【摘要】 目的 研究肺癌患者的气道高反应性和肺通气功能情况，并探讨其易感因素，为肺癌患者肺通气功能的临床评估提供依据。 方法 对2010年4月-2011年4月收治的40例肺癌患者（A组）进行术前肺功能检测及气管激发试验，选取同期的健康体检者40例做对照组（B组），并采用logistic逐步回归分析肺癌患者的气道高反应性的易感因素。 结果 ①A组患者的用力肺活量、第1秒用力呼气容积（forced expiratory volume in one second，FEV1）、最高呼气流量（peak expiratory flow，PEF）以及最大呼气中期流量均小于B组，且差异有统计学意义（P=0.000）；②A组的FEV1估计异常人数和PEF估计异常人数均多于B组（Plt;0.05）；③A组组胺气道激发试验阳性者多于B组（χ2=5.000，P=0.025），且A组PD20FEV1低于对照组[分别为（4.69±0.82）、（8.32±1.43）μmol/L；t=13.930，P=0.000]；④logistic逐步回归分析表明影响A组患者的气道高反应性的因素为年龄、分型、TNM分期、病史、吸烟。 结论 肺癌气道反应性增高，且肺功能下降，由于肺癌气道高反应性的易感因素较多，因此需对合并因素较多者进行及时的预防，防止由于气道阻力增加和气道狭窄引起的胸闷、咳嗽、喘息和呼吸困难等症状。【Abstract】 Objective To learn the condition of bronchial hyper-reactivity and pulmonary function in patients with lung cancer, and explore the risk factors for bronchial hyper-reactivity in order to provide clinical reference for pulmonary function evaluation in patients with lung cancer. Methods Forty patients with lung cancer treated in our hospital from April 2010 to April 2011 (research group) took pulmonary function and tracheal stimulation tests before operation, and in the meanwhile, 40 healthy people were chosen as controls. The logistic regression analysis was employed to analyze the risk factors for bronchial hyper-reactivity. Results The forced vital capacity, forced expiratory volume in one second (FEVl), peak expiratory flow (PEF) and maximal mid expiratory flow in the research group patients were all significantly lower than those in the control group patients (P=0.000). The number of patients with estimated FEVl and PEF abnormality in the research group was more than that in the control group (P=0.05). The number of patients positive in histamine bronchial provocation test in the research group was more than that in the control group (χ2=5.000, P=0.025), and the PD20FEV1 level of the research group was lower than that of the control group [(4.69±0.82) and (8.32±1.43) μmol/L; t=13.930, P=0.000]. Logistic regression analysis showed that the risk factors for bronchial hyper-reactivity in patients with lung cancer were age, type, TNM stage, history of lung cancer, and smoking. Conclusions The airway reactivity elevates and the lung cancer pulmonary function decreases in lung cancer patients. Because there are many risk factors, prevention should be taken for patients with combined risk factors to avoid the occurrence of chest distress, cough, gasp and dyspnea caused by increased airway resistance and stricture.
Objective To investigate the changes of small airway function and diffusing capacity in patients with mild asthma before and after bronchial provocation test (BPT).Methods BPT was performed in suspected asthma patients with chief complaints of paroxysmal wheeze,chest tightness and cough，but with normal chest X-ray and baseline pulmonary function.BPT positive group was regarded as asthma group，while BPT negative group as control group.Lung volume，ventilatory function and diffusing capacity were measured before and after BPT and compared between the asthma and control groups.Results （A）No statistical differences were found in FEV1%，FEV1/FVC，FVC%，VC%，TLC%，FRC%，RV%，RV/TLC between the asthma and control groups before BPT.FEV1/FVC and FVC% were significantly decreased (all Plt;0.01)，while FRC% (Plt;0.05)，RV% (Plt;0.01) and RV/TLC (Plt;0.01) increased significantly in the asthma group after BPT compared with the control group.The decline rate of FEV1/FVC and FVC% and the increase rate of TLC%，RV%，RV/TLC were significantly higher in the asthma group than those in the control group (all Plt;0.01).（B）Compared with the control group，FEF25%-75% (Plt;0.05)，Vmax75% (Plt;0.01) and Vmax50% (Plt;0.05) were significantly lowered before BPT，while the above parameters and Vmax25% were significantly decreased after BPT in the asthma group (all Plt;0.01).The decline rate of FEF25%-75%，Vmax75%，Vmax50% and Vmax25% was significantly higher in the asthma group than those in the control group (all Plt;0.01).（C）There was no statistical difference in DLCO in both groups before and after BPT.Conclusions Patients with mild asthma had small airways impairment before BCT which further declined after BPT.However,no impairment of diffusion capacity was found before or after BPT.
