A prospective study of salvational intervention with ICS/LABA for reducing chronic obstructive pulmonary disease exacerbation under severe air pollution (SIRCAP) in Beijing: protocol of a multi-center randomized controlled trial.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality all over the world. Acute exacerbation of COPD (AECOPD) not only accelerates the progression of disease, but also causes hospital administration and death events. Epidemiologic studies have shown air pollution is a high risk factor of AECOPD. However, there are rare technics or treatment strategies recommended to reduce severe air pollution related AECOPD. METHODS: This is a multi-center, prospective, randomized and standard treatment parallel control clinical trial. Seven hundred sixty-four stable COPD patients in group B, C and D according to GOLD 2017 will be recruited and equally divided into two parallel groups, salvational intervention (SI group) and control group (CT group). Original treatments for participants include tiotropium (18µg once q.d), budesonide/formoterol (160µg/4.5µg once or twice b.i.d) or budesonide/formoterol (160µg/4.5µg once or twice b.i.d) with tiotropium (18µg once q.d). The savational intervention for SI group is routine treatment plus budesonide/formoterol (160µg/4.5µg once b.i.d) from the first day after severe air pollution (air quality index, AQI ≥200) to the third day after AQI < 200. CT group will maintain the original treatment. The intervention will last for 2 years. Primary outcome is the frequency of AECOPD per year and the secondary outcomes include the incidence of unplanned outpatient visits, emergency visits, hospitalization, medical cost and mortality associated with AECOPD per year. DISCUSSION: The salvational intervention is a novel strategy for COPD management under severe air pollution. Results of the present study will provide reference information to guide clinical practice in reducing the air pollution related exacerbation of COPD. TRIAL REGISTRATION: This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03083067 ) in 17 March, 2017.

[Analysis of factors associated with decline of FEV1 among community population in urban area of Beijing].

OBJECTIVE: To investigate risk factors correlated to the decline of FEV1among community population in the urban area of Beijing. METHOD: Subjects no younger than 40 years old were recruited from three communities in the urban area of Beijing. All of them were asked to fill in a questionnaire in regard to general health conditions, past medical history, medication usage, smoking history, etc. FEV1and FEV6 were measured by Vitalograph COPD-6 spirometer using the standard protocol. Two years after the first visit, questionnaire survey and spirometry were repeated. RESULT: Four hundred and fifty two subjects fulfilled the inclusion criteria and finished the 2nd visit, with an average age of (58.8 ± 8.6) years, 29% male and 71% female. The mean decline rate of FEV1in the cohort was (43 ± 114) ml per year. There was no significant difference of mean FEV1decline between different gender and age groups. A mean decline of FEV1by (64 ± 125) ml per year was observed in smokers (including former smokers and current smokers) whereas the decline rate in non-smokers was (36 ± 109) ml per year (P = 0.030). There was no significant statistical difference among current smokers, former smokers, passive smokers and subjects who never smoke. A higher decline rate of FEV1was observed in subjects with a history of COPD or airway hyperreactivity, chronic cough, diabetes, hypertension and coronary heart disease. The difference, however, was not statistically significant. Binary logistic regression was used to screen risk factors affected the FEV1decline rate between rapid decline (ΔFEV1 ≥ 30 ml/y) and non-rapid decline (ΔFEV1 < 30 ml/y), and found smoking was an independent risk factor of FEV1decline rate. CONCLUSION: The mean rate of FEV1 decline in 2.6 years in the surveyed community population in the urban area of Beijing was (43 ± 114) ml per year; Smoking is an independent risk factor of FEV1decline.

Serum surfactant protein D, lung function decline, and incident chronic obstructive pulmonary disease: a longitudinal study in Beijing.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a major public-health problem in China. Surfactant protein D (SP-D) is a very promising biomarker and therapeutic target for COPD. To assess whether baseline serum SP-D is associated with lung function decline and incident COPD. METHODS: This longitudinal study was initiated in 2009 in a community in Beijing. Data were collected on spirometry, and the baseline level of serum SP-D was measured in 772 non-COPD subjects aged 40-70 years old. In 2012, spirometry was repeated in 364 individuals, 37 of whom subjects had incident COPD. RESULTS: From 2009 to 2012, subjects with incident COPD had a more rapid decline in FEV1 (MD 98.27 vs. MD 43.41 mL) compared with those without COPD. There was no association between baseline serum SP-D and the COPD incidence. Smoking (OR =2.72; P=0.002) and age (OR =1.06; P=0.000) were risk factors for COPD. The rate of FEV1 decline varies widely in the general population, and the univariate analysis showed that baseline serum SP-D levels (R=-0.169; P=0.003), income level, home-road distance, and statin use were inversely correlated with the decline in FEV1. After multivariable analyses, only smoking was consistently associated with the decline in FEV1. CONCLUSIONS: There was no correlation between baseline serum SP-D levels and incident COPD in a general population. Smoking and age were major risk factors for COPD. The effect of serum SP-D levels on the decline in FEV1 needs further investigation.

