We prospectively enrolled 20 CRSwNP patients and counseled them on both biologic and surgical options. Patients were able to decide on either therapy, and data collected at baseline and 3-, 6-, 9-, and 12-months with subjective outcomes including the nasal congestion score (NCS) and SNOT-22 questionnaires, and objectively by degree of smell (UPSIT-40) and nasal polyp score (NPS). Results: All subjects met criteria for either biologic therapy or surgery, with NPS >5, Lund-Mackay score (LMK-CT)>16, SNOT-22>54, and were graded as anosmic/hyposmic. There were no significant differences in age, sex, comorbid asthma/Aspirin Exacerbated Respiratory Disease, or prior FESS between groups. Both dupilumab and FESS significantly improved outcomes by one year in patients with severe CRSwNP when compared to baseline. At one-year, patients on dupilumab had greater improvement in NCS, UPSIT and asthma control relative to one year post FESS. In a subgroup of patients with a history of prior sinus surgery and asthma, dupilumab had lower polyp recurrence rate compared to one year post FESS. Conclusions: Both dupilumab and FESS can significantly improve outcomes by one year in CRSwNP patients. However, in those with a history of asthma and prior surgery, dupilumab is more effective in reducing polyp recurrence and improving sinonasal outcomes than FESS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A pilot prospective longitudinal study comparing dupilumab to surgery in CRSwNP

Chang

Narendran

Samargandy

et al. 2023

Preprint

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“…In the superior turbinate tissue of patients with CRSwNP, elevated gene expression of the EOS marker Charcot-Leyden crystal protein is positively correlated with interleukin-5 (IL-5) but negatively correlated with olfactory function ( Lavin et al, 2017 ). OD in patients with CRSwNP is particularly associated with type 2 cytokine levels in OC mucus and OM ( Soler et al, 2020 ; Gomes et al, 2023 ). Levels of Galectin-10, a major constituent of human EOSs, in both OC mucus and OM, are positively correlated with tissue eosinophilic counts but negatively correlated with olfactory function ( Liu et al, 2023 ).…”

Section: Eoss and Od Secondary To Crsmentioning

confidence: 99%

“…Eosinophilic infiltration rather than inflammation in the postoperative ethmoid sinus mucosa may predict negative olfactory improvement after ESS ( Zhang et al, 2019 ). A recent study shows that reboot surgery can improve olfactory function for at least 6 months in patients with ECRSwNP by completing the removal of inflamed mucosa in the ethmoid sinus ( Gomes et al, 2023 ).…”

Section: Eoss and Od Secondary To Crsmentioning

confidence: 99%

Apoptosis and turnover disruption of olfactory sensory neurons in eosinophilic chronic rhinosinusitis

Chen,

Li,

2024

Front. Cell. Neurosci.

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Olfactory dysfunction (OD) is one of the important and difficult-to-treat symptoms of eosinophilic chronic rhinosinusitis (CRS), which is typically associated with type 2 inflammation where eosinophils (EOSs) function as both effectors and initiators. Eosinophilic infiltration in the olfactory mucosa (OM) is associated with severe OD, mucosal erosion, and more loss of olfactory sensory neurons (OSNs). Active EOS-derived cytokines, chemokines, and eosinophil granule proteins may lead to aggravation of inflammation, tissue damage, and impairment of the survival and regeneration of OSNs. Recent studies show that EOSs can lead to apoptosis of OSNs through axonal and neural body damage, turnover disorder of OSNs through the loss of immature OSNs and globose basal cells (GBCs), changed proliferative activity of horizontal basal cells (HBCs), and dysfunction of OSNs through the breakdown of neuroepithelial integrity and alteration of ion concentration in OSNs and mucin. In this review, we outline the current progress on the role of EOSs on OD in patients with eosinophilic CRS and the mechanism of EOS-associated injury of the OM and OSNs in experimental animal models with sinonasal inflammation. Further investigations on the molecular mechanisms of tissue eosinophilia-induced injury of OSNs are warranted to obtain new therapeutic targets and achieve better restoration of olfactory function.

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“…This condition is defined by the manifestation of symptoms such as hyposmia or anosmia, nasal congestion, nasal discharge, and facial pain or pressure that persist for a minimum duration of 12 consecutive weeks without relief. Furthermore, this disorder is distinguished by the manifestation of symptoms such as anosmia or hyposmia [ 4 ]. Individuals diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) may present with elevated concentrations of eosinophil cationic protein (ECP), which serves as an indicator of active eosinophils that have undergone degranulation.…”

Section: Introductionmentioning

confidence: 99%

Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab

Ledda,

Costanzo,

Sambugaro

et al. 2023

Life

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Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a “type 2” (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. Methods: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. Results: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. Conclusions: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%.

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Olfaction in nasal polyp patients after Reboot surgery: an endotype-based prospective study

Cited by 9 publications

References 38 publications

A pilot prospective longitudinal study comparing dupilumab to surgery in CRSwNP

A pilot prospective longitudinal study comparing dupilumab to surgery in CRSwNP

Apoptosis and turnover disruption of olfactory sensory neurons in eosinophilic chronic rhinosinusitis

Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab

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