To investigate whether eosinophilic bronchitis without airway hyperresponsiveness will develop bronchial asthma in allergic mice.
Mice were sensitized with OVA on days 0, 7, and 14, challenged on days 21 to 23 (1st OVA challenge), and re-challenged on days 46 to 48 (2nd OVA challenge), intranasally with 10 (the EB group) and 200 (the AS group) μg OVA. Lung resistance (RL) was assessed 24 h after each challenge and on day 45 followed by analysis of leukocyte distribution in the bronchoalveolar lavage (BAL) fluid and histological examination.
Twenty-four hours after the 1st OVA challenge, aerosolized methacholine caused a dose-dependent increase in RL in all groups. At doses ≥1.56 mg/mL, RL in the AS group was significantly higher than that of the NS-1 group (P<0.01 or 0.05) and at doses ≥12.5 mg/mL, RL was markedly higher in the AS group than that of the EB group (P<0.01). The percentage of eosinophils in both the EB group and the AS group was markedly higher than that of the control group. Twenty-four hours after the 2nd OVA challenge, at doses ≤12.5 mg/mL, there was no significant difference in RL among all groups (P>0.05). At doses ≥12.5 mg/mL, RL in the AS group was significantly higher than that of the control group and EB group (P<0.01 or 0.05). The percentage of eosinophils in the AS group was noticeably higher than that of the EB group(P<0.05). Furthermore, there was apparent infiltration by inflammatory cells, predominantly eosinophils, into the sub-epithelial region of the bronchus and the bronchioles and around the vessels in the EB and AS group.
Re-challenge with low doses of ovalbumin did not increase airway reactivity and failed to induce bronchial asthma in mice with ovalbumin-induced EB.
Conventional chemotherapy and radiation therapy against non-small cell lung cancer (NSCLC) are relatively insensitive and unsatisfactory. Para-toluenesulfonamide (PTS), a unique antitumor drug for local intratumoral injection, shows an efficacy of severely suppressing solid tumor growth with mild side effects in clinical trials. The aim of this study was to investigate the effect of PTS on lung cancer H460 cells in vivo in nude mice and its underlying mechanisms in vitro.
A lung cancer model for in vivo experiment was established in BALB/c nude mice using H460 cells to examine the effect of local injection of PTS on tumor suppression. We also assessed the injury to the normal tissue by subcutaneous injection of PTS. In vitro, PTS was diluted into different doses for study on its antitumor mechanisms. We evaluated the necrotic effect of PTS on H460 cells by PI and Hoechst 33342 staining. Cell viability and membrane permeability were also determined by using CCK-8 and LDH assays respectively. All these tests were conducted in comparison with traditional local injection of anhydrous ethanol.
PTS was shown to significantly inhibit the growth of H460 tumor xenografts in nude mice by inducing necrosis of the tumor histologically. Its effect on tumor growth was significantly stronger than that of anhydrous ethanol. By contrast, the injured normal tissue by PTS injection was less than that by ethanol. In vitro, PTS still demonstrated excellent necrotizing effect on H460 cells when diluted to a lower concentration. Detailed analysis of PTS on H460 cells indicated that PTS had a better effect on attenuating the cell viability and increasing the cell membrane permeability than ethanol at the same level.
PTS exhibits excellent inhibition effect on the growth of lung cancer by necrotizing tumor in vivo and in vitro, reducing tumor cell viability and augmenting the membrane permeability in vitro, with only mild injury to normal tissue. The antitumor effect of PTS on lung cancer in vivo and in vitro is stronger than that of ethanol.
Para-toluenesulfonamide (PTS); lung cancer; necrosis; therapy; antitumor agent
Cough is one of the most common complaints for which patients seek medical attention. Misdiagnosis and mistreatment of cough exist commonly in China. The prevalence of acute cough caused by upper airway infection fluctuates between 9% and 64% in the community, for chronic cough, the prevalence >10% in most surveys, ranging from 7.2%-33%. The common causes of chronic cough are upper airway cough syndrome (previously called as post nasal drip syndrome [PNDS]), cough variant asthma (CVA), gastroesophageal reflux related cough (GERD) and eosinophilic bronchitis (EB). There is a regional discrepancy regarding the prevalence of common causes of cough and distribution of gender among China, UK, USA, the most common cause of chronic cough in China are CVA, followed by UACS, EB and atopic cough (AC), the male is almost equal to female in numbers in China. The risk factors for cough includes cold air, smoking, environmental pollutants, noxious substances and allergens, and unreasonable diet habits.