Objective To explore the effects of Aspergillus fumigatus（A. fumigatus） spores on airway inflammation and responsiveness in asthmatic rats.Methods Seventy male Wistar rats were randomly divided into Ⅰ and Ⅱ groups（n=35 in each group），then Group Ⅰ and Group Ⅱ were subdivided into a normal control group（n=5），an asthma group（n=10），a spores-treated control group（n=10），and a spores-treated asthma group（n=10）.The rats were sensitized to ovalbumin（OVA） and challenged with aerosol OVA to establish the asthma model.The effects of A. fumigatus spores on asthmatic rats before and after OVA aerosol challenging were investigated in Group Ⅰ and Group Ⅱ，respectively.The parameters associated with bronchial epithelial damage were observed by total protein concentration in BALF measured by BCA method.Total and differential cell counts in BALF were also counted.The airway resistance and airway responsiveness were calculated by transpulmonary pressure and gas flow rate.Results In Group Ⅰ，the total protein in BALF in the asthma group treated with A. fumigatus spores before OVA challenging（Group CA） was increased remarkably compared to the asthma group（Group A1）[（1.125±0.254）μg/mL vs（0.825±0.173）μg/mL，Plt;0.01].The nonspecific airway resistances induced by different concentration of acetylcholine in Group CA ［（0.997±0.196）cm H2O•mL-1•s-1，（1.123±0.142）cm H2O•mL-1•s-1，（1.130±0.197）cm H2O•mL-1•s-1］were increased significantly compared to Group A1 [（0.655±0.089）cm H2O•mL-1•s-1，（0.687±0.048）cm H2O•mL-1•s-1，（0.821±0.043）cm H2O•mL-1•s-1]（all Plt;0.05）.In Group Ⅱ，however，the above parameters in the asthma group treated with A. fumigatus spores after OVA challenging（Group AC） were not dramatically increased compared with the asthma group（Group A2）（all Pgt;0.05）.The differences in the total and differential cell counts in BALF in Group CA were not remarkable compared to other subgroups in Group Ⅰ（all Pgt;0.05）.But the BALF neutrophil count in Group AC was increased obviously compared to Group A2 ［（2.488±0.420）×106 vs （0.936±0.459）×106，Plt;0.05］.Conclusion These data indicate that exposure to A. fumigatus spores before challenging causes aggravated epithelial damage and increased airway resistance in an asthma rat model.
Objective To investigate the relationship of small airway function with airway sensitivity and reactivity and assess the factors influencingairway hyperresponsiveness (AHR).Methods Data of consecutive subjects with suspected asthma who had a≥20% reduction in FEV1 after ≤12.8 mmol/L cumulative doses of methacholine were analyzed from January 2005 to April 2006.Airway sensitivity was assessed by the cumulative dose of methacholine required to cause 20% reduction in FEV1 (PD20).Airway reactivity was analyzed using the slope of the dose-response curve (DRS).The DRS was defined as the reduction in FEV1 from baseline after the final dose of methacholine inhaled divided by the cumulative dose inhaled.Because of their highly skewed distribution，DRS was logarithmically transformed (log10) for all analysis.Results A total of 184 consecutive subjects aged 16 to 80 years was enrolled.There were 70 male (38.0%) and 114 female (62.0%) subjects.Subjects with higher airway sensitivity，indicated by lower PD20，also had a lower Vmax50% and Vmax25%，and vise versa.PD20 was negatively correlated wit log10DRS (r=-0.874，Plt;0.01).In a simple linear regression model，log10DNS was significantly correlated with FEV1%，Vmax50% or Vmax25% respectively (the determinant r2 were 0.062，0.097 and 0.085，respectively，all Plt;0.01).In a multiple linear regression model that included age，height，and percentage of predicted FEV1，Vmax50% and Vmax25% accounted for 3.9% and 2.6%，respectively，of variability in airway reactivity.The association between Vmax50% and log10DNS was significant in both male and female subjects.The r2 was higher in male subjects.The subjects were divided into three age groups and the association between Vmax50% or Vmax25% and log10DNS was higher in female than in male for age≤25 years，higher in male than in female for 25 -45 years.No association was found for agegt;45 years in both males and females.Conclusions Impaired small airway function is associated with higher airway sensitivity and reactivity to methacholine in subjects with suspected asthma.
