[Advances in research on impaired ventilatory efficiency in cardiopulmonary exercise testing and chronic obstructive pulmonary disease].

The investigation of the pathophysiological mechanisms and potential applications of impaired ventilatory efficiency in cardiopulmonary exercise testing has received considerable attention in the field of chronic obstructive pulmonary disease (COPD) research worldwide. A growing body of evidence supports the notion that impaired ventilatory efficiency is an important indicator of exertional dyspnea, reduced exercise capacity, and mortality in patients with COPD. As a result, ventilatory efficiency is emerging as a promising therapeutic target for alleviating dyspnea in COPD patients. This review aims to provide a comprehensive summary of the research progress into impaired ventilatory efficiency in patients with COPD. The primary objective of this review is to improve the understanding of COPD patients with impaired ventilatory efficiency, with the ultimate goal of facilitating the comprehensive assessment and management of COPD.

[Chronic exposure of biomass ambient particulate matter induces signal-regulatory protein α (SIRPα) and surfactant protein D expression in rat alveolar macrophages].

Objective: To observe the expression of signal-regulatory protein α (SIRPα), surfactant protein (SP) A, and SPD by, and the phagocytic function of alveolar macrophages (AMs) in the rats exposed to biomass ambient particulate matter (BMF). Methods: Seventy-two male SD rats were randomly divided into BMF group and clean air group. Protein levels of SIRPα, SPA, and SPD in AMs were determined by Western blotting and immunofluorescent assay after 4 days, 1 month, and 6 months of BMF exposure. Fluorescent labeled Glucose aureus and Pseudomonas aeruginosa were used to detect the phagocytic ability of AMs in rats at three time points. Results: After 4 days of BMF exposure, there was no significant difference in the protein levels of SIRPα and SPD compared with the clean air group (P>0.05). The relative levels of SIRPα and SPD were (1.73±0.64) and (2.01±0.78) at 1 month of BMF exposure, and those at 6 months of BMF exposure were (1.49±0.28) and (1.48±0.34), both of which were higher than those in the clean air group (P<0.05). The relative level of Staphylococcus aureus median fluorescence intensity (MFI) and Pseudomonas aeruginosa MFI at 1 month BMF group were (0.56±0.16) and (0.80±0.09), and those at 6 months BMF group were (0.67±0.11) and (0.76±0.16), both of which were lower than those in clean air group, and the difference was statistically significant (P<0.05). Conclusions: BMF induces upregulation of SIRPα and SPD in AMs and inhibits the phagocytosis of AMs.

Red blood cell distribution width is an independent predictor of mortality for an acute exacerbation of COPD.

BACKGROUND: The prognostic role of the red blood cell distribution width (RDW) on an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is incompletely understood.OBJECTIVE: To investigate the effect of the RDW on in-hospital and 1-year mortality after an AECOPD.DESIGN: For 442 AECOPD patients, the RDW was measured and clinical characteristics, comorbidities and laboratory measurements were recorded. The RDW that discriminated survivors and non-survivors was determined using a receiver operator characteristic (ROC) curve. The risk factors for in-hospital and 1-year mortality were identified through logistic regression analysis and Cox regression analysis, respectively.RESULTS: Of 442 study patients, 31 died, and 411 survived while in hospital. The area under the ROC curve for RDW for in-hospital death was 0.726 (95%CI 0.631-0.822), with sensitivity of 0.71 and specificity of 0.64 for a cut-off point of 13.75%. An RDW ≥13.75% was a risk factor for in-hospital mortality (relative risk 4.30, 95%CI 1.98-9.58; P < 0.001). Univariate and multivariate Cox regression analysis showed that an RDW ≥13.75% was an independent risk factor for death at 1 year (univariate analysis, hazard ration [HR] 2.33, 95%CI 1.55-3.51; multivariate analysis, HR 1.64, 95%CI 1.08-2.50).CONCLUSION: The RDW was a strong and independent risk factor for in-hospital and 1-year death for AECOPD patients.

[The mechanism of nicotine on human bronchial smooth muscle cell contraction].

