ABSTRACT
BACKGROUND: There is no in vitro test to diagnose aspirin-intolerant asthma (AIA). The aim of this study was to test if challenge with aspirin of sputum cells from subjects with AIA triggers the release of cysteinyl leukotrienes (CysLTs), known to be mediators of bronchoconstriction in AIA. METHODS: Sputum induction was performed at baseline and at another visit 2 h after a lysine-aspirin bronchoprovocation in 10 subjects with AIA and 9 subjects with aspirin-tolerant asthma (ATA). The isolated sputum cells were incubated for ex vivo challenge. RESULTS: Release of CysLTs by sputum cells from patients with AIA was not induced by lysine-aspirin ex vivo, neither when cells were collected at baseline nor in sputum cells recovered after lysine-aspirin-induced bronchoconstriction, whereas release of CysLTs from sputum cells was triggered by an ionophore on both occasions. However, the CysLT levels elicited by the ionophore were higher in the AIA group both at baseline (AIA vs. ATA: 3.3 vs. 1.6 ng/million cells; p < 0.05) and after the lysine-aspirin bronchoprovocation (3.9 vs. 1.7 ng/million cells; p < 0.05). This difference in the amount of CysLTs released between the groups appeared to be related to the number of eosinophils. CONCLUSIONS: Intolerance to aspirin could not be triggered in sputum cells isolated from subjects with AIA. Together with the previous inability to demonstrate intolerance to non-steroidal anti-inflammatory drugs in isolated blood cells, these results support the requirement of tissue-resident cells in the adverse reaction. However, ex vivo stimulation of sputum cells may be developed into a new test of capacity for LT release in inflammatory cells recovered from airways.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Asthma, Aspirin-Induced/immunology , Sputum/cytology , Sputum/immunology , Adult , Asthma/immunology , Asthma, Aspirin-Induced/etiology , Asthma, Aspirin-Induced/metabolism , Basophils/cytology , Basophils/immunology , Bleeding Time , Cysteine/metabolism , Drug Hypersensitivity/etiology , Drug Hypersensitivity/metabolism , Eosinophils/cytology , Eosinophils/immunology , Female , Humans , Leukocyte Count , Leukotrienes/metabolism , Male , Middle AgedSubject(s)
Arachidonate 5-Lipoxygenase/metabolism , Hydroxyurea/analogs & derivatives , Leukotriene Antagonists/pharmacology , Leukotriene B4/analysis , Saliva/chemistry , Adult , Arachidonate 5-Lipoxygenase/drug effects , Chromatography, High Pressure Liquid , Double-Blind Method , Evaluation Studies as Topic , Female , Flow Cytometry , Humans , Hydroxyurea/pharmacology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Middle AgedABSTRACT
Genomic amplifications of the long arm of chromosome 8q are frequently detected in a number of tumor types, including neoplasias of the urothelium. DNA level amplification and increased expression of at 8q24 is commonly associated with chromosomal gains in this region. Using a urothelial cancer tissue microarray, the authors investigated the 8q24 amplification on bladder tumors and metastases. High-copy 8q24 amplification was detected in 9% (12 of 131) of primary tumors and 33% (6 of 18) of distant metastases. Additionally, the authors investigated the expression profiles of two frequently used biomarkers, p53 and Ki67, on the same arrays that had been analyzed for the 8q24 amplification. 8q24 amplification was positively correlated with Ki67 protein expression ( < 0.005), whereas a similar correlation with p53 did not reach statistical significance ( = 0.19). The authors conclude that 8q24 amplification occurs in a small subgroup of primary bladder tumors and in a more significant group of distant metastases.
