Airway Excitation Test The Impact On Patients With Bronchial Asthma Airway Inflammation And Joint Inhaled Fluticasone Propionate And Salmeterol Castro Evaluation Of Efficacy

【Background】Asthma is a chronic inflammatory disorder of the airways. The chronic inflammation is associated with airway hyperresponsiveness that can be measured by bronchial challenge test. For asthmatic patients with symptoms consistent with recurrent episodes of breathlessness or coughing, particularly at night or in the early morning, but with normal lung function, bronchial challenge test may help establish a diagnosis of asthma. But the measurement of airway hyperresponsiveness can not reflect the airway inflammation and maybe induce airway inflammation. Exhaled breath condensate (EBC) is a newly developed non-invasive measurement to assess the inflammatory status of airway. It has been found that the change of some inflammation biomakers in EBC are associated with the severity of inflammation in the airways or lungs of some respiratory diseases. Comparing with the classical methods such as collection of induced sputum, and bronchoalvoelar lavage fluid, EBC has the advantages of noninvasiveness and can be performed repeatedly in patients.【Objectives】1. To investigate the influence of methacholine bronchial challenge test on the inflammation mediators in EBC and pulmonary function of atypical asthmatic patients.2. To evaluate the safety and endurance of methacholine bronchial challenge test for asthmatic patients by using modified Borg scale.3. To investigate the effects of inhaled glucocorticosteroids combinated with long-acting inhaledβ₂ agonist on the inflammation mediators in EBC, pulmonary function, and asthma control test score of asthmatic patients.【Methods】 1. 12 healthy subjects and 33 atypical asthmatic patients with symptoms of recurrent episodes of breathlessness or coughing, particularly at night or in the early morning were enrolled. Pulmonary function tests were performed. EBC were collected before and after methacholine bronchial challenge test for asthmatic patients, breathlessness before and after methacholine bronchial challenge test were graded by using the modified Borg scale (MBS). EBC were collected once for the healthy supjects. Levels of LTB₄, 8-isoprostane and IL-4 in EBC were measured by specific enzyme immunoassay kits.2. Inhaled Fluticasone combinated with salmeterol were administrated for one month to 19 atypical asthmatic patients of positive methacholine bronchial challenge test. Before and after drug treatment, asthma control test (ACT) were administrated to assess the control of asthma, EBC were collected and pulmonary function test were also performed before and after drug treatment. and levels of 8-isoprostane and LTB₄ in EBC were measured by specific enzyme immunoassay kits.【Results】1. 8-isoprostane levels in EBC of asthmatic patients before and after methacholine bronchial challenge test were increased compare with healthy subjects (5.58±2.48 and 6.01±2.44 versus 3.43±1.19 pg/ml, P＜0.01 and P＜0.001 respectively). 8-isoprostane levels in EBC of asthmatic patients after methacholine bronchial challenge test were no significant difference compared to baseline. LTB₄ levels in EBC of asthmatic patients before and after methacholine bronchial challenge test were increased compared with healthy subjects (14.50±6.13 and 16.4±5.69 versus 7.10±1.72 pg/ml, P＜0.001 respectively). LTB₄ levels in EBC of asthmatic patients were increasered compared to baseline after methacholine bronchial challenge test. IL-4 was undectab]e in all the EBC samples. The MBS scores of asthmatic patients were increasered compared to baseline after methacholine bronchial challenge test. After inhaling rapid-actingβ2-agonists at the end of methacholine bronchial challenge test, the pulmonary function parameters of the asthmatic patients were decreased compared to the baseline. 8-isoprostane and LTB₄ levels in EBC of asthmatic patients were no correlation with age, course of disease and pulmonary function parameters.2. After administration of inhaled Fluticasone combinated with salmeterol for one month, the pulmonary function parameters of the asthmatic patients were increased compared to the baseline. LTB₄ levels in EBC of asthmatic patients were decreased compared to baseline(9.00±1.82 versus 14.18±6.26 pg/ml, P＜0.05), and were no significant difference compared with healthy subjects(9.00±1.82 versus 7.10±.72 pg/ml, P＞0.05). 8-isoprostane levels in EBC of asthmatic patients were no significant difference compared to baseline(4.89±1.28 versus 5.35±2.02 pg/ml, P＞0.05). ACT scores of asthmatic patients were increasered compared to baseline(23.8±1.6 versus 14.5±3.8, P＜0.001). Baseline ACT scores of asthmatic patients were correlated positively with FEV1 per predict of baseline (r=0.470, P=0.042). After administration of inhaled Fluticasone combined with salmeterol, ACT scores of asthmatic patients were correlated positively with FEV1 per predict (r=0.487, P=0.034), FEV1 per predict (r=0.472, P=0.041), FVC(r=0.598, P=0.007), and FVC per predict(r=0.488, P=0.034).【Conclusion】1. EBC is a completely noninvasive method for obtaining samples that reflect airway lining fluid composition. Being a measurement, collecting EBC is an easy and feasible process. Some inflammation mediators in EBC such as 8-isoprostane and LTB₄ can be detected and can be used to assessing and monitoring the airway inflammation of asthma.2. Dyspnea provocated by methacholine bronchial challenge test can be apperceived in all the asthmatic patients with atypical symptoms, and the dyspnea extent can be endured. The airway inflammation level of asthmatic patients is increased after methacholine bronchial challenge test.3. The airway neutrophil cell inflammation of asthmatic patients was controlled by administrated with inhaled Fluticasone combinated with salmeterol, but oxidative stress was not controlled by administrated with inhaled Fluticasone combinated with salmeterol. Anti oxidative stress treatment for the asthmatic patients should be considered in the future.4. ACT was a validated measure for assessing clinical control of asthma but could not reflect the airway inflammation and oxidative stress status. When ACT combinated with the inflammation mediators in EBC, asthma control can be assessed more comprehensive.