Objective To observe the eotaxin expression of rat airway smooth muscle cells ( ASMCs) induced by serum from asthmatic rats, and explore the possible mechanism. Methods ASMCs isolated fromrat tracheas were cultured in vivo. Then they were treated with serum from asthmatic rats, or treated with serum and dexamethasone simultaneously. The level of eotaxin protein in supernatant and eotaxin mRNA in ASMCs were measured by ELISA and reverse transcription-polymerase chain reaction. The expression of cAMP in ASMCs was examined by radioimmunoassay. Results After the treatment with sensitized serum, the eotaxin level in supernatant and mRNA expression in ASMCs were significantly higher [ ( 107. 09 ±7. 12) ng/L vs. ( 0. 63 ±0. 56) ng/L, P lt; 0. 05; 1. 39 ±0. 04 vs. 0. 05 ±0. 01, P lt;0. 05] , and the level of cAMP in ASMCs was significantly lower compared with the control group [ ( 17. 58 ±3. 62) ng/L vs. ( 32. 39 ±3. 36) ng/L, P lt; 0. 05] . After intervened by the sensitized serum and dexamethasone simultaneously, the protein and mRNA expressions of eotaxin were lower compared with those intervened by sensitized serumalone [ ( 64. 18 ±4. 04) ng/L and 0. 77 ±0. 19] . The level of eotaxin in supernatant was negatively correlated with cAMP level in ASMCs ( r = - 0. 788, P lt; 0. 01) . Conclusions There is anautocrine function in ASMCs as inflammatory cells after stimulation with sensitized serum. Eotaxin may play an important roll in the pathogenesis of asthma via a cAMP-dependent pathway.
Objective To explore the effect of leukotriene receptor antagonist montelukast on physicochemical property of sputum and airway mucus hypersecretion in patients with acute exacerbation of bronchiectasis. Methods Eighty-four inpatients with acute exacerbation of bronchiectasis were randomly divided into a control group and an experiment group, with 42 cases in each group. The control group received conventional therapy and the experiment group took orally montelukast 10 mg before sleep every day based on conventional therapy for two weeks. At admission and 15 days after admission, the amount in 24 hours, dry/wet weight ratio and viscosity of sputum were observed while the levels of neutrophil elastase (NE) and mucin MUC5ac in sputum were determined by ELISA. The pulmonary ventilation function, airway resistance and blood gas analysis were also measured. Results The sputum amount in 24 hours, dry/wet weight ratio and viscosity of sputum, NE and MUC5ac of sputum, pulmonary ventilation function, blood gas analysis and airway resistance were declined or improved remarkably after treatment compared with before treatment in two groups (P<0.05). Meanwhile, the sputum amount in 24 hours [(5.62±1.83) g vs. (7.53±2.32) g], NE [(3.85±0.97) μg/ml vs. (4.54±1.03) μg/ml], MUC5ac [(0.65±0.21) μg/ml vs. (0.82± 0.29) μg/ml] and the airway resistance [(119.16±11.76)% vs. (128.37±12.08)%] were declined remarkably in the experiment group compare with the control group after treatment (all P<0.05). The viscosity of sputum between the two groups after treatment showed no significant difference. Conclusion In patients with acute exacerbation of bronchiectasis, montelukast can reduce amount of sputum and airway resistance, reduce expression of mucin MUC5ac through down-regulation of NE, thus inhibit airway mucus hypersecretion.
