Thymic stromal lymphopoietin (TSLP) in naturally occurring asthma exacerbations in adults

INTRODUCTION: TSLP is released from the airway epithelium in response to damage and is pivotal in orchestrating type 2 immune responses seen in allergic asthma. However, the role of TSLP in exacerbations of asthma has not been evaluated. AIM: We sought to investigate whether the epithelial damage associated with an asthma exacerbation would increase TSLP expression and whether this in turn would promote an increase in sputum eosinophils. METHODS: During 12 months, adult asthmatics, admitted to hospital with an asthma exacerbation, were recruited. Induced sputum was collected within 24 hours of admission. TSLP mRNA was quantified using Droplet Digital PCR. RESULTS: A total of 47 patients were recruited, of which 28 had sputum samples suitable for gene expression analysis (age 19-43, 61% females). Expression of TSLP mRNA in sputum correlated with the total count of non-squamous cells (Spearman9s rho 0.52, p=0.004). There was an inverse correlation between TSLP mRNA and %-eosinophils (rho -0.46, p=0.02), while there was no correlation with the percentage of neutrophils, macrophages, lymphocytes or columnar epithelial cells, respectively. In patients with suitable sputum at both exacerbation and follow-up (n=18), there was not a significant difference in TSLP expression (p=0.174). The same inverse correlation with TSLP and %-eosinophils was seen at follow-up (rho -0.49, p=0.04). CONCLUSIONS: TSLP expression in sputum correlates with total cell count, and, somewhat surprisingly, inversely with %-eosinophils. While TSLP is well described as a master switch of type 2 inflammation in stable asthma, these results indicate that other factors determine the inflammatory phenotype during asthma exacerbations.