[Influencing factors of poor treatment adherence in uncontrolled asthma patients in China].

Objective: To evaluate the influencing factors of poor treatment adherence in patients with uncontrolled asthma in China. Methods: From April 2017 to April 2018, all asthma patients with uncontrolled asthma and poor compliance in 32 third-class hospitals in 28 provinces and cities of China mainland included in the "National Mobile Asthma Assessment and Management Project" were selected as the subjects. A total of 923 patients were enrolled in the study including 388 males and 535 females. By analyzing the baseline data of the patients at the initial visit when enrolled, the influencing factors of poor adherence of adult asthma was analyzed by inter-group comparison and χ2 test. Results: Poor compliance in asthma was related to the following factors: age from 59 to 68 years old, course of disease more than 20 years, low education level, non-local follow-up, having obstructive ventilation dysfunction and low awareness of the disease[P values were 0.026(t=1.20), 0.004(t=3.97), 0.001(t=4.92), 0.003(t=3.98), 0.032(t=1.22) and 0.001(t=4.99), respectively]. Totally, 243 patients (26.33%) answered all the questions about asthma correctly. Their medication adherence rating scale (MARS-A) scores were significantly higher than those who answered incompletely correctly (36.23±5.85 vs. 31.77±5.74, P=0.001). Conclusions: The adherence of adult asthma patients was affected by individual and external environment factors. Clinicians should choose individualized methods based on the characteristics of patients. Patient education should be strengthened to improve patients' awareness of the disease at the same time.

[Construction and evaluation of a novel diagnosis pathway for 2019-Corona Virus Disease].

Objective: To construct and evaluate a diagnosis pathway (Xiangya pathway) for Corona Virus Disease 2019 (COVID-19). Methods: Consecutive subjects aged ≥12 years old who were screened for COVID-19 were included in Xiangya Hospital of Central South University from January 23 to February 3, 2020, and the subjects were further divided into the inception cohort and the validation cohort. The gender, age, onset time of disease of the subjects were recorded. The information of epidemiological history, fever, and the declined blood lymphocytes were collected as clinical indicators, CT scan was used to evaluate the possibility of COVID-19 and range of lung involvement. According to the current Chinese national standards, throat swabs of suspected cases were collected and the nucleic acid of COVID-19 was detected by reverse transcription-polymerase chain reaction (RT-PCR). The Xiangya pathway was constructed with multi-indexes, compared with clinical indicators, CT results and Chinese national standards, their effectiveness of detecting confirmed cases were verified in the inception and validation cohort. Results: A total of 382 consecutive adults who was screened for COVID-19 were included, and 261 cases were in the inception cohort and 121 cases were in the validation cohort. Among the 382 cases, 192 were males (50.3%) and 190 were females (49.7%), with a median age of 35 years (range: 15-92 years). There were 183 cases (47.9%) with epidemiological history, 275 cases (72.0%) with fever, 212 cases (55.5%) with decreased peripheral blood lymphocytes, 114 cases (29.8%) with positive CT findings, 43 cases (11.3%) with positive CT-COVID-19, and 30 cases (7.9%) with positive virus nucleic acid by throat swab. Compared with clinical indicators, the sensitivity and specificity of CT were 0.950 and 0.704, respectively. The accuracy of CT to make a definite diagnosis was higher than that of epidemiological history, fever, and declined blood lymphocyte count (0.809 vs 0.660, 0.532, 0.596, P=0.001, 0.002, 0.003, respectively). The sensitivity of this pathway and the pathway recommended by the Health Commission of China were both high (all were 1.000), while the specificity and accuracy of the Xiangya pathway were higher than the one recommended by the Health Commission (0.872 vs 0.765, 0.778 vs 0.592, both P<0.001). The CT-COVID-19 reduced the missed diagnosis rate caused by false negative of nucleic acid test (31 vs 64), with difference rate of 51.6%, and the positive rate of nucleic acid test was 64.5% (20/31). In validation cohort, the specificity and accuracy of the Xiangya pathway was 0.967, the positive rate of nucleic acid test was 76.9%(10/13). Conclusions: The Xiangya pathway can predict the nucleic acid test results of COVID-19, and can be applied as a reliable strategy to screen patients with suspected COVID-19 among people aged ≥12 years in areas other than Hubei during the epidemic period of COVID-19. The cohort size needs to be increased for further validation.

