Biomarkers improve prediction of nasal polyp recurrence after surgery
Published: March 16, 2022
Endoscopic sinus surgery (ESS) is a well-established treatment for patients with chronic rhinosinusitis with nasal polyps (CRSwNP), however, polyp recurrence after ESS is not infrequent. The identified biological and immunological risk factors for polyp recurrence include some clinical risk factors as well as measures of tissue eosinophil density but the relative importance of clinical variables and inflammation biomarkers has not been extensively investigated in Western countries. Additionally, the investigators wanted to evaluate whether autoantibodies like anti-dsDNA IgG which had been previously found at elevated levels in nasal polyp tissue had prognostic value.
To characterize prognostic factors for polyp recurrence in CRSwNP patients 2 to 5 years after ESS, Bai and colleagues performed this retrospective analysis of prospectively collected clinical data and specimens from patients undergoing ESS at Northwestern Memorial Hospital. Ninety-four CRSwNP patients were evaluated with patient-reported outcome measures (PROMs) and endoscopic and radiographic scoring pre- and post- ESS. Biomarkers were measured on nasal polyp tissue obtained at the time of surgery and analyzed for correlation. Interestingly, they demonstrated that anti-dsDNA IgG autoantibodies were moderately but significantly correlated with IL-13 and IL-5 and fell into the same cluster as other type 2 biomarkers like eosinophilic cationic protein (ECP), a biomarker of eosinophil density, based on its intercorrelation.
The ability of clinical variables and biomarkers to predict polyp recurrence was then assessed using separate relaxed LASSO regressions of all 11 pre-surgical clinical variables, and all 17 biomarkers measured in nasal polyp tissue. The LASSO regression aids selection and optimization of variables in multivariate regression and the discriminability of the model was assessed and compared using logistic regression (LR), receiver operating characteristic curves (ROC), and the corresponding area under the curve (AUC). To evaluate whether consideration of clinical variables and biomarkers improved prognostic accuracy, a further model incorporating all 28 biomarkers and clinical variables was also created using the relaxed LASSO model, and further verified by a random forest analysis. These findings were recently reported in The Journal of Allergy and Clinical Immunology (JACI).
Polyp recurrence was found in 39.4% of patients, despite highly significant improvements in modified Lund-Mackay (MLM) radiographic scores and 22-item Sinonasal Outcomes Test (SNOT-22) scores (both p < 0.0001) in the overall cohort. Polyp recurrence was associated with worse post-ESS MLM, modified Lund-Kennedy (MLK), and SNOT-22 scores (p < 0.0001, p < 0.0001, and p < 0.01, respectively). Using the relaxed LASSO analysis, an unbiased variable selection process, they identified two clinical predictors (pre-ESS MLM and asthma) and three biomarker predictors Eosinophilic Cationic Protein (ECP), IL-5, and anti-dsDNA IgG achieved optimal efficiency for predicting PR. Using clinical- or biomarker-only predictors resulted in models of equivalent predictive power, with AUC of 0.79 and 0.78, respectively. However, when integrating both types of predictors, the model selected the same five variables but also demonstrated an improved predictive AUC of 0.89. Notably, these regression models computationally selected anti-dsDNA IgG as an independent predictor for polyp recurrence. Additionally, random forest analysis quantified the prognostic value of each variable and also identified the same five variables as the topmost predictors of PR: ECP, pre-ESS MLM, asthma, IL-5, and anti-dsDNA IgG.
Polyp recurrence after ESS had strong associations with worse PROMs, endoscopic and radiographic severity. Combining nasal polyp tissue biomarkers like ECP, IL-5, and anti-dsDNA IgG with clinical variables like pre-ESS MLM, asthma could accurately predict polyp recurrence. Their results suggest that tissue inflammation biomarkers have the potential to augment individual patient characteristics for predicting outcomes of endoscopic sinus surgery. Patients with high levels of these biomarkers and disease characteristics may derive the greatest benefit from adjunctive therapies to prevent subsequent polyp recurrence.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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