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Disease heterogeneity in patients with\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      remains poorly understood. This study aimed to identify endotypes of\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      patients with at least 1\u2010year postoperative follow\u2010up. Difficult\u2010to\u2010treat\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      was characterized in each generated cluster.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven subject clusters were identified. Cluster 1 (13.01%) was comparable to the classic well\u2010defined eosinophilic\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      with polyps, having severe disease and the highest proportion of difficult\u2010to\u2010treat\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      . Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively lower proportions of presence of polyps and presented mild inflammation with moderate proportions of difficult\u2010to\u2010treat cases. Subjects in cluster 2 were highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by severe or moderate neutrophilic inflammation, respectively, and with elevated levels of\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20108 and high proportions of difficult\u2010to\u2010treat\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      . Cluster 5 (4.07%) was a unique group characterized by the highest levels of\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u201010 and lacked difficult\u2010to\u2010treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom severity, a low proportion of difficult\u2010to\u2010treat\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      , and low inflammation load. Finally, we found that difficult\u2010to\u2010treat\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      was associated with distinct clinical features and biomarkers in the different clusters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Distinct clinicopathobiologic clusters of\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      display differences in clinical response to treatments and characteristics of difficult\u2010to\u2010treat\n                      <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  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