Snail1-dependent cancer-associated fibroblasts induce epithelial-mesenchymal transition in lung cancer cells via exosomes.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is an essential component of metastasis. Our previous study demonstrated that cancer-associated fibroblasts (CAFs) induce EMT in lung cancer cells. In recent years, many studies have demonstrated that CAFs induce metastasis and drug resistance in cancer cells via exosomes. AIM: We sought to discover the mechanism underlying how CAFs induce EMT in lung cancer cells, unveiling the role of exosomes in lung cancer progression. DESIGN: We cultured lung cancer cell (i) with control medium, normal fibroblasts (NFs) or CAFs; (ii) with SNAI1-transfected or NC (negative control)-transfected CAFs; (iii) with exosomes extracted from NF- or CAF-conditioned medium; (iv) with exosomes released by SNAI1 or NC-transfected CAFs; (v) with CAF-conditioned medium or exosome-depleted CAF-conditioned medium. METHODS: qRT-PCR was conducted to examine the expression of CDH1 (gene of E-cadherin) and VIM (gene of Vimentin), western blotting was conducted to examine E-cadherin and vimentin levels in lung cancer cells. RESULTS: Exosomes released by CAFs-promoted EMT in lung cancer cells. Interestingly, SNAI1 levels in exosomes secreted from CAFs were correlated with SNAI1 expression in CAFs. Furthermore, the level of SNAI1 in exosomes was crucial for inducing EMT in lung cancer cells. Finally, treatment of CAFs with GW4869, an inhibitor of exosome release, noticeably inhibited their EMT-inducing effect on recipient epithelial cells. CONCLUSIONS: The molecular mechanism underlying how CAFs induce EMT in cancer cells may be that CAFs deliver SNAI1 to recipient cancer cells via exosomes.

[Seasonal distribution of patient hospitalization due to asthma exacerbation in 7 geographic areas in China].

Objective: To understand the seasonal distribution of patient hospitalization due to asthma exacerbation in 7 geographic areas in China. Methods: This was a retrospective study which involved patients hospitalized for asthma exacerbation in 29 hospitals throughout 7 geographic areas in the mainland of China (northeast, north, central, east, south, northwest and southwest). The numbers of asthmatic patients and total inpatients of the respiratory department of each hospital were recorded. The monthly ratio of asthmatic patients to the total inpatients in every area was calculated and compared. Results: During the study period, 6 480 patients were admitted for asthma exacerbation, accounting for 3.14% of all the 206 135 patients admitted to the respiratory departments in the 29 hospitals. The ratio of asthmatic patients to total inpatients in the northeast area (5.61%) was highest, and the ratio in east area was lowest (1.97%). Statistical analysis showed that the difference among different areas was significant (P<0.000 1). In most areas, both the number and proportion of hospitalized asthmatic patients peaked in spring (February-April) and autumn (September-October). In the northeast area, east area and south area, the peaks in spring were more obvious, while in the north area and southwest area, the peaks in autumn were more obvious. In the northwest area the peaks occurred in winter (December-January) and summer (June-August), respectively. The differences in hospitalization due to asthma among different months were significant in the northeast, north, and southwest areas (P<0.005). Conclusion: The number of patients hospitalized for asthma exacerbation fluctuated with season in different areas in China. In most areas, more asthmatic patients were admitted to hospitals in spring and autumn.

[A retrospective study of the mortality and death-related risk factors of patients hospitalized for asthma exacerbation in Chinese urban areas].