ObjectiveTo evaluate the effect of airway management drugs on the respiratory function and postoperative recovery of patients who had moderate or severe chronic obstructive pulmonary diseases(COPD) undergoing an open chest surgery. MethodThere were a total of 22 patients suffering from both lung cancer, esophageal cancer or gastroesophageal junction carcinoma and moderate to severe COPD(of which there were 16 males and 6 females; accepting traditional operation 5 cases and minimally-invasive operation 17 cases; lung cancer 16 cases, esophageal cancer 4 cases and gastroesophageal junction carcinoma 2 cases as the observation group). To statistic the respiratory function and arterial blood gas analysis before and after treating with airway management drugs. And compare the postoperative pulmonary complications(PPCs) and hospital-stay with 50 patients who have no COPD(of which there were 34 males and 16 females; accepting traditional operation 17 cases and minimally-invasive operation 33 cases; lung cancer 35 cases, esophageal cancer 11 cases and gastroesophageal junction carcinoma 4 cases as the control group). ResultThere was a statistical difference of forced expiratory volume in one second(FEV1), forced vital capacity(FVC) and maximal voluntary ventilation(MVV) after the above treatment by 7 to 10 days and comparing with prior treatment(P<0.05). Partial pressure of oxygen(PaO2) increased with no statistical difference(P>0.05) while PaCO2 decreased with a statistical difference(P<0.05）. Comparing with patients without COPD, the incidences of PPCs and postoperative hospital stay were of no statistical difference(P>0.05). ConclusionPatients with moderate or severe COPD with airway management drugs(antibiotics,glucocorticoids, bronchodilators and phlegm dissolving agent) in perioperative period could improve the respiratory function and operation tolerance effectively, reduce the incidence of PPCs and shorten postoperative hospital stay.
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 effects of 1, 25-( OH) 2D3 on the expression of matrix metalloprotease-9 ( MMP-9) and nuclear factor κB ( NF-κB) activity in a murine model of chronic asthma. Methods BALB/ c mice were sensitized and challenged with ovalbumin to establish chronic asthmatic model. The animals were randomly divided into a control group, an asthma group and a VD group. Lung sections from the mice were stained by HE and Masson’s trichrome, respectively. Morphometric analysis of the stained sections was performed using computerized image analysis system. Nuclear translocation of NF-κB p65 was examined using Western blot. The level of IκBαwas detected with real-time quantitative PCR ( RTPCR) and Western blot. In addition, the expression of MMP-9 in both activity and mRNA level was detected by gelatin zymograph and RT-PCR, respectively. Results Prominent airway remodeling developed in the asthma group, including the inflammatory cell infiltration, subepithelial collagen deposition and increased airway smooth muscle mass. In contrast, 1, 25-( OH) 2D3 attenuated these established structural changes of the airways. Stimulation with OVA induced a 7. 87-fold increase in the MMP-9 activity compared with that in the control group, and 1, 25-( OH) 2D3 treatment only induced a 3. 46-fold increase in the MMP-9 activity compared with that in the control group ( P lt;0. 05) . The mRNA level of MMP-9 in the VD group ( 3.16 ± 0.09) was decreased compared with the asthma group ( 5.74 ±0.13) ( P lt;0.05) , but itwas still higher than that in the control group ( 0.57 ±0.08) ( P lt;0.05) . 1, 25-( OH) 2D3 reduced the nuclear translocation of NF-κB p65 while up-regulated the IκBα level in lung tissue of chronic asthma. Conclusions 1, 25- ( OH) 2D3 can inhibit the NF-κB activity and down-regulate the expression of MMP-9 in lung tissue of chronic asthma, thus alleviating the established chronic asthma-induced airway remodeling.
Obstractive To observe the clinical effects and safety of endobronchial electrocautery treatment for tracheobronchial obstructive lesions in inoperable tracheobronchial squamous cell carcinoma.Methods Ninety-five patients with advanced and inoperable tracheobronchial squamous cell carcinoma were included. Thirty-four patients with central airway obstruction were treated with endobronchial electrocautery plus chemotherapy ( group A) and 61 patients without central airway obstruction were treated with chemotherapy alone ( group B) . The chemotherapy consisted of cisplatin or carboplatin, plus another thirdgeneration chemotherapy agent. Results In groug A, there were mean improvements in FEV1 of 41. 1% and in peak expiratory flow( PEF) of 65. 6% . There was no significant difference in the survival rates of the patients with and without central airway obstruction. Median survival time of group A was 11. 3 months and those of group B was 11. 6 months. 3, 6, and 12-month survival rates in group A were 87% , 68% and 39% respectively, and those in group B were 93% , 76% , and 45% respectively. Conclusion Endobronchial electrocautery is an effective and safe approach for inoperable tracheobronchial obstructive malignancies with few complications.
