Massive cryptogenic hemoptysis undergoing pulmonary resection: clinical and pathological characteristics and management.

Massive cryptogenic hemoptysis is a common presenting symptom and cause of hospitalization for respiratory diseases, and represents a challenging condition in the clinical. This study aimed to analyze the clinical and pathologic data and management of patients with massive cryptogenic hemoptysis. We retrospectively reviewed 12 patients with massive cryptogenic hemotysis in our hospital between January 2003 and December 2012. Bronchoscopy showed submucosal vascular abnormalities in 4 patients. Of 6 patients managed with conservative measures, bleeding was completely controlled in 2 patients. Of 10 hemoptysis patients, three were controlled by bronchial arterial embolization, and seven by surgery. Pathological examination showed a superficial dysplastic, tortuous and dilated bronchial artery under the bronchial epithelium in 4 patients, and bronchiole dilation in 2 patients, indicating Dieulafoy's disease of the bronchus and bronchiectasis. No malignance developed within the follow-up. In conclusion, Dieulafoy's disease of the bronchus and bronchiectasis should be suspected in patients with massive cryptogenic hemoptysis. BAE and surgical treatment should be considered in case that massive hemoptysis could not be controlled by conservative management.

Roxithromycin suppresses airway remodeling and modulates the expression of caveolin-1 and phospho-p42/p44MAPK in asthmatic rats.

Roxithromycin (RXM) expresses anti-asthmatic effects that are separate from its antibiotic activity, but its effects on airway remodeling are still unknown. Here, we evaluated the effects of RXM on airway remodeling and the expression of caveolin-1 and phospho-p42/p44mitogen-activated protein kinase (phospho-p42/p44MAPK) in chronic asthmatic rats. The chronic asthma was induced by ovalbumin/Al(OH)3 sensitization and ovalbumin challenge, RXM (30mg/kg) or dexamethasone (0.5mg/kg) was given before airway challenge initiation. We measured the thickness of bronchial wall and bronchial smooth muscle cell layer to indicate airway remodeling, and caveolin-1 and phospho-p42/p44MAPK expression in lung tissue and airway smooth muscle were detected by immunohistochemistry and western blot analysis, respectively. The results demonstrated that RXM treatment decreased the thickness of bronchial wall and bronchial smooth muscle cell layer, and also downregulated the phospho-p42/p44MAPK expression and upregulated the caveolin-1 expression. The above effects of RXM were similar to dexamethasone. Our results suggested that pretreatment with RXM could suppress airway remodeling and regulate the expression of caveolin-1 and phospho-p42/p44MAPK in chronic asthmatic rats.

[Functional role of caveolin-1 in airway smooth muscle cells proliferation and regulatory effect of roxithromycin].

OBJECTIVE: To explore the functional role of caveolin-1 in airway smooth muscle cells (ASMCs) proliferation and examine the regulatory effect of roxithromycin. METHODS: The rat model of bronchial asthma was established. Electron microscope was employed to observe the status of caveolae and light microscope for the histological changes in pulmonary tissues. The primarily cultured ASMCs were divided into 5 groups: control (group A), asthmatic ASMCs (group B), PD98059 (group C), roxithromycin (group D) and methyl-ß-cyclodextrin (group E). Cell proliferation was detected by Cell Counting Kit-8 (CCK-8). And the expressions of caveolin-1, extracellular regulated protein kinases (ERK) and monocyte chemotactic protein (MCP)-1 were detected by Western blot and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The cell proliferation of asthmatic ASMCs (0.68 ± 0.15, 0.63 ± 0.13) in groups C and D were significantly less than those in group B (0.96 ± 0.14) (both P < 0.05) while group E was more than group B (1.26 ± 0.11 vs 0.96 ± 0.14, P < 0.05). The content of caveolin-1 (0.392 ± 0.064, 0.332 ± 0.057) in groups C and D were higher than those in group B (0.237 ± 0.032) (both P < 0.05) while ERK1/2 protein level in groups C and D (0.241 ± 0.017, 0.268 ± 0.007) were less than those in group B (0.346 ± 0.009) (both P < 0.01). And MCP-1 protein level in groups C and D (0.198 ± 0.015, 0.286 ± 0.019) were less than those in group B (0.482 ± 0.026) (both P < 0.01). The ERK mRNA level in groups C and D (0.277 ± 0.043, 0.338 ± 0.026) were less than those in group B (0.591 ± 0.022) (both P < 0.01). And also MCP-1 mRNA in groups C and D (0.212 ± 0.042, 0.249 ± 0.032) were less than those in group B (0.676 ± 0.053) (all P < 0.01) CONCLUSIONS: Caveolin-1 preventing the proliferation of asthmatic ASMCs is most likely mediated by ERK1/2 signal pathway and a down-regulation of MCP-1 expression. And roxithromycin reduces the proliferation of asthmatic ASMCs through up-regulating the expression of caveolin-1 and inhibiting the expression of MCP-1.

