Alarmin Expression in the Upper and Lower Airways of Asthmatics with Allergic Rhinitis

Abstract

<b>Rationale:</b> Allergic inflammation of the upper and lower airways may be manifestations of a single inflammatory process; hence, overexpression of epithelial alarmins should be present in both upper and lower allergic airways. To evaluate this we examined expression of TSLP and IL-33 in allergic asthmatics with comorbid allergic rhinitis. <b>Methods:</b> We collected endobronchial biopsies from allergic asthmatics (AA, n=23) non-asthmatic controls (NA, n=11), and inferior nasal turbinate biopsies from AA with comorbid allergic rhinitis (AR, n=8) and non-AA/non-AR controls (NR, n=5). Biopsies were stained for IL-33 and TSLP and immunopositive cells in epithelium and laminae propria were expressed per mm2 of tissue. <b>Results:</b> In the lower airways of AA there were more TSLP (p=0.021) and IL-33 (p=0.01) immunopositive cells than in the upper airways of AR. In controls TSLP (p=0.0018) but not IL-33 was more highly expressed in the lower airways than in upper airways.&nbsp;In lower airways IL-33 expression was greater in AA versus NA (p=0.005) with no difference in TSLP expression (p=0.31). In upper airways TSLP and IL-33 were expressed at similar levels in AR versus NR (p&gt;0.05). <b>Conclusion:</b> Both TSLP and IL-33 were more highly expressed in lower compared to upper airways of allergic subjects.&nbsp;This may reflect heightened sensitivity to stimuli detected in the lungs, even under baseline conditions. In the lower airways of allergic asthma IL-33 expression was higher than in controls.. However, TSLP is present at similar levels between allergic subjects and controls in both upper and lower airways demonstrating constitutive expression under baseline conditions.