Cluster analysis and prediction of treatment outcomes for chronic rhinosinusitis
Zachary M Soler, J Madison Hyer, Luke Rudmik, Viswanathan Ramakrishnan, Timothy L Smith, Rodney J Schlosser, Zachary M Soler, J Madison Hyer, Luke Rudmik, Viswanathan Ramakrishnan, Timothy L Smith, Rodney J Schlosser
Abstract
Background: Current clinical classifications of chronic rhinosinusitis (CRS) have weak prognostic utility regarding treatment outcomes. Simplified discriminant analysis based on unsupervised clustering has identified novel phenotypic subgroups of CRS, but prognostic utility is unknown.
Objective: We sought to determine whether discriminant analysis allows prognostication in patients choosing surgery versus continued medical management.
Methods: A multi-institutional prospective study of patients with CRS in whom initial medical therapy failed who then self-selected continued medical management or surgical treatment was used to separate patients into 5 clusters based on a previously described discriminant analysis using total Sino-Nasal Outcome Test-22 (SNOT-22) score, age, and missed productivity. Patients completed the SNOT-22 at baseline and for 18 months of follow-up. Baseline demographic and objective measures included olfactory testing, computed tomography, and endoscopy scoring. SNOT-22 outcomes for surgical versus continued medical treatment were compared across clusters.
Results: Data were available on 690 patients. Baseline differences in demographics, comorbidities, objective disease measures, and patient-reported outcomes were similar to previous clustering reports. Three of 5 clusters identified by means of discriminant analysis had improved SNOT-22 outcomes with surgical intervention when compared with continued medical management (surgery was a mean of 21.2 points better across these 3 clusters at 6 months, P < .05). These differences were sustained at 18 months of follow-up. Two of 5 clusters had similar outcomes when comparing surgery with continued medical management.
Conclusion: A simplified discriminant analysis based on 3 common clinical variables is able to cluster patients and provide prognostic information regarding surgical treatment versus continued medical management in patients with CRS.
Trial registration: ClinicalTrials.gov NCT00799097 NCT01332136.
Keywords: Chronic rhinosinusitis; cluster; outcomes; prediction; quality of life; sinusitis; treatment.
Conflict of interest statement
Conflict(s) of Interest / Financial Disclosures: Zachary M. Soler and Timothy L. Smith are supported for this investigation by a grant from the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health, Bethesda, MD (R01 DC005805; PI/PD: TL Smith). Public clinical trial registration (http://www.clinicaltrials.gov) #NCT01332136. Zachary M. Soler is also supported for this investigation by another grant from the NIDCD (R03 DC013651-01). Timothy L. Smith is a consultant for IntersectENT, which is not associated with this manuscript. Zachary M. Soler is a consultant for Olympus, which is not affiliated with this manuscript. Rodney J. Schlosser is supported by grants from OptiNose and IntersectENT, neither are associated with this manuscript. Dr. Schlosser is also a consultant for Olympus and Arrinex which are not affiliated with this study.
Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4826845/bin/nihms754338f1.jpg)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4826845/bin/nihms754338f2.jpg)
Figure 3
SNOT-22 outcomes by individual domain…
Figure 3
SNOT-22 outcomes by individual domain between clusters treated with surgery or continuing medication…
Figure 4
RSDI outcomes by subscale score…
Figure 4
RSDI outcomes by subscale score between clusters treated with surgery or continuing medication…
- Using preoperative unsupervised cluster analysis of chronic rhinosinusitis to inform patient decision and endoscopic sinus surgery outcome.Adnane C, Adouly T, Khallouk A, Rouadi S, Abada R, Roubal M, Mahtar M. Adnane C, et al. Eur Arch Otorhinolaryngol. 2017 Feb;274(2):879-885. doi: 10.1007/s00405-016-4315-8. Epub 2016 Sep 24. Eur Arch Otorhinolaryngol. 2017. PMID: 27665096
- Identification of chronic rhinosinusitis phenotypes using cluster analysis.Soler ZM, Hyer JM, Ramakrishnan V, Smith TL, Mace J, Rudmik L, Schlosser RJ. Soler ZM, et al. Int Forum Allergy Rhinol. 2015 May;5(5):399-407. doi: 10.1002/alr.21496. Epub 2015 Feb 17. Int Forum Allergy Rhinol. 2015. PMID: 25694390 Free PMC article.
- Patient-centered decision making: the role of the baseline SNOT-22 in predicting outcomes for medical management of chronic rhinosinusitis.Steele TO, Rudmik L, Mace JC, DeConde AS, Alt JA, Smith TL. Steele TO, et al. Int Forum Allergy Rhinol. 2016 Jun;6(6):590-6. doi: 10.1002/alr.21721. Epub 2016 Feb 8. Int Forum Allergy Rhinol. 2016. PMID: 26852743 Free PMC article.
