Risk factors associated with comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: a cross-sectional study.

BACKGROUND: Although 20-60% of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have asthma, the risk factors associated with comorbid asthma are not clear. The aim of the study was to investigate the factors associated with asthma, and develop a practical scoring system to screen asthma comorbidity in CRSwNP patients. METHODS: This report describes a cross-sectional study with consecutive CRSwNP patients. Two cohorts of CRSwNP patients named "modelling" group and "validation" group were investigated respectively. Logistic regression analysis was performed based on demographic and clinical data collected from patients in the modelling group to determine the risk factors associated with asthma, and establish a scoring system for screening comorbid asthma. Receiver operating characteristic curve was constructed to evaluate the screening system; the optimal cut-off point was established by means of the Yoden Index. The consistency between the diagnosis of asthma by the Global Initiative for Asthma (GINA) criteria and by the screening system was assessed by Kappa value in the validation group. RESULTS: Totally 150 patients in modelling group and 78 patients in validation group were enrolled. Female gender (odds ratio [OR] = 6.4; P < 0.001), allergic rhinitis (OR = 2.9; P = 0.021), serum total (T)-immunoglobulin (Ig) E ≥ 69.0kU/L (OR = 12.0; P < 0.001), and blood eosinophil count ≥ 0.35 × 109/L (OR = 4.0; P = 0.001) were shown to be independent risk factors for asthma in patients with CRSwNP. Based on these variables, a scoring system (FAIE) ranging from 0(no risk) to 6(high risk); was developed. The area under the receiver operating characteristic curve of the system was 0.823, and the optimal cut-off value was 3 points, with sensitivity 83.8% and specificity 68.6% for screening asthma. The asthma comorbidity determined with FAIE score ≥ 3 points in the validation group, was moderately consistent with that defined by GINA (Kappa = 0.513, P < 0.001), with sensitivity 76.9% and specificity 74.4%. CONCLUSIONS: Female gender, allergic rhinitis, serum T-IgE level, and blood eosinophil count are independent risk factors for asthma comorbidity in patients with CRSwNP, and the FAIE system may be practical for screening comorbid asthma in these patients.

New-onset COVID-19-related diabetes: an early indicator of multi-organ injury and mortally of SARS-CoV-2 infection.

Objective: The pandemic of 2019 coronavirus (SARS-CoV-2) disease (COVID-19) has imposed a severe public health burden worldwide. Most patients with COVID-19 were mild. Severe patients progressed rapidly to critical condition including acute respiratory distress syndrome (ARDS), multi-organ failure and even death. This study aims to find early multi-organ injury indicators and blood glucose for predicting mortality of COVID-19. Methods: Fasting blood glucose (FBG) ≥7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as new-onset COVID-19-related diabetes (CRD). Indicators of injuries for multiple organs, including the lung, heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting death. Results: A total of 120 patients with a severity equal to or greater than Moderate were hospitalized. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). Univariable analysis indicated that CRD, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK) and creatinine (Cr) were associated with death. Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Abnormal glucose homeostasis or CRD occurred earlier than other indicators for predicting poor outcomes. Indicators of multiple organ injury were in parallel with the expression patterns of ACE2 (the SARS-CoV-2 receptor) in different organs including pancreatic islet. Conclusions: New-onset COVID-19-related diabetes is an early indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be helpful for predicting poor outcomes to facilitate appropriate intensive care.

Clinical and cytokine patterns of uncontrolled asthma with and without comorbid chronic rhinosinusitis: a cross-sectional study.