Cough; Epidemiology; Etiology; Risk factor; Quality of life
The outbreaks of emerging infectious diseases caused by pathogens such as SARS coronavirus, H5N1, H1N1, and recently H7N9 influenza viruses, have been associated with significant mortality and morbidity in humans. Neutralizing antibodies from individuals who have recovered from an infection confer therapeutic protection to others infected with the same pathogen. However, survivors may not always be available for providing plasma or for the cloning of monoclonal antibodies (mAbs).
The genome and the immunoglobulin genes in rhesus macaques and humans are highly homologous; therefore, we investigated whether neutralizing mAbs that are highly homologous to those of humans (human-like) could be generated. Using the H5N1 influenza virus as a model, we first immunized rhesus macaques with recombinant adenoviruses carrying a synthetic gene encoding hemagglutinin (HA). Following screening an antibody phage display library derived from the B cells of immunized monkeys, we cloned selected macaque immunoglobulin heavy chain and light chain variable regions into the human IgG constant region, which generated human-macaque chimeric mAbs exhibiting over 97% homology to human antibodies. Selected mAbs demonstrated potent neutralizing activities against three clades (0, 1, 2) of the H5N1 influenza viruses. The in vivo protection experiments demonstrated that the mAbs effectively protected the mice even when administered up to 3 days after infection with H5N1 influenza virus. In particular, mAb 4E6 demonstrated sub-picomolar binding affinity to HA and superior in vivo protection efficacy without the loss of body weight and obvious lung damage. The analysis of the 4E6 escape mutants demonstrated that the 4E6 antibody bound to a conserved epitope region containing two amino acids on the globular head of HA.
Our study demonstrated the generation of neutralizing mAbs for potential application in humans in urgent preparedness against outbreaks of new influenza infections or other virulent infectious diseases.
Indacaterol is a novel, once-daily (od), inhaled, long-acting ß2-agonist bronchodilator for maintenance treatment of airflow limitation in patients with COPD. The aim of this study was to evaluate the efficacy of indacaterol on dyspnea, using available randomized placebo-controlled trials.
A systematic search was made of MEDLINE, EMBASE, the Cochrane trials databases, and a manual search of journals. Randomized placebo-controlled trials of 12 weeks or more comparing indacaterol with placebo were reviewed, and eligible studies were included in a meta-analysis. The odds ratio (OR) for likelihood of achieving TDI score ≥ 1 after 12 weeks of treatment was used as an outcome measure to compare indacaterol to placebo.
Six trials were included in the analysis. Relative to placebo, the overall ORs for response were: indacaterol 75 μg od 1.784 (95% CI 1.282 to 2.482); indacaterol 150 μg od 2.149 (95% CI 1.746 to 2.645); and indacaterol 300 μg od 2.458 (95% CI 2.010 to 3.006). Overall OR for response in TDI tended to increase with higher indacaterol doses.
Patients receiving indacaterol had clinically significant improvements in symptoms of dyspnea compared to placebo. Incremental benefits in TDI were observed with increasing doses. Indacaterol may provide patients and physicians with a useful treatment option in symptomatic patients with dyspnea.
Breathlessness; Baseline dyspnea index; Transition dyspnea index; Meta-analysis; COPD
Pulmonary hypertension (PH) is a lethal disease with no cure currently available. Sodium Tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component from salvia miltiorrhiza, a kind of Chinese herbal medicine. We investigate the efficacy of STS towards treatment of PH patients.