Objective: To study the mortality and death-related risk factors of patients hospitalized for asthma exacerbation in Chinese urban areas. Methods: A retrospective study was carried out in 29 hospitals of 29 provinces throughout mainland China. Patients hospitalized for asthma exacerbation during 2013-2014 in each hospital were included. For each patient, information about demography, admission time, comorbidities, severity of diseases, intense care unit (ICU) admission, use of mechanical ventilation and the outcome was obtained. The mortality of patients hospitalized for asthma exacerbation was calculated, and the basic information and causes of death of the patients who died were summarized. The death-related risk factors and numbers of comorbidities were compared between the patients who survived and those who died during hospitalization. Results: A total of 3 240 patients (median age 57.0) were included and among them 8 patients (median age 68.5) died. The mortality of patients hospitalized for asthma exacerbation was 0.25%. All the patients who died were admitted during the winter and spring. One patient died of acute myocardial infarction, one of cardiac shock, one of tension pneumothorax, one of sudden death, one of respiratory failure and three of unknown causes. The average number of comorbidities of patients who died was 1.10, larger than that of patients who survived (0.83) (P>0.05). More patients had diabetes, coronary artery diseases and hypertension as comorbidities in the patients who died (2/8) than those who survived[7.6% (246/3 232), 7.6% (246/3 232), 22.6% (731/3 232), respectively](all P>0.05). Conclusions: The in-hospital mortality of patients hospitalized for asthma exacerbation of China in this study is low. The patients who died are much older, and with more comorbidities, and a higher percentage of comorbidities such as diabetes, coronary artery diseases, and hypertension.

[A retrospective study of the treatment of patients hospitalized for asthma exacerbation in China].

Objective: To study the treatment of patients hospitalized for asthma exacerbation in China. Methods: This was a retrospective study and involved patients hospitalized for asthma exacerbation in 29 hospitals throughout China during Jan 2013 to Dec 2014. Information of the demographic features, the severity of the exacerbation, the medicine prescribed during the hospitalization and the use of mechanical ventilation were collected and analyzed. Results: During the study period, there were 3 240 patients hospitalized for asthma exacerbation, and 1 369(42.3%) of them were males 1 871(57.7%)were females. Patients of mild, moderate, severe, and life-threatening exacerbation counted for 41.7%, 37.8%, 19.2% and 1.0%, respectively of the total patients. Of all the patients, 72.6% used bronchodilators by nebulizer, 70.8% used inhaled corticosteroids by nebulizer, 60.5% used intravenous corticosteroids, 17.3% used oral corticosteroids, and 80.5% used antibiotics. The percentages of patients using systemic corticosteroids and antibiotics were higher in patients with more severe exacerbation. In patients with mild exacerbation, there were 74.9% and 52.2% who used antibiotics and systemic corticosteroids, respectively. A total of 73 patients (2.3%) used mechanical ventilation, and 62 of them used noninvasive ventilation, 16 used invasive ventilation, and 5 used both. Conclusions: Nebulizer therapy has been accepted as the main administration route of medicine in the treatment of asthma exacerbation. A large amount of patients used antibiotics and systemic corticosteroids during hospitalization, indicating there may be some overuse of these medicines.

[Trends of asthma control, disease management and perception in China].

Objective: To evaluate the changes of asthma control, disease management and perception in recent years in China. Methods: We conducted 2 multi-center, cross-sectional surveys. Outpatient asthmatic patients from 10 cities in mainland China (2007-2008) and 30 central cities from 30 provinces in China (except Tibet)(2015-2016) were recruited respectively. Data of asthma control, disease management and perception from the 2 surveys were compared for 10 cities which took part in both of the 2 surveys. Chi-square test was used for comparison between groups. Results: The asthma control level improved from 28.7%(839/2 928) in 2007-2008 to 39.2%(533/1 361) in 2015-2016(P<0.01). The rate of emergency visits was 18.2%(248/1 362) in 2015-2016, which was lower than that in 2007-2008(33.9%, 1 032/3 044)(P<0.01). The rate of peak flow meter (PFM) usage was 17.9%(244/1 360) in 2015-2016, which was slightly lower than the PFM usage rate in 2007-2008(21.8%, 660/3 030)(P=0.004). 56.0%(763/1 362) of the patients used inhaled corticosteroid (ICS) + formoterol to control asthma when asthma symptoms deteriorated in 2015-2016, which was higher than the result of 2007-2008(31.8%, 803/2 524)(P<0.01). 71.1%(968/1 361) of the patients in 2015-2016 had a right perception on disease nature, while the result in 2007-2008 was 63.3%(1 889/2 986)(P<0.01). 61.6%(839/1 362) of the patients in 2015-2016 had a right perception on medication choice on daily-use first-line medication for chronic asthma, while the result in 2007-2008 was 51.0%(1 500/2 942)(P<0.01). Conclusion: The current level of asthma control and disease perception in China improved significantly in recent years, while the rate of PFM usage showed no significant improvement. Asthma action plan including PFM monitoring and asthma self-management should be further promoted nationwide.