[Prognostic factors for patients with pulmonary thromboembolism after orthopaedic surgery].

OBJECTIVE: To investigate the changes of serum enzymes and their prognostic value in patients with pulmonary thromboembolism after orthopaedic surgery. METHODS: Clinical data of 134 cases of confirmed pulmonary thromboembolism after orthopaedic surgery from 1997 to 2010 were reviewed.The 134 cases were divided into dead group (n=28) and survival group (n=106). The clinical presentation, electrocardiogram, arterial oxygen pressure (PaO2), chest X-ray, echocardiography,and serum enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (γ-GT), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) were analyzed. And multivariable Logistic regression was conducted to identify the risk factors of in-hospital death. RESULTS: The average age of dead patients was higher than that of survival patients (P=0.043), while the P(O2) of dead patients was much lower than that of survival patients (P=0.035). The percentage of syncope, hypotension, right bundle-branch block and SIQIIITIII, pulmonary hypertension and right ventricular dysfunction in dead patients were higher than those in survival patients (P=0.009, P=0.041, P=0.018, P=0.030, P=0.042 and P=0.038), respectively. There were significant differences of elevated serum ALT, LDH and CK-MB levels between dead patients and survival patients (P=0.042, P=0.035 and P=0.017). Logistic regression indicated that the risk factors for death of patients with PTE after orthopaedic surgery were age (OR, 1.182; 95% CI, 1.010-1.383; P=0.036), hypoxemia (OR, 1.128; 95% CI, 1.018-1.249; P=0.022), hypotension (OR, 3.346; 95% CI, 1.116-10.031; P=0.031), right ventricular dysfunction (OR, 4.083; 95% CI, 1.040- 16.035; P=0.044) and elevated serum CK-MB levels (OR, 3.466; 95% CI, 1.054-11.400; P=0.041). CONCLUSION: The incidence rate of elevated serum ALT, LDH and CK-MB levels in patients who died of pulmonary thromboembolism after orthopaedic surgery was higher than that of survival patients; Age, hypoxemia, hypotension and right ventricular dysfunction were independent risk factors of in-hospital death; The CK-MB might be a useful biomarker for risk stratification of acute PTE.

Laryngoscope-assisted and cotton ball wiping methods in prevention of oral and pulmonary infection in patients receiving mechanical ventilation and the influence on hypersensitive C-reactive protein and procalcitonin.

Effects of laryngoscope-assisted and cotton ball wiping methods on the prevention of oral and pulmonary infection in patients receiving mechanical ventilation were compared to explore the influence of the two methods on high-sensitivity C-reactive protein (hs-CRP) and procalcitonin (PCT). In total, 152 patients who underwent mechanical ventilation in the ICU of Beijing Jishuitan Hospital from May 2005 to January 2018 were assigned and equally divided into two groups: 76 patients who had their oropharynxes scrubbed and rinsed by an electric toothbrush under direct vision by the use of a laryngoscope were selected as the laryngoscope group, and 76 patients who received the conventional cotton ball wiping method and the flushing method for oropharyngeal cleaning were assigned in the cotton ball group. Detection of serum hs-CRP and PCT levels in a 2-ml sample of fasting venous blood was performed on both groups of patients before hospitalization, and on the 5th and 10th day of hospitalization. The incidence rate of oral infection and ventilator-associated pneumonia, as well as the length of the cleaning time were recorded. The incidence rate of oral infection and ventilator-associated pneumonia in the laryngoscope group was statistically much lower than that in the cotton ball group (P<0.05). Before the experiment, there was no significant difference in the hs-CRP and PCT levels between the two groups (P>0.050), whereas the laryngoscope group had significantly lower hs-CRP and PCT levels at the 5th and 10th day of hospitalization than those in the cotton ball group (P<0.05). The hs-CRP and PCT levels at the three time-points in the same group were statistically different (P<0.05). In conclusion, oropharyngeal scrub and rinse by an electric toothbrush assisted by a laryngoscope, can not only better prevent oral infection and reduce the incidence of ventilator-associated pneumonia, but it also has shorter cleaning time and results in lower levels of inflammatory factors, which make this method beneficial in the clinic.