Methods and results
Five hospitalized patients were randomly enrolled for this study. These patients were suffering from various types of serious PH without getting sufficient benefits from sildenafil treatment (20 mg tid) for at least three months. The efficacy of STS on PH was evaluated by measuring the pulmonary arterial systolic pressure (PASP), RV size by echocardiography, 6-minute walking distance (6MWD), Borg dyspnea score, and WHO functional class of PH. Patients aged from 17 to 46 (average 33±11) years old, pulmonary arterial systolic pressure (PASP) ranged from 60 to 140 mmHg, RV size ranged from 25 to 39 mm were included in study. At the endpoint of observation for 8 weeks of STS infusion, they obtained reduction of PASP in the range of 14-45 (average 28.6±12.5) mmHg, RV size in the range of 0-10 (average 4.2±1.6). All patients exhibited improved exercise capacity with an increase of 6MWD from 63 to 268 (average 138.4±40.7) meters, significantly reduced Borg dyspnea score from maximum 9 down to 1 or 0, and reduced WHO functional class of PH from III or IV down to II.
These results indicate that STS exhibits remarkable beneficiary effects on treating PH patients either alone or in concert with sildenafil.
Pulmonary hypertension; pulmonary arterial hypertension; tanshinone IIA sulfonate
Detection for cough in mice has never yielded clearly audible sounds, so there is still a great deal of debates as to whether mice can cough in response to tussive stimuli. Here we introduce an approach for detection of mouse cough based on sound monitoring and airflow signals. 40 Female BALB/c mice were pretreated with normal saline, codeine, capasazepine or desensitized with capsaicin. Single mouse was put in a plethysmograph, exposed to aerosolized 100 µmol/L capsaicin for 3 min, followed by continuous observation for 3 min. Airflow signals of total 6 min were recorded and analyzed to detect coughs. Simultaneously, mouse cough sounds were sensed by a mini-microphone, monitored manually by an operator. When manual and automatic detection coincided, the cough was positively identified. Sound and sound waveforms were also recorded and filtered for further analysis. Body movements were observed by operator. Manual versus automated counts were compared. Seven types of airflow signals were identified by integrating manual and automated monitoring. Observation of mouse movements and analysis of sound waveforms alone did not produce meaningful data. Mouse cough numbers decreased significantly after all above drugs treatment. The Bland-Altman and consistency analysis between automatic and manual counts was 0.968 and 0.956. The study suggests that the mouse is able to present with cough, which could be detected by sound monitoring and respiratory airflow waveform changes.
COPD is often underdiagnosed in a primary care setting where the spirometry is unavailable. This study was aimed to develop a simple, economical and applicable model for COPD screening in those settings.
First we established a discriminant function model based on Bayes’ Rule by stepwise discriminant analysis, using the data from 243 COPD patients and 112 non-COPD subjects from our COPD survey in urban and rural communities and local primary care settings in Guangdong Province, China. We then used this model to discriminate COPD in additional 150 subjects (50 non-COPD and 100 COPD ones) who had been recruited by the same methods as used to have established the model. All participants completed pre- and post-bronchodilator spirometry and questionnaires. COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria. The sensitivity and specificity of the discriminant function model was assessed.
The established discriminant function model included nine variables: age, gender, smoking index, body mass index, occupational exposure, living environment, wheezing, cough and dyspnoea. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, accuracy and error rate of the function model to discriminate COPD were 89.00%, 82.00%, 4.94, 0.13, 86.66% and 13.34%, respectively. The accuracy and Kappa value of the function model to predict COPD stages were 70% and 0.61 (95% CI, 0.50 to 0.71).
This discriminant function model may be used for COPD screening in primary care settings in China as an alternative option instead of spirometry.