- Surgical therapy vs continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis.Patel ZM, Thamboo A, Rudmik L, Nayak JV, Smith TL, Hwang PH. Patel ZM, et al. Int Forum Allergy Rhinol. 2017 Feb;7(2):119-127. doi: 10.1002/alr.21872. Epub 2016 Nov 11. Int Forum Allergy Rhinol. 2017. PMID: 27863163 Review.
- The clinical efficacy of surgical interventions for empty nose syndrome: A systematic review.Leong SC. Leong SC. Laryngoscope. 2015 Jul;125(7):1557-62. doi: 10.1002/lary.25170. Epub 2015 Feb 3. Laryngoscope. 2015. PMID: 25647010 Review.
- Current insight into treatment of chronic rhinosinusitis: Phenotypes, endotypes, and implications for targeted therapeutics.Chapurin N, Wu J, Labby AB, Chandra RK, Chowdhury NI, Turner JH. Chapurin N, et al. J Allergy Clin Immunol. 2022 Jul;150(1):22-32. doi: 10.1016/j.jaci.2022.04.013. Epub 2022 Apr 22. J Allergy Clin Immunol. 2022. PMID: 35469844 Review.
- Benchmarking off-the-shelf statistical shape modeling tools in clinical applications.Goparaju A, Iyer K, Bône A, Hu N, Henninger HB, Anderson AE, Durrleman S, Jacxsens M, Morris A, Csecs I, Marrouche N, Elhabian SY. Goparaju A, et al. Med Image Anal. 2022 Feb;76:102271. doi: 10.1016/j.media.2021.102271. Epub 2021 Oct 26. Med Image Anal. 2022. PMID: 34974213 Free PMC article.
- Latest advances in chronic rhinosinusitis with nasal polyps endotyping and biomarkers, and their significance for daily practice.Maniu AA, Perde-Schrepler MI, Tatomir CB, Tănase MI, Dindelegan MG, Budu VA, Rădeanu GD, Cosgarea M, Mogoantă CA. Maniu AA, et al. Rom J Morphol Embryol. 2020 Apr-Jun;61(2):309-320. doi: 10.47162/RJME.61.2.01. Rom J Morphol Embryol. 2020. PMID: 33544783 Free PMC article.
- Olfaction: Sensitive indicator of inflammatory burden in chronic rhinosinusitis.Yan X, Whitcroft KL, Hummel T. Yan X, et al. Laryngoscope Investig Otolaryngol. 2020 Oct 28;5(6):992-1002. doi: 10.1002/lio2.485. eCollection 2020 Dec. Laryngoscope Investig Otolaryngol. 2020. PMID: 33364387 Free PMC article. Review.
- Characterization of epithelial cells, connective tissue cells and immune cells in human upper airway mucosa by immunofluorescence multichannel image cytometry: a pilot study.Giotakis AI, Dudas J, Glueckert R, Dejaco D, Ingruber J, Fleischer F, Innerhofer V, Pinggera L, Bektic-Tadic L, Gabriel SAM, Riechelmann H. Giotakis AI, et al. Histochem Cell Biol. 2021 Mar;155(3):405-421. doi: 10.1007/s00418-020-01945-y. Epub 2020 Nov 29. Histochem Cell Biol. 2021. PMID: 33251550 Free PMC article.
- Multicenter Study
- Observational Study
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Algorithms
- Chronic Disease
- Clinical Decision-Making / methods*
- Cluster Analysis
- Decision Support Techniques*
- Discriminant Analysis
- Drug Therapy, Combination
- Female
- Follow-Up Studies
- Humans
- Logistic Models
- Male
- Middle Aged
- Prognosis
- Prospective Studies
- Quality of Life
- Respiratory System Agents / therapeutic use*
- Rhinitis / drug therapy*
- Rhinitis / surgery*
- Sinusitis / drug therapy*
- Sinusitis / surgery*
- Treatment Outcome
- Young Adult
- Respiratory System Agents
- ClinicalTrials.gov/NCT00799097
- ClinicalTrials.gov/NCT01332136
- Full Text Sources
- Other Literature Sources
- Medical
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![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4826845/bin/nihms754338f3.jpg)
Figure 4
RSDI outcomes by subscale score…
Figure 4
RSDI outcomes by subscale score between clusters treated with surgery or continuing medication…
- Using preoperative unsupervised cluster analysis of chronic rhinosinusitis to inform patient decision and endoscopic sinus surgery outcome.Adnane C, Adouly T, Khallouk A, Rouadi S, Abada R, Roubal M, Mahtar M. Adnane C, et al. Eur Arch Otorhinolaryngol. 2017 Feb;274(2):879-885. doi: 10.1007/s00405-016-4315-8. Epub 2016 Sep 24. Eur Arch Otorhinolaryngol. 2017. PMID: 27665096
- Identification of chronic rhinosinusitis phenotypes using cluster analysis.Soler ZM, Hyer JM, Ramakrishnan V, Smith TL, Mace J, Rudmik L, Schlosser RJ. Soler ZM, et al. Int Forum Allergy Rhinol. 2015 May;5(5):399-407. doi: 10.1002/alr.21496. Epub 2015 Feb 17. Int Forum Allergy Rhinol. 2015. PMID: 25694390 Free PMC article.
