New Advances in the Diagnosis and Treatment of Allergic Bronchopulmonary Aspergillosis.

Allergic bronchopulmonary aspergillosis is one of major pulmonary fungal diseases. Although it is not a rare in clinical settings,the misdiagnosis rate is high and the treatment effectiveness remains unstable. This article reviews the recent advances in the diagnosis and treatment of this disease.

Research Advances in Molecular Mechanisms of the Invasion and Metastasis of Lung Cancer.

The basic way of invasion and metastasis of lung cancer is that the tumor cells shed in the extracellular matrix, invade the basement membrane and the surrounding tissue, infiltrate into blood flow, and then survive and transport via the blood flow. After having been extravasated, migrated and arrested in the distant site, they finally form a metastatic lesion. Some basic mechanisms are required in these steps, such as tumor stem cells, diffusion and activity of tumor cells, escaping from apoptosis, angiogenesis and lymphangiogenesis, infiltration into blood flow, circulation and exudation, and distant metastasis proliferation. A better understanding of the mechanisms of the invasion and metastasis of lung cancer will facilitate the prevention and treatment of lung cancer.

Association of chronic obstructive pulmonary disease with coronary artery disease.

BACKGROUND: The relationship between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) remains largely unknown. This study aimed to explore the association of COPD with CAD, especially with multi-vessel disease (VD). METHODS: The data of 354 patients who underwent multi-detector computed tomography (MDCT) for suspected CAD were analyzed. Luminal narrowing was defined as at least one lesion 50% or greater stenosis. The analysis of serum biochemistry profile and spirometry were performed on all eligible patients, and the diagnosis of COPD was defined as the criteria of Global Initiative for Chronic Obstructive Lung Disease. RESULTS: Patients with CAD had a significantly higher complication of COPD than those without CAD (11.8% vs. 3.7%, P < 0.001). Comparing with patients without COPD, those with COPD were more likely to have multi-VD, proportion of smoking and high C-reactive protein (CRP) (P < 0.001). Multivariate Logistic regression analysis revealed that the multi-VD was significantly correlated with COPD (P=0.012) and CRP (P=0.015). CONCLUSIONS: There was a high complication of COPD in patients with CAD, and COPD may be a critical risk factor for CAD, especially for multi-VD. CAD and COPD were closely associated and the interplay of systemic inflammation might in part explain the relationship between them.

[Risk factors for acute exacerbation of chronic obstructive pulmonary disease in patients who survived the Wenchuan earthquake].

OBJECTIVE: To investigate the major risk factors for acute exacerbations of chronic obstructive pulmonary disease (COPD) and the role of mental status in patients who survived the Wenchuan Earthquake. METHODS: A questionnaire survey was conducted in 301 COPD patients from the earthquake and non-earthquake areas in Sichuan one month, three months and 12 months after the Wenchuan Earthquake. RESULTS: A total of 269 patients with COPD completed this study, which included 133 patients earthquake area and 136 from non-earthquake area. (1) Patients from earthquake area had significant higher incidence of acute exacerbations of COPD than those from non-earthquake area 3 months (0.57 +/- 0.688 vs. 0.40 +/- 0.601) and 12 months (1.82 +/- 1.375 vs. 1.47 +/- 1.366) after the earthquake. (2) Patients from earthquake area had significant higher Modified British Medical Research Council (mMRC) grades of COPD than those from non-earthquake area 12 months (P < 0.05) after the earthquake. (3) Patients from earthquake area had significant higher prevalence of posttraumatic stress disorder (PTSD) and higher scores of Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) than those from non-earthquake area within one month and 3 months after the earthquake. The difference in PTSD prevalence remained significant 12 months after the earthquake. (4) No significant differences in the prevalence of PTSD and the scores of SAS and SDS were found within one month and 3 months after the earthquake, though significant improvements were observed 12 months after the earthquake for both participants from the earthquake and non-earthquake areas (P < 0.01). (5) Patients from earthquake area lived in worse environment than those from non-earthquake area during the first 3 months after the earthquake (P < 0.001). The living environments of both groups improved significantly 12 months later (P < 0.001). (6) Binary logistic regression showed that older age, worse pulmonary function, psychological disorder, worse living environment were risk factors of acute exacerbation of COPD after the Wenchuan Earthquake. CONCLUSION: The earthquake caused serious psychological trauma in COPD patients. Older age, worse pulmonary function, psychological disorder, worse living environment are risk factors associated with acute exacerbation of COPD. COPD patients should receive psychotherapy and better living arrangement as early as possible after serious disasters.

Relationship between 6-minute walk test and pulmonary function test in stable chronic obstructive pulmonary disease with different severities.