BACKGROUND: Asthma is significantly related to chronic rhinosinusitis (CRS) both in prevalence and severity. However, the clinical patterns of uncontrolled asthma with and without comorbid CRS are still unclear. This study aimed to explore the clinical characteristics and cytokine patterns of patients with uncontrolled asthma, with and without comorbid CRS. METHODS: 22 parameters associated with demographic characteristics, CRS comorbidity, severity of airflow obstruction and airway inflammation, and inflammation type of asthma were collected and assessed in 143 patients with uncontrolled asthma. Different clusters were explored using two-step cluster analysis. Sputum samples were collected for assessment of Th1/Th2/Th17 and epithelium-derived cytokines. RESULTS: Comorbid CRS was identified as the most important variable for prediction of different clusters, followed by pulmonary function parameters and blood eosinophil level. Three clusters of patients were determined: Cluster 1 (n = 46) characterized by non-atopic patients with non-eosinophilic asthma without CRS, demonstrating moderate airflow limitation; Cluster 2 (n = 54) characterized by asthma patients with mild airflow limitation and CRS, demonstrating higher levels of blood eosinophils and immunoglobulin E (IgE) than cluster 1; Cluster 3 (n = 43) characterized by eosinophilic asthma patients with severe airflow limitation and CRS (46.5% with nasal polyps), demonstrating worst lung function, lowest partial pressure of oxygen (PaO2), and highest levels of eosinophils, fraction of exhaled nitric oxide (FeNO) and IgE. Sputum samples from Cluster 3 showed significantly higher levels of Interleukin (IL)-5, IL-13, IL-33, and tumor necrosis factor (TNF)-α than the other two clusters; and remarkably elevated IL-4, IL-17 and interferon (IFN)-γ compared with cluster 2. The levels of IL-10 and IL-25 were not significantly different among the three clusters. CONCLUSIONS: Uncontrolled asthma may be endotyped into three clusters characterized by CRS comorbidity and inflammatory cytokine patterns. Furthermore, a united-airways approach may be especially necessary for management of asthma patients with Type 2 features.

Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP + AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP + AS. METHODS: A total of 195 subjects; including 65 CRSwNP + AS patients, 99 CRSwNP-alone patients, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP + AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. RESULTS: Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP + AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP + AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP + AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP + AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP + AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP + AS. CONCLUSIONS: Patients with CRSwNP + AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.

Gender Differences in Patients With COVID-19: Focus on Severity and Mortality.

Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.

Effects of propofol pretreatment on myocardial cell apoptosis and SERCA2 expression in rats with hepatic ischemia/reperfusion / Efeitos do pré-tratamento com propofol sobre a apoptose de células miocárdicas e expressão de SERCA2 em ratos com isquemia/reperfusão hepática

Abstract Introduction: Hepatic ischemia-reperfusion injury is a common pathophysiological process in liver surgery. Whether Propofol can reduce myocardial ischemia-reperfusion injury induced by hepatic ischemia-reperfusion injury in rats, together with related mechanisms, still needs further studies. Objective: To investigate if propofol would protect the myocardial cells from apoptosis with hepatic ischemia-reperfusion injury. Methods: Male Sprague-Dawley rats (n = 18) were randomly allocated into three groups: Sham Group (Group S, n = 6), Hepatic Ischemia-reperfusion Injury Group (Group IR, n = 6) and Propofol Group (Group P, n = 6). Group S was only subjected to laparotomy. Group IR was attained by ischemia for 30 min and reperfusion for 4 h. Group P was subjected identical insult as in Group IR with the administration of propofol started 10 min before ischemia with 120 mg.kg−1, following by continuous infusion at 20 mg.kg−1.h−1. Cell apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Endoplasmic reticulum Ca2+-ATPase2 (SERCA2) and cysteine-containing aspartic acid cleaved-caspase3 (cleaved-caspase3) were assayed by western blot and Altimeter polymerase chain reaction. Results: Apoptosis rate was increased, with mRNA and protein of SERCA2 down-regulated and cleaved-caspase3 up-regulated in Group IR compared with Group S (p < 0.01). Apoptosis rate was decreased, with mRNA and protein of SERCA2 up-regulated and cleaved-caspase3 down-regulated in Group P compared with Group IR (p < 0.01). Conclusions: Propofol can reduce hepatic ischemia-reperfusion injury-induced myocardial cell apoptosis, meanwhile, can up-regulate mRNA and protein of SERCA2 in rats.