Objective: To investigate the molecular mechanism of contractility dysfunction of human bronchial smooth muscle cells induced by nicotine. Methods: Primary human bronchial smooth muscle cells were cultured in vitro. The cells were divided into a control group and a nicotine group which was treated with 10(-5) mol/L nicotine for 48 h and transfected with or without α7nAChR-siRNA (The siNC group, siNC + nicotine group and siα7nAChR + nicotine group). The effects of nicotine on the cell contractile function were examined by collagen gel shrinkage assay. The expressions of α7nAChR and TRPC6 protein in nicotine-treated human bronchial smooth muscle cells were detected by Western blotting. The change of intracellular calcium concentration by nicotine was detected by calcium ion imaging system.Data were analyzed by t test or single factor analysis of variance. Results: The area of collagen gel in the nicotine group (24±8)% was significantly lower than that in the control group (59±14)% (t=3.78, P<0.05). Compared with the control group, the expression of α7nAChR protein in nicotine-induced group (173±16)% was significantly higher than that of controls 100±0)%, t=-6.848, P<0.05. Compared with the siNC group [(72±10)%, (0.79±0.07), (0.41±0.04) and (0.17±0.02) respectively], the collagen gel area of siNC + nicotine group was significantly reduced by (37±10)%. However, the basal calcium level (1.04±0.02), store operated calcium entry level (SOCE, 0.68±0.03) and receptor operated calcium entry level (ROCE, 0.36±0.02) were remarkably elevated in the nicotine treated group (all P<0.05). Furthermore, compared with siNC + nicotine group, the area of collagen gel in siα7nAChR + nicotine group was significantly increased (62±10)%, and the basal calcium level (0.78±0.06), SOCE level (0.39±0.05) and ROCE level (0.15±0.02) were significantly reduced (all P<0.05). Conclusions: Nicotine can increase the expression of TRPC6 protein, SOCE and ROCE level, and increase the intracellular calcium concentration by upregulating the expression of α7nAChR protein, thereby promoting smooth muscle cell contraction.

[Preliminary analysis of lung function of population with biofuel smoke exposure].

Objective: To analyse the impaired lung functions of people with biofuel smoke exposure. Methods: Nonsmokers with biofuel smoke exposure were selected as research objects in a mountainous area of northern Guangdong where the families used biofuels as main energies and the nonsmokers without biofuel smoke exposure in the same area as control. Questionnaire interviews and spirometry tests were performed on all subjects. To analyse the differences of lung functions in both. Results: Seventy hundred and seventeen subjects were enro1led in this study.There were 530 nonsmokers with biofuel smoke exposure(observation group) including 442 women and 88 men, average age 54±10. There were 187 nonsmokers without biofuel smoke exposure(control group) including 141 women and 46 men, average age 54±10. There was no significant difference between two groups in age, height, weight, BMI, waist circumference, hip circumference and waist/hip ratio(P>0.05). The pulmonary ventilation function index(FEV(1)%Pred, FEV(1)/FVC) in the observation group was significantly less than that in control group [(100±18) vs.(106±25); (80±10) vs.(83±6) respectively, P<0.05]. Small airway function index(PEF25, PEF50, PEF75, MMPEF and MMPEF%Pred) was significantly less than that in control group(P<0.01). According to the univariate regression analysis and multivariate regression analysis, regression coefficients between BIOFUEL-INDEX and FEV/FVC was -0.1, 95%CI(-0.1, -0.1, P<0.01). According to the threshold analysis, the vertice of BIOFUEL-INDEX was 46.0, where the predicted Y value was 81.76, 95%CI (80.2, 83.33). When BIOFUEL-INDEX<46.0, the regression coefficient was 0, 95%CI (-0.1, 0.0)(P>0.05); when BIOFUEL-INDEX> 46.0, the regression coefficient 2 was -0.1, 95%CI (-0.2, -0.1)(P<0.01). The difference between coefficient 2 and 1 was -0.1, 95%CI (-0.2, 0.0), which was statistically significant (P<0.05). The Log-Likelihood ratio between Model I and Model Ⅱ had statistical significance (P=0.019). Conclusions: The biofuel smokes exposure causes damages in lung function.

[Establishment and application effect appraisement of community chronic obstructive pulmonary disease integrated management system].