- Patient-centered decision making: the role of the baseline SNOT-22 in predicting outcomes for medical management of chronic rhinosinusitis.Steele TO, Rudmik L, Mace JC, DeConde AS, Alt JA, Smith TL. Steele TO, et al. Int Forum Allergy Rhinol. 2016 Jun;6(6):590-6. doi: 10.1002/alr.21721. Epub 2016 Feb 8. Int Forum Allergy Rhinol. 2016. PMID: 26852743 Free PMC article.
- Surgical therapy vs continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis.Patel ZM, Thamboo A, Rudmik L, Nayak JV, Smith TL, Hwang PH. Patel ZM, et al. Int Forum Allergy Rhinol. 2017 Feb;7(2):119-127. doi: 10.1002/alr.21872. Epub 2016 Nov 11. Int Forum Allergy Rhinol. 2017. PMID: 27863163 Review.
- The clinical efficacy of surgical interventions for empty nose syndrome: A systematic review.Leong SC. Leong SC. Laryngoscope. 2015 Jul;125(7):1557-62. doi: 10.1002/lary.25170. Epub 2015 Feb 3. Laryngoscope. 2015. PMID: 25647010 Review.
- Current insight into treatment of chronic rhinosinusitis: Phenotypes, endotypes, and implications for targeted therapeutics.Chapurin N, Wu J, Labby AB, Chandra RK, Chowdhury NI, Turner JH. Chapurin N, et al. J Allergy Clin Immunol. 2022 Jul;150(1):22-32. doi: 10.1016/j.jaci.2022.04.013. Epub 2022 Apr 22. J Allergy Clin Immunol. 2022. PMID: 35469844 Review.
- Benchmarking off-the-shelf statistical shape modeling tools in clinical applications.Goparaju A, Iyer K, Bône A, Hu N, Henninger HB, Anderson AE, Durrleman S, Jacxsens M, Morris A, Csecs I, Marrouche N, Elhabian SY. Goparaju A, et al. Med Image Anal. 2022 Feb;76:102271. doi: 10.1016/j.media.2021.102271. Epub 2021 Oct 26. Med Image Anal. 2022. PMID: 34974213 Free PMC article.
- Latest advances in chronic rhinosinusitis with nasal polyps endotyping and biomarkers, and their significance for daily practice.Maniu AA, Perde-Schrepler MI, Tatomir CB, Tănase MI, Dindelegan MG, Budu VA, Rădeanu GD, Cosgarea M, Mogoantă CA. Maniu AA, et al. Rom J Morphol Embryol. 2020 Apr-Jun;61(2):309-320. doi: 10.47162/RJME.61.2.01. Rom J Morphol Embryol. 2020. PMID: 33544783 Free PMC article.
- Olfaction: Sensitive indicator of inflammatory burden in chronic rhinosinusitis.Yan X, Whitcroft KL, Hummel T. Yan X, et al. Laryngoscope Investig Otolaryngol. 2020 Oct 28;5(6):992-1002. doi: 10.1002/lio2.485. eCollection 2020 Dec. Laryngoscope Investig Otolaryngol. 2020. PMID: 33364387 Free PMC article. Review.
- Characterization of epithelial cells, connective tissue cells and immune cells in human upper airway mucosa by immunofluorescence multichannel image cytometry: a pilot study.Giotakis AI, Dudas J, Glueckert R, Dejaco D, Ingruber J, Fleischer F, Innerhofer V, Pinggera L, Bektic-Tadic L, Gabriel SAM, Riechelmann H. Giotakis AI, et al. Histochem Cell Biol. 2021 Mar;155(3):405-421. doi: 10.1007/s00418-020-01945-y. Epub 2020 Nov 29. Histochem Cell Biol. 2021. PMID: 33251550 Free PMC article.
- Multicenter Study
- Observational Study
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Algorithms
- Chronic Disease
- Clinical Decision-Making / methods*
- Cluster Analysis
- Decision Support Techniques*
- Discriminant Analysis
- Drug Therapy, Combination
- Female
- Follow-Up Studies
- Humans
- Logistic Models
- Male
- Middle Aged
- Prognosis
- Prospective Studies
- Quality of Life
- Respiratory System Agents / therapeutic use*
- Rhinitis / drug therapy*
- Rhinitis / surgery*
- Sinusitis / drug therapy*
- Sinusitis / surgery*
- Treatment Outcome
- Young Adult
- Respiratory System Agents
- ClinicalTrials.gov/NCT00799097
- ClinicalTrials.gov/NCT01332136
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4826845/bin/nihms754338f4.jpg)
Source: PubMed