Biological clustering supports both Dutch andBritish hypotheses of Asthma and COPD
Michael A Ghebre
University of Leicester
III Annual PGR ConferenceUniversity of Leicester, UK
31st March 2014
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Table of contents
1 Introduction and Objectives
2 Asthma and COPD Biological Clustering
3 Asthma and COPD Validation StudyValidating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
4 Summary and Conclusion
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Table of contents
1 Introduction and Objectives
2 Asthma and COPD Biological Clustering
3 Asthma and COPD Validation StudyValidating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
4 Summary and Conclusion
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Introduction and Objectives
Severe asthma and chronic obstructive pulmonary disease (COPD)are complex and heterogeneous diseases.
”Dutch hypothesis” => Asthma and COPD are the same diseasewith the same underlying mechanism.
”British hypothesis” => Asthma and COPD are two distinctdisease with di↵erent underlying mechanism.
We investigated whether they represent distinct or overlappingconditions in terms of their available measurements
We do have access to a large number of measurements on 86asthma and 75 COPD subjects; i.e.
Demographic characteristics
Clinical and lung function
Biological characteristics (i.e sputum cytokines)
This study was validated on an independent severe asthma (n=166)and COPD (n=58) using two approaches.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary statistics of some characteristics...
Table 1. Demographic, lung function and clinical characteristics across Asthma and COPDVariable Asthma=86 COPD=75 P-valueMale [n(%)] 43 (50) 53 (70.7) 0.008Current or Ex- smokers [n (%)] 32 (37.2) 72 (96.0) < 0.0001Pack -year history 4.6 (2.98 - 7.26) 40 (34.46 - 46.39) < 0.0001Age (years)+ 54 (1.3) 69 (1.1) < 0.0001Duration of Disease (years) 21 (16.4 - 26.5) 5 (4.12 - 6.55) < 0.0001BMI (kg/m2)+ 30.4 (0.8) 25.7 (0.5) < 0.0001Pre FEV1/FVC ratio (%)+ 67.6 (1.5) 49.8 (1.6) < 0.0001Pre FEV1 Predicted (%)+ 74.6 (2.4) 45.4 (2.1) < 0.0001Post FEV1 Predicted (%)+ 79.8 (2.4) 47.1 (2.1) < 0.0001Sputum Neutrophil count (%)+ 63.2 (2.5) 69.7 (2.5) 0.07Sputum Eosinophil count (%)+ 2.1 (1.38 - 3.1) 1.4(0.98 - 1.93) 0.14Sputum Macrophage count (%)+ 16.7 (13.41 - 20.78) 16.2 (13.3 - 19.8) 0.84Data presented as Geometric mean with corresponding confidence interval unless stated, + Mean (SEM)
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Cytokines across Asthma and COPD
Figure : A=Higher in Asthma and B=Higher in COPD
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Where Asthma(A) and COPD (C) overlap?