[Evaluation of asthma disease perception from China national asthma control survey].

Objective: In order to evaluate disease perception of asthma patients in urban China and provide evidence for further specific patient education. Methods: A multi-center, cross-sectional, questionnaire-based survey was carried out in 30 general hospitals dispersed in 30 provinces of mainland China (except for Tibet) during Oct 2015 to May 2016. Information of disease perception [Question 1: the disease nature of asthma; Question 2: medication choice of first-line in chronic asthma; Question 3: the occasion of using short-acting aerosols of receptor agonists; Question 4: perception of asthma treatment goal; Question 5: reason for not using peak flow meter (PFM)] were collected from asthma patients of outpatient department. These results were compared with the same type of survey results from 2007-2008. Results: Altogether 3 875 asthmatic outpatients were recruited. 69.0% (2 660/3 857) of the patients had right perception on the disease nature of asthma, 60.2% (2 321/3 857) of the patients considered inhaled corticosteroids (ICS)/inhaled corticosteroids plus long-acting beta2-agonists (ICS+ LABA) as daily-used first-line medication for chronic asthma. 85.7% (3 277/3 823) of the patients had right perception on the condition of using short-acting beta2-agonists (SABA). 75.4% (2 761/3 661) of the patients had right perception on asthma treatment goal. Only 10.1% (388/3 837) of the patients used PFM. Of the reasons for not using PFM, 65.2% (2 518/3 860) of the patients chose doctors never introduced. Among the 10 cities, which were also involved in the asthma control survey in 2007-2008, 71.1% (968/1 361) of the patients had right perception on the disease nature of asthma, 61.6% (839/1 362) of the patients considered ICS/ICS+ LABA as daily-used first-line medication for chronic asthma. 88.7% (1 207/1 361) of the patients had right perception on the condition of using SABA. 74.5% (1 013/1 360) of the patients had right perception on asthma treatment goal. 17.9% (244/1 360) of the patients used PFM. Of the reasons for not using PFM, 76.2% (931/1 221) of the patients chose doctors never introduced. Compared to the survey conducted in 2007-2008, the perception on disease nature and medication choice as daily-used first-line medication for chronic asthma significantly improved, the perception on occasion of using SABA and asthma treatment goal was comparable, while the rate of PFM usage showed no significant improvement. In reasons of not using PFM, doctors never introduced ranked the first. Conclusions: Compared to the similar survey conducted in 2007-2008, the overall status of disease perception of asthma patients has been improved in urban China, while the rate of PFM usage showed no significant improvement. Asthma education on asthma and asthma self-management should be further pushed forward.

[Evaluation of asthma management from the surveys in 30 provinces of China in 2015-2016].

Objective: To evaluate the general level of asthma management in urban areas of China and further promote the national asthma management plan. Methods: A multi-center, cross-sectional survey was carried out in 30 provinces of China (except for Tibet) during Oct 2015 to May 2016. It's a questionnaire-based face-to-face survey which included asthma management using peak flow meter (PFM) and pulmonary function test, medication choice of maintenance therapy and asthma education. Results: A total of 3 875 asthmatic outpatients were recruited including 2 347(60.6%) females and 1 528(39.4%) males. The mean age was (50.7±16.7) years ranging from 14 to 99. Only 10.1%(388/3 837) patients used PFM as monitoring, whereas 62.1%(2 405/3 874) patients underwent pulmonary function test during the past year. There were 57.4%(2 226/3 875) patients treated with inhaled cortical steroid plus long-acting ß(2)-agonist combinations (ICS+LABA) as daily medication. 43.3%(1 661/3 836) patients were followed up by physicians. Among this population, 1 362 asthmatic outpatients were recruited, who also took part in the asthma control survey in 2007-2008 in 10 cities. In this subgroup, 17.9%(244/1 360) were tested by PFM and 66.6%(907/1 362) by pulmonary function test during last year. As to the medication, 63.1%(860/1 362) selected ICS+LABA for daily control. There were 50.4%(685/1 359) patients in the follow-up cohort by physicians. Compared to the similar survey conducted in 2007-2008, the proportion of patients with ICS+LABA regimen and follow-up by physicians were markedly higher, while the rate of PFM use did not have significant improvement. Conclusion: Although the present level of asthma management in China is still far from ideal, asthma management has improved compared to 8 years ago. Yet the use of PFM does not significantly improve. Asthma action plan and application of PFM should be further promoted to improve the level of asthma management.