BACKGROUND: The relationship between the 6-minute walk test (6MWT) and pulmonary function test in stable chronic obstructive pulmonary disease (COPD) remains unclear. We evaluate the correlation of 6MWT and spirometric parameters in stable COPD with different severities. 6MWT data assessed included three variables: the 6-minute walk distance (6MWD), 6-minute walk work (6MWORK), and pulse oxygen desaturation rate (SPO(2)%). METHODS: 6MWT and pulmonary function test were assessed for 150 stable COPD patients with different severities. Means and standard deviations were calculated for the variables of interest. Analysis of variance was performed to compare means. Correlation coefficients were calculated for 6MWT data with the spirometric parameters and dyspnea Borg scale. Multiple stepwise regression analysis was used to screen pulmonary function-related predictors of 6MWT data. RESULTS: The three variables of 6MWT all varied as the severities of the disease. The 6MWD and 6MWORK both correlated with some spirometric parameters (positive or negative correlation; the absolute value of r ranging from 0.34 to 0.67; P < 0.05) in severe and very severe patients, and the SPO2% correlated with the dyspnea Borg scale in four severities (r = -0.33, -0.34, -0.39, -0.53 respectively; P < 0.05). The 6MWD was correlated with the 6MWORK in four severities (r = 0.56, 0.57, 0.72, 0.81 respectively, P < 0.05), and neither of them correlated with the SPO(2)%. The percent of predicted forced expiratory volume in 1 second (FEV(1)% predicted) and residual volume to total lung capacity ratio (RV/TLC) were predictors of the 6MWD, and the maximum voluntary ventilation (MVV) was the predictor of the 6MWORK. CONCLUSIONS: 6MWT correlated with the spirometric parameters in severe and very severe COPD patients. 6MWT may be used to monitor changes of pulmonary function in these patients.

Long-term non-invasive positive pressure ventilation in severe stable chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: The evidence for non-invasive positive pressure ventilation (NIPPV) used in patients with severe stable chronic obstructive pulmonary disease (COPD) is insufficient. The aim of the meta-analysis was to assess the treatment effects of long-term NIPPV on gas change, lung function, health-related quality of life (HRQL), survival and mortality in severe stable COPD patients. METHODS: Randomized controlled trials (RCTs) and crossover studies comparing the treatment effects of NIPPV with conventional therapy were identified from electronic databases and reference lists from January 1995 to August 2010. Two reviewers independently assessed study quality. Data were combined using Review Manager 5.0. Both pooled effects and 95% confidence intervals were calculated. RESULTS: Five RCTs and one randomized crossover study with a total of 383 severe stable COPD patients were included. NIPPV improved gas change significantly when using a higher inspiratory positive airway pressures. The weighted mean difference (WMD) for the partial pressure of carbon dioxide in artery (PaCO2) was -3.52 (-5.26, -1.77) mmHg and for the partial pressure of oxygen in artery (PaO2) 2.84 (0.23, 5.44) mmHg. There were significant improvements in dyspnea and sleep quality, but gained no benefits on lung function. The standardized mean difference (SMD) for the forced expiratory volume in 1 second (FEV(1)) was 0.00 (0.29, 0.29). And the benefits for exercise tolerance, mood, survival and mortality remained unclear. CONCLUSIONS: Patients with severe stable COPD can gain some substantial treatment benefits when using NIPPV, especially improvements in gas change, dyspnea and sleep quality. Studies of high methodological quality with large population, especially those based on a higher inspiratory positive airway pressures are required to provide more evidences.

[Effect of peroxisome proliferators activated receptor gamma and its ligand on airway mucus hypersecretion in rats].

