Abstract
Background: Extrinsic allergic alveolitis (EAA) patients form heterogenous group with different clinical manifestation and different prognosis. We aimed to determine how to phenotype distinct EAA subgroups. Predictive role of the bronchoalveolar lavage fluid (BALF) IL-4Rα concentration at the time of diagnosis with regard to the clinical behavior in EAA patients was studied. Methods: Concentrations of MMP-7, IL-4Rα, TNF-α, and PAR-2 were measured in the BALF od 71 EAA patients at the time of diagnosis. Lung functions and outcome data were assessed at 12 months after the diagnosis. Correlations between the BALF protein concentration, cell profile, lung functions and patient outcome were determined. Results: We found positive correlations between BALF IL-4Rα concentration and BALF eosinophils (p = 0,006), negative correlation between IL-4Rα BALF concentration and diffusing capacity (DLco) (p = 0,003), negative correlation between IL-4Rα BALF concentration and forced vital capacity (FVC) (p = 0,004) and negative correlation between IL-4Rα concentration and BALF lymphocytes (p = 0,04). The BALF concentration of IL-4Rα was significantly higher in acute exacerbation patients (p = 0,0032) and in patients progressing despite corticosteroid treatment (p = 0,04). We observed a positive correlation between MMP-7 BALF concentration and the BALF lymphocytes (p = 0.05), negative correlation between the PAR-2 BALF concentration and DLco (p = 0.04) and a negative correlation between the BALF TNF-α concentration and DLco (p = 0.03). Conclusions: Specific subgroup of EAA patients with more severe functional impact, distinct BALF cell profile and higher IL-4Rα BALF concentration can be differentiated. Correlations between the BALF concentrations of PAR-2, MMP-7 and TNF-α with clinical parameters may reflect the role of inflammation in the pathogenesis of EAA.
Highlights
Extrinsic allergic alveolitis (EAA) patients form heterogenous group with different clinical manifestation and different prognosis
We further studied the predictive role of bronchoalveolar lavage fluid (BALF) IL-4Rα concentrations at the time of diagnosis with regard to the clinical behavior of the disease in the subgroup of patients with EAA
The present study shows that baseline BALF IL-4Rα concentrations are higher in EAA
Summary
Extrinsic allergic alveolitis (EAA) patients form heterogenous group with different clinical manifestation and different prognosis. Extrinsic allergic alveolitis (EAA) continue to attract the interest of medical doctors and scientists because of the lack of efficient treatment in patients with dominant fibrotic impairment. Eventhough pathogenesis of fibrotic EAA needs to be elucidated, several cytokines have been shown to play role. Exposure to IL-4 triggers matrix metalloproteinase 7 (MMP-7) induced Fas ligand cleavage from bronchial epithelial cells and may contribute to airway damage and inflammation [2]. TNF-α together with hypoxia stimulates production of MMP-7 by macrophages and increases expression of proteinase activated receptor-2 (PAR-2) [3]. Activation of PAR-2 was shown to increase invasivity of various cell types, mainly through MMP production and was shown to downregulate cytokine induced epithelial apoptosis [4]
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