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Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis

Background Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis... Full description

Journal Title: Journal of allergy and clinical immunology 2013, Vol.133 (6), p.1557-1563.e5
Main Author: Moore, Wendy C., MD
Other Authors: Hastie, Annette T., PhD , Li, Xingnan, PhD, MS , Li, Huashi, MS , Busse, William W., MD , Jarjour, Nizar N., MD , Wenzel, Sally E., MD , Peters, Stephen P., MD, PhD , Meyers, Deborah A., PhD , Bleecker, Eugene R., MD
Format: Electronic Article Electronic Article
Language: English
Subjects:
Age
Quelle: Alma/SFX Local Collection
Publisher: New York, NY: Elsevier Inc
ID: ISSN: 0091-6749
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title: Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis
format: Article
creator:
  • Moore, Wendy C., MD
  • Hastie, Annette T., PhD
  • Li, Xingnan, PhD, MS
  • Li, Huashi, MS
  • Busse, William W., MD
  • Jarjour, Nizar N., MD
  • Wenzel, Sally E., MD
  • Peters, Stephen P., MD, PhD
  • Meyers, Deborah A., PhD
  • Bleecker, Eugene R., MD
subjects:
  • Abridged Index Medicus
  • Adolescent
  • Adult
  • Age
  • Age Factors
  • Allergy and Immunology
  • Analysis
  • Asthma
  • Asthma - blood
  • Asthma - diagnosis
  • Asthma - physiopathology
  • Biological and medical sciences
  • Body mass index
  • Cluster Analysis
  • Colleges & universities
  • Discriminant analysis
  • eosinophils
  • Family medical history
  • Female
  • Fundamental and applied biological sciences. Psychology
  • Fundamental immunology
  • Genetic aspects
  • Granulocytes
  • Humans
  • Immunopathology
  • Leukocyte Count
  • Male
  • Medical colleges
  • Medical sciences
  • Middle Aged
  • Multivariate analysis
  • Neutrophils
  • Pharmacogenetics
  • Phenotype
  • Respiratory Function Tests
  • Risk Factors
  • Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
  • severe asthma
  • Severe Asthma Research Program
  • Severity of Illness Index
  • sputum
  • Sputum - cytology
  • Statistical methods
  • Young Adult
ispartof: Journal of allergy and clinical immunology, 2013, Vol.133 (6), p.1557-1563.e5
description: Background Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. Objective To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Results Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. Conclusion This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0091-6749
fulltext: fulltext
issn:
  • 0091-6749
  • 1097-6825
url: Link


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titleSputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis
sourceAlma/SFX Local Collection
creatorMoore, Wendy C., MD ; Hastie, Annette T., PhD ; Li, Xingnan, PhD, MS ; Li, Huashi, MS ; Busse, William W., MD ; Jarjour, Nizar N., MD ; Wenzel, Sally E., MD ; Peters, Stephen P., MD, PhD ; Meyers, Deborah A., PhD ; Bleecker, Eugene R., MD
creatorcontribMoore, Wendy C., MD ; Hastie, Annette T., PhD ; Li, Xingnan, PhD, MS ; Li, Huashi, MS ; Busse, William W., MD ; Jarjour, Nizar N., MD ; Wenzel, Sally E., MD ; Peters, Stephen P., MD, PhD ; Meyers, Deborah A., PhD ; Bleecker, Eugene R., MD ; National Heart, Lung, and Blood Institute's Severe Asthma Research Program
descriptionBackground Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. Objective To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Results Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. Conclusion This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation.
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subjectAbridged Index Medicus ; Adolescent ; Adult ; Age ; Age Factors ; Allergy and Immunology ; Analysis ; Asthma ; Asthma - blood ; Asthma - diagnosis ; Asthma - physiopathology ; Biological and medical sciences ; Body mass index ; Cluster Analysis ; Colleges & universities ; Discriminant analysis ; eosinophils ; Family medical history ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Genetic aspects ; Granulocytes ; Humans ; Immunopathology ; Leukocyte Count ; Male ; Medical colleges ; Medical sciences ; Middle Aged ; Multivariate analysis ; Neutrophils ; Pharmacogenetics ; Phenotype ; Respiratory Function Tests ; Risk Factors ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; severe asthma ; Severe Asthma Research Program ; Severity of Illness Index ; sputum ; Sputum - cytology ; Statistical methods ; Young Adult
ispartofJournal of allergy and clinical immunology, 2013, Vol.133 (6), p.1557-1563.e5
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1Hastie, Annette T., PhD
2Li, Xingnan, PhD, MS
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4Busse, William W., MD
5Jarjour, Nizar N., MD
6Wenzel, Sally E., MD
7Peters, Stephen P., MD, PhD
8Meyers, Deborah A., PhD
9Bleecker, Eugene R., MD
10National Heart, Lung, and Blood Institute's Severe Asthma Research Program
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0Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis
1Journal of allergy and clinical immunology
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descriptionBackground Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. Objective To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Results Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. Conclusion This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation.
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27Medical colleges
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30Multivariate analysis
31Neutrophils
32Pharmacogenetics
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36Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
37severe asthma
38Severe Asthma Research Program
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42Statistical methods
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titleSputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis
authorMoore, Wendy C., MD ; Hastie, Annette T., PhD ; Li, Xingnan, PhD, MS ; Li, Huashi, MS ; Busse, William W., MD ; Jarjour, Nizar N., MD ; Wenzel, Sally E., MD ; Peters, Stephen P., MD, PhD ; Meyers, Deborah A., PhD ; Bleecker, Eugene R., MD
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1Adolescent
2Adult
3Age
4Age Factors
5Allergy and Immunology
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7Asthma
8Asthma - blood
9Asthma - diagnosis
10Asthma - physiopathology
11Biological and medical sciences
12Body mass index
13Cluster Analysis
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20Fundamental immunology
21Genetic aspects
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23Humans
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28Medical sciences
29Middle Aged
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abstractBackground Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. Objective To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Results Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. Conclusion This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation.
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