Objective: To establish the COPD community integrated management system suitable for our national situation and assess its effects in the prevention and treatment for COPD. Methods: The COPD community integrated management system based on the electronic management system was established, including the functional modules of preliminary screening for COPD, electronic health record, grading management and dual referral system, ect. Two townships were randomly selected from the rural areas in north Guangdong as Observational Community and Control Community, respectively. Resident families were randomly selected from the two communities. One resident aged 40 or higher who was selected randomly from each family was enrolled in the trial and followed up for 2 years.Of a total of 460 participants from the Observational Community, 340 participants accomplished the two-years the follow-up, among whom there were 45 COPD patients, 117 high risk population, 178 common population. Of a total of 380 participants from the Control Community, 212 participants accomplished the follow-up, among whom there were 39 COPD patients, 68 high risk population, 105 common population.According to the COPD community integrated management system, the health cares including preliminary screening for COPD, grading management and dual referral, ect. were implemented in the Observational Community. Essential diagnosis and treatment services were performed in the Control Community. The effects of the system were appraised by comparisons of the pulmonary function change, acute exacerbation, quality of life and change of risk factors, ect. between the two communities. Results: After the intervention, the follow-up rate, smoking-quitting rate, the proportions of decline in current smoking, passive smoking and switching to clean energy for cooking in the Observational Community were significantly greater than those in the Control Community(73.9% vs. 55.8%, 70.8% vs. 9.1%, 24.2% vs. 7.1%, 32.6% vs. 3.5%, 67.8% vs. 3.2%, respectively, P<0.05). COPD knowledge rates of residents in the Observational Community, including "knowing about COPD" , "knowing about the symptoms of COPD" , "Whether COPD can be prevented and treated" and "lung function test" were significantly greater than before (84.7% vs.30.0%, 76.4% vs.7.6%, 71.5% vs.6.8%, 72.1% vs.27.4%, respectively, P<0.05) and greater than those in the Control Community(84.7% vs.73.6%, 76.4% vs.9.4%, 71.5% vs.7.1%, 72.1% vs.32.5%, P<0.05). In the Observational Community, FEV(1) and FEV(1) %Pred were significantly greater than before (1.88±0.71 vs. 1.74±0.64, 75.6±25.0 vs. 69.4±20.5, respectively, P<0.05). The values of the difference before and after the experiment in the patients of GOLD 1 grade COPD in the Observational Community were greater than those in the Control Community(P<0.05). In the Control Community, FEV(1)、FEV(1) %Pred had no significant difference before and after experiment(P>0.05). In the Observational Community, 6MWD, standard treatment rate and exercises>3 days per week were significantly greater than before(550.5±76.0 vs. 474.7±75.9, 64.4% vs. 8.9%, 100% vs. 22.2%, respectively, P<0.05) and greater than those in the Control Community(550.5±76.0 vs. 404.5±56.7, 64.4% vs. 10.3%, 100% vs. 30.8%, respectively, P<0.05), acute exacerbation was significantly less than before (4.4% vs. 17.8%, P<0.05). In the Control Unit, 6MWD was significantly less than before (404.5±56.7 vs. 469.8±58.5, P<0.05). Conclusions: The COPD community integrated management system can play a great role in community integrated prevention for COPD.

[PM2.5 from traffic-related ambient air and wood smoke induces epithelial-mesenchymal transition in human bronchial epithelial cells].

Objective: To observe if arterial traffic ambient PM2.5 (TAPM2.5) and wood smoke PM2.5(WSPM2.5) exposure can induce epithelial-mesenchymal transition (EMT) in human bronchial cells (HBEC). Methods: PM2.5 was collected from an arterial traffic road and a typical southern kitchen, and then the collections were extracted by DMSO. The viability of HBEC was measured by Cell Counting Kit (CCK-8) after culture with PM2.5-DMSO extracts for 24 hours. The expressions of EMT markers, including E-cadherin, cytokeratin, α-smooth muscle actin (α-SMA), vimentin and collagen typeⅠ (COL-Ⅰ) in HBEC were assayed by cell immunofluorescence and Western blot analysis after exposed to two different sources of PM2.5-DMSO extracts for 14 days. Results: The cell viability of HBEC increased at low concentrations (1, 2, 10 µg/ml and 1, 5, 10 µg/ml, corresponding to [(118.4±13.7)%, (118.2±8.0)%, (123.0±19.6)% and (112.4±4.1)%, (120±5.4)%, (117.8±7.0)%, respectively, all P<0.05], and then declined at high levels [20, 100, 200 µg/ml and 15, 20, 30, 40 µg/ml, corresponding to (100.7±12.1)%, (53.4±15.3)%, (9.4±1.7)% and (106.8±10.0)%, (93.8±7.9)%, (60.9±9.5)%, (46.2±3.6)%, respectively, P values were 0.923, 0.000, 0.000 and 0.231, 0.278, 0.000, 0.000, respectively] in both TAPM2.5-DMSO and WSPM2.5-DMSO incubation. After exposure for 14 days, the cells lost their typical cobblestone-like shape which implied that EMT might occur. The same treatment caused decreased positive signals of E-cadherin and cytokeratin in a small proportion of the cells. The decreased expressions of cytokeratin were verified by Western blot (TAPM2.5 and WSPM2.5 were 0.063±0.109 and 0.039±0.313, P values were 0.033 and 0.030, respectively), while α-SMA was only significantly upregulated in the WSPM2.5-DMSO group (7.853±4.784, P=0.049). The expressions of E-cadherin decreased in both groups but not statistically significant in Western blot (0.862±0.096 and 0.817±0.212, P values were 0.228 and 0.117, respectively). Another marker of EMT, COL-I, markedly increased in both PM2.5 treatment groups (2.549±1.037 and 3.658±1.207, P values were 0.034 and 0.001). Conclusions: Both PM2.5 from arterial traffic ambient air and wood smoke could induce EMT in human bronchial epithelial cells, while WSPM2.5 appeared to have a more significant influence on EMT in HBEC.