[A retrospective study of the inducing factors and clinical characteristics of patients hospitalized for asthma exacerbation in China in 2013-2014].

Objective: To study the inducing factors and clinical characteristics of patients hospitalized for asthma exacerbation in China. Methods: Patients hospitalized for asthma exacerbation at 29 hospitals in China were retrospectively recruited during 2013-2014. Results: Clinical data of 3 240 asthmatic patients were collected and analyzed including 1 369(42.3%) males and 1 871(57.7%) females. The patients hospitalized for asthma exacerbation counted for 2.95% (6 375/215 955) of all patients hospitalized during the same period. The leading six inducing factors, in sequence, were acute upper respiratory tract infection [42.3%(1 370/3 240)], changes of weather [22.8%(738/3 240)], noxious gas [(4.3%(140/3 240), allergy challenges [3.5%(115/3 240)], strenuous exercise [1.8%(57/3 240)], and air pollution [1.5%(49/3 240)]. In older patients, more exacerbations were induced by weather changes, yet less sensitive to allergy challenges. As to middle-aged patients, they were less sensitive to upper respiratory tract infections, however the difference was not statistically significant (P>0.05). In winter more asthma patients were induced by upper respiratory tract infections, while in autumn more patients were induced by weather changes, strenuous exercise and air pollution. In spring and summer more patients were induced by allergy challenges, but the differences failed to achieve statistical significance (P>0.05). In northern cities more patients were induced by upper respiratory infections, whereas in southern cities more by noxious gases. Allergy challenges and air pollution tended to affect more patients in northern cities, but the difference was of no significance (P>0.05). The differences of inducing factors among patients of different gender, with or without a smoking history, and with different exacerbation severity didn't show any statistical significance. The patients with severe and life-threatening exacerbations counted for 20.1% (652/3 240). The percentage of patients older than 60 years was higher in patients with severe or life-threatening exacerbations than in whose with mild or moderate exacerbations, so did the percentage of male patients, of patients with disease duration longer than 10 years, with smoking history, and with a history of hospitalization or emergency department visits due to asthma exacerbation during the last year. Conclusion: The acute upper respiratory tract infection ranks top among all the inducing factors. Senility, male gender, long duration of disease, smoking history, and a history of frequent hospital visits might be the risk factors for severe or life-threatening asthma exacerbations.

[Seasonal characteristics of patients hospitalized for asthma exacerbation in China].

Objective: To study the seasonal characteristics of patients hospitalized for asthma exacerbation in China. Methods: This was a retrospective study which involved patients hospitalized for asthma exacerbation in 29 hospitals throughout mainland China during 2013-2014. The number of patients hospitalized for asthma exacerbation in each hospital was calculated, as well as the ratio of asthmatic patients to all the hospitalized patients. The analysis by month was conducted. The number and ratio of asthmatic patients in the northern and southern cities were calculated respectively. Results: During the study period, there were 6 480 patients hospitalized for asthma exacerbation, accounting for 3.14% (6 480/206 135) of all the hospitalized patients of the respiratory department in 29 hospitals. The analysis by month showed that the ratio of patients hospitalized for asthma exacerbation was highest in March (3.49%), then declined from April to June, then rose again from July, reaching a second peak at September (3.28%), and then declined again from October to December. The ratio of asthmatic patients in every month was higher in northern cities than in southern cities. Conclusions: The ratio of patients hospitalized for asthma exacerbation in China fluctuates with the changes of seasons, and March and September are the two peak months. Northern cities have a higher ratio of asthmatic patients than southern cities.

[Warning symptoms of asthma attack and asthma self-management: a national asthma control survey from China].