[The expression and implications of human alpha-defensin 1-3 in serum and induced sputum in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To measure the levels of human alpha-defensin 1-3 (HNP1-3) in the serum and induced sputum in patients with chronic obstructive pulmonary disease (COPD) and therefore to investigate the possible roles of HNP1-3 in COPD. METHODS: Thirty patients with acute exacerbation of COPD, 21 patients with stable COPD, and 22 healthy subjects were recruited. The concentrations of HNP1-3 and interleukin-8 (IL-8) in serum and induced sputum were measured by enzyme-linked immunosorbent assay (ELISA). The correlations among HNP1-3, neutrophils, IL-8, and lung functions were investigated. The data were analyzed using a statistical software package (SPSS 11.5). Variables were compared with One-Way ANOVA or Chi-square test. The correlations between variables were analyzed using Pearson's correlation coefficient or Spearman correlation coefficient. RESULTS: The sputum HNP1-3 level was significantly higher in AECOPD patients [9,652(4,272 -12,576) ng/L] than in healthy subjects [4,194 (700 -10,505) ng/L, chi2 =7.53, P <0.01] and in stable COPD patients [7,011(6,658 -7,319) ng/L, chi2 = 10.24, P <0.01]. There was significant difference among the three groups (chi2 =7.31, P <0.05). There was no significant difference in the serum HNP1-3 level among the three groups: AECOPD group [51(39 - 173) ng/L], stable COPD group [135(113 - 241) ng/L], healthy subjects group [130(13 - 160) ng/ L], chi2 = 5.75, P > 0.05. The sputum HNP1-3 level was positively correlated with the number, percentage of sputum neutrophils, and sputum IL-8 level (r = 0.29 to 0.53, respectively P <0.01). The sputum HNP1-3 level was negatively correlated with FEV1/predicted values, FEV1/FVC, and PaO2 (r= -0.33 to -0.44, respectively P <0.01). CONCLUSIONS: HNP1-3 may be involved in the pathogenesis of airway inflammation in COPD. Sputum HNP1-3 may be a noninvasive marker of severity of COPD.

The Effect of Mechanical Ventilation on TASK-1 Expression in the Brain in a Rat Model.

BACKGROUND AND OBJECTIVE: TWIK-related acid-sensitive potassium channel 1 (TASK-1) is closely related to respiratory central control and neuronal injury. We investigated the effect of MV on TASK-1's functions and explored the mechanism using a rat model. METHODS: Male Sprague-Dawley rats were randomized to three groups: (1) high tidal volume (HVt): MV for four hours with Vt at 10 mL/kg; (2) low Vt (LVt): MV for four hours with Vt at 5 mL/kg; (3) basal (BAS): anesthetized and unventilated animals. We measured lung histology and plasma and brain levels of proteins (IL-6, TNF-α, and S-100B) and determined TASK-1 levels in rat brainstems as a marker of respiratory centre activity. RESULTS: The LISs (lung injury scores) were significantly higher in the HVt group. Brain inflammatory cytokines levels were different to those in serum. TASK-1 levels were significantly lower in the MV groups (P = 0.002) and the HVt group tended to have a lower level of TASK-1 than the LVt group. CONCLUSION: MV causes not only lung injury, but also brain injury. MV affects the regulation of the respiratory centre, perhaps causing damage to it. Inflammation is probably not the main mechanism of ventilator-related brain injury.

Pleural Effusion in Multiple Myeloma.