[Bone morphogenetic protein 4 increases canonical transient receptor potential protein expression by activating bone morphogenetic protein receptor â ¡/Smad signaling pathways in pulmonary arterial smooth muscle cells].

OBJECTIVE: To observe the effect of bone morphogenetic protein 4 (BMP4) on the Smad signaling pathway in rat distal pulmonary artery smooth muscle cells (PASMCs), and to explore the role of the transient receptor potential ion channel (TRPC) protein 1 and 6(TRPC1, 6) in rat distal PASMCs. METHODS: Distal pulmonary arteries were isolated from adult male Wistar rats(n=6, 280-300 g). The endothelium-denuded pulmonary artery tissue was digested using Collagenase and PASMCs were cultured. Activation of BMP4 signaling pathway in Smad was detected by Western blotting. Western blotting was used for the measurement of protein to determine the involvement of BMP4/BMPRⅡ signaling in BMP4-inducd TRPC1 and TRPC6 protein expression, and Smad signaling was inhibited by the specific BMPRⅡ small interfering RNA (BMPRⅡSiRNA). RESULTS: Rapid phosphorylation of Smad1/5/8 was seen after 15 min of stimulation with BMP4, which was reduced with time. The BMPR Ⅱ proteins was effectively down-regulated in the PASMCs after transfection with BMPRⅡ SiRNA, and the phosphorylation of Smad1/5/8 BMP4-induced was decreased in the PASMCs transfected with BMPR Ⅱ SiRNA compared to the normal PASMCs. In addition, transfection of BMPRⅡsiRNA also attenuated BMP4-induced TRPC1 and TRPC6 protein expression compared with transfection of NT-target siRNA in distal PASMCs. PASMCs transfected with BMPRⅡsiRNA showed a markedly decreased ability for BMP4 induction as assessed by gray value ratio of Western blotting, 2.7 times and 2.5 times by TRPC1/ß-actin and TRPC6/ß-actin respectively, compared with NT siRNA-treated cells(P<0.05). CONCLUSION: TRPC1 and TRPC6 protein expression can be up-regulated through Smad1/5/8 signaling activation by combination of BMP4 and BMPRⅡ in PASMCs.

Development and validation of a chronic obstructive pulmonary disease screening questionnaire in China.

OBJECTIVE: To develop a brief, reliable screening questionnaire for chronic obstructive pulmonary disease (COPD) for use in primary care settings. METHODS: We developed a COPD Screening Questionnaire (COPD-SQ) using data collected from 19,800 subjects aged ≥40 years obtained from an epidemiological study of COPD in China in 2002 (Phase I). A stepwise logistic regression method was adopted for item reduction and scoring. We then assessed the COPD-SQ through a cross-sectional study (Phase II) among 3231 subjects aged ≥40 years. RESULTS: The final COPD-SQ consisted of seven items: age, smoking pack-years, body mass index, cough, dyspnoea, family history of respiratory diseases and exposure to biomass smoke from cooking. Using the questionnaire to screen for COPD in Phase II, we obtained high classification accuracy with an area under the curve of 0.812 (95%CI 0.786-0.838). The sensitivity, specificity and correct classification rates for COPD diagnosis were respectively 60.6%, 85.2% and 82.7% at a cut-off score of 16. CONCLUSIONS: The COPD-SQ can be used in first-level screening for COPD.

Influence of environmental characteristics and climatic factors on mites in the dust of air-conditioner filters.