Resumo Introdução: A lesão hepática por isquemia-reperfusão é um processo fisiopatológico comum em cirurgias hepáticas. Mais estudos ainda são necessários para avaliar se o propofol pode reduzir a lesão de isquemia-reperfusão miocárdica induzida pela lesão de isquemia-reperfusão hepática em ratos, juntamente com os mecanismos que estão relacionados. Objetivo: Investigar se propofol protege as células do miocárdio da apoptose com a lesão hepática por isquemia-reperfusão. Métodos: Ratos machos da raça Sprague-Dawley (n = 18) foram alocados aleatoriamente em três grupos: Grupo Sham (Grupo S, n = 6), Grupo Lesão Hepática por Isquemia-reperfusão (Grupo IR, n = 6) e Grupo Propofol (Grupo P, n = 6). O Grupo S foi submetido apenas à laparotomia. O grupo IR foi submetido à isquemia por 30 min e reperfusão por 4 h. O grupo P foi submetido à mesma isquemia do grupo IR, com a administração de 120 mg.kg-1 de propofol iniciada 10min antes da isquemia, seguida de infusão contínua a 20 mg.kg-1.h-1. A apoptose celular foi examinada por meio do ensaio de marcação de terminações dUTP pela deoxinucleotidil transferase. Retículo endoplasmático Ca2+-ATPase2 (SERCA2) e caspase-3 do ácido aspártico contendo cisteína (caspase-3 clivada) foram avaliados com o ensaio western blot e reação em cadeia da polimerase. Resultados: A taxa de apoptose foi maior com mRNA e proteína de SERCA2 regulados para baixo e caspase-3 clivada suprarregulada no Grupo IR, em comparação com o Grupo S (p < 0,01). A taxa de apoptose foi menor com mRNA e proteína de SERCA2 suprarregulada e caspase-3 clivada sub-regulada no Grupo P, em comparação com o Grupo IR (p < 0,01). Conclusões: O propofol pode reduzir a apoptose de células miocárdicas induzida por lesão hepática por isquemia-reperfusão. Entretanto, pode suprarregular o mRNA e a proteína de SERCA2 em ratos.

[Effects of propofol pretreatment on myocardial cell apoptosis and SERCA2 expression in rats with hepatic ischemia/reperfusion]. / Efeitos do pré­tratamento com propofol sobre a apoptose de células miocárdicas e expressão de SERCA2 em ratos com isquemia/reperfusão hepática.

INTRODUCTION: Hepatic ischemia-reperfusion injury is a common pathophysiological process in liver surgery. Whether Propofol can reduce myocardial ischemia-reperfusion injury induced by hepatic ischemia-reperfusion injury in rats, together with related mechanisms, still needs further studies. OBJECTIVE: To investigate if propofol would protect the myocardial cells from apoptosis with hepatic ischemia-reperfusion injury. METHODS: Male Sprague-Dawley rats (n=18) were randomly allocated into three groups: Sham Group (Group S, n=6), Hepatic Ischemia-reperfusion Injury Group (Group IR, n=6) and Propofol Group (Group P, n=6). Group S was only subjected to laparotomy. Group IR was attained by ischemia for 30min and reperfusion for 4h. Group P was subjected identical insult as in Group IR with the administration of propofol started 10min before ischemia with 120mg.kg-1, following by continuous infusion at 20mg.kg-1.h-1. Cell apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Endoplasmic reticulum Ca2+-ATPase2 (SERCA2) and cysteine-containing aspartic acid cleaved-caspase3 (cleaved-caspase3) were assayed by western blot and Altimeter polymerase chain reaction. RESULTS: Apoptosis rate was increased, with mRNA and protein of SERCA2 down-regulated and cleaved-caspase3 up-regulated in Group IR compared with Group S (p<0.01). Apoptosis rate was decreased, with mRNA and protein of SERCA2 up-regulated and cleaved-caspase3 down-regulated in Group P compared with Group IR (p<0.01). CONCLUSIONS: Propofol can reduce hepatic ischemia-reperfusion injury-induced myocardial cell apoptosis, meanwhile, can up-regulate mRNA and protein of SERCA2 in rats.

Emphysema and bronchiectasis in COPD patients with previous pulmonary tuberculosis: computed tomography features and clinical implications.