COPD; Bayes’ Rule; spirometry
Recently, several genome-wide association studies (GWAS) have identified many susceptible single nucleotide polymorphisms (SNPs) for chronic obstructive pulmonary disease (COPD) and lung cancer which are two closely related diseases. Among those SNPs, some of them are shared by both the diseases, reflecting there is possible genetic similarity between the diseases. Here we tested the hypothesis that whether those shared SNPs are common predictor for risks or prognosis of COPD and lung cancer. Two SNPs (rs6495309 and rs1051730) located in nicotinic acetylcholine receptor alpha 3 (CHRNA3) gene were genotyped in 1511 patients with COPD, 1559 lung cancer cases and 1677 controls in southern and eastern Chinese populations. We found that the rs6495309CC and rs6495309CT/CC variant genotypes were associated with increased risks of COPD (OR = 1.32, 95% C.I. = 1.14–1.54) and lung cancer (OR = 1.57; 95% CI = 1.31–1.87), respectively. The rs6495309CC genotype contributed to more rapid decline of annual Forced expiratory volume in one second (FEV1) in both COPD cases and controls (P<0.05), and it was associated with advanced stages of COPD (P = 0.033); the rs6495309CT/CC genotypes conferred a poor survival for lung cancer (HR = 1.41, 95%CI = 1.13–1.75). The luciferase assays further showed that nicotine and other tobacco chemicals had diverse effects on the luciferase activity of the rs6495309C or T alleles. However, none of these effects were found for another SNP, rs1051730G>A. The data show a statistical association and suggest biological plausibility that the rs6495309T>C polymorphism contributed to increased risks and poor prognosis of both COPD and lung cancer.
Lung cancer and chronic obstructive pulmonary disease (COPD) share a common risk factor in cigarette smoking and a large portion of patients with lung cancer suffer from COPD synchronously. We therefore hypothesized that COPD is an independent risk factor for lung cancer. Our aim was to investigate the intrinsic linkage of COPD (or emphysema, chronic bronchitis and asthma) and lung cancer.
The present hospital-based case-control study included 1,069 patients with newly diagnosed lung cancer and 1,132 age frequency matched cancer-free controls. The odds ratios (ORs) for the associations between each previous pulmonary disease and lung cancer were estimated with logistic regression models, adjusting for age, sex, family history of cancer, BMI and pack year smoking. In meta-analysis, the pooled effects of previous pulmonary diseases were analyzed with random effects models; and stratification analyses were conducted on smoking status and ethnicity.
In the case-control study, previous COPD was associated with the odds for increased risk of lung cancer (OR = 1.29, 95% confidence interval [CI] = 1.00∼1.68); so were emphysema (OR = 1.55, 95%CI = 1.03∼2.32) and chronic bronchitis (OR = 1.22, 95%CI = 0.99∼1.67); while asthma was associated with odds for decreased risk of lung cancer (OR = 0.29, 95%CI = 0.16∼0.53). These associations were more pronounced in smokers (P<.05 for all strata), but not in non-smokers. In meta-analysis, 35 studies (22,010 cases and 44,438 controls) were identified. COPD was significantly associated with the odds for increased risk of lung cancer (pooled OR = 2.76; 95% CI = 1.85–4.11), so were emphysema (OR = 3.02; 95% CI = 2.41–3.79) and chronic bronchitis (OR = 1.88; 95% CI = 1.49–2.36); and these associations were more pronounced in smokers than in non-smokers (P<.001 respectively). No significant association was observed for asthma.
Previous COPD could increase the risk of lung cancer, especially in smokers.
Chronic cough is a very common complaint in clinics throughout China. Clinical and basic science research on chronic cough started late, but in recent years the effort has yielded promising findings regarding the etiological diagnosis, treatment and pathogenesis. We found that inflammation in nonasthmatic eosinophilic bronchitis has some similarities to cough variant asthma but also a number of distinct differences. Recent evidence has also suggested a mechanistic link between airway neurogenic inflammation and and gastroesophageal reflux cough (GERC). Cough-related animal models have been developed, including models for esophageal reflux, nonasthmatic eosinophilic bronchitis and allergic rhinitis. Normal reference values for differential cell counts in induced sputum, cough sensitivity and esophageal 24-h pH monitoring in Chinese healthy subjects have been established. By using a modified algorithm for the etiological diagnosis of chronic cough, the causes of chronic cough have been investigated across a number of cities in China. The most common causes of chronic cough are cough variant asthma, eosinophilic bronchitis, upper airway cough symptoms, atopic cough and GERC, however, there are some regional variations. The Chinese National Guidelines on Diagnosis and Management of Chronic Cough were drafted in 2005, updated in 2009, and have been widely publicized and disseminated through many channels since their publication.
