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

Area of Science:

• Pulmonology
• Immunology
• Genetics

Background:

• Previous cluster analysis of the Severe Asthma Research Program (SARP) identified five asthma subphenotypes.
• Sputum analysis revealed four inflammatory cellular patterns, with concurrent eosinophilia and neutrophilia indicating very severe asthma.

Purpose of the Study:

• To integrate inflammatory cellular measures and clinical variables for a refined asthma subphenotype analysis.
• To better understand the interactions between inflammation and clinical asthma subphenotypes.

Main Methods:

• Unsupervised cluster analysis was performed on 423 SARP participants who underwent sputum induction.
• Fifteen clinical and inflammatory variables were selected using factor analysis.

Main Results:

• Four phenotypic clusters were identified, ranging from mild-to-moderate allergic asthma to moderate-to-severe asthma.
• Clusters C and D (n=164) had more severe asthma, frequent healthcare use, and predominantly neutrophilic or mixed granulocytic sputum inflammation (>83%).
• Baseline lung function and sputum neutrophil percentage were key determinants of cluster assignment.

Conclusions:

• A multivariate approach identified four asthma subphenotypes across the severity spectrum.
• These subphenotypes range from mild allergic asthma with minimal inflammation to severe asthma with neutrophil-predominant inflammation.