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Distinct eicosanoid patterns in severe recalcitrant nasal polyposis
Sophiahemmet University.ORCID iD: 0000-0003-2314-3322
Sophiahemmet University.ORCID iD: 0000-0002-1075-8515
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2023 (English)In: International Forum of Allergy & Rhinology, ISSN 2042-6984, Vol. 13, no 11, p. 2043-2054Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Although altered eicosanoid levels are related to disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP), identifying patients prone to recurrent NPs is still difficult. We investigated levels of nasally secreted eicosanoids before and after NP surgery in patients with or without NP recurrence and explored potential endotypes based on pre-surgical eicosanoid levels.

METHODS: Levels of leukotriene (LT) E4 , LTB4 , prostaglandin (PG) D2 , PGE2 and 15(S) hydroxyeicosatetraenoic acid (15(S)-HETE) were measured in nasal secretions with specific immunoassays at pre-surgery (n = 38) and six- and 12-months post-surgery (n = 35) where NP recurrence was identified endoscopically. Pre- and post-surgical levels were compared between patients with and without NP recurrence. Eicosanoid patterns among patients were explored with cluster analysis and evaluated with clinical parameters.

RESULTS: Patients with recurrent NPs had pronounced pre-surgical levels of nasal 15(S)-HETE, PGD2 and LTE4 . From pre-surgery to 12-months after, NP recurrence was associated with significant decrease of 15(S)-HETE and PGD2 relative to non-recurrence whereas levels of LTE4 decreased at six-months but increased again at 12-months. Clustering revealed three potential endotypes. Cluster 1 and 3 featured high and low eicosanoid levels, respectively. Cluster 2 had higher levels of LTE4 and PGD2 , lower levels of PGE2 and LTB4 , and more cases of recurrent NPs and previous NP surgeries.

CONCLUSION: Elevated nasal LTE4 , 12-month post-surgery, in NP recurrent subjects suggests that postoperative LTE4 measurements may indicate rapid NP regrowth. A distinct nasal eicosanoid profile may be used for the identification of the most severe recalcitrant patients in need of targeted immunomodulatory therapies. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
2023. Vol. 13, no 11, p. 2043-2054
Keywords [en]
Biomarker, Chronic Rhinosinusitis, Disease Severity, Eosinophilic rhinitis and nasal polyposis, Post-Operative
National Category
Otorhinolaryngology
Identifiers
URN: urn:nbn:se:shh:diva-4917DOI: 10.1002/alr.23181PubMedID: 37179460OAI: oai:DiVA.org:shh-4917DiVA, id: diva2:1759269
Available from: 2023-05-25 Created: 2023-05-25 Last updated: 2024-04-22Bibliographically approved
In thesis
1. Exploring eicosanoids as biomarkers in severe chronic rhinosinusitis with nasal polyps
Open this publication in new window or tab >>Exploring eicosanoids as biomarkers in severe chronic rhinosinusitis with nasal polyps
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chronic rhinosinusitis (CRS) is one of the most common inflammatory chronic conditions, leading to a persistent nasal congestion, nasal discharge, and a loss of smell. Despite sinus surgery and frequent use of oral corticosteroids, a large proportion of individuals with CRS are difficult to treat and have recurrent inflammation. They are usually referred to as individuals with recalcitrant disease and having recurrent nasal polyps (NPs; CRSwNP). The disease poses a significant impact on the patients' health-related quality of life (HrQoL), mainly because of a complete loss of smell. Pharmacological treatment with biological therapies has recently been developed, targeting mediators of the type 2 inflammatory response. However, not everyone benefits from the biological therapy, and it has proven difficult to identify and characterise patients that are responsive to these new medications. Eicosanoids, being arachidonic acid derived bioactive lipid mediators, has been shown to be implicated in CRSwNP. Although there is a clear link between an imbalanced biosynthesis of pro- and anti-inflammatory eicosanoids and type 2 inflammation, to date research has not focused on them as biomarkers in CRSwNP.

The overall aim of this thesis was to explore the potential role of eicosanoids as biomarkers and characterise changes over time in HrQoL as well as the degree of smell loss in patients with severe recalcitrant CRSwNP. The project involved immunoassay analysis of levels of various inflammatory mediators, including a selection of eicosanoids, in nasal tissue, nasal secretions and urine from patients with CRSwNP as well as gene expression analyses regarding biosynthetic enzymes and receptors for eicosanoids in nasal tissues. HrQoL was assessed with SNOT-22 and RAND-36, along with point-of-care tests as eosinophil blood count, fractional exhaled nitric oxide (FeNO) and smell tests with Burghart Sniffin’ Sticks.

Levels of eicosanoids in nasal secretions were found to associate with the disease severity, defined as the extent of NP growth (paper I). One of the eicosanoids, leukotriene E4 (LTE4), were correlated to the degree of smell loss (paper I). An increase in LTE4 between six and 12 months after surgery was demonstrated in patients with recurrent NPs (paper II). Recurrent NPs were identified endoscopically 12 months after surgery and a distinct eicosanoid profile involving LTE4, prostaglandin D2 and 15(S) hydroxyeicosatetraenoic acid was found to be more common in those with recurrence (paper II). A similar eicosanoid profile, based on measurements from nasal tissue samples instead, was also associated with NP recurrence (paper III).

Levels of eicosanoids in nasal tissue and nasal secretions were correlated suggesting that analysis of biomarkers in nasal secretions reflects release from the nasal tissue (paper III). Patients with recurrent NPs had elevated blood eosinophil counts before their surgery, and their sense of smell was significantly impaired both before and after (paper IV). This finding suggests that loss of smell may be the first symptom during recurrence. Although measures of HrQoL could not distinguish patients with recurrent NPs, there was a strong correlation to the degree of smell loss suggesting that loss of smell has a significant impact on the HrQoL (paper IV).

In summary, the results from this thesis contribute to an extended knowledge regarding characteristics relevant for identifying severe recalcitrant CRSwNP. Characteristics of interest included a distinct eicosanoid profile, severe loss of smell and eosinophil involvement, all of which may be possible prognostic markers for severe recalcitrant CRSwNP with rapid NP growth. It may be concluded that such biomarkers can guide the choice of treatment for these severely ill patients – repeated surgery or pharmacological treatment with the newly developed biological therapies.

Place, publisher, year, edition, pages
Stockholm: Sophiahemmet, 2024. p. 91
Series
Sophiahemmet University Dissertations, ISSN 2004-7479, E-ISSN 004-7460 ; 5
National Category
Health Sciences
Identifiers
urn:nbn:se:shh:diva-5274 (URN)978-91-988733-8-2 (ISBN)978-91-988733-9-9 (ISBN)
Public defence
2024-05-15, Erforssalen, Sophiahemmet Högskola, Valhallavägen 91, hus R, Stockholm, 09:30 (English)
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Available from: 2024-04-22 Created: 2024-04-22 Last updated: 2024-05-15Bibliographically approved

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Nordström, AxelSvedberg, MarieKumlin, Maria

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