Background: Pulmonary tuberculosis (PTB) is a risk factor for COPD, but the clinical characteristics and the chest imaging features (emphysema and bronchiectasis) of COPD with previous PTB have not been studied well. Methods: The presence, distribution, and severity of emphysema and bronchiectasis in COPD patients with and without previous PTB were evaluated by high-resolution computed tomography (HRCT) and compared. Demographic data, respiratory symptoms, lung function, and sputum culture of Pseudomonas aeruginosa were also compared between patients with and without previous PTB. Results: A total of 231 COPD patients (82.2% ex- or current smokers, 67.5% male) were consecutively enrolled. Patients with previous PTB (45.0%) had more severe (p=0.045) and longer history (p=0.008) of dyspnea, more exacerbations in the previous year (p=0.011), and more positive culture of P. aeruginosa (p=0.001), compared with those without PTB. Patients with previous PTB showed a higher prevalence of bronchiectasis (p<0.001), which was more significant in lungs with tuberculosis (TB) lesions, and a higher percentage of more severe bronchiectasis (Bhalla score ≥2, p=0.031), compared with those without previous PTB. The overall prevalence of emphysema was not different between patients with and without previous PTB, but in those with previous PTB, a higher number of subjects with middle (p=0.001) and lower (p=0.019) lobe emphysema, higher severity score (p=0.028), higher prevalence of panlobular emphysema (p=0.013), and more extensive centrilobular emphysema (p=0.039) were observed. Notably, in patients with TB lesions localized in a single lung, no difference was found in the occurrence and severity of emphysema between the 2 lungs. Conclusion: COPD patients with previous PTB had unique features of bronchiectasis and emphysema on HRCT, which were associated with significant dyspnea and higher frequency of severe exacerbations. While PTB may have a local effect on bronchiectasis, its involvement in airspace damage in COPD may be extensive, probably through interactions with cigarette smoke.

Chronic rhinosinusitis is associated with higher prevalence and severity of bronchiectasis in patients with COPD.

BACKGROUND AND PURPOSE: Bronchiectasis revealed by high-resolution computed tomography (HRCT) is common in chronic obstructive pulmonary disease (COPD), but the causes and risk factors remain to be determined. Chronic rhinosinusitis (CRS) is closely associated with bronchiectasis or COPD, but whether it is associated with comorbid bronchiectasis in COPD (COPD-Bx) is unknown. PATIENTS AND METHODS: Patients with stable COPD were enrolled consecutively and evaluated for the presence of CRS by questionnaire and paranasal sinus computed tomography. The presence and severity of bronchiectasis on lung HRCT were evaluated by the Smith and severity scores. COPD symptoms were evaluated by COPD Assessment Test (CAT) and Modified British Medical Research Council Questionnaire. The sputum cell differentials and concentrations of interleukin (IL)-6, IL-8, IL-5, matrix metalloproteinases-9 (MMP-9), and tissue inhibitor of matrix metalloproteinases-1 were measured. RESULTS: We enrolled 136 patients with stable COPD, of which 66 (48.5%) were diagnosed with CRS according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) criteria. The prevalence of bronchiectasis was 57.6% in patients with CRS, but 37.1% in those without CRS (P=0.017). COPD-Bx patients with CRS showed a significantly higher severity score of bronchiectasis than those without CRS (P=0.034). COPD patients with CRS had a higher percentage of eosinophils, higher levels of IL-8, IL-6, and MMP-9 in sputum as compared to those without CRS. In COPD-Bx patients with CRS, the percentage of eosinophils and the levels of IL-6 and MMP-9 in sputum were increased as compared to those without CRS. In all the subjects, Sino-Nasal Outcome Test-20 correlated with CAT score (r=0.315, P<0.01) and in COPD patients with CRS, Lund-MacKay scores correlated with forced expiratory volume in 1 s (% pred) (r=-0.251, P<0.05). CONCLUSIONS: CRS was associated with COPD-Bx and this was probably due to increased airway inflammation.

Factors associated with bronchiectasis in patients with moderate-severe chronic obstructive pulmonary disease.