Abstract: Objective To compare the sensitivity and accuracy of autofluorescence bronchoscope (AFB) and white light bronchoscope (WLB) in airway examination for patients with central type lung cancer. Methods From September 2009 to May 2010, 46 patients including 36 males and 10 females with an average age of 62.1 years underwent both AFB and WLB procedures in People’s Hospital of Peking University. Among them, 35 were preliminary diagnostic cases and 11 were postoperative surveillance cases. Local anaesthesia of glottis and airway, and general anaesthesia with continuous intravenous drugs were given before electric bronchoscope was adopted. All patients underwent WLB examination followed by AFB procedure. All suspicious abnormal visual findings were recorded for biopsy and pathological examination. Results All procedures were carried out safely without death or severe complications. We performed bronchoscopy 48 times for all 46 patients and 159 tissues of various sites were taken out for biopsy and pathologic examination which showed 64 malignancies and 95 none malignancies. In 64 malignancies, AFB found all but WLB missed 15 with a missed diagnosis rate of 23.4%. Thirtysix times of examination were performed for the 35 preliminary diagnostic cases and 56 sites of malignancy were found. AFB found all, while WLB missed 12, and 6 sites of malignancy found by AFB were larger in size than those found by WLB. AFB detected 3 cases of multisite malignancy, but WLB missed these diagnoses. The results of AFB and WLB were the same for 26 patients. Twelve times of bronchoscopy were performed for the 11 postoperative surveillance cases and 8 sites of malignancy were found. AFB found them all while WLB missed 3 which were two recurrent cases during the early period after lung cancer surgery. The sensitivity of AFB and WLB was 100.0 % and 76.6%(Plt;0.05) respectively, and the negative predictive value of AFB and WLB was 100.0% and 84.5%(P=0.002) respectively. Conclusion AFB has a better sensitivity and negative predictive value than WLB in detecting mucous canceration lesions in central type lung cancer, and is more accurate in assessment of tumor margins, more sensitive in finding multiple lesions in airway and detecting early cancer recurrence in postoperative surveillance patients.
ObjectiveTo investigate the protecting effect of rosiglitazone for lung in airway-instillation- lipopolysaccharides and smoke-induced chronic obstructive pulmonary disease (COPD) rat models.MethodsFifty male Wistar rats with the SPF standard were randomly divided into 5 groups (n=10). The rats were treated by airway-instillation-lipopolysaccharides and exposing to smoking to establish COPD rat models excepted normal group, and the treatment groups were received gavage rosiglitazone of 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg rosiglitazone daily for 30 days, and the normal group or model group was received gavage normal saline. All rats were sacrificed after 30 days' treatment, and the lung tissue section was stained by hematoxylin and eosin. The mean linear intercept (MLI) and mean alveolar numbers (MAN) were measured in all groups. In addition, the protein levels of p-Stat3 and p-NF-κB were detected by immunohistochemistry.ResultsCompared with normal group, the inflammation and emphysema were observed in the lung of rats in model group, and the symptoms of the group treated with rosiglitazone were lighter than normal group. The lungs of rats treated with highest dose of rosiglitazone (0.2 mg/kg) were evaluated with lowest pathology assessment score among three treatment groups, but there was no significant difference of MLI or MAN among three treatment groups. Compared with normal group, the protein levels of p-Stat3 and p-NF-κB were increased in the lung and tracheal epithelium and lymphoid tissue of rats in model group, while the protein levels of p-NF-κB were decreased in these tissues and the protein levels of p-Stat3 were decreased in the lymphoid tissue after treatment with rosiglitazone, but the protein levels of p-Stat3 were not changed in the lung and tracheal epithelium.ConclusionRosiglitazone has a protective effect on the COPD rat models by inhibiting NF-κB pathway to reduce the inflammation of the lung parenchyma.