Objective To investigate the role of endogenous Hydrogen Sulfide ( H2S) in airway inflammation and responsiveness in a rat model of chronic passive-smoking. Methods Male SD rats were randomly divided into a control group ( breathing fresh air) and a passive smoking group [ cigarette smoking( CS) passively] , with 18 rats in each group. Six rats in each group were randomly intraperitoneally injected with normal saline, sodium hydrosulfide ( NaHS) or propargylglycine ( PPG, an irreversible inhibitor of cystathionine- γ-lyase) . The animals were divided into six subgroups, ie. Con group, NaHS group, and PPG group, CS group, CS+ NaHS group, and CS + PPG group. After 4 months, lung histological change and airway tension were measured. The H2S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay. The expression of cystathionine-γ-lyase ( CSE) was measured by western blot. Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group( P lt;0. 05) ; the H2 S levels of plasma were significantly higher in CS group, NaHS group and CS + NaHS group, and much lower in PPG group ( P lt; 0. 05, respectively) . Compared with CS group, the H2S levels of plasma were significantly higher in CS + NaHS group, and much lower in CS + PPG group( P lt; 0. 05, respectively) . The H2S level of lung tissue in each group had no significant difference ( P gt; 0. 05) . Compared with Con group,score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to ACh and KCl was significant augmented in CS group. Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS +NaHS group( P lt;0. 05) , and vise versa in CS + PPG group( P lt; 0. 01) . Conclusion H2S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airwayinflammation and airway responsiveness.
Objective To study the concentration of neurotrophins( including NGF, BDNF, NT3 and NT4) in the lung of SD rats infected by respiratory syncytial virus( RSV) , and to explore the relationship between the concentration of the neurotrophins, airway hyperresponsiveness and airway neural plasticity.Methods Twenty SD newborn rats were randomly divided into a control group and a RSV-infected group with ten rats in each group. The RSV-infected group were infected with 5 ×104 TCID50/0. 1 mL RSV each week. After 8 weeks, the bronchial responsiveness of the SD rats was assessed. The bronchial inflammation was assessed by HE staining with left lung. Synaptophysin and neurofilament expressions in the lung of SD rats were assayed by the immunohistochemistry staining. In situ hybridization was used to detect the RSV RNA in the lung. The concentration of neurotrophins in the lung of SD rats were detected by ELISA. Results The RSV-infected group showed elevated airway hyperresponsiveness and more inflammatory cells infiltrated in the lung; In situ hybridization showed positive signal of RSV RNA in lung interstitium of the RSV-infected rats. Synaptophysin and neurofilame levels in the airway were increased in the RSV-infected group. Supernatant levels of NGF and BDNF were significantly increased compared with the control group ( P lt;0. 05) . The NT3 and NT4 levels had no significant difference in all groups. The expressions of NGF and BDNF were positively related to the expressions of synaptophysin( r1 = 0. 892, r2 = 0. 995, P lt; 0. 05) and neurofilament( r1 = 0. 949, r2 =0. 936, P lt;0. 05) , also positively related to the airway hyperresponsiveness ( r1 =0. 929, r2 = 0. 910, P lt; 0. 05) . Conclusion RSV infection results in increased expressions of NGF and BDNF in the lung, which are correlated to the change of airway neural plasticity and airway hyperresponsiveness.
