Abstract
Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail. Objective: To identify associations between inflammatory endotypes and clinical presentations in CRS. Methods: We compared 121 patients with nonpolypoid CRS (CRSsNP) and 134 patients with polypoid CRS (CRSwNP) and identified inflammatory endotypes using markers including IFN-γ (T1), eosinophil cationic protein (T2), Charcot-Leyden crystal galectin (T2), and IL-17A (T3). We collected clinical parameters from medical and surgical records and examined whether there were any associations between endotype and clinical features. Results: The presence of nasal polyps, asthma comorbidity, smell loss, and allergic mucin was significantly associated with the presence of T2 endotype in all patients with CRS. The T1 endotype was significantly more common in females, and the presence of pus was significantly associated with T3 endotype in all patients with CRS. We further analyzed these associations in CRSsNP and CRSwNP separately and found that smell loss was still associated with T2 endotype and pus with the T3 endotype in both CRSsNP and CRSwNP. Importantly, patients with CRS with T2 and T3 mixed endotype tended to have clinical presentations shared by both T2 and T3 endotypes. Conclusions: Clinical presentations are directly associated with inflammatory endotypes in CRS. Identification of inflammatory endotypes may allow for more precise and personalized medical treatments in CRS.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2812-2820.e3 |
| Journal | Journal of Allergy and Clinical Immunology: In Practice |
| Volume | 7 |
| Issue number | 8 |
| DOIs | |
| State | Published - Nov 1 2019 |
Keywords
- Chronic rhinosinusitis
- Clinical presentation
- Endotype-phenotype association
- Inflammatory endotype
ASJC Scopus subject areas
- Immunology and Allergy
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Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis. / Stevens, Whitney W.; Peters, Anju T.; Tan, Bruce K.; Klingler, Aiko I.; Poposki, Julie A.; Hulse, Kathryn E.; Grammer, Leslie C.; Welch, Kevin C.; Smith, Stephanie S.; Conley, David B.; Kern, Robert C.; Schleimer, Robert P.; Kato, Atsushi.
In: Journal of Allergy and Clinical Immunology: In Practice, Vol. 7, No. 8, 01.11.2019, p. 2812-2820.e3.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis
AU - Stevens, Whitney W.
AU - Peters, Anju T.
AU - Tan, Bruce K.
AU - Klingler, Aiko I.
AU - Poposki, Julie A.
AU - Hulse, Kathryn E.
AU - Grammer, Leslie C.
AU - Welch, Kevin C.
AU - Smith, Stephanie S.
AU - Conley, David B.
AU - Kern, Robert C.
AU - Schleimer, Robert P.
AU - Kato, Atsushi
N1 - Funding Information: This research was supported in part by the National Institutes of Health (grant nos. R01 AI104733, KL2 TR001424, R37 HL068546, R01 AI137174, and U19 AI106683) and by grants from the Parker B. Francis Fellowship Foundation, the HOPE APFED/American Academy of Allergy,Asthma & Immunology Pilot Grant Award, and the Ernest S. Bazley Foundation.Conflicts of interest: W. W. Stevens personally received a grant from Parker B. Francis Fellowship Program, the American Partnership for Eosinophilic Disorders/American Academy of Allergy,Asthma & Immunology (AAAAI) HOPE Pilot Grant Award, and KL-2 Award (grant no. KL2 TR001424) for this work. B. K. Tan's institution received a grant from the National Institutes of Health (NIH) (grant no. U19 AI106683) for this work. L. C. Grammer's institute received a grant and support for travel from the NIH and a grant from Bazley Foundation for this work; the institution received grants from the NIH, the Food Allergy Network, and the Bazley Foundation for other works. L. C. Grammer personally received consultancy fees from Astellas Pharmaceuticals; is employed by Northwestern University and Northwestern Medical Faculty Foundation; received payment for lectures from the AAAAI, Mount Sinai, New York, NY; and receives royalties from the AAAAI, Mount Sinai. S. S. Smith's institution received Triological Society Career Development Award for this work; she is employed by Northwestern Medicine/Northwestern University. R. P. Schleimer's institution received a grant from the NIH. R. P. Schleimer personally received consultancy fees from Intersect