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Table of contents
1 Introduction and Objectives
2 Asthma and COPD Biological Clustering
3 Asthma and COPD Validation StudyValidating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
4 Summary and Conclusion
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
Cluster analysis is unsupervised statistical techniques which identifieshomogeneous subgroups and creates labels for further supervisedtechniques (like linear regression or discriminant analysis)
The main aim this study is to segment Asthma and COPD patientsin to subgroups by their biological (i.e. sputum cytokines)characteristics
This might help to identify subjects phenotype rather than diseasespecific categorisation( which is already labelled as asthma orCOPD)
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
Cluster analysis is unsupervised statistical techniques which identifieshomogeneous subgroups and creates labels for further supervisedtechniques (like linear regression or discriminant analysis)
The main aim this study is to segment Asthma and COPD patientsin to subgroups by their biological (i.e. sputum cytokines)characteristics
This might help to identify subjects phenotype rather than diseasespecific categorisation( which is already labelled as asthma orCOPD)
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
Cluster analysis is unsupervised statistical techniques which identifieshomogeneous subgroups and creates labels for further supervisedtechniques (like linear regression or discriminant analysis)
The main aim this study is to segment Asthma and COPD patientsin to subgroups by their biological (i.e. sputum cytokines)characteristics
This might help to identify subjects phenotype rather than diseasespecific categorisation( which is already labelled as asthma orCOPD)
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
Cluster analysis is unsupervised statistical techniques which identifieshomogeneous subgroups and creates labels for further supervisedtechniques (like linear regression or discriminant analysis)
The main aim this study is to segment Asthma and COPD patientsin to subgroups by their biological (i.e. sputum cytokines)characteristics
This might help to identify subjects phenotype rather than diseasespecific categorisation( which is already labelled as asthma orCOPD)
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Clustering heterogeneous subjects
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Clustering heterogeneous subjects
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Clustering heterogeneous subjects
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
There are 18 sputum cytokines measurements
Factor analysis was performed on these cytokines, and fourindependent factor scores were extracted
The factor scores were used as input variables in K-means clusteranalysis
Thus, three biological clusters was identified
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
There are 18 sputum cytokines measurements
Factor analysis was performed on these cytokines, and fourindependent factor scores were extracted
The factor scores were used as input variables in K-means clusteranalysis
Thus, three biological clusters was identified
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
There are 18 sputum cytokines measurements
Factor analysis was performed on these cytokines, and fourindependent factor scores were extracted
The factor scores were used as input variables in K-means clusteranalysis
Thus, three biological clusters was identified
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
There are 18 sputum cytokines measurements
Factor analysis was performed on these cytokines, and fourindependent factor scores were extracted
The factor scores were used as input variables in K-means clusteranalysis
Thus, three biological clusters was identified
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Asthma and COPD Biological Clustering
There are 18 sputum cytokines measurements
Factor analysis was performed on these cytokines, and fourindependent factor scores were extracted