Airway inflammation; Chronic cough; Diagnosis; Epidemiology; Pathogenesis
Patients with chronic asthma have thicker intrapulmonary airways measured on high resolution computed tomography (HRCT). We determined whether the presence of lower airway bacteria was associated with increased airway wall thickness.
In 56 patients with stable severe asthma, sputum specimens obtained either spontaneously or after induction with hypertonic saline were cultured for bacteria and thoracic HRCT scans obtained. Wall thickness (WT) and area (WA) expressed as a ratio of airway diameter (D) and total area, respectively, were measured at five levels.
Positive bacterial cultures were obtained in 29 patients, with H. influenzae, P. aeruginosa and S. aureus being the commonest strains. Logistic regression analysis showed that this was associated with the duration of asthma and the exacerbations during the past year. In airways > 2 mm, there was no significant difference in WA (67.5 ± 5.4 vs 66.4 ± 5.4) and WT/D (21.6 ± 2.7 vs 21.3 ± 2.4) between the culture negative versus positive groups. Similarly, in airways (≤ 2 mm), there were no significant differences in these parameters. The ratio of √wall area to Pi was negatively correlated with FEV1% predicted (p < 0.05).
Bacterial colonization of the lower airways is common in patients with chronic severe asthma and is linked to the duration of asthma and having had exacerbations in the past year, but not with an increase in airway wall thickness.
Severe asthma; Airway wall thickness; Sputum bacteria
The associations between sensitizations and severity of allergic diseases are controversial. This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitivity in allergic patients in China.
A cross-sectional survey was performed in 6,304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire related to the respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. 2,268 of them were taken blood for serum specific IgE (sIgE) measurements for 16 common aeroallergens.
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was related to skin wheal size and sIgE to Artemisia vulgaris and Ambrosia artemisifolia (P < 0.001). Moderate-severe asthma was associated with increasing in skin and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (P < 0.001). Moderate-severe rhinitis and asthma were also associated with increasing in number of skin and sIgE sensitized allergens.
Outdoor allergen sensitizations are significantly associated with severity of intermittent rhinitis and indoor allergen sensitizations are significantly associated with severity of asthma in patients in China. Number of allergen sensitization is also related to severity of rhinitis and asthma.
Upper airway inflammation could be reflected by nasal lavage cytology test, which is characterized by advantages of non-invasive, simple, objective and costless. However, reference values nasal lavage cytology was not established. To establish reference values and positive standard for nasal lavage cytology through screening normal healthy subjects and patients with allergic rhinitis according to strict inclusion criteria.
To establish reference values and positive standard for nasal lavage cytology through screening normal healthy subjects and patients with allergic rhinitis according to strict inclusion criteria.
There was no statistical significance in gender constitutional proportion, age, height and weight among each group. 95% CI of neutrophils, eosinophils was (0∼12.61)/×200 and (0∼1.70)/×200, respectively. The median (interquartile range) of neutrophils were 0(0.65)/×200 in AR group, which showed no statistical difference (P > 0.05) with that of normal group [0(0)/×200]. A significant difference was found in the median (interquartile range) of eosinophils [6.90(22.40)/×200] in AR group as compared with that of normal control group [0(0.10)/×200, P < 0.001].
Establishment of reference values of nasal lavage cytology test is helpful to discriminate normal individuals and patients with allergic rhinitis, but also a non-invasive tool for objective reflection on upper airway inflammation, which is of great value for scientific and clinical purposes.
Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer.
Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8+ T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect.
Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy.
The association between sensitizations and severity of allergic diseases is controversial.
This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitization in allergic patients in China.
A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire documenting their respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. Among the recruited subjects, 2268 provided blood samples for serum measurement of specific IgE (sIgE) against 16 common aeroallergens.