Objective To investigate the application and long-termresults of epiglottic in reconstruction of the traumatic laryngotracheal stenosis.Methods From January 1988 to February 2002, 42 patients with traumatic laryngotracheal stenosis were treated, including 33 laryngeal stenosis and9 laryngotracheal stenosis. The following surgical treatment were performed: ① lowered epiglottic andbi-pedicled sternohyoid myofascial flap and ② lowered epiglottic and bipedicledsternohyoid myofascial flap and sternocleidomastoideus clavicle membrane flap. Results Thirty-seven patients(88.1%) were successfully decannulated 10 to 75 daysafter operation. Feeding tube lasted from 9 to 24 days, all the patients rehabilitated deglutition after surgery. The time of using stent was 9 to 19 days in 25cases.All patients were followed up 1 year to 3 years and 4 months. The function of larynx recovered completely in 37 decannulated patients and partially in 5cannulated patients. Conclusion Epiglottic- has the advantages of easy gain, high antiinfection and survival rate, and stable structure. A combination of epiglottic and the bipedicled sternohyoid myofascial flap plus sternocleidomastoideus clavicle membrane flap can repair large laryngeal and tracheal defects.
ObjectiveTo study immunodepression effect of bone marrow-derived mesenchymal stem cell (BMSC) on acute asthmatic airway inflammation by galectin-1 (gal-1) in vivo.MethodsEighty-five female BALB/c mice were equally randomized into normal control group, asthmatic group, BMSC treatment group, gal-1 treatment group and BMSC and gal-1 inhibitor group. Ovalbumin (OVA) was used to establish acute asthmatic model. Total cell number and differential cell analysis in each group in bronchoalveolar lavage fluid (BALF) were determined. Furthermore, hematoxylin-eosin and periodic-acid Schiff staining was used to compare airway inflammation among five groups. Measurement of cytokines, including interleukin (IL) -4, IL-5 and gal-1 in BALF and OVA specific IgE (OVA-IgE) in serum were evaluated by enzyme linked immunosorbent assay. Moreover, dendritic cell (DC) in lung tissue was sorted by immunomagnetic beads and its MAPK signal pathway was analyzed by western blotting among five groups.ResultsAccumulation of inflammation cells, particularly eosinophils around airway and in BALF was evident in asthmatic mouse model, meanwhile hyperplasia of Goblet cell was also obvious in asthmatic group. BMSC engraftment or gal-1 infusion significantly reduced airway inflammation and hyperplasia of Goblet cell and the number of inflammation cells in BALF, especially eosinophils attenuated dramatically. However, there was no effect on airway inflammation and hyperplasia of Goblet Cell by simultaneous infusion BMSC engraftment and gal-1 inhibitor. Compared to normal control group, the level of IL-4, IL-5 in BALF and OVA-IgE in serum was increased remarkably in asthmatic group, but the level of gal-1 reduced obviously. Moreover, infusion of BMSC or gal-1 could mitigate the level of IL-4, IL-5 in BALF and OVA-IgE in serum and increase the level of gal-1 in asthmatic mouse. However, infusion with both BMSC and gal-1 inhibitor exerted no effect on cytokine and OVA-IgE in asthmatic mouse. DC was sorted by immunomagnetic beads and western blotting was used to detect the expression of MAPK signal pathway among five groups. The expression of ERK phosphorylation in asthmatic group was much lower than that in normal control group. On the contrary, the expression of p38 phosphorylation was much higher than that in normal control group. BMSC engraftment or gal-1 infusion significantly activated the ERK pathway and inhibited the p38 MARP pathway on asthmatic mouse DC. Nevertheless, the expression of ERK phosphorylation and p38 phosphorylation for group with BMSC and gal-1 inhibitor infusion was between the level of asthmatic group and normal control group.ConclusionsBMSC infusion alleviates airway inflammation in asthmatic mouse, especially weakens eosinophils infiltration, and the underlying mechanism might be protective effect of gal-1 secreted by BMSC which plays a role in lung tissue DC and regulates the DC expression of MAPK signal pathway.