A high prevalence of bronchiectasis was found by chest computed tomography (CT) in patients with moderate-severe chronic obstructive pulmonary disease (COPD), and it was shown to be associated with more severe symptoms, higher frequency of exacerbations and mortality. The risk factors for bronchiectasis in COPD are not yet clarified.High-resolution computed tomography (HRCT) of chest was performed in patients with moderate-severe COPD, and the presence and the extent of bronchiectasis were evaluated by two radiologists. Demographic data, respiratory symptoms, lung function, previous pulmonary tuberculosis, serum inflammatory markers, serum total immunoglobulin E (T-IgE), and sputum culture of Pseudomonas aeruginosa were compared between those with and without bronchiectasis. Multivariate logistic regression analysis was used to determine the independent factors associated with bronchiectasis.We enrolled 190 patients with stable COPD, of which 87 (87/190, 45.8%) had bronchiectasis on HRCT. Compared with those without bronchiectasis, COPD patients with bronchiectasis were more likely to be males (P = 0.021), had a lower body mass index (BMI) (P = 0.019), a higher prevalence of previous tuberculosis (P = 0.005), longer history of dyspnea (P < 0.001), more severe dyspnea (P = 0.041), higher frequency of acute exacerbation (P = 0.002), higher serum concentrations of C-reactive protein (CRP) (P = 0.017), fibrinogen (P = 0.016), and T-IgE [P = 0.004; for log10(T-IgE), P <0.001]. COPD patients with bronchiectasis also showed poorer lung function (for FEV1/FVC, P = 0.013; for FEV1%predicted, P = 0.012; for global initiative for chronic obstructive lung disease (GOLD) grades, P = 0.035), and a higher positive rate of sputum P aeruginosa (P = 0.020). Logistic regression analysis demonstrated that male gender (P = 0.021), previous tuberculosis (P = 0.021), and increased level of serum T-IgE [for log10(T-IgE), P < 0.001] were risk factors for coexistent bronchiectasis. More notably, the level of serum T-IgE [log10(T-IgE)] was positively correlated with the extent of bronchiectasis in COPD patients (r = 0.208, P = 0.05).Higher serum T-IgE, male gender, and previous tuberculosis are independent risk factors for coexistent bronchiectasis in COPD. The association of T-IgE with the extent of bronchiectasis also suggests that further investigations are needed to explore the potential role of IgE in the pathogenesis of bronchiectasis in COPD.

Bronchiectasis as a Comorbidity of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies. Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression. METHODS: Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts. A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients. Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. Odds ratios (ORs) were pooled by random effects models. RESULTS: Fourteen observational studies were eligible for the study. Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29-3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16-7.82), severe airway obstruction (1.31, 95% CI, 1.09-1.58) and mortality (1.96, 95% CI, 1.04-3.70). CONCLUSIONS: The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality.

The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function.

BACKGROUND: Allergy and Aspergillus hypersensitivity (AH) were shown to be associated with severe symptoms or worse lung function in COPD patients. The prevalence of elevated total IgE (T-IgE) and its association with clinical symptoms and lung function in COPD have not been studied. The prevalence of AH and its correlation with clinical characteristics in a COPD cohort of larger sample size is also lacking. METHODS: 273 patients with COPD were evaluated by respiratory symptoms, blood test, chest HRCT, lung function, serum detection of T-IgE and Aspergillus specific IgE. Patients with T-IgE ≥ 1000 KU/L were further investigated for allergic bronchopulmonary aspergillosis (ABPA). RESULTS: The prevalence of elevated T-IgE and AH in patients with COPD was 47.3% and 15.0%, respectively. Eight patients (2.9%) met the diagnostic criteria for ABPA. Compared with the normal T-IgE group, patients with elevated T-IgE had a longer history of dyspnea (p < 0.01), an earlier onset of dyspnea after chronic cough/expectoration (p < 0.01), and were more likely to wheeze (p < 0.01). They also showed worse lung functions and more severe GOLD staging (p < 0.01). Analysis of the clinical data in male patients with smoking as the risk factor showed the same results. To evaluate the clinical characteristics of COPD with AH, patients with elevated T-IgE were further divided into subgroups with and without AH. When compared with the normal T-IgE group, both the two subgroups showed longer history of dyspnea (p < 0.01), an earlier onset of dyspnea (p < 0.01) and a worse status of lung function (p < 0.05). Correlation analysis demonstrated that T-IgE was correlated positively with the time length of dyspnea (r = 0.401, p < 0.001), and the ratio of duration of dyspnea to that of chronic cough/expectoration (r = 0.59, p < 0.001), but negatively with FEV1/FVC% (r = -0.194, p = 0.001), and FEV1%predicted (r = -0.219, p < 0.001). CONCLUSIONS: There was a high prevalence of elevated serum T-IgE and AH in patients with COPD. Serum T-IgE level was correlated with symptoms such as dyspnea and impairment of lung function. Allergens other than Aspergillus may have similar effects on disease expression or progression of COPD.