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was associated with the skin wheal size and the level of sIgE to Artemisia vulgaris and Ambrosia artemisifolia (p < 0.001). Moderate-severe asthma was associated with increasing wheal size and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (p < 0.001). Moderate-severe rhinitis and asthma were also associated with increase in number of positive skin prick test and sIgE.
Artemisia vulgaris and Ambrosia artemisifolia sensitizations are associated with the severity of intermittent rhinitis and D. pteronyssinus and D. farinae sensitizations are associated with increasing severity of asthma in China. Increase in number of allergens the patients are sensitized to may also increase the severity of rhinitis and asthma.
sensitization; aeroallergens; disease severity; allergic rhinitis; asthma; association.
Objective To evaluate the effects of a community based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China.
Design Cluster randomised controlled trial.
Setting Eight healthcare units in two communities.
Participants Of 1062 people aged 40-89, 872 (101 with COPD and 771 without COPD) who fulfilled the inclusion and exclusion criteria were allocated to the intervention or the usual care programmes.
Intervention Participants randomly assigned to integrated intervention (systematic health education, intensive and individualised intervention, treatment, and rehabilitation) or usual care.
Main outcome measures Annual rate of decline in forced expiratory rate in one second (FEV1) before use of bronchodilator.
Results Annual rate of decline in FEV1 was significantly lower in the intervention community than the control community, with an adjusted difference of 19 ml/year (95% confidence interval 3 to 36) and 0.9% (0.1% to 1.8%) of predicted values (all P<0.05), as well as a lower annual rate of decline in FEV1/FVC (forced vital capacity) ratio (adjusted difference 0.6% (0.1% to 1.2%) P=0.029). There were also higher rates of smoking cessation (21% v 8%, P<0.004) and lower cumulative death rates from all causes (1% v 3%, P<0.009) in the intervention community than in the control community during the four year follow-up. Improvements in knowledge of COPD and smoking hazards, outdoor air quality, environmental tobacco smoke, and working conditions were also achieved (all P<0.05). The difference in cumulative incidence rate of COPD (both around 4%) and cumulative death rate from COPD (2% v 11%) did not reach significance between the two communities.
Conclusions A community based integrated intervention can have a significant impact on the prevention and management of COPD, mainly reflected in the annual rate of decline in FEV1.
Trial registration Chinese Clinical Trials Registration (ChiCTR-TRC-00000532).
There is increasing evidence for a possible association between chronic obstructive pulmonary disease (COPD) and the use of biomass fuels for cooking and heating in developing countries. Data on the prevalence of COPD and objective measurements of indoor pollution from biomass fuel have not been widely available from China. A study was undertaken to investigate the prevalence of COPD in two study communities in Guangdong province in China and to measure the association between COPD and indoor biomass fuel air pollution.
A cluster disproportional random sampling survey was performed in populations aged over 40 years in urban (Liwang) and rural (Yunyan) areas in Guangdong, China. Spirometry was performed in all subjects and a post‐bronchodilator ratio of the forced expiratory volume in 1 s to forced vital capacity of <0.70 was defined as COPD. Measurements of indoor and outdoor air pollutants were also performed in a random sample of households.
The overall prevalence of COPD in the two areas (Liwang and Yunyan) was 9.4%. The prevalence of COPD in both the whole population and a subpopulation of non‐smoking women in rural Yunyan was significantly higher than in urban Liwang (12.0% vs 7.4%, and 7.2% vs 2.5%, respectively). The use of biomass fuel was higher in rural Yunyan than in urban Liwang (88.1% vs 0.7%). Univariate analysis showed a significant association between COPD and exposure to biomass fuel for cooking. Multivariate analysis showed a positive association between COPD and urban/rural area (surrogate for fuel type and local exhaust ventilation in kitchen) after adjustment for sex, age group, body mass index, education, occupational exposure, respiratory disease in family, smoking status, life quality and cough in childhood; similar results were found in non‐smoking women. Pollutants measurements showed that concentrations of carbon monoxide, particulate matter with an aerodynamic diameter ⩽10 μm, sulphur dioxide and nitrogen dioxide in the kitchen during biomass fuel combustion were significantly higher than those during LPG combustion.