ENT, GlaxoSmithKline, Allakos, Aurasense, Merck, BioMarck, Sanofi, AstraZeneca/Medimmune, Genentech, Exicure, Inc, Otsuka, Inc, and Aqualung Therapeutics Corp; received stock options from Allakos, Aurasense, BioMarck, Exicure, Inc, and Aqualung Therapeutics Corp. A. Kato's institution received grants from the NIH (grant nos. R01AI104733, R01 AI137174, U19AI106683, and R37HL068546). A. T. Peters’ institution received grants from AstraZeneca. A.T. Peters received consultancy fees from Sanofi Regeneron, Novartis, and AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest. This research was supported in part by the National Institutes of Health (grant nos. R01 AI104733, KL2 TR001424, R37 HL068546, R01 AI137174, and U19 AI106683) and by grants from the Parker B. Francis Fellowship Foundation, the HOPE APFED/ American Academy of Allergy,Asthma & Immunology Pilot Grant Award, and the Ernest S. Bazley Foundation. Conflicts of interest: W. W. Stevens personally received a grant from Parker B. Francis Fellowship Program, the American Partnership for Eosinophilic Disorders/ American Academy of Allergy,Asthma & Immunology (AAAAI) HOPE Pilot Grant Award, and KL-2 Award (grant no. KL2 TR001424) for this work. B. K. Tan's institution received a grant from the National Institutes of Health (NIH) (grant no. U19 AI106683) for this work. L. C. Grammer's institute received a grant and support for travel from the NIH and a grant from Bazley Foundation for this work; the institution received grants from the NIH, the Food Allergy Network, and the Bazley Foundation for other works. L. C. Grammer personally received consultancy fees from Astellas Pharmaceuticals; is employed by Northwestern University and Northwestern Medical Faculty Foundation; received payment for lectures from the AAAAI, Mount Sinai, New York, NY; and receives royalties from the AAAAI, Mount Sinai. S. S. Smith's institution received Triological Society Career Development Award for this work; she is employed by Northwestern Medicine/Northwestern University. R. P. Schleimer's institution received a grant from the NIH. R. P. Schleimer personally received consultancy fees from Intersect ENT, GlaxoSmithKline, Allakos, Aurasense, Merck, BioMarck, Sanofi, AstraZeneca/Medimmune, Genentech, Exicure, Inc, Otsuka, Inc, and Aqualung Therapeutics Corp; received stock options from Allakos, Aurasense, BioMarck, Exicure, Inc, and Aqualung Therapeutics Corp. A. Kato's institution received grants from the NIH (grant nos. R01AI104733, R01 AI137174, U19AI106683, and R37HL068546). A. T. Peters’ institution received grants from AstraZeneca. A.T. Peters received consultancy fees from Sanofi Regeneron, Novartis, and AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest. We gratefully acknowledge Ms Lydia Suh, Mr James Norton, Mr Roderick Carter, Ms Caroline P.E. Price, Ms Julia H. Huang, and Ms Kathleen E. Harris (Northwestern University Feinberg School of Medicine) for their skillful technical assistance. We gratefully acknowledge Ms Chen Yeh, MS, at Northwestern University Feinberg School of Medicine for her support of statistical analysis. This research was supported in part by the National Institutes of Health (grant nos. R01 AI104733, KL2 TR001424, R37 HL068546, R01 AI137174, and U19 AI106683) and by grants from the Parker B. Francis Fellowship Foundation, the HOPE APFED/ American Academy of Allergy,Asthma & Immunology Pilot Grant Award, and the Ernest S. Bazley Foundation. Conflicts of interest: W. W. Stevens personally received a grant from Parker B. Francis Fellowship Program, the American Partnership for Eosinophilic Disorders/ American Academy of Allergy,Asthma & Immunology (AAAAI) HOPE Pilot Grant Award, and KL-2 Award (grant no. KL2 TR001424) for this work. B. K. Tan's institution received a grant from the National Institutes of Health (NIH) (grant no. U19 AI106683) for this work. L. C. Grammer's institute received a grant and support for travel from the NIH and a grant from Bazley Foundation for this work; the institution received grants from the NIH, the Food Allergy Network, and the Bazley Foundation for other works. L. C. Grammer personally received consultancy fees from Astellas Pharmaceuticals; is employed by Northwestern University and Northwestern Medical