The factor scores were used as input variables in K-means clusteranalysis
Thus, three biological clusters was identified
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Three biological Asthma and COPD clusters
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Pattern of cytokines across the biological clusters
Table 2. Summary statistics across the three identified biological clusters in the test study
Variable Cluster 1 Cluster 2 Cluster 3 C1 vs. C2 C1 vs. C3 C2 vs.C3
(Asthma=55, COPD=3) (Asthma=28, COPD=19) (Asthma=2, COPD=39) P-value P-value P-value
Male [n (%)] 32 (55.2) 26 (55.3) 28 (68.3) 0.99 0.19 0.21
Current or Ex-smokers [n (%)] 22 (37.9) 29 (61.7) 40 (97.6) 0.015 <0.0001 <0.000
Age (years) + 55 (1.5) 60 (2.1) 67 (1.8) 0.038 <0.0001 0.008
Pre FEV1/FVC ratio (%)+ 69.0 (1.9) 58.5 (2.3) 49.7 (2.4) <0.0001 <0.0001 0.011
Pre FEV1 Predicted (%)+ 77.0 (2.7) 59.9 (3.7) 47.0 (3) <0.0001 <0.0001 0.01
Post FEV1 Predicted (%)+ 81.7 (2.7) 63.9 (3.9) 49.1 (3) <0.0001 <0.0001 0.005
Sputum Neutrophil count (%)+ 58.8 (3.1) 77.2 (3) 59.1 (3.1) <0.0001 0.95 <0.0001
Sputum Eosinophil count (%) 3.9 (2.4 - 6.4) 0.7 (0.5 - 0.9) 2.0 (1.25 - 3.17) <0.0001 0.039 <0.0001
CFU >107/ml or positive culture (n[%]) 8 (13.8) 26(55.3) 9 (21.9) <0.0001 0.29 0.001
IL-1� (pg/ml) 39.5 (30.8 - 50.8) 379.5 (257.3 - 559.8) 23.5 (17.2 - 32.2) <0.0001 0.025 <0.0001
IL-5 (pg/ml) 2.6 (1.6 - 4.2) 2.2 (1.4 - 3.4) 1.4 (0.9 - 2.2) 0.56 0.083 0.22
IL-6 (pg/ml) 21.3 (15 - 30.4) 271.4 (192.2 - 383.3) 486.2 (327.7 - 721.4) <0.0001 <0.0001 0.031
IL-6R (pg/ml) 163.2 (126.0 - 211.6) 433.4 (344.2 - 545.6) 112.4 (88.6 - 142.6) <0.0001 0.04 <0.0001
IL-10 (pg/ml) 0.33 (0.25 - 0.45) 5.5 (3.5 - 8.7) 0.34 (0.2 - 0.6) <0.0001 0.89 <0.0001
IL-13 (pg/ml) 10.4 (7.7 - 14.0) 4.8 (3.8 - 6.2) 3.5 (2.4 - 5.2) 0.001 <0.0001 0.18
CCL-26 (pg/ml) 12.4 (7.8 - 19.9) 5.0 (3.4 - 7.5) 2.9 (1.9 - 4.6) 0.004 <0.0001 0.081
TNF↵ (pg/ml) 1.4 (1. 1 - 1.9) 29.9 (19.5 - 45.9) 1.7 (1.1 - 2.5) <0.0001 0.62 <0.0001
Data presented as Geometric mean with corresponding confidence interval unless stated, + Mean (SEM) ; CFU= colony forming units;C=cluster
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Table of contents
1 Introduction and Objectives
2 Asthma and COPD Biological Clustering
3 Asthma and COPD Validation StudyValidating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
4 Summary and Conclusion
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation Study
This study was validated on independent severe asthma and COPDstudies.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation Study
This study was validated on independent severe asthma and COPDstudies.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Asthma and COPD Validation Study
For validation, independent severe asthma (n=166) and COPD(n=58) patients were used
Two classification techniques were applied; i.e.
1. Linear discriminant analysis (LDA)
2. The diseases status (Asthma or COPD), and IL-1� cuto↵ for theoverlap
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Asthma and COPD Validation Study
For validation, independent severe asthma (n=166) and COPD(n=58) patients were used
Two classification techniques were applied; i.e.
1. Linear discriminant analysis (LDA)
2. The diseases status (Asthma or COPD), and IL-1� cuto↵ for theoverlap
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Asthma and COPD Validation Study
For validation, independent severe asthma (n=166) and COPD(n=58) patients were used
Two classification techniques were applied; i.e.
1. Linear discriminant analysis (LDA)
2. The diseases status (Asthma or COPD), and IL-1� cuto↵ for theoverlap
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Asthma and COPD Validation Study
For validation, independent severe asthma (n=166) and COPD(n=58) patients were used
Two classification techniques were applied; i.e.
1. Linear discriminant analysis (LDA)
2. The diseases status (Asthma or COPD), and IL-1� cuto↵ for theoverlap
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Asthma and COPD Validation Study
For validation, independent severe asthma (n=166) and COPD(n=58) patients were used
Two classification techniques were applied; i.e.