Indoor pollutants from biomass fuels may be an important risk factor for COPD in rural South China.
The sleep apnea cardiovascular endpoints (SAVE) study (Clinical Trials Registration Number: NCT00738170) is an academic initiated and conducted, multinational, open, blinded endpoint, randomised controlled trial designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the incidence of serious cardiovascular events in patients with established cardiovascular disease. The answer to this question is of major importance to populations undergoing ageing and lifestyle changes all over the world. The SAVE study brings together respiratory, sleep and cardiovascular clinician-scientists in a unique interdisciplinary collaborative effort with industry sponsors to conduct the largest and most ambitious clinical trial yet conducted in the field of sleep apnea, with a global recruitment target of 5000 patients. Following its launch in Australia and China in late 2008, SAVE has now entered a phase of international expansion with new recruitment networks being established in New Zealand, India and Latin America. This article describes the rationale for the SAVE study, the considerations behind its design, and progress thus far in establishing the recruitment network. The report emphasises the important role that Chinese sleep and cardiovascular investigators have played in the start-up phase of this landmark international project.
obstructive sleep apnea; continuous positive airways pressure; sleep apnea cardiovascular endpoints (SAVE) study
There is an increasing need for establishment of biobanks for human cancer, which may facilitate basic and clinical researches as well as the development of novel approaches to early diagnostics, prevention and treatment, including personalized medicine. Herein we report the establishment of a lung cancer biobanks using biological samples from a lung cancer patient population in Southern China. Since 2007, we have collected lung cancer tissue from 1,054 patients with lung cancer, from whom 11,895 frozen tumor and normal matched tissues, 4,899 tissue paraffin blocks, and 3,562 blood serum samples were accumulated. The information on clinical manifestations, laboratory tests, and follow-up was maintained by an independent information management system, including three data sets. The primary data set included frozen tissue specimens, formalin-fixed paraffin-embedded tissues, blood specimens and clinical and long-term follow-up data. The secondary data set included DNA, RNA and proteins extracted from corresponding tissue specimens. And the tertiary data set contained improved genome, RNA and proteomics correlation analysis with relevant clinical and long-term follow-up data. The lung cancer biobanks is accessible to academic research and public services. To our best knowledge, this biobanks represents the first lung cancer tissue reservoir in China and should facilitate the basic and clinical research of this disease and developing diagnostic markers and novel therapeutic modalities.
lung cancer; biobanks; tissue bank; southern Chinese population
Unrestrained plethysmography has been used to monitor bronchoconstriction because of its ease of use and ability to measure airway responsiveness in conscious animals. However, its reliability remains controversial.
To investigate if unrestrained plethysmography could provide a valid interpretation of airway responsiveness in allergic BALB/c mice.
Ovalbumin sensitized BALB/c mice were randomized to receive either a single-dose Ovalbumin challenge (OVA-1D group) or a three-dose Ovalbumin challenge (OVA-3D group). The OVA-1D group was further divided into OVA-1D-I (measured invasively, using lung resistance as the index of responsiveness) and OVA-1D-N group (measured non-invasively, using Penh as the index of responsiveness). Similarly the OVA-3D group was divided into OVA-3D-I and OVA-3D-N groups based on the above methods. The control groups were sensitized and challenged with normal saline. Bronchial alveolar lavage fluid was taken and airway histopathology was evaluated for airway inflammation. Nasal responsiveness was tested with histamine challenge.
Compared with controls, a significant increase in airway responsiveness was shown in the OVA-1D-N group (P < 0.05) but not in the OVA-1D-I group. Both OVA-3D-I and OVA-3D-N groups showed higher responsiveness than their controls (P < 0.05). The nasal mucosa was infiltrated by eosinophic cells in all Ovalbumin immunized groups. Sneezing or nasal rubbing in allergic groups appeared more frequent than that in the control groups.
Penh can not be used as a surrogate for airway resistance. The invasive measurement is specific to lower airway. Penh measurement (done as a screening procedure), must be confirmed by a direct invasive measurement specific to lower airway in evaluating lower airway responsiveness.