OBJECTIVE: Pleural effusion is rarely observed in patients with multiple myeloma (MM). Myeloma cell infiltration or invasion to the pleura is very rare. This study aimed to investigate the clinical characteristics of pleural effusion in patients with MM. METHODS: We retrospectively reviewed the medical records of patients diagnosed with pleural effusion, MM, and pleural effusion with MM between 2004 and 2014 at Beijing Jishuitan Hospital. The present study included patients with pleural effusion who underwent cytological, bacteriological, biochemical and other testing. The cytopathology of abnormal pleural effusion cells was not diagnostic, thus flow cytometry was performed. MM was defined using the diagnosis standard of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2014 for MM. RESULTS: This study included 3,480 pleural effusion patients and 319 MM patients. There were 34 patients with both MM and pleural effusion (17 men and 17 women). The average age was 63 years (range, 48-84 years). Pleural effusion with MM was caused by congestive heart disease, chronic renal failure, hypoalbuminemia, pulmonary infarctions, cirrhosis, pulmonary arterial hypertension, parapneumonic effusion, tuberculous pleural effusion, and myelomatous pleural effusion (MPE). The diagnosis of MPE was confirmed by the detection of myeloma cells in the pleural fluid using flow cytometric analyses. There were only 2 MPE cases in our study. The first MPE case was a woman. The first clinical manifestation was pleural effusion, and the diagnosis was non-secretory MM, DSS stage IIIA (Durie-Salmon staging system); ISS stage I (the International Staging System). The second MPE case was a man who was diagnosed with MM IgA-κ, DSS stage IIIA; ISS stage II. CONCLUSION: The detection rate of MPE was very low. MPE tended to present with yellow exudates and the lack of physical and chemical characteristics. Furthermore, patients with MPE exhibited many yellow nodules on the pleura. These nodules were lobulated and had abundant blood supply. The routine pleural effusion pathological examination had low sensitivity. Flow cytometry may be more useful for improving the detection rate of MPE.

Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough.

BACKGROUND: The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. METHODS: We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing <100 m, 100-200 m, and >200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate (EBC) pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. RESULTS: Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1% -1.54, 95% confidence interval [CI]: -0.20 to -2.89). The odds ratio for chronic cough was 2.54 (95% CI: 1.57-4.10) for category 1 and 1.97 (95% CI: 1.16-3.37) for category 2, compared with category 3. EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] = 0.176, P < 0.001). CONCLUSIONS: Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.

[The COX regression analysis on the use of corticosteroids in the treatment of SARS].

OBJECTIVE: To explore the effectiveness of corticosteroids (GCS) and to determine how to use it in the treatment of SARS. METHODS: All reported probable cases in Beijing were reviewed. Those who fulfilled the diagnostic criteria with an integrity clinical record were recruited in the study. A database was established and all the clinical data, including patients' personal information, epidemiological history, underlying diseases, clinical manifestations, laboratory tests and therapies after hospitalization, as well as the outcome of the disease, were inputted under a quality control. Unifactor and COX multifactor regression analysis were done. The dose of GCS was all expressed in that of methylprednisolone. RESULTS: 1291 cases were in consistence with the demands mentioned above. Among them, 1084 cases (83.96%) had used GCS and 207 did not in the course of SARS. There was no significant difference of average age (t = -1.08, P = 0.2808) and the time from SARS onset to hospitalization (P = 0.2797) between the two groups. COX regression showed that the risk of fatality in the GCS group was higher than that of those who did not use GCS (RR = 1.334, 95% of CI: 0.588 - 3.026). In the patients with comorbidities, RR was 2.086 (95% of CI: 0.694 - 6.267), and RR was 0.536 (95% of CI: 0.146 - 1.970) in the patients with no comorbidity. In those without any comorbidity, the initial doses, maximal doses, average doses and cumulative doses all showed a 'J' shape change. An appropriate dose could keep RR to be the lowest whereas the doses either higher or lower than it could increase RR. The initial dose with the lowest RR was 80 - 160 mg/d, the maximum 80 - 160 mg/d, the average < 80 mg/d and the cumulative one 1000 - 3000 mg although there was no statistical significance (all P > 0.05). RR was less than 1 in non-comorbidity patients who initiated GCS therapy before the 15th day of the disease. RR was 1.415 (95% of CI: 0.195 - 10.257) in the patients who began to use GCS over this period. Counting from hospitalization, the time of GCS use also showed a 'J' type change of RR. The initiation of GCS from day 5 to 7 had the lowest RR (0.282, 95% of CI: 0.043 - 1.828) and that from day 8 to 14 was 1 (95% of CI: 0.150 - 6.654). CONCLUSION: In the treatment of SARS, GCS seems to be effective. An appropriate dose and a right time of application decrease the risk of death. The use of GCS in SARS patients with comorbidities should be with caution.