1. Linear discriminant analysis (LDA)
2. The diseases status (Asthma or COPD), and IL-1� cuto↵ for theoverlap
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Characteristics of the Validation study
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Table of contents
1 Introduction and Objectives
2 Asthma and COPD Biological Clustering
3 Asthma and COPD Validation StudyValidating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
4 Summary and Conclusion
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validating Asthma and COPD using LDA
Classification model was developed from the Test study using LDA
Then subjects were assigned to subgroups in which he/she has thehighest discriminant score/posterior probability.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validating Asthma and COPD using LDA
Classification model was developed from the Test study using LDA
Then subjects were assigned to subgroups in which he/she has thehighest discriminant score/posterior probability.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validating Asthma and COPD using LDA
Classification model was developed from the Test study using LDA
Then subjects were assigned to subgroups in which he/she has thehighest discriminant score/posterior probability.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validating Asthma and COPD using LDA
Classification model was developed from the Test study using LDA
Then subjects were assigned to subgroups in which he/she has thehighest discriminant score/posterior probability.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validating Asthma and COPD using LDA
Table 3. Coe�cients (betas) and prior probability of each cluster in the teststudy which used to predict class membership in the validation studyVariables Cluster 1 (�1k) Cluster 2 (�2k) Cluster 3 (�3k)IL-1� 1.63 2.17 0.96IL-5 -6.31 -6.50 -6.79IL-6 -2.62 -1.17 0.14IL-6R 6.28 5.58 4.72IL-8 6.64 7.59 7.31CCL-2 5.56 5.66 6.98CCL-4 3.59 3.83 4.66CCL-5 -1.36 -0.80 -2.83CCL-13 -0.04 -0.49 -0.21CCL-17 2.13 1.09 1.09CXCL-11 0.48 0.51 0.29TNF↵ -5.77 -5.28 -6.57Constant -63.39 -75.75 -79.11Prior Probability 0.33 0.33 0.33
Unit of all cytokines is pg/ml
Sij = �j + �j1Y1i + �j2Y2i + · · ·+ �jkYki + log(Pj)
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Patterns of characteristics across validation subgroups
Table 4. Summaries across the validation subgroups which were identified using linear discriminant analysis (LDA)
Variable Group 1 Group 2 Group 3 G1 vs. G2 G1 vs. G3 G2 vs.G3
(Asthma=94, COPD=12) (Asthma=55, COPD=18) (Asthma=7, COPD=28) P-value P-value P-value
Male [n (%)] 65 (61.3) 40 (54.8) 25 (71.4) 0.38 0.28 0.1
Current or Ex-smokers 37 (34.9) 42 (57.5) 33 (94.3) 0.003 <0.0001 <0.0001
Age (year)+ 53 (1.3) 56 (2.0) 66 (2.0) 0.15 <0.0001 0.002
Pre FEV1/FVC ratio (%)+ 68.2 (1.4) 61.8 (1.9) 57.3 (1.8) 0.004 <0.0001 0.14
Pre FEV1 Predicted (%)+ 67.6 (2.2) 64.7 (2.9) 65.5 (3.2) 0.4 0.65 0.85
Sputum Neutrophil count (%)+ 59.1 (2.8) 72.3 (2.5) 58.4 (4.0) 0.001 0.88 0.003
Sputum Eosinophil count (%) 6.3 (4.9 - 8.2) 3.0 (2.4 - 3.8) 3.2 (2.3 - 4.4) <0.0001 0.003 0.79
IL-1� (pg/ml) 54.1 (42.7 - 68.5) 526.6 (375.5 - 738.4) 42.4 (26 - 69.2) <0.0001 0.36 <0.0001
IL-5 (pg/ml) 1.4 (1.1 - 1.8) 1.2 (0.8 - 1.7) 0.9 (0.5 - 1.5) 0.43 0.085 0.34
IL-6 (pg/ml) 26.1 (19.9 - 34.3) 273.3 (210.6 - 354.6) 344.2 (237.2 - 499.3) <0.0001 <0.0001 0.32
IL-6R (pg/ml) 186.0 (135.5 - 255.3) 589.8 (476.6 - 729.8) 90.5 (50.3 - 162.8) <0.0001 0.013 <0.0001
IL-10 (pg/ml) 1.9 (1.5 - 2.4) 3.9 (2.8 - 5.4) 0.5 (0.3 - 0.9) 0.001 <0.0001 <0.0001
TNF↵ (pg/ml) 1.4 (1.2 - 1.7) 23.3(16.1 - 33.7) 1.8 (1.1 - 3.0) ¡0.0001 0.32 <0.0001
Data presented as geometric mean with corresponding confidence interval unless stated, + Mean (SEM); G=Group
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Cytokines profiles in the test and validation subgroups
