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Prognostic factors for polyp recurrence in chronic rhinosinusitis with nasal polyps - 04/08/22

Doi : 10.1016/j.jaci.2022.02.029 
Junqin Bai, PhD a, Julia H. Huang, DDS, MS a, Caroline P.E. Price, BS a, Jacob M. Schauer, PhD c, Lydia A. Suh, BS b, Regan Harmon, BS a, David B. Conley, MD a, Kevin C. Welch, MD a, Robert C. Kern, MD a, Stephanie Shintani-Smith, MD, MS a, Anju T. Peters, MD, MS a, b, Whitney W. Stevens, MD, PhD a, b, Atsushi Kato, PhD a, b, Robert P. Schleimer, PhD a, b, Bruce K. Tan, MD, MS a, b,
a Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill 
b Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill 
c Department of Preventive Medicine-Biostatistics, Northwestern University Feinberg School of Medicine, Chicago, Ill 

Corresponding author: Bruce K. Tan, MD, MS, Department of Otolaryngology—Head and Neck Surgery, Northwestern University Feinberg School of Medicine, 676 N St Clair Street, Suite 1325, Chicago, IL 60611.Department of Otolaryngology—Head and Neck SurgeryNorthwestern University Feinberg School of Medicine676 N St Clair StreetSuite 1325ChicagoIL60611

Abstract

Background

Chronic rhinosinusitis with nasal polyps is frequently managed with endoscopic sinus surgery (ESS). Prior studies describe individual clinical variables and eosinophil density measures as prognostic for polyp recurrence (PR). However, the relative prognostic significance of these have not been extensively investigated.

Objectives

We sought to evaluate the impact of PR on measures of disease severity post-ESS and quantify the prognostic value of various clinical variables and biomarkers.

Methods

Ninety-four patients with chronic rhinosinusitis with nasal polyps and prospectively biobanked polyp homogenates at the time of ESS were recruited 2 to 5 years post-ESS. Patients were evaluated with patient-reported outcome measures and endoscopic and radiographic scoring pre- and post-ESS. Biomarkers in polyp homogenates were measured with ELISA and Luminex. Relaxed least absolute shrinkage and selection operator regression optimized predictive clinical, biomarker, and combined models. Model performance was assessed using receiver-operating characteristic curve and random forest analysis.

Results

PR was found in 39.4% of patients, despite significant improvements in modified Lund-Mackay (MLM) radiographic and 22-item Sinonasal Outcomes Test scores (both P < .0001). PR was significantly associated with worse post-ESS MLM, modified Lund-Kennedy, and 22-item Sinonasal Outcomes Test scores. Relaxed least absolute shrinkage and selection operator identified 2 clinical predictors (area under the curve = 0.79) and 3 biomarkers (area under the curve = 0.78) that were prognostic for PR. When combined, the model incorporating these pre-ESS factors: MLM, asthma, eosinophil cationic protein, anti–double-stranded DNA IgG, and IL-5 improved PR predictive accuracy to area under the curve of 0.89. Random forest analysis identified and validated each of the 5 variables as the strongest predictors of PR.

Conclusions

PR had strong associations with patient-reported outcome measures, endoscopic and radiographic severity. A combined model comprised of eosinophil cationic protein, IL-5, pre-ESS MLM, asthma, and anti–double-stranded DNA IgG could accurately predict PR.

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Key words : Chronic rhinosinusitis with nasal polyps, polyp recurrence, clinical variables, biomarker, PROMs, relaxed LASSO, random forest

Abbreviations used : AIC, anti-dsDNA, AUC, CRS-PRO, CRSwNP, ECP, ESS, LASSO, LR, MIP, MLK, MLM, NP, PR, PROMs, RF, ROC, SNOT-22, TPS


Plan


 This work was supported by the National Institutes of Health (grants R01 AI134952 and R01 DC016645) and the Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2) (grant P01, AI145818).
 Disclosure of potential conflict of interest: D. B. Conley has received consulting fees for Intersect ENT and XORAN. K. C. Welch has received consultant fees from Baxter, OptiNose, and Acclarent. R.C. Kern is a consultant for Lyra Therapeutics, GlaxoSmithKline, Sanofi/Regeneron, and Novartis/Genentech. A. T. Peters has received personal fees from AstraZeneca and GlaxoSmithKline and personal fees and grants from Sanofi Regeneron, Merck, and OptiNose. A. Kato has received a consultant fee from Astellas Pharma and a gift for his research from Lyra Therapeutics. W.W. Stevens has served on advisory boards for GlaxoSmithKline, Genentech, and Bristol Meyers Squibb. R. P. Schleimer has received personal fees from Intersect ENT, Merck, GlaxoSmithKline, Sanofi, AstraZeneca/Medimmune, Genentech, Actobio Therapeutics, Lyra Therapeutics, Astellas Pharma Inc, and Otsuka Inc; and has Siglec-8– and Siglec-8 ligand–related patents licensed by Johns Hopkins to Allakos Inc. B. K. Tan has received personal fees from Sanofi Regeneron/Genzyme. The rest of the authors declare that they have no relevant conflicts of interest.


© 2022  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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