UNLABELLED: To investigate mites in the dust of air-conditioner filters (MACF) in China, a total of 652 dust samples were collected from six cities: Guangzhou (n = 129), Nanchang (n = 127), Shanghai (n = 113), Xian (n = 93), Beijing (n = 93), and Shenyang (n = 79). Tarsonemus granarius was the most dominant species (87.2%). Dermatophagoides pteronyssinus and Dermatophagoides farinae only represented 7.0 and 3.0% of total mites, respectively. With latitude increasing, both mite occurrence rate (P < 0.001) and density (mites/g dust) (P < 0.001) were significantly decreasing. Multivariate regression analysis suggested that the annual average temperature and minimum temperature in different cities had dominant influences on MACF density. The logistic regression analysis revealed that the presence of MACF was positively associated with air-conditioner age, utilization time and power. Wall and window type air-conditioner had higher risk of finding MACF than the floor type air-conditioner. As far as the cleaning interval time of ACF was concerned, higher risk ratio and the highest density of MACF were found in the time stage of >3, < or =12 months. It was also suggested that house type could influence the presence of MACF. A negative association between the house floor and the MACF prevalence was found as well. PRACTICAL IMPLICATIONS: Mites present in the dust of air-conditioner filters are potential indoor threat to asthma and allergy sufferers. In this study, we find that the storage mite Tarsonemus granarius is the predominant species of mites in the dust of air-conditioner filters (MACF). Thus, the possible clinical importance of T. granarius should cause more our attentions in the future. The abundance and distribution of MACF are also found significantly varied in different climatic regions of China. When we try to assess the possible risk of MACF, more attentions should be focused on subtropical region than temperate region. The influence analysis of environmental characteristics on the prevalence of MACF will shed light on the establishment of mite control strategy and the design of mite defense air-conditioner.

Localization of Per a 3 allergen in the gut and faecal pellets of the American cockroach (Periplaneta americana).

Cockroach-derived materials are known to be a major source of potent aeroallergens, causing allergic respiratory diseases such as asthma and allergic rhinitis. The aim of this study was to determine the localization of the major allergen, Per a 3 (Cr-PI), within the American cockroach (Periplaneta americana), which might reveal the relative importance of excreted materials and nonexcreted cockroach components as allergen sources. American cockroaches (P. americana) and their faecal pellets were embedded in paraffin, and serial sections were cut and collected on glass slides. After being stained with mouse polyclonal antiserum against Per a 3, the sections were incubated sequentially with biotin-labelled sheep antimouse immunoglobulin G (IgG) and a preformed fluorescent isothiocyanate (FITC)-avidin complex. Finally, the sections were mounted and examined under a fluorescent microscope. Examination of Per a 3 immunoreactivity on the sections of the American cockroaches (P. americana) revealed that the midgut mucosa, gut contents and faecal pellets were all strongly labelled. Per a 3 immunoreactive products were not detected in any other internal organs of the American cockroaches. These results suggest that Per a 3 allergen might be synthesized in and secreted from the epithelia of the midgut mucosa and excreted from the body in the faecal pellets.

Increasing COPD awareness.

Early diagnosis and smoking cessation are the only available methods to stop the progression of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the effects of early detection of airflow limitation (AL) in a population with high risk for COPD, using spirometric screening. Smokers aged 40 yrs with a smoking history of 10 pack-yrs were invited to visit a local outpatient chest clinic for simple spirometry (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Smoking history was recorded, followed by smoking cessation advice relating the results of spirometry to the smoking behaviour. Subjects who did not fulfil the above criteria (younger and/or nonsmokers) were also screened. A total 110,355 subjects were investigated; they were aged 53.5+/-11.5 yrs and 58.2% were males. Of the total amount of subjects, 64% were current smokers, 25.1% were former smokers and 10.9% were lifelong nonsmokers. Spirometry tests were within normal values for 70.3%, and 20.3% showed signs of AL: this was mild in 7.6%, moderate in 6.7% and severe in 5.9%. The remaining 8.3% of subjects presented with a restrictive pattern of ventilatory impairment. Airflow limitation was found in 23% of smokers aged 40 yrs with a history of 10 pack-yrs. This study concluded that large-scale voluntary spirometry screening of the population with high risk for COPD detects a large number of subjects with AL.

[The effects of persantine on pulmonary arterial pressure of rats exposed to hypoxia].

In the chronic hypoxic model of pulmonary hypertension, the increased wall thickness can be attributed in part to proliferation of endothelial cells, medial smooth muscle cell, and adventitial fibroblasts. The cellular mechanisms responsible for this proliferative response to chronic hypoxia may be due to the action of specific growth factors released in areas of vascular injury. Some growth factors such as platelet-derived growth factor and epidermal growth factor, released from activated platelets at sites of tissue injury and thrombus formation, may play a crucial role in this proliferative process. This paper reported the effects of persantine (dipyridamole), an inhibitor of platelet function, on pulmonary arterial pressure of rats exposed to hypoxia for 2 weeks. The results showed that persantine could prevent elevation of pulmonary arterial pressure and increase of right ventricle weight of hypoxic rats.