Figure : Test Figure : Validation
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation Results: Using LDA
Validation Results
The sputum cellular and cytokines patterns were very similar between thetest and validation subgroups.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validating Asthma and COPD using LDA
Table 3. Coe�cients (betas) and prior probability of each cluster in the teststudy which used to predict class membership in the validation studyVariables Cluster 1 (�1k) Cluster 2 (�2k) Cluster 3 (�3k)IL-1� 1.63 2.17 0.96IL-5 -6.31 -6.50 -6.79IL-6 -2.62 -1.17 0.14IL-6R 6.28 5.58 4.72IL-8 6.64 7.59 7.31CCL-2 5.56 5.66 6.98CCL-4 3.59 3.83 4.66CCL-5 -1.36 -0.80 -2.83CCL-13 -0.04 -0.49 -0.21CCL-17 2.13 1.09 1.09CXCL-11 0.48 0.51 0.29TNF↵ -5.77 -5.28 -6.57Constant -63.39 -75.75 -79.11Prior Probability 0.33 0.33 0.33
Unit of all cytokines is pg/ml
Sij = �j + �j1Y1i + �j2Y2i + · · ·+ �jkYki + log(Pj)
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Table of contents
1 Introduction and Objectives
2 Asthma and COPD Biological Clustering
3 Asthma and COPD Validation StudyValidating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
4 Summary and Conclusion
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
IL-1� across the three clusters
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
IL-1� across the three clusters at 130 pg/ml
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation using IL-1� cuto↵ for the overlap and diseases
Since IL-1� performed well in discriminating the overlap group in thetest study at 130 pg/ml cuto↵
This cuto↵ point was applied to the validation studies
With assumption that asthma and COPD are clinicallydistinguishable diseases
Then the validation dataset classified in to three subgroups
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation using IL-1� cuto↵ for the overlap and diseases
Since IL-1� performed well in discriminating the overlap group in thetest study at 130 pg/ml cuto↵
This cuto↵ point was applied to the validation studies
With assumption that asthma and COPD are clinicallydistinguishable diseases
Then the validation dataset classified in to three subgroups
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation using IL-1� cuto↵ for the overlap and diseases
Since IL-1� performed well in discriminating the overlap group in thetest study at 130 pg/ml cuto↵
This cuto↵ point was applied to the validation studies
With assumption that asthma and COPD are clinicallydistinguishable diseases
Then the validation dataset classified in to three subgroups
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation using IL-1� cuto↵ for the overlap and diseases
Since IL-1� performed well in discriminating the overlap group in thetest study at 130 pg/ml cuto↵
This cuto↵ point was applied to the validation studies
With assumption that asthma and COPD are clinicallydistinguishable diseases
Then the validation dataset classified in to three subgroups
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation using IL-1� cuto↵ for the overlap and diseases
Since IL-1� performed well in discriminating the overlap group in thetest study at 130 pg/ml cuto↵
This cuto↵ point was applied to the validation studies
With assumption that asthma and COPD are clinicallydistinguishable diseases
Then the validation dataset classified in to three subgroups
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Patterns of characteristics across the groups in validation
Table 5. Summaries across the validation subgroups which were identified using IL-1� cuto↵ and diseases status (asthma or COPD)
Variable Group 1 Group 2 Group 3 G1 vs. G2 G1 vs. G3 G2 vs.G3
(Asthma=103) (Asthma=63, COPD=26) (COPD=32) P-value P-value P-value
Male [n (%)] 66 (64.1) 51 (57.3) 22 (68.7) 0.34 0.63 0.26
Current or Ex-smokers 28 (27.2) 54 (60.7) 32 (100) <0.0001 <0.0001 <0.0001