[Clinical analyses of sarcoidosis with ocular involvement].

OBJECTIVE: To explore the clinical characteristics and systemic manifestations of sarcoidosis with ocular involvement. METHODS: The clinical data of 19 cases of sarcoidosis with ocular involvement confirmed by pathology at Beijing Tongren Hospital from March 2004 to February 2014 were analyzed retrospectively. The ocular manifestations, chest imaging findings, laboratory tests and pathological diagnosis were reviewed. And the clinical features of sarcoidosis with ocular involvement were summarized. RESULTS: Among them, there were 6 males and 13 females with an average age of (47 ± 14) (16-76) years. The ocular symptoms were the initial presenting manifestations of sarcoidosis in 12 cases while 2 cases presented ocular symptoms during the course of disease. And aother 5 cases without ocular symptoms were confirmed to have ocular involvement by eye examination. The main manifestations of ocular sarcoidosis were uveitis (n = 16), chorioretinitis (n = 3), retinal vasculitis (n = 2), optic neuritis (n = 1) and orbital mass (n = 3). The key feature of sarcoidosis was bilateral hilar lymphadenopathy (BHL) (14/16) on chest film. The diagnosis in 17 cases was confirmed by biopsy of extra-ocular organs. The positive diagnostic rate of bronchial biopsy was 8/9. CONCLUSIONS: Ocular involvement in sarcoidosis is relatively common due to a variety of ocular manifestations and serious vision impairment in some patients. Ophthalmologic examination is essential in the clinical management of sarcoidosis. Chest imaging and bronchial biopsy are important for the diagnosis of sarcoidosis with initial ocular manifestations.

Effects of edaravone on the expression of ß-defensin-2 mRNA in lung tissue of rats with myocardial ischemia reperfusion.

The aim of this study was to investigate the effects of edaravone on lung injury caused by myocardial ischemia reperfusion (I/R) in rats. Wistar rats (n=24) were randomly divided into 4 groups: the sham operation (S group) and myocardial I/R groups (C group) and two edaravone­treated groups (E1 and E2 groups). Rats in the E1 and E2 groups were injected with 3 or 10 mg/kg edaravone, respectively, 1 min before reperfusion. The rats were sacrificed and the lung tissue, bronchoalveolar lavage (BAL) fluid and serum were obtained. The concentration of serum creatine kinase isoenzyme (CK-MB) was determined, the lung permeability index (PPI) was calculated and ß-defensin-2 (BD-2) mRNA expression in the lung tissue and BD-2 and TNF-α protein content levels were determined. Serum CK-MB activity and the PPI were increased, while BD-2 mRNA and BD­2 and TNF-α protein levels in the lung tissue were upregulated in the C, E1 and E2 groups compared with the S group. The above­mentioned indicators were decreased in the E1 and E2 groups compared with the IR group. The level of the decrease for indicators in the E2 group was significantly different compared with that in the E1 group. In conclusion, edaravone reduced the lung injury caused by myocardial I/R in rats. Its mechanism of action was not only oxygen free radical scavenging, but was also associated with a suppression of the inflammatory response of the lung tissue.

[Allergic bronchopulmonary aspergillosis in patients with chronic obstructive pulmonary disease: report of 3 cases].