Impaired iNOS-sGC-cGMP signalling contributes to chronic hypoxic and hypercapnic pulmonary hypertension in rat.

Nitric oxide (NO) is an important vascular modulator in the development of pulmonary hypertension. NO exerts its regulatory effect mainly by activating soluble guanylate cyclase (sGC) to synthesize cyclic guanosine monophosphate (cGMP). Exposure to hypoxia causes pulmonary hypertension. But in lung disease, hypoxia is commonly accompanied by hypercapnia. The aim of this study was to examine the changes of sGC enzyme activity and cGMP content in lung tissue, as well as the expression of inducible nitric oxide synthase (iNOS) and sGC in rat pulmonary artery after exposure to hypoxia and hypercapnia, and assess the role of iNOS-sGC-cGMP signal pathway in the development of hypoxic and hypercapnic pulmonary hypertension. Male Sprague-Dawley rats were exposed to hypoxia and hypercapnia for 4 weeks to establish model of chronic pulmonary hypertension. Weight-matched rats exposed to normoxia served as control. After exposure to hypoxia and hypercapnia, mean pulmonary artery pressure, the ratio of right ventricle/left ventricle+septum, and the ratio of right ventricle/body weight were significantly increased. iNOS mRNA and protein levels were significantly increased, but sGC α(1) mRNA and protein levels were significantly decreased in small pulmonary arteries of hypoxic and hypercapnic exposed rat. In addition, basal and stimulated sGC enzyme activity and cGMP content in lung tissue were significantly lower after exposure to hypoxia and hypercapnia. These results demonstrate that hypoxia and hypercapnia lead to the upregulation of iNOS expression, downregulation of sGC expression and activity, which then contribute to the development of pulmonary hypertension.

[Changes of airway smooth muscle cell apoptosis in asthmatic airway remodeling and the effect of dexamethasone in rats].

OBJECTIVE: To observe the changes of airway smooth muscle cells (ASMC) apoptosis in the airway remodeling process of asthma, and to evaluate the effect of dexamethasone on ASMC apoptosis and the possible mechanisms. METHODS: Thirty six male Sprague-Dawley rats were randomly divided into 3 groups, including a control group, an asthma group and a dexamethasone treated group. The rats were sensitized with ovalbumin and Al(OH)(3), and repeatedly exposed to aerosolized ovalbumin. ASMC apoptosis was measured by the technique of TdT-mediated dUTP-biotin nick end labeling (TUNEL). Bcl-2 protein and mRNA, and Bax protein and mRNA in airway smooth muscles were measured by immunohistochemistry and in situ hybridization respectively. SPSS version 11.5 was used for statistical analysis. Data were presented as ((-x) +/- s), and means were compared with analysis of variance. The correlation of two variables was analysed by linear correlation analysis. RESULTS: The apoptosis index (AI) of ASMC was separately 0.201 +/- 0.022, 0.030 +/- 0.016, 0.118 +/- 0.043 in the control, the asthma, and the dexamethasone asthma, treated group. Immunohistochemistry showed that the expression of Bcl-2 protein (A) in airway smooth muscles in above groups was 0.060 +/- 0.012, 0.112 +/- 0.028 0.080 +/- 0.010. In situ hybridization showed that the level of Bcl-2 mRNA in airway smooth muscles in the control, the asthma, and the dexamethasone treated group was 0.065 +/- 0.019, 0.157 +/- 0.019 and 0.099 +/- 0.029. The expression of Bax protein in each group was 0.120 +/- 0.020, 0.062 +/- 0.012 and 0.093 +/- 0.010 respectively. Accordingly the level of Bax mRNA in each group was 0.155 +/- 0.025, 0.074 +/- 0.019 and 0.118 +/- 0.031 respectively. The AI of ASMC was negatively correlated with Wam/Pbm (r = -0.860, P < 0.01) and the relative content of Bcl-2 protein (r = -0.783, P < 0.01), but was positively correlated with the relative content of Bax protein (r = 0.873, P < 0.01). CONCLUSIONS: The reduction of ASMC apoptosis may participate in the remodeling process of asthma. Dexamethasone induces ASMC apoptosis possibly by the increase of Bax expression and the decrease of Bcl-2 expression in airway smooth muscles.