Age (year)+ 49 (1.2) 57 (1.8) 68 (1.6) <0.0001 <0.0001 0.001
Pre FEV1/FVC ratio (%)+ 70.1 (1.2) 61.0 (1.7) 56.6 (2.4) <0.0001 <0.0001 0.16
Pre FEV1 Predicted (%)+ 71.2 (2.3) 64.1 (2.5) 60.2 (3.6) 0.033 0.019 0.4
Sputum Neutrophil count (%)+ 59.0 (2.8) 70.4 (2.5) 59.2 (4.2) 0.003 0.97 0.023
Sputum Eosinophil count (%) 5.6 (4.3 - 7.3) 3.5 (2.8 - 4.4) 3.9 (2.5 - 5.9) 0.009 0.12 0.68
IL-1� (pg/ml) 37.0 (29.1 - 47) 527.1(407.1 - 682.5) 40.0 (28.2 - 56.6) <0.0001 0.75 <0.0001
IL-5 (pg/ml) 1.2 (1.0 - 1.5) 1.3 (1.0 - 1.9) 1.0 (0.6 - 1.7) 0.69 0.45 0.37
IL-6 (pg/ml) 34.7 (25.6 - 47) 190 (138.4 - 261) 157.7 (88.8 - 280.2) <0.0001 <0.0001 0.56
IL-6R (pg/ml) 153(102.7 - 228.6) 549.4 (454.9 - 663.6) 101.7(74.1-139.5) <0.0001 0.17 <0.0001
IL-10 (pg/ml) 2.2 (1.8 - 2.6) 3.1 (2.2 - 4.3) 0.4 (0.2 - 0.6) 0.063 < 0.0001 <0.0001
TNF- (pg/ml) 1.6 (1.3 - 2.0) 14.4 (9.8 - 21.2) 1.3 (0.7 - 2.1) <0.0001 0.39 <0.0001
Data presented as geometric mean with corresponding confidence interval unless stated, + Mean (SEM) ; CFU= colony forming units; G=Group
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Cytokines profiles in the test and validation subgroups
Figure : Test Figure : Validation ( using IL-1�)
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Validation Results: Using diseases and IL-1� cuto↵
Validation Results
The sputum cellular and cytokines patterns were also very similarbetween the test and validation subgroups.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
Cytokine profiles in the test and validation by clusters
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
TNF↵ as alternative for IL-1�
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
TNF↵ as alternative for IL-1�
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Validating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
TNF↵ as alternative for IL-1�
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Table of contents
1 Introduction and Objectives
2 Asthma and COPD Biological Clustering
3 Asthma and COPD Validation StudyValidating Asthma and COPD using LDAValidating Asthma and COPD using IL-1� cuto↵
4 Summary and Conclusion
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
Three biological clusters were identified which are...
Cluster 1
Eosinophilic asthma predominant (95% asthma) high Th-2 cytokines
Cluster 2
Neutrophilic asthma and COPD overlap representing about one-third ofeach disease group, high in Th-1 and proinflmmatory(PI) cytokines
Cluster 3
Non-neutrophilic COPD predominant (95% COPD) and high in PIcytokines
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
Three biological clusters were identified which are...
Cluster 1
Eosinophilic asthma predominant (95% asthma) high Th-2 cytokines
Cluster 2
Neutrophilic asthma and COPD overlap representing about one-third ofeach disease group, high in Th-1 and proinflmmatory(PI) cytokines
Cluster 3
Non-neutrophilic COPD predominant (95% COPD) and high in PIcytokines
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
Three biological clusters were identified which are...
Cluster 1
Eosinophilic asthma predominant (95% asthma) high Th-2 cytokines
Cluster 2
Neutrophilic asthma and COPD overlap representing about one-third ofeach disease group, high in Th-1 and proinflmmatory(PI) cytokines
Cluster 3
Non-neutrophilic COPD predominant (95% COPD) and high in PIcytokines
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
Three biological clusters were identified which are...
Cluster 1
Eosinophilic asthma predominant (95% asthma) high Th-2 cytokines
Cluster 2
Neutrophilic asthma and COPD overlap representing about one-third ofeach disease group, high in Th-1 and proinflmmatory(PI) cytokines
Cluster 3
Non-neutrophilic COPD predominant (95% COPD) and high in PIcytokines
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
Three biological clusters were identified which are...
