Olfaction: Sensitive indicator of inflammatory burden in chronic rhinosinusitis

Xing, Yan; Whitcroft, Katherine L.; Hummel, Thomas

doi:10.1002/lio2.485

Cited by 16 publications

(18 citation statements)

References 135 publications

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“…Smell perception after six months of therapy as measured by UPSIT score (+11.16±9.54) improved significantly comparable to results obtained in previous studies with dupilumab in CRSwNP and in N-ERD patients (13,25,26). Although the underlying mechanism is not yet fully understood, it is thought that both the impaired nasal airflow and the direct effect of inflammatory processes on the mucosa and olfactory neurons play a role in the olfactory loss in CRS (27). In fact, cytokines associated with type 2 inflammation, which are known to be elevated in N-ERD patients (9,28), as well as TNF-α have been shown to have a direct negative impact on olfactory neurogenesis and regeneration (29, 30).…”

Section: Discussionsupporting

confidence: 83%

Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease

Schneider

Poglitsch

Morgenstern³

et al. 2022

Eur Respir J

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Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps, asthma, and intolerance to NSAIDs. Dupilumab treatment, targeting the IL-4 receptor alpha, significantly reduces polyp burden as well as asthma symptoms. Here we aimed to investigate the effect of dupilumab on aspirin intolerance, burden of disease, as well as on nasal cytokine profiles in patients suffering from N-ERD. In this open-label trial, adult patients with confirmed N-ERD were treated with dupilumab for six months. Clinical parameters (e.g., total polyp scores, quality of life questionnaires, smell test, spirometry), oral aspirin provocation testing, blood, nasal and urine sampling were monitored up to six months after starting dupilumab therapy at regular intervals. Of the thirty-one patients included in the study, thirty completed both aspirin provocation testing. After six months of treatment with dupilumab, 23.3% (n=7/30) of patients developed complete aspirin tolerance and an additional 33.3% of patients (n=10/30) tolerated higher doses. Polyp burden was significantly reduced (total polyp score: −2.68±1.84, p<0.001) and pulmonary symptoms (asthma control test: +2.34±3.67, p<0.001), as well as olfactory performance improved (UPSIT: +11.16±9.54, p<0.001) in all patients after therapy. Patients with increased aspirin tolerance showed a significant decrease in urine leukotriene E4 levels and their improvement in clinical parameters was associated with the reduction of eotaxin-1, CCL17, IL-5, IL-17A and IL-6. 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.

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Section: Discussionsupporting

confidence: 83%

Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease

Schneider

Poglitsch

Morgenstern³

et al. 2022

Eur Respir J

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“…In fact, CRS is the most frequent etiology of olfactory dysfunction ( Kohli et al, 2017 ). In particular, CRS with polyps, which is usually characterized by mucosal type 2 inflammation, is associated with a high prevalence of olfactory dysfunction ( Yan et al, 2020 ). The accompanying eosinophilia is associated with the release of several neurotoxins, such as eosinophilic cationic protein (ECP), major basic protein, and β-glucuronidase.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Kikuta

Kuboki

Yamasoba

2021

Front. Neural Circuits

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Insulin is present in nasal mucus and plays an important role in the survival and activity of individual olfactory sensory neurons (OSNs) via insulin receptor-mediated signaling. However, it is unclear whether insulin acts prophylactically against olfactotoxic drug-induced olfactory epithelium (OE) injury, and whether the degree of damage is affected by the concentration of insulin in the nasal mucus. The apoptosis-inducing drug methimazole was administered to the nasal mucus of diabetic and normal mice along with different concentrations of insulin. Immunohistochemical analysis was used to assess the relationship between damage to the OE and the mucus insulin concentration and the protective effect of insulin administration against eosinophilic cationic protein (ECP)-induced OE injury. Diabetic mice had lower concentrations of insulin in their nasal mucus than normal mice (diabetic vs. normal mice, p < 0.001). Methimazole administration reduced the number of OSNs in normal mice and had a more marked effect in diabetic mice. However, unilateral insulin administration prevented the methimazole-induced reduction in the number of OSNs on the ipsilateral side but not on the contralateral side (OSNs; Insulin vs. contralateral side, p < 0.001). Furthermore, intranasal ECP administration damaged the OE by inducing apoptosis (OSNs; ECP vs. contralateral side, p < 0.001), but this damage was largely prevented by insulin administration (OSNs; Insulin + ECP vs. contralateral side, p = 0.36), which maintained the number of mature OSNs. The severity of methimazole-induced damage to the OE is related to the insulin concentration in the nasal mucus (Correlation between the insulin concentration in nasal mucus and the numbers of OSNs, R2 = 0.91, p < 0.001), which may imply that nasal insulin protects OSNs and that insulin administration might lead to the development of new therapeutic agents for ECP-induced OE injury.

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“…Inflammatory cytokines can be toxic to the dendritic processes of olfactory receptor neurons and result in sensorineural impairment 18 . In cases when the OC was unobstructed with no changes in nasal airflow, and when removal of polyps did not improve olfaction, sensorineural changes seemed to contribute more to olfactory loss than conductive mechanisms 19 …”

Section: Discussionmentioning

confidence: 99%

“…18 In cases when the OC was unobstructed with no changes in nasal airflow, and when removal of polyps did not improve olfaction, sensorineural changes seemed to contribute more to olfactory loss than conductive mechanisms. 19…”

Section: Mechanisms Of Olfactory Impairmentmentioning

confidence: 99%

Association of computed tomography scores to psychophysical measures of olfaction: A systematic review and meta‐analysis

Chen

Chidarala

Young

et al. 2022

Int Forum Allergy Rhinol

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Background: While various sinus computed tomography (CT) scoring systems have been proposed and used in the literature, no single system has been identified as superior. The strength of associations between CT scoring systems and measures of olfaction also remains unclear.Methods: A systematic review of PubMed, CINAHL, Scopus, and the Cochrane Library was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that reported both CT scores and measures of olfaction in a cross-sectional manner were included. Results: A total of 37 studies were eligible for meta-analysis. Of 8035 patients with chronic rhinosinusitis, 55.6% were male patients and 53.2% had chronic rhinosinusitis with nasal polyps. Analysis by meta-regression was performed of Lund-Mackay (LM) versus Smell Identification Test-40 (SIT-40; 12 studies), Brief Smell Identification Test (BSIT; 10 studies), Sniffin' Sticks (SS; 10 studies), and Toyota & Takagi (T&T) olfactometry (four studies). A significant moderate association was found between LM and SIT-40 (R 2 = 0.612, p < 0.001) and LM and SS (R 2 = 0.612, p < 0.001). An association between LM and BSIT approached significance (R 2 = 0.461, p = 0.054). No significant associations were noted between LM and T&T olfactometry and between LM and SS when stratified by nasal polyp status. Conclusion: There is a significant moderate association of current CT scoring systems to SIT-40 and SS. Further research should focus on associations of objective measures of olfaction to CT scores of the nasal cavity, sinuses, and olfactory cleft, as well as other disease markers.

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Olfaction: Sensitive indicator of inflammatory burden in chronic rhinosinusitis

Cited by 16 publications

References 135 publications

Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease

Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease

Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Association of computed tomography scores to psychophysical measures of olfaction: A systematic review and meta‐analysis

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