Objective: To investigate warning symptoms of asthma attack and evaluate asthma self-management status of asthma patients in urban China. Methods: A multi-center, cross-sectional, questionnaire-based survey was carried out from 30 general hospitals dispersed in 30 provinces of mainland China (except for Tibet) during Oct 2015 to May 2016. Information of frequency and warning symptoms of asthma attack, the time from warning symptoms to asthma attack, the impact of asthma attack and asthma self-management were collected from asthma patients of outpatient department. Results: Altogether 3 875 asthmatic outpatients were recruited. 78.1% (3 026/3 875) of the patients reported restriction of exercise and daily activities during asthma exacerbation. 82.5% (3 160/3 829) of the patients had warning symptoms before asthma attack, the most common warning symptoms were cough, chest tightness and shortness of breath. The median time from warning symptoms to asthma attack was 2 h, the mean time was 90 h. Only 4.4% (167/3 829) of the patients had definite confidence to control asthma when symptoms deteriorated. 76.7% (2 937/3 828) of the patients used medications to control asthma when asthma symptoms deteriorated. Medication choice: inhaled corticosteroid (ICS) + formoterol 45.8% (1 776/3 875), short-acting beta-agonist (SABA) 23.9% (927/3 875). Conclusions: Most asthma patients have warning symptoms before asthma attack, the most common symptoms are cough, chest tightness and shortness of breath. The proportion of patients conducting effective asthma self-management remains low.

[The level of asthma control in China from a national asthma control survey].

Objective: To assess the overall asthma control level in urban China. Methods: A multi-center, cross-sectional, questionnaire-based survey was carried out in 30 provinces in China (except Tibet). Asthmatic outpatients who met the inclusion criteria were recruited consecutively from 30 sub-centers from October 2015 to May 2016. Data of demographic characteristics, asthma control, asthma management, asthma exacerbations and self-management, and disease perception were collected by face-to-face interviews. Results: Totally 3 875 asthmatic outpatients were recruited. Asthma control level was assessed according to GINA 2015. The prevalence of asthma control was 28.5%(1 099/3 854). Among 10 cities, which were also involved in the asthma control survey in 2008, the level of asthma control improved from 28.7% in 2008 to 39.2%(533/1 361) in 2016. The rate of hospitalizations due to asthma exacerbations was 26.4%(1 017/3 858) and the rate of emergency visits was 22.4%(864/3 858). Among adult patients, 18.4%(568/3 092) of them had been absent from work while 63.6%(63/99) adolescent patients had been absent from school because of asthma attacks in the previous year. Conclusion: Although the level of asthma control in China is still far from ideal at present, the status has been improved in some cities. Poorly controlled asthma resulted in increase of hospitalizations, emergency department visits and work/school absences.

[A multi-center study for the association between the perception and control of disease among asthmatic patients in Chinese urban areas].

Objective: To investigate the current perception of disease among asthmatic patients in Chinese urban areas, and to address its association with asthma control. Methods: This was a nationwide, multi-center, cross-sectional study covering 30 third-level, grade A hospitals in 30 provinces, municipalities and autonomous regions (not including Tibet) across Chinese mainland. The survey was carried out from October 2015 to May 2016. Asthmatic outpatients were selected to receive face-to-face questionnaire survey on asthma control including Asthma Control Test (ACT) score, classification of asthma control level[according to the Global Initiative for Asthma (GINA) 2015 classification system, as assessed by the physician completing the survey], perception of asthma (including question 1: nature of asthma as a disease; question 2: selection of first-line therapeutic agents to be regularly used daily for asthma; question 3: appropriate timing of the use of short-acting aerosols of ß(2) receptor agonists; and question 4: therapeutic goals for asthma). Results: A total of 3 875 asthmatic outpatients were included; among them, 69.0% (2 660/3 857) were aware that asthma is "an airway inflammatory disorder resulting from the combined effects of heredity and environment" ; 60.2% (2 321/3 857) considered "inhaled glucocorticoids or their compound preparations" to be the first-line therapeutic agents to be regularly used daily for patients with persistent chronic asthma; 85.7% (3 277/3 823) considered it appropriate to use short-acting aerosols of ß(2) receptor agonists "as needed in the event of disease aggravation or acute exacerbation" ; and 75.4% (2 761/3 661) were aware that asthma "can be adequately or completely controlled in the long term" . The ACT score[20 (16, 23) vs 19 (16, 22) points; Z=-3.928, P<0.001]and asthma control rate (29.92% vs 25.31%; χ(2)=8.616, P=0.003) were significantly higher, and the rate of uncontrolled asthma (19.92% vs 23.48%; χ(2)=6.267, P=0.012) was significantly lower among the 2 660 (69.0%) patients correctly answering question 1 than among the 1 197 (31.0%) patients giving incorrect answer. The ACT score[21 (17, 23) vs 19 (15, 22) points; Z=-9.190, P<0.001] and asthma control rate (32.66% vs 22.20%; χ(2)=49.614, P<0.001) were significantly higher, and the rate of uncontrolled asthma (18.40% vs 25.00%; χ(2)=24.267, P<0.001) was significantly lower among the 2 321 (60.2%) patient correctly answering question 2 than among the 1 536 (39.8%) patients giving incorrect answer. Conclusions: Compared to previous surveys, there has been improved perception of disease among asthmatic patients in Chinese urban areas. Correct perception of disease is favorable for improving asthma control level.