Cluster 1
Eosinophilic asthma predominant (95% asthma) high Th-2 cytokines
Cluster 2
Neutrophilic asthma and COPD overlap representing about one-third ofeach disease group, high in Th-1 and proinflmmatory(PI) cytokines
Cluster 3
Non-neutrophilic COPD predominant (95% COPD) and high in PIcytokines
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
This study was validated on independent study using two methods,and reveal very similar pattern in cytokines and sputum cellular
IL-1� (at 130 pg/ml) and TNF↵ (at 5 pg/ml) preformed reasonablywell in discriminating the overlap subgroup, and could be potentialfuture markers
Conclusion
In conclusion, sputum cytokines can determine distinct and overlappinggroups of patients with severe asthma and COPD, and may contribute toimproved patients classification to enable stratified medicine!
However,for generalisation this findings need to be replicate inmulti-studies
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
This study was validated on independent study using two methods,and reveal very similar pattern in cytokines and sputum cellular
IL-1� (at 130 pg/ml) and TNF↵ (at 5 pg/ml) preformed reasonablywell in discriminating the overlap subgroup, and could be potentialfuture markers
Conclusion
In conclusion, sputum cytokines can determine distinct and overlappinggroups of patients with severe asthma and COPD, and may contribute toimproved patients classification to enable stratified medicine!
However,for generalisation this findings need to be replicate inmulti-studies
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
This study was validated on independent study using two methods,and reveal very similar pattern in cytokines and sputum cellular
IL-1� (at 130 pg/ml) and TNF↵ (at 5 pg/ml) preformed reasonablywell in discriminating the overlap subgroup, and could be potentialfuture markers
Conclusion
In conclusion, sputum cytokines can determine distinct and overlappinggroups of patients with severe asthma and COPD, and may contribute toimproved patients classification to enable stratified medicine!
However,for generalisation this findings need to be replicate inmulti-studies
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
This study was validated on independent study using two methods,and reveal very similar pattern in cytokines and sputum cellular
IL-1� (at 130 pg/ml) and TNF↵ (at 5 pg/ml) preformed reasonablywell in discriminating the overlap subgroup, and could be potentialfuture markers
Conclusion
In conclusion, sputum cytokines can determine distinct and overlappinggroups of patients with severe asthma and COPD, and may contribute toimproved patients classification to enable stratified medicine!
However,for generalisation this findings need to be replicate inmulti-studies
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Summary and Conclusion
This study was validated on independent study using two methods,and reveal very similar pattern in cytokines and sputum cellular
IL-1� (at 130 pg/ml) and TNF↵ (at 5 pg/ml) preformed reasonablywell in discriminating the overlap subgroup, and could be potentialfuture markers
Conclusion
In conclusion, sputum cytokines can determine distinct and overlappinggroups of patients with severe asthma and COPD, and may contribute toimproved patients classification to enable stratified medicine!
However,for generalisation this findings need to be replicate inmulti-studies
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
References
Carolan BJ and Sutherland ER (2013); Clinical phenotypes of chronic obstructivepulmonary disease and asthma: Recent advances.
Tabachnick BG and Fidell LS (2007); Using Multivariate Statistics. FIFTH ed.
Everitt B (2011); An Introduction to Applied Multivariate Analysis with R.
Gregory R and Samuelsen KM (2008); Advances in Latent Variable MixtureModels.
Barnes PJ (2008); The cytokine network in asthma and chronic COPD disease.
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
Introduction and ObjectivesAsthma and COPD Biological Clustering
Asthma and COPD Validation StudySummary and Conclusion
References
Acknowledgement
Prof Chris Brightling, Prof Paul Burton & Dr Chris Newby
Dr Mona Bafadhel & Dr Dhan Desai
Michael A Ghebre University of Leicester Biological clustering supports both Dutch and British hypotheses of Asthma and COPD
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