Rationale:
A proportion of severe asthma patients suffers fro
m persistent airflow limitation, often
associated with
more symptoms and exacerbations
.
Little is known
about the underlying
mechanisms. Aiming for discovery of unexplored potential mechanisms, we used Gene Set Variation
Analysis (GSVA), a sensitive technique that can detect underlying pathways in heterogeneous
samples.
Methods:
Severe asthma patients from
the U
-BIOPRED cohort with persistent airflow limitation
(post
-bronchodilator FEV
1
/FVC ratio < lower limit of normal) were compared to those without
persistent airflow limitation. Gene expression was assessed on the total RNA of sputum cells, nasal
brushin
gs and endobronchial brushings and biopsies. GSVA was applied to identify differentially
-
enriched pre
-defined gene signatures based on all available gene expression publications and data on
airways disease.
Results:
Differentially
-enriched gene signatures
were identified in nasal brushings (1), sputum (9),
bronchial brushings (1) and bronchial biopsies (4), that were associated with response to inhaled
steroids, eosinophils, IL
-13, IFN
-alpha, specific CD4+ T
-cells and airway remodeling.
Conclusion:
Persiste
nt airflow limitation in severe asthma has distinguishable underlying gene
networks that are associated with treatment, inflammatory pathways and airway remodeling. These
results point towards targets for the therapy of persistent airflow limitation in sev
ere asthma.