[A multi-center retrospective study of clinical characteristics and hospitalization costs of patients hospitalized for asthma exacerbation in China during 2013-2014].

Objective: To study the characteristics of patients hospitalized for asthma exacerbation in 29 teaching hospitals in China and to evaluate the hospitalization costs of these patients. Methods: This was a retrospective study and involved patients hospitalized for asthma exacerbation in 29 hospitals throughout China during 2013-2014. Information about the demographic features, conditions before the admission, the outcome, the complications, and the costs was collected using the pre-designed case report form. The influencing factors of the hospitalization costs were analyzed. Results: 3 240 asthmatic patients (1 369 males and 1 871 females) were included and data were analyzed. There were 41.5% (1 346/3 240) patients who had a history of previous hospitalization or emergency department visits during the last year. Only 28.0% (907/3 240) patients had used asthma-controlling medications regularly before the admission. Seventy-three(2.3%) patients were admitted to ICU and used mechanical ventilation. Mortality among these patients hospitalized for asthma exacerbation was 0.25% (8/3 240). The median hospitalization costs was 9 045(6 431, 13 035) RMB. The costs of medications, examinations and treatment accounted for 52.1%, 27.6%, and 9.6% respectively. The costs of asthma medications accounted for only 22.7% of the total medication costs, while the costs of antibiotics accounted for 44.0%. The patients who were admitted to ICU, used mechanical ventilation, complicated with pneumonia, or had a history of hospitalization or emergency department visits during the last year due to asthma exacerbations tended to cost more. Conclusion: In this study, we demonstrated that only a minority of the patients had used asthma controllers regularly before the admissions with exacerbations. The in-hospital mortality of asthma patients in this study was much lower than that reported in other countries. The average cost of hospitalization was much higher than the yearly cost of maintenance therapy. Medication was the predominant component of the total hospitalization costs, and the costs of antibiotics made up the major part of the total medication costs.

Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials.

BACKGROUND: Afatinib 40 mg/day is approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). In the case of drug-related grade ≥3 or selected prolonged grade 2 adverse events (AEs), the dose can be reduced by 10 mg decrements to a minimum of 20 mg. Here, we evaluate the influence of afatinib dose reduction on AEs, pharmacokinetics and progression-free survival (PFS) in the phase III LUX-Lung 3 and 6 (LL3/6) trials. PATIENTS AND METHODS: Treatment-naïve patients with advanced EGFR mutation-positive NSCLC in LL3 (global) and LL6 (China, Thailand, South Korea) were randomized to afatinib or chemotherapy. All afatinib-treated patients (LL3, n = 229; LL6, n = 239) were included in the post hoc analyses. Incidence and severity of common AEs before and after afatinib dose reduction were assessed. Afatinib plasma concentrations were compared in patients who reduced to 30 mg versus those remaining at 40 mg. PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not. RESULTS: Dose reductions occurred in 53.3% (122/229) and 28.0% (67/239) of patients in LL3 and LL6, respectively; most (86.1% and 82.1%) within the first 6 months of treatment. Dose reduction led to decreases in the incidence of drug-related AEs, and was more likely in patients with higher afatinib plasma concentrations. On day 43, patients who dose reduced to 30 mg (n = 59) had geometric mean afatinib plasma concentrations of 23.3 ng/ml, versus 22.8 ng/ml in patients who remained on 40 mg (n = 284). The median PFS was similar in patients who dose reduced during the first 6 months versus those who did not {LL3: 11.3 versus 11.0 months [hazard ratio (HR) 1.25]; LL6: 12.3 versus 11.0 months (HR 1.00)}. CONCLUSIONS: Tolerability-guided dose adjustment is an effective measure to reduce afatinib-related AEs without affecting therapeutic efficacy. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT00949650 and NCT0112393.