OBJECTIVE: To explore the effect and the molecular mechanisms of peroxisome proliferators activated receptor gamma (PPAR-gamma) and its ligand on airway mucus hypersecretion. METHODS: Thirty-six Sprague-Dawley rats were randomized into the following groups: (1) Rats in the saline control group (n = 6) received normal saline inhalation; (2) Rats in the rosiglitazone control group (n = 6) received inhaled saline and oral rosiglitazone 8 mg/kg simultaneously; (3) Rats in the acrolein group (n = 6) received inhaled acronine 3.0 mg/L, 6 h/day, for 12 days; (4) Rats in the rosiglitazone intervention group (n = 18) received inhaled acrolein and oral rosiglitazone 2 mg/kg, 4 mg/kg, 8 mg/kg, respectively, as the low dose, the moderate dose and the high dose intervention groups (n = 6 each). The lung tissue sections were stained with HE for histopathological examination. The changes of airway mucus were examined with AB-PAS. Expressions of MUC5AC and PPAR-gamma protein in the bronchial epithelium were detected by immunohistochemistry. The expression of mRNA was measured with real time RT-PCR. The data were analyzed with SPSS 10.0 software. Variables were compared with One-Way ANOVA and q test. The correlations between variables were analyzed using Pearson's correlation coefficient. RESULTS: The levels of airway mucus were (60.2 +/- 9.3)%, (4.9 +/- 1.0)%, (53.3 +/- 8.5)%, (26.5 +/- 7.4)%, (12.5 +/- 3.7)% respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 93.80, P < 0.01). The protein expressions of MUC5AC in the bronchial epithelium examined by immunohistochemistry were 4339 +/- 453, 1636 +/- 282, 3996 +/- 346, 3048 +/- 331, 2376 +/- 343 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 67.74, P < 0.01). The protein expressions of PPAR-gamma were 1159 +/- 184, 838 +/- 151, 1272 +/- 189, 1568 +/- 282, 1872 +/- 270 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 21.53, P < 0.01). The mRNA expressions of MUC5AC (the relative copies) were 35.3 +/- 10.0, 2.2 +/- 0.7, 30.5 +/- 10.2, 18.6 +/- 5.3, 10.8 +/- 2.6 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 29.67, P < 0.01). The mRNA expressions of PPAR-gamma (the relative copies) were 7.8 +/- 1.9, 2.0 +/- 0.6, 9.8 +/- 2.8, 18.6 +/- 5.3, 31.6 +/- 8.9 in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 39.47, P < 0.01). The expression of MUC5AC mRNA was negatively correlated with the protein expression of PPAR-gamma in the acrolein group (r = -0.880, P < 0.01). CONCLUSIONS: PPAR-gamma was involved in airway mucus hypersecretion induced by acrolein. PPAR-gamma and its ligand rosiglitazone inhibited acrolein-induced airway mucus hypersecretion, possibly through downregulation of MUC5AC.

[Interventions of enalapril on airway inflammation in rat models induced by acrolein].

OBJECTIVE: To observe the effect of enalapril on airway inflammation in rat models induced by inhaling acrolein and to explore its mechanism. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 4 groups (n = 6): 1) control group (inhaled 0.9% normal saline for 3 hours, twice every day); 2) enalapril self-control group [intragastrically administrated enalapril 0.5 mg/(kg x d) only]; 3) model group (stimulated with 4 mg/L acrolein for 3 hours, twice every day); 4) enalapril interventive group [inhaled acrolein and intragastrically administrated enalapril 0.5 mg/(kg x d)]. Lung tissue was acquired after the rats were sacrificed on the 21st day. Histopathology examination of lung tissue section stained with HE. Nuclear factor-kappa B and angiotensin II were assayed by immunohistochemistry. Nuclear factor-kappa B were also detected by Western blot. IL-8 and TNF-alpha in BALF were estimated by ELISA. RESULTS: Compared with the control group and the enalapril interventive group, the expression of Ang II and NF-kappa B in the model group was significantly increased (all P < 0.05). Compared with the control group and the enalapril interventive group, the ratio of NF-kappa B nuclear translocation in the model group was remarkably increased. Neutrophils and the level of IL-8 and TNF-alpha in BALF were higher in model group than those in control group. Enalapril can suppress them significantly. CONCLUSION: Acrolein inhalation could upregulate the expression of Ang II and NF-kappa B and also increase nuclear translocation ratio of NF-kappa B. Enalapril can suppress the airway inflammation induced by acrolein.

[Effect of gefinitib on airway mucus hypersecretion induced by acrolein in rats].

OBJECTIVE: To test the effect of gefinitib, an EGFR-TKI, on airway mucus hypersecretion induced by acrolein in rats. METHODS: Thirty six rats were randomly divided into six groups, each with six rats. Group A did not get any intervention; group B had airway mucus hypersecretion induced by inhaled acrelein; Gefitinib intervention was given to group C, D, and E, with a dose of 10 mg/kg,20 mg/kg, and 30 mg/kg of gefitnib administered by gavage, respectively, 30 min before exposure to acrolein inhalation; group F served as a control group, with gefitinib (30 mg/kg) administered by gavage 30 min before exposure to saline inhalation. After three weeks, the rats were sacrificed. The lung tissue sections were obtained. The immunohistochemistry and RT-PCR were performed to detect the MUC5AC and its mRNA expression. The EGFR was detected by immunohistochemical staining. The goblet cells were identified with Alician Blue-periodic Acid Schiff (AB-PAS). RESULTS: Overexpression of MUC5AC, EGFR and increased goblet cells in the lungs of the rats were found in the rats exposed to acrolein inhalations. Gefitinib intervention inhibited the expression of MUC5AC and the increase of goblet cells induced by acrolein. Gefitinib also reduced the expression of EGFR in the lungs. CONCLUSION: Acrolein increases the expression of MUC5AC through activating EGFR, which indicates that EGFR-TKI such as gefitinib can be useful in the treatment of mucus hypersecretion by regulating the signal transduction pathways of EGFR.