Faculty Foundation; received payment for lectures from the AAAAI, Mount Sinai, New York, NY; and receives royalties from the AAAAI, Mount Sinai. S. S. Smith's institution received Triological Society Career Development Award for this work; she is employed by Northwestern Medicine/Northwestern University. R. P. Schleimer's institution received a grant from the NIH. R. P. Schleimer personally received consultancy fees from Intersect ENT, GlaxoSmithKline, Allakos, Aurasense, Merck, BioMarck, Sanofi, AstraZeneca/Medimmune, Genentech, Exicure, Inc, Otsuka, Inc, and Aqualung Therapeutics Corp; received stock options from Allakos, Aurasense, BioMarck, Exicure, Inc, and Aqualung Therapeutics Corp. A. Kato's institution received grants from the NIH (grant nos. R01AI104733, R01 AI137174, U19AI106683, and R37HL068546). A. T. Peters’ institution received grants from AstraZeneca. A.T. Peters received consultancy fees from Sanofi Regeneron, Novartis, and AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Conflicts of interest: W. W. Stevens personally received a grant from Parker B. Francis Fellowship Program , the American Partnership for Eosinophilic Disorders / American Academy of Allergy,Asthma & Immunology (AAAAI) HOPE Pilot Grant Award, and KL-2 Award (grant no. KL2 TR001424 ) for this work. B. K. Tan's institution received a grant from the National Institutes of Health (NIH) (grant no. U19 AI106683 ) for this work. L. C. Grammer's institute received a grant and support for travel from the NIH and a grant from Bazley Foundation for this work; the institution received grants from the NIH , the Food Allergy Network , and the Bazley Foundation for other works. L. C. Grammer personally received consultancy fees from Astellas Pharmaceuticals; is employed by Northwestern University and Northwestern Medical Faculty Foundation; received payment for lectures from the AAAAI , Mount Sinai , New York, NY; and receives royalties from the AAAAI, Mount Sinai. S. S. Smith's institution received Triological Society Career Development Award for this work; she is employed by Northwestern Medicine/Northwestern University. R. P. Schleimer's institution received a grant from the NIH . R. P. Schleimer personally received consultancy fees from Intersect ENT, GlaxoSmithKline, Allakos, Aurasense, Merck, BioMarck, Sanofi, AstraZeneca/Medimmune, Genentech, Exicure, Inc, Otsuka, Inc, and Aqualung Therapeutics Corp; received stock options from Allakos, Aurasense, BioMarck, Exicure, Inc, and Aqualung Therapeutics Corp. A. Kato's institution received grants from the NIH (grant nos. R01AI104733 , R01 AI137174 , U19AI106683 , and R37HL068546 ). A. T. Peters’ institution received grants from AstraZeneca. A.T. Peters received consultancy fees from Sanofi Regeneron, Novartis, and AstraZeneca . The rest of the authors declare that they have no relevant conflicts of interest. Original Article Funding Information: This research was supported in part by the National Institutes of Health (grant nos. R01 AI104733, KL2 TR001424, R37 HL068546, R01 AI137174, and U19 AI106683) and by grants from the Parker B. Francis Fellowship Foundation, the HOPE APFED/American Academy of Allergy,Asthma & Immunology Pilot Grant Award, and the Ernest S. Bazley Foundation.Conflicts of interest: W. W. Stevens personally received a grant from Parker B. Francis Fellowship Program, the American Partnership for Eosinophilic Disorders/American Academy of Allergy,Asthma & Immunology (AAAAI) HOPE Pilot Grant Award, and KL-2 Award (grant no. KL2 TR001424) for this work. B. K. Tan's institution received a grant from the National Institutes of Health (NIH) (grant no. U19 AI106683) for this work. L. C. Grammer's institute received a grant and support for travel from the NIH and a grant from Bazley Foundation for this work; the institution received grants from the NIH, the Food Allergy Network, and the Bazley Foundation for other works. L. C. Grammer personally received consultancy fees from Astellas Pharmaceuticals; is employed by Northwestern University and Northwestern Medical Faculty Foundation; received payment for lectures from the AAAAI, Mount Sinai, New York, NY; and receives royalties from the AAAAI, Mount Sinai. S. S. Smith's institution received Triological Society