Elevated Urine Leukotriene<scp>E4</scp>Is Associated With Worse Objective Markers in Nasal Polyposis Patients

Choby, Garret; O’Brien, Erin; Smith, Alyssa J.; Barnes, Jason H.; Hagan, John B.; Stokken, Janalee K.; Strumpf, Andrew; Mattos, José L.; Payne, Spencer C.; Divekar, Rohit

doi:10.1002/lary.29137

Cited by 10 publications

(23 citation statements)

References 40 publications

(63 reference statements)

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“…Urinary LTE 4 is a marker of more severe CRSwNP, 29 levels of which are reduced after endoscopic sinus surgery. 30 As found in other studies, baseline urinary LTE 4 levels were significantly greater in patients with NSAID‐ERD than in patients without NSAID‐ERD, with greater reductions from baseline observed with dupilumab treatment in patients with NSAID‐ERD versus those without NSAID‐ERD.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps and a clinical diagnosis of NSAID‐ERD: Results from two randomized placebo‐controlled phase 3 trials

Mullol

Laidlaw

Bachert

et al. 2021

Allergy

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Background About one‐tenth of patients with difficult‐to‐treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease (NSAID‐ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)‐4/IL‐13 receptor component, is an approved add‐on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID‐ERD. Methods Data were pooled from the phase 3 SINUS‐24 and SINUS‐52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment–subgroup interactions were assessed for patients with and without NSAID‐ERD. Results Of 724 patients, 204 (28.2%) had a diagnosis of NSAID‐ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund–Mackay computed tomography, 22‐item Sinonasal Outcome Test (SNOT‐22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six‐item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p < .0001) in patients with NSAID‐ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID‐ERD for NC (p = .0044), SNOT‐22 (p = .0313), TSS (p = .0425), and PNIF (p = .0123). Conclusions In patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient‐reported symptoms to a greater extent in the presence of comorbid NSAID‐ERD than without. Dupilumab was well tolerated in patients with/without NSAID‐ERD.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps and a clinical diagnosis of NSAID‐ERD: Results from two randomized placebo‐controlled phase 3 trials

Mullol

Laidlaw

Bachert

et al. 2021

Allergy

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“…However, uLTE4 levels were not associated with subjective markers of disease severity, including Sinonasal Outcome Test - 22 (SNOT-22) scores and asthma control test (ACT) scores. 18…”

Section: Discussionmentioning

confidence: 99%

“…Patients with elevated LT excretion may be considered to have a biomarker rationale for using montelukast or possibly zileuton. 18 Indeed, several studies have investigated this question. Cai et al 65 examined pulmonary response to montelukast in asthmatic patients.…”

Section: Implications For Clinical Practicementioning

confidence: 99%

Urine Leukotriene E4: Implications as a Biomarker in Chronic Rhinosinusitis

Choby¹,

Low²,

Levy³

et al. 2021

Otolaryngol.--head neck surg.

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Objective To provide a comprehensive state-of-the-art review of the emerging role of urine leukotriene E4 (uLTE4) as a biomarker in the diagnosis of chronic rhinosinusitis (CRS), aspirin-exacerbated respiratory disease (AERD), and asthma. Data Sources Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Review Methods A state-of-the-art review was performed investigating the role of uLTE4 as a diagnostic biomarker, predictor of disease severity, and potential marker of selected therapeutic efficacy. Conclusions uLTE4 has been shown to be a reliable and clinically relevant biomarker for CRS, AERD, and asthma. uLTE4 is helpful in ongoing efforts to better endotype patients with CRS and to predict disease severity. Implications for Practice Aside from being a diagnostic biomarker, uLTE4 is also able to differentiate aspirin-tolerant patients from patients with AERD and has been associated with objective disease severity in patients with CRS with nasal polyposis. uLTE4 levels have also been shown to predict response to medical therapy, particularly leukotriene-modifying agents.

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“…14 Also, the concentration of leukotriene E4 in the urine is elevated in AERD patients and correlates well with objective clinical parameters that indicate the degree of clinical manifestation of disease, as is the Lund-Mackay CT score. 15 On the other hand, there is no correlation between urinary leukotriene E4 and subjective parameters, such as the severity of NP symptoms. 15 The role of neuropeptides in the pathogenesis of NP is poorly understood and, by literature review, we did not find studies related to the measurement of neuropeptide levels in nasal secretions in patients with AERD.…”

Section: Introductionmentioning

confidence: 99%

“…15 On the other hand, there is no correlation between urinary leukotriene E4 and subjective parameters, such as the severity of NP symptoms. 15 The role of neuropeptides in the pathogenesis of NP is poorly understood and, by literature review, we did not find studies related to the measurement of neuropeptide levels in nasal secretions in patients with AERD. Unlike cytokines and chemokines in nasal secretion samples, which have been found to be able to correlate with clinical disease parameters, 1,13 it is unclear whether this also applies to neuropeptides.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of substance P and bradykinin levels in nasal secretions of patients with nasal polyposis with and without sensitivity to non‐steroidal anti‐inflammatory drugs

Perić

Matkovic

Barać

et al. 2022

Laryngoscope Investig Oto

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Objective: The role of neurogenic inflammation in pathogenesis of chronic rhinitis is well known. However, very little is known about its importance in pathogenesis of nasal polyposis (NP), especially in form of NP which appears as a part of aspirinexacerbated respiratory disease (AERD). The aim of this study was to examine the concentrations of neuropeptides substance P (SP) and bradykinin (BK) in nasal secretions of patients with NP.Methods: Fourteen patients with NP as a part of AERD with mild persistent asthma, 14 patients with NP without aspirin sensitivity, and 14 control subjects without nasal inflammation (C) entered this cross-sectional study. Clinical parameters (symptoms, endoscopic, and radiological findings) were assessed. The concentrations of SP and BK were measured in the nasal secretion samples using commercial human enzyme immunoassay kits. Results:The concentration of SP in nasal secretions was significantly higher in NP patients without aspirin sensitivity and AERD patients compared to controls (p = .022; p < .0001, respectively), but higher in AERD than in non-AERD patients (p = .018). The level of BK in nasal fluid was higher in non-AERD and AERD NP patients than in controls (p < .0001; p < .0001, respectively), but also higher in AERD than in non-AERD patients (p < .0001). We found high positive correlations between BK in nasal fluid and Lund-Mackay computed tomography (CT) score in both non-AERD and AERD groups of NP patients. Conclusion:Our results suggest more intense release of SP and BK from the nasal mucosa in patients with AERD than in patients with NP who do not have aspirin sensitivity. The strong correlation between concentration of BK in nasal secretions and CT score suggests that BK in nasal fluid could be used as a marker for disease severity as measured by the Lund-Mackay score.

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Elevated Urine LeukotrieneE4Is Associated With Worse Objective Markers in Nasal Polyposis Patients

Cited by 10 publications

References 40 publications

Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps and a clinical diagnosis of NSAID‐ERD: Results from two randomized placebo‐controlled phase 3 trials

Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps and a clinical diagnosis of NSAID‐ERD: Results from two randomized placebo‐controlled phase 3 trials

Urine Leukotriene E4: Implications as a Biomarker in Chronic Rhinosinusitis

Evaluation of substance P and bradykinin levels in nasal secretions of patients with nasal polyposis with and without sensitivity to non‐steroidal anti‐inflammatory drugs

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