The role of atopy in the pathogenesis of bleomycin pulmonary toxicity

Bleomycin pulmonary toxicity (BPT) is a potentially life-threatening consequence of bleomycin usage in patients. An overproduction of epithelium-derived cytokines, habitually linked to allergic inflammation, has been recently revealed in experimental models of BPT. We assessed retrospectively our co...

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Bibliographic Details
Published in:Respiratory medicine 2019-08, Vol.155, p.1-5
Main Authors: Ozyigit, Leyla Pur, Aktas, Esin Cetin, Senbas, Zarif Asucan, Ozturk, Ayse Bilge, Ozturk, Erman, Ergonul, Mehmet Onder, Tabak, Levent, Ferhanoglu, Burhan, Cetiner, Mustafa, Deniz, Gunnur
Format: Article
Language:English
Subjects:
Allergies
Amphiregulin
Atopy
Bleomycin
Bleomycin hydrolase
Blood
Cell culture
Chemokines
Cytokines
Demographics
Disease
Eotaxin
Epithelium
Fibrosis
Hodgkin's lymphoma
Hydrolase
Inflammation
Interleukin 1
Levels
Lymphoma
Pathogenesis
Pulmonary fibrosis
Pulmonary toxicity
R&D
Research & development
Risk analysis
Risk factors
Thymic stromal lymphopoietin
Tomography
Toxicity
Tumor necrosis factor-TNF
Tumor necrosis factor-α
γ-Interferon
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Summary:Bleomycin pulmonary toxicity (BPT) is a potentially life-threatening consequence of bleomycin usage in patients. An overproduction of epithelium-derived cytokines, habitually linked to allergic inflammation, has been recently revealed in experimental models of BPT. We assessed retrospectively our cohort of patients with Hodgkin Lymphoma treated with bleomycin between 2014 and 2016 for their demographic, clinical features, including BPT development, atopy status and risk factors for BPT. Then they were invited for allergy testing and blood sample collection. The samples were stimulated with different stimuli (Bleomycin, IL-33, TSLP) for 24 h on cell culture. The culture supernatants were analysed for TGF-β, Galectin3, Arginin, Amphiregulin, Eotaxin, IFNγ, TNFα, IL1β, 4, 5, 6, 10, 13, 17, MIP-1α, and bleomycin hydrolase (BLH) levels. The cohort consisted of 51 patients showed that atopy was the only significant risk factor for BPT occurrence (OR: 7.2, p = 0.007). Fourteen subjects were included for blood analysis. The analysis of supernatants at the unstimulated condition revealed that BLH and Amphiregulin were significantly lower in patients who had BPT than controls. The BLH cut-off that best identified a history of BPT was 175.31 (Sensitivity: 62.5%, specificity: 100%). Following the stimulation, BLH reduced compared to the unstimulated condition and the difference between groups remained significant (p 
ISSN:0954-6111
1532-3064
DOI:10.1016/j.rmed.2019.06.020