Comprehensive Cluster Analysis for COPD Including Systemic and Airway Inflammatory Markers

Area of Science:

• Pulmonology
• Respiratory Medicine
• Clinical Phenotyping

Background:

• Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous respiratory condition.
• Understanding COPD heterogeneity is crucial for effective patient management and treatment strategies.
• Previous phenotyping efforts have yielded varied results, necessitating further investigation.

Purpose of the Study:

• To identify distinct clinical phenotypes in adults with stable chronic obstructive pulmonary disease (COPD) using cluster analysis.
• To characterize these COPD phenotypes based on a comprehensive set of clinical, inflammatory, and atopy markers.
• To investigate the influence of sex, airway obstruction, and inflammation on COPD clustering.

Main Methods:

• Retrospective analysis of 178 stable COPD patients recruited from ambulatory care.
• Application of Hierarchical Clustering on Principal Components (HCPC) after multiple imputation for missing data.
• Consensus clustering to classify patients into homogeneous groups based on 84 variables, including smoking history, lung function, inflammation markers, and atopy.

Main Results:

• Three distinct COPD clusters were identified, primarily differentiated by sex, airway obstruction severity, and neutrophilic inflammation.
• Cluster 1: Men with moderate airway obstruction (n=67).
• Cluster 2: Men with severe airflow limitation, prone to exacerbations, and exhibiting intense airway and systemic neutrophilic inflammation (n=56).
• Cluster 3: Women with moderate airway obstruction (n=55).
• All clusters showed low bacterial colonization, low fractional exhaled nitric oxide (FeNO), and minimal allergen sensitization.
• The COPD Assessment Test (CAT) score did not significantly differ between the identified clusters.

Conclusions:

• This study successfully identified three COPD clusters significantly shaped by sex, airway obstruction, and neutrophilic inflammation.
• The identified phenotypes were not clearly distinguished by symptoms (CAT score) or T2 biomarkers (FeNO, atopy).
• These findings highlight the importance of integrating systemic inflammation markers and sex into COPD phenotyping for a more refined understanding of the disease.