In allergic asthma, Th2 lymphocytes are believed to play important roles in orchestrating airway eosinophilia and inflammation. Resetting the Th1/Th2 imbalance may have a therapeutic role in asthma. The mycobacterium tuberculosis 30-kilodalton major secretory protein (antigen 85B, Ag85B) can protect animals from M. tuberculosis infection by inducing a Th1-dominant response.
In this study, the Ag85B gene was cloned into pMG plasmids to yield the pMG-Ag85B plasmid. The expression of Ag85B gene in murine bronchial epithelia cells was detected by Western blotting and immunohistochemical staining after intranasal immunization with reconstructed pMG-Ag85B plasmids. The protective effect of pMG-Ag85B plasmids immunization in airway inflammation was evaluated by histological examination and bronchoalveolar lavage (BAL). IL-4 and IFN-γ levels in the BAL and supernatant from splenocyte culture were determined using ELISA kits.
The Ag85B gene was successfully expressed in murine bronchial epithelia cells by intranasal immunization with reconstructed pMG-Ag85B plasmids. Using a murine model of asthma induced by ovalbumin (OVA), pMG-Ag85B immunization significantly inhibited cellular infiltration across the airway epithelium with a 37% decrease in the total number of cells (9.6 ± 2.6 × 105/ml vs. 15.2 ± 3.0 × 105/ml, p < 0.05) and a 74% decrease in the number of eosinophils (1.4 ± 0.2 × 105/ml vs. 5.4 ± 1.1 × 105/ml, p < 0.01) compared with the OVA-sensitized control group. There was no difference in the number of neutrophils in BAL fluid between the pMG-Ag85B group, the OVA-sensitized control group and the empty pMG group. IL-4 production was significantly decreased in the BAL fluid (32.0 ± 7.6 pg/ml vs. 130.8 ± 32.6 pg/ml, p < 0.01) and in the splenocyte supernatant (5.1 ± 1.6 pg/ml vs. 10.1 ± 2.3 pg/ml, p < 0.05) in the pMG-Ag85B group compared with the OVA-sensitized control group, while IFN-γ production was increased in the BAL fluid (137.9 ± 25.6 pg/ml vs. 68.4 ± 15.3 pg/ml, p < 0.05) and in the splenocyte supernatant (20.1 ± 5.4 pg/ml vs. 11.3 ± 3.2 pg/ml, p < 0.05).
In a murine model of asthma induced by OVA, intranasal immunization with pMG-Ag85B significantly reduced allergic airway inflammation with less eosinophil infiltration. This protective effect was associated with decreased IL-4 and increased IFN-γ production in the BAL fluid and in the supernatant of cultured splenocytes.
Despite the rapid increase in research in China, little is known about the quality of clinical trials conducted there.
A systematic review and critical appraisal of randomised controlled trials (RCTs) conducted in China and published in 2004 was undertaken to describe their characteristics, assess the quality of their reporting, and where possible, the quality of their conduct. Randomised controlled trials in all disease areas and types of interventions, which took place in China and included Chinese citizens were identified using PubMed and hand searching the Journal Series of the Chinese Medical Association. Quality was assessed against a subset of criteria adapted from the CONSORT statement.
Three hundred and seven RCTs were included. One hundred and ninety-nine (64.8%) failed to report methods of randomization and 254 (82.4%) did not mention blinding of either participants or investigators. Reporting of baseline characteristics, primary outcome and length of follow-up was inadequate in a substantial proportion of studies. Fewer than 11% of RCTs mentioned ethical approval and only 18.0% adequately discussed informed consent. However, dropout rates were very favourable with nearly 44% of trials reporting a zero dropout rate.
Reporting of RCTs in China requires substantial improvement to meet the targets of the CONSORT statement. The conduct of Chinese RCTs cannot be directly inferred from the standard of reporting; however without good reporting the methods of the trials cannot be clearly ascertained.
China's experience with SARS has important implications worldwide, and may improve preparedness for an epidemic if bird flu spreads to humans