The Cytokines Character After Bronchoprovocational Test And The Small Airway Function Of Cough Variant Patients

Objective: 1 To clarify the cytokine profiles in cough variant asthma patients after having been diagnosed through histamine brochoprovocational test(BPT), in order to find out the changing of inflammation in these atypical asthma patients. 2. To investigate the changing and significant of small airway function in CVA patients.Method: CVA patients and healthy volunteers were enrolled in this randomized, double blind, self-controlled, crossover trial. After having been except other diseases. 66 chronic cough patients were requested to have a bronchoprovocational test. CVA group has 34 patients who had been defined having CVA when the test result was positive; Control subjects were required to have a lifelong absence of any symptoms indicative of allergi,immune disease and other acute disease, their lung functions are normal. Bronchial dilated drugs, Corticosteroid, and anti-allergic drugs are inhibited before the provocational test. The airway resistant were measured via FOT (Forced Oscillationary Technology (before and after the test. Drew venous blood from CVA patients lOminutes after challenge, while in healthy patients without challenge. After having anticoagulated with heparin, PBMC were extracted and resuspended at a density of 2*106 cells/ml. Cell cultures were carried out with PHA stimulated as demanded in sterile 24-well culture plates at 37C in a humidified atmosphere with 5% CO2 for 48h. Cell-free supernatant was then harvested and stored at -30 C . IL-2,IL-4,IL-5,IL-13 were quantified by ELISA according to the manufacturer's instructions. SPSS11.0 software was used in Statistical analysis ,differences associated with probability of P< 0.05 were considered significant.RESULTS: (1) The spontaneous IL-5 concentration in cultures of PBMC were significantly increased in CVA group compared with that in normal controls, while the PHA induced IL-4, IL-13 were lower than controls. The concentrations of IL-2 and IL2/IL-4 were not significantly different between the two groups. Meanwhile, in CVA groups,the concentration of IL-4 and IL-13 after PHA stimulated was positively correlated. (2) All the cytokines measured and lung functions,PD20(prevocational cumulative dose when FEV1 decreased 20%) were not related to each other. (3) MEF50%(the ratio of MEF50 decrease after BPT) was positively related to FEVl%(the ratio of FEV1 decrease after BPT) and RO-d).Meanwhile,MEF50 was significant lower in CVA patients compared with control subjects, whereas RO was higher in CVA patients.Conclusions: (1) The small airway function of CVA patients may have been defected ,while the marker frequently used to indicate asthma : FEV1 and PEF are normal. (2) Although CVA patients have the same character as asthma, airway hyperresponsiveness and airway inflammation, the manifestation of their cytokines are different with typical asthma. In this paper, the concentration of IL-5 in PBMC of CVA patients after histamine challenge increased, while the PHA induced IL-4 and IL-13 concentration decreased. So we concluded that shortly after challenged, TH2 cells transfer into the lung parenchyma and airway, excretion and release IL-4,IL-5,IL-13. IL-4 and IL-13 temporal aggregate in the airway and take effect. At the same time, IL-5 enter the circulation immediately,and accelerate airway inflammation. (3 ) Because of the complexity of cytokines in asthma, immunity therapy of anti-interleukin is still limited.