Career Development Award for this work; she is employed by Northwestern Medicine/Northwestern University. R. P. Schleimer's institution received a grant from the NIH. R. P. Schleimer personally received consultancy fees from Intersect ENT, GlaxoSmithKline, Allakos, Aurasense, Merck, BioMarck, Sanofi, AstraZeneca/Medimmune, Genentech, Exicure, Inc, Otsuka, Inc, and Aqualung Therapeutics Corp; received stock options from Allakos, Aurasense, BioMarck, Exicure, Inc, and Aqualung Therapeutics Corp. A. Kato's institution received grants from the NIH (grant nos. R01AI104733, R01 AI137174, U19AI106683, and R37HL068546). A. T. Peters? institution received grants from AstraZeneca. A.T. Peters received consultancy fees from Sanofi Regeneron, Novartis, and AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: © 2019 American Academy of Allergy, Asthma & Immunology
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail. Objective: To identify associations between inflammatory endotypes and clinical presentations in CRS. Methods: We compared 121 patients with nonpolypoid CRS (CRSsNP) and 134 patients with polypoid CRS (CRSwNP) and identified inflammatory endotypes using markers including IFN-γ (T1), eosinophil cationic protein (T2), Charcot-Leyden crystal galectin (T2), and IL-17A (T3). We collected clinical parameters from medical and surgical records and examined whether there were any associations between endotype and clinical features. Results: The presence of nasal polyps, asthma comorbidity, smell loss, and allergic mucin was significantly associated with the presence of T2 endotype in all patients with CRS. The T1 endotype was significantly more common in females, and the presence of pus was significantly associated with T3 endotype in all patients with CRS. We further analyzed these associations in CRSsNP and CRSwNP separately and found that smell loss was still associated with T2 endotype and pus with the T3 endotype in both CRSsNP and CRSwNP. Importantly, patients with CRS with T2 and T3 mixed endotype tended to have clinical presentations shared by both T2 and T3 endotypes. Conclusions: Clinical presentations are directly associated with inflammatory endotypes in CRS. Identification of inflammatory endotypes may allow for more precise and personalized medical treatments in CRS.
AB - Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail. Objective: To identify associations between inflammatory endotypes and clinical presentations in CRS. Methods: We compared 121 patients with nonpolypoid CRS (CRSsNP) and 134 patients with polypoid CRS (CRSwNP) and identified inflammatory endotypes using markers including IFN-γ (T1), eosinophil cationic protein (T2), Charcot-Leyden crystal galectin (T2), and IL-17A (T3). We collected clinical parameters from medical and surgical records and examined whether there were any associations between endotype and clinical features. Results: The presence of nasal polyps, asthma comorbidity, smell loss, and allergic mucin was significantly associated with the presence of T2 endotype in all patients with CRS. The T1 endotype was significantly more common in females, and the presence of pus was significantly associated with T3 endotype in all patients with CRS. We further analyzed these associations in CRSsNP and CRSwNP separately and found that smell loss was still associated with T2 endotype and pus with the T3 endotype in both CRSsNP and CRSwNP. Importantly, patients with CRS with T2 and T3 mixed endotype tended to have clinical presentations shared by both T2 and T3 endotypes. Conclusions: Clinical presentations are directly associated with inflammatory endotypes in CRS. Identification of inflammatory endotypes may allow for more precise and personalized medical treatments in CRS.
KW - Chronic rhinosinusitis
KW - Clinical presentation
KW - Endotype-phenotype association
KW - Inflammatory endotype
UR - http://www.scopus.com/inward/record.url?scp=85067178919&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067178919&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2019.05.009
DO - 10.1016/j.jaip.2019.05.009
M3 - Article
C2 - 31128376
AN - SCOPUS:85067178919
VL - 7
SP - 2812-2820.e3
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
SN - 2213-2198
IS - 8
ER -