[Influence of the agents which maintain the coordination between spontaneous breathing and mechanical ventilation on haemodynamics and respiration].

OBJECTIVE: To investigate the haemodynamic and respiratory changes following intravenous administration with midazolam, pavulon or both of them in the patients having incoordination between spontaneous breathing and mechanical ventilation. METHODS: Thirty patients having incoordination between spontaneous breathing and mechanical ventilation were randomly assigned to receiving intravenous injection of pavulon (group 1), midazolam (group 3), and both (group 2) respectively with 10 cases in each group. The degree of coordination between spontaneous breathing and mechanical ventilation, blood pressure (BP), heart rate (HR), respiration frequency (RF), oxygen saturation of pulse (SpO(2)) were observed before the medication and at 5, 15, 30 and 60 minutes following the administration of drugs in all the patients. RESULTS: Incoordination between spontaneous breathing and mechanical ventilation, fast RF, decreased SpO(2) were observed before the drug in all patients. Improvement of respiratory was significant in group 2. Patients in group 2 were in excellent coordination between spontaneous breathing and mechanical ventilation, reaching 100% within 30 minutes after administration, and lasting longer. The haemodynamics maintained stable and a significant improvement in respiration and SpO(2) were found. BP and HR were elevated significantly, and RF and hypoxemia were improved, and the degree of coordination between spontaneous breathing and mechanical ventilation reached 100% 5 minutes after the drug, but with shorter duration in group 1. There were no obvious changes in BP, HR, RF and hypoxemia, and the degree of coordination between spontaneous breathing and mechanical ventilation was lowest in group 3. CONCLUSION: The combined use of midazolam and pavulon has little influence on circulation, and it also can maintain the coordination between spontaneous breathing and mechanical ventilation. It is suggested that the combined use of midazolam and pavulon is an optimal way to improve the ventilatory function in mechanical ventilation.

[Study on soluble guanylate cyclase in pulmonary hypertension rat model].

OBJECTIVE: To investigate the mRNA and protein expressions of soluble guanylate cyclase (sGC) and its enzyme activity in pulmonary hypertension rat model which was reproduced by hypoxia and hypercapnia. METHODS: Male Sprague-Dawley rats were randomly divided into hypoxic and hypercapnic group (HH group) and control group (C group). The protein expressions of sGC alpha(1) and sGC beta(1) subunits in medial and small pulmonary arteries was measured by immunohistochemistry method with a polycolonal antibody. The mRNA expression of sGC alpha(1) subunit of lung tissue was detected by in situ hybridization using sGC oligonuclear probe. Basal sGC enzyme activity and sodium nitroprusside (SNP)-stimulated sGC activity in lung homogenates were assayed with enzyme kinetic analysis. RESULTS: The mean pulmonary artery pressure (mPAP), the ratio of right ventricle/left ventricle + septum [RV/(LV + S)] and the ratio of right ventricle/body weight (RV/BW) were significantly higher in HH group than those in C group. The protein expressions of sGC alpha(1) and sGC beta(1) subunits and mRNA expressions of sGC alpha(1) subunit were significantly decreased in the small and medium pulmonary arteries in HH group as compared with those in C group (P < 0.01). Basal sGC enzyme activity in HH group (32.03 +/- 7.17 pmol cGMP synthesized.mg protein(-1).min(-1)) was significantly lower than that in C group (114.76 +/- 18.37 pmol cGMP synthesized.mg protein(-1).min(-1), P < 0.01). The SNP significantly increased the sGC enzyme activity but the SNP-stimulated sGC enzyme activity of lung homogenates in HH group was significantly lower than that in C group (P < 0.01). CONCLUSIONS: The mRNA and protein expressions of sGC subunits and their enzyme activities in lung tissue of pulmonary hypertension rat model were reduced.