[Role of miR-155 in invasion and metastasis of lung adenocarcinoma A549 cells].

OBJECTIVE: To investigate the role and mechanism of miR-155 in invasion and metastasis of lung adenocarcinoma A549 cells. METHODS: Real-time PCR and fluorescence in situ hybridization were used to detect the miR-155 expression in patients' lung adenocarcinoma and adjacent tissue and lymph nodes. Scratch test and Transwell migration assay were used to assess the effect of miR-155 on the A549 cell migration and invasion capability. Bioinformatics software was used to predict the target genes of miR-155, and using luciferase to assay the target gene. Western blot and real-time PCR were performed to confirm the role of miR-155 expression in the regulation of target gene PTEN. RESULTS: The real-time quantitative PCR showed that the miR-155 expression levels in adjacent normal tissue, lung adenocarcinoma and metastatic lymph nodes were 4.1±0.5, 9.6±3.1 and 7.8±2.2, respectively. The in situ hybridization showed that the expression rates of miR-155 in the adjacent normal tissue, lung adenocarcinoma and metastatic lymph nodes were (23.2±15.3)%, (75.4±20.2)% and (60.4±25.1)%, respectively. The Scratch assay showed that the wound healing rates in the miR-155 mimics group, miR-155 mimics NC group, miR-155 inhibitor group and miR-155 inhibitor NC group at 24 h were (43.2±2.2)%, (21.3±4.2)%, (24.3±5.3)%, and (35.2±5.1)%, and that at 48 h were (75.2±4.5)%, (52.6±5.2)%, (39.4±4.2)%, and (51.5±4.3)%, respectively. Dual luciferase reporter gene assay showed that the value of the luciferase in the miR-155 mimics group co-transfected with PTEN 3'UTR-containing wild-type and mutant plasmids were 4.7±0.5 and 7.3±0.7, and the miR-155 mimics luciferase values of the control group co-transfected with PTEN 3'UTR-containing wild-type and mutant plasmids were 7.8±0.9 and 7.5±0.8, respectively. The real-time quantitative fluorescence PCR showed that the relative expression of PTEN protein in the miR-155 mimics group, miR-155 mimics control group, miR-155 mimics inhibitor group, and miR-155 inhibitor control group were 0.5±0.3, 1.0±0.1, 2.2±0.2 and 1.2±0.1, respectively. The Western blot assay detected that the relative expression of PTEN protein levels in the miR-155 mimics group, miR-155 mimics control group, miR-155 inhibitor group and miR-155 inhibitor control group were 0.4±0.1, 1.0±0.3, 2.8±0.2 and 1.4±0.1, respectively. The differences in PTEN mRNA and protein expressions of the four groups were statistically significant (P<0.05 for all). CONCLUSIONS: miR-155 may promote the invasion and metastasis of lung adenocarcinoma through reducing the target PTEN gene expression.

Membrane disruption and anti-quorum sensing effects of synergistic interaction between Lavandula angustifolia (lavender oil) in combination with antibiotic against plasmid-conferred multi-drug-resistant Escherichia coli.

AIM: The aim of this study was to investigate the mode of action of the lavender essential oil (LV) on antimicrobial activity against multi-drug-resistant Escherichia coli J53 R1 when used singly and in combination with piperacillin. METHOD AND RESULTS: In the time-kill analysis, a complete killing of bacteria was observed based on colony counts within 4 h when LV was combined with piperacillin during exposure at determined FIC concentrations. Analysis of the membrane permeabilizing effects of LV on treated cultures through their stability against sodium dodecyl sulphate revealed that the LV played a role in disrupting the bacterial cell membrane. The finding is further supported by scanning electron microscopy analysis and zeta potential measurement. In addition, reduction in light production expression of E. coli [pSB1075] by the LV showed the presence of potential quorum sensing (QS) inhibitors. CONCLUSIONS: These results indicated that the LV has the potential to reverse bacterial resistance to piperacillin in E. coli J53 R1. It may operate via two mechanisms: alteration of outer membrane permeability and inhibition of bacterial QS. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings offer a novel approach to develop a new option of phytopharmaceuticals against multi-drug-resistant E. coli.