Objective To study the efect of montelukast for improving bronchial hyperresponsiveness (BHR) in treatment of bronchiolitis. Methods Four hundreds infants, 3 to 24 months old, hospitalized with acute bronchiolitis in three Hospitals (Urumqi Children’s Hospital, Pediatrics Department of First Ailiated Hospital of Xinjiang Medical University, and Pediatrics Department of Army General Hospital) from January, 2007 to January, 2008, were randomly assigned into four groups: placebo group (n=92), budesonide group (n=91), montelukast short-course group (7 days, n=88), and montelukast long-course group (28 days, n=90). Main outcome measure was BHR ater treatment, including recurrent bronchiolitis wheezing and asthma incidence rate. Secondary measures were changes in serum T-IgE level and eosinophilic cationic protein (ECP) level. Results All four groups were comparable at baseline. No signiicant diferences were observed between placebo group and budesonide group in changes of serum T-IgE (F=6.17, P=0.00), ECP (F=8.13, P=0.00), recurrent post-bronchiolitis-wheezing (χ2=49.46, P=0.00) and asthma incidence rate (χ2=27.21, P=0.00). Ater treatment with montelukast, there was statistical signiicance in T-IgE and ECP level, times of recurrent bronchiolitis wheezing and asthma incidence rate, as follows, montelukast short-course group versus placebo group (F=12.56, P=0.00), montelukast short-course group versus budesonide group (F=7.22, P=0.00), montelukast long-course group versus placebo group (F=20.48, P=0.00), montelukast long-course group versus budesonide group (F=13.56, P=0.00), montelukast short-course group versus montelukast long-course group (F=1.04, P=0.00). Conclusions Budesonide treatment for 7 days can not improve bronchial hyperresponsiveness induced by bronchiolitis, while montelukast does, that is, montelukast can decrease both the times of bronchiolitis wheezing and asthma incidence rate. Long-course treatment of montelukast is superior to that of short-course.
Objective To investigate the changes of small airway function，airway resistance and responsiveness of extrathoracic airway in chronic cough patients before and after bronchial provocation test (BPT)．Methods 68 chronic cough patients were requested to conduct lung function test and BPT．The airw ay resistance were measured via forced oscillationary technology before and after BPT．Results BPT revealed airway hyperresponsiveness in 52％subjects．MEF50 and R0 before BPT were significantly different between the patients with or without airway hyperresponsiveness．Post BPT changes in MEF50(MEF50％) were correlated positively to the changes in FEV1(FEVl％)，and negatively to the changes in R0[Ro-d]． Extrathoracic airway hyperresponsivenes(EAHR)was f0und in13 patients，in which 6 patients were not revealed by routine BPT．Conclusion There is small airway function abnormalities in chronic cough patients．Extrathoracic airway responsiveness test is a valuable supplementary index to routine BPT．
ObjectiveTo explore the effects of Aspergillus fumigatus (A. fumigatus) on airway inflammation, airway responsiveness and total serum IgE in asthmatic rats. MethodsEighteen male Wistar rats were divided into three groups randomly, ie. a normal control group, an asthmatic model group, and an A. fumigatus group. The rats in the model group and the A.fumigatus group were sensititized and challenged with ovalbumin to establish asthmatic model. After establishment of asthmatic model, the rats in the A. fumigatus group were treated with chronic A. fumigatus spores inhalation. Subsequently, airway responsiveness/sensitivity to methacholine(Ach), levels of serum IgE and airway inflammation were assessed and compared among three groups. ResultsCompared with the asthmatic rats, the rats treated with A. fumigatus showed higher airway responsiveness (Penh/baselin value was significantly increased at the Mch concentration of 12.5, 25 and 50 mg/mL), increased inflammatory cells infiltration in pulmonary tissue slices and increased serum IgE level (P < 0.05). Most importantly, serum IgE level was detected in close relationship with PC100 which was defined as the dose of Mch causing 100% increase of enhance pause (Penh) value without Mch challenge (r=-0.873, P < 0.01). Serum IgE level was also closely related to the percentage of eosinophils in bronchoalveolar lavage fluid (r=0.937, P < 0.01). ConclusionsChronic A. fumigatus inhalation aggravates airway inflammation, bronchial hyperresponsiveness and serum IgE level in asthma. IgE may play an important role in facilitating the development of bronchial responsiveness and eosinophilic inflammation.