OBJECTIVE: To improve the clinical knowledge on allergic bronchopulmonary aspergillosis (ABPA) combined with COPD by report of cases. METHODS: We retrospectively analyzed the clinical information of 3 cases of ABPA combined with COPD diagnosed in our hospital from Jan. 2009 to Dec. 2012. RESULTS: The 3 patients were all males, and aged from 68 to 82 years. The main complaints of all the patients were exertional dyspnea, cough and sputum production, with episodes of wheezing. All patients denied the history of allergic diseases, e.g., asthma, rhinitis, sinusitis, eczema, and family history of asthma. They all had a history of heavy smoking. The pulmonary function tests indicated obstructive impairment, and the ratio of FEV1 to FVC (FEV1/FVC) after bronchodilators were 30%, 33% and 43%, respectively, with no significant bronchodilator reversibility, which were consistent with the diagnostic criteria for COPD, with 1 case in GOLD grade III and 2 cases in GOLD grade IV based on the GOLD spirometric criteria for COPD severity. Lung HRCT showed emphysema with or without bulla formation. All cases showed immediate positive response to Aspergillus antigen by skin prick test (SPT), increased serum total IgE > 1000 kU/L, increased serum level of Aspergillus specific IgE (>0.35 kU/L) and IgG (>40 mg/L). Central bronchiectasis was also evident on HRCT scan in the 3 patients. In addition, the eosinophil percentage in peripheral blood was all >5%. Pulmonary infiltrates, brown phlegm plugs, and growth of Aspergillus fumigatus were also noted in some cases. After the diagnosis of ABPA, the patients were all given oral prednisone therapy, with notable improvement in dyspnea and FEV1. CONCLUSIONS: ABPA in COPD is uncommon, but early identification and initiation of systemic corticosteroid therapy can lead to improvement in symptoms and prognosis. For COPD patients with recurrent attacks of wheezing or are unresponsive to combination therapy of inhaled long-acting bronchodilators and corticosteroids, concurrent ABPA should be suspected and investigated accordingly.

Disturbance of the OPG/RANK/RANKL pathway and systemic inflammation in COPD patients with emphysema and osteoporosis.

BACKGROUND: Osteoporosis is one of the systemic features of COPD. A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear. Experimental studies indicate that IL-1ß, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema. The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis. Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied. METHODS: Eighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires. Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1ß, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA). Twenty age-matched healthy volunteers were recruited as controls. RESULTS: Among these eighty patients, thirty-six had normal BMD and forty-four had low BMD. Age, BMI and CAT score showed significant differences between these two COPD groups (p < 0.05). The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; p < 0.0001). Forward logistic regression analysis showed that only LAA% (p = 0.005) and BMI (p = 0.009) were selected as explanatory variables. The level of IL-1ß was significantly higher in the COPD patients as compared to the normal controls (p < 0.05), but the difference between the two COPD groups did not reach significance. The levels of IL-6 and TNF-α among the three groups were significantly different (p < 0.05). The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (p < 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%. CONCLUSIONS: Radiographic emphysema is correlated with low BMD in current and former smokers with COPD. IL-1ß, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD.

[Sarcoidosis with upper airway involvement as the presenting symptoms: case report and literature review].

OBJECTIVE: To investigate the clinical characteristics of sarcoidosis with upper airway (including nose/paranasal sinus, pharynx, larynx and middle ear) involvement as the presenting symptoms, and therefore to minimize the misdiagnosis of sarcoidosis with special manifestations. METHODS: Four cases of sarcoidosis with upper airway involvement as the presenting symptoms diagnosed at our hospital were described. The clinical data were analyzed and related literatures were reviewed. RESULTS: Three female patients aged 52, 53, 34 years and one 15-year-old male patient, with the main complaints as "mycteric mass", "chronic otitis media", "hoarseness" and "chronic tonsillitis" respectively, were referred to our hospital for further evaluation. The diagnosis of sarcoidosis was finally confirmed by biopsy of bronchial mucous membrane, enlarged peripheral lymph nodes, and otorhinolaryngological lesions. Physical examination and imaging findings showed involvements of the lungs and/or the lymph nodes in 3 patients. Seven Chinese articles about upper airway sarcoidosis (all involving the nose) were found after literature search with "sarcoidosis" as the key word at the CNKI database (1915 - 2011). English literature search with the same key word at "Pubmed" showed that the rate of upper airway involvement in sarcoidosis varied from 2.3% - 6.0%, mostly concurrent with thoracic and lymph node diseases, whereas cases of sarcoidosis presenting with otorhinolaryngological symptoms were occasionally reported. CONCLUSIONS: Although upper airway sarcoidosis was rare, it may be the cause of chronic otorhinolaryngological disease which responded poorly to routine treatments. Careful collection of medical history, physical examination and necessary accessory examinations, especially better understanding of the exceptional manifestations of sarcoidosis, can help to minimize misdiagnosis and therefore to improve the prognosis of the patients.