Quality changes of clinical practice guidelines for respiratory diseases in China: A systematic review.

BACKGROUND: After the low quality of Chinese clinical practice guidelines (CPGs) for respiratory diseases published from 1979 to 2013 was reported, some handbooks were published to standardize guidelines' development recently. There was a great increase in the production and dissemination of CPGs annually in China, whose quality and potential impact were unknown. METHODS: A systematic search of four literature databases was performed for the period January 2013 to December 2018 to identify Chinese CPGs for respiratory diseases. Eligible CPGs were evaluated using the appraisal of guidelines for research and evaluation II (AGREE II) instrument. RESULTS: A total of 197 CPGs were identified for review. Compared with the result of previous study, the increased scores of the six AGREE II domains were screened: Scope and purpose (57.3% vs. 57.8%), Stakeholder involvement (17.6% vs. 25.0%), Rigor of development (10.2% vs. 13.2%), Clarity and presentation (55.2% vs. 58.4%), Applicability (9.3% vs. 25.9%), and Editorial independence (1.1% vs. 6.3%). The improved overall assessment for included CPGs were: Recommended (4, 2.0% vs. 0, 0%) and Recommended with modifications (26, 13.2% vs. 3, 2.8%). The improved level of evidence used to make recommendations were 59, 11.9% versus 168, 22.4% and 88, 17.7% versus 195, 26.0%, A and B, respectively. CONCLUSIONS: The overall quality of CPGs for respiratory diseases published from 2013 to 2018 in China was slightly improved, but had a big gap with the optimum level, especially in Rigor of development and Editorial independence. Increased efforts are required to enable the development of high-quality evidence-based CPGs for respiratory diseases.

A comparative study of the five-repetition sit-to-stand test and the 30-second sit-to-stand test to assess exercise tolerance in COPD patients.

Purpose: The sit-to-stand test (STST) has been used to evaluate the exercise tolerance of patients with COPD. However, mutual comparisons to predict poor exercise tolerance have been hindered by the variety of STST modes used in previous studies, which also did not consider patients' subjective perceptions of different STST modes. Our aim was to compare the five-repetition sit-to-stand test (5STS) with the 30-second sit-to-stand test (30STS) for predicting poor performance in the six-minute walking test and to evaluate patients' subjective perceptions to determine the optimal mode for clinical practice. Patients and methods: Patients with stable COPD performed 5STS, 30STS and the 6MWT and then evaluated their feelings about the two STST modes by Borg dyspnea score and a questionnaire. Moreover, we collected data through the pulmonary function test, mMRC dyspnea score, COPD assessment test and quadriceps muscle strength (QMS). A receiver operating characteristic curve analysis of the 5STS and 30STS results was used to predict 6-minute walk distance (6MWD) <350 m. Results: The final analysis included 128 patients. Similar moderate correlations were observed between 6MWT and 5STS (r=-0.508, P<0.001) and between 6MWT and 30STS (r=0.528, P<0.001), and there were similar correlations between QMS and 5STS (r=-0.401, P<0.001) and between QMS and 30STS (r=0.398, P<0.001). The 5STS and 30STS score cutoffs produced sensitivity, specificity and positive and negative predictive values of 76.0%, 62.8%, 56.7% and 80.3% (5STS) and 62.0%, 75.0%, 62.0% and 75.0% (30STS), respectively, for predicting poor 6MWT performance. The 5STS exhibited obvious superiority in terms of the completion rate and the subjective feelings of the participants. Conclusion: As a primary screening test for predicting poor 6MWD, the 5STS is similar to the 30STS in terms of sensitivity and specificity, but the 5STS has a better patient experience.

Rapid on-site evaluation of routine biochemical parameters to predict right ventricular dysfunction in and the prognosis of patients with acute pulmonary embolism upon admission to the emergency room.

INTRODUCTION: Patients with acute pulmonary embolism(APE)who present with right ventricular dysfunction (RVD) have a worse prognosis. This study aimed to evaluate the value of routine biochemical parameters in predicting RVD and 30-day mortality in patients with APE. METHODS: We retrospectively collected the clinical data for 154 enrolled patients, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), D-dimer, cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP). We analyzed the correlation between RVD and the parameters and conducted a receiver operating characteristic (ROC) curve to confirm the cut-off values for predicting RVD and 30-day mortality. Formulas were built with relevant parameters to predict RVD and 30-day mortality. RESULTS: Age, NLR, PLR, D-dimer, the ratio of cTnI (+), and NT-proBNP (+) were significantly higher in RVD (+) patients. The ratio of cTnI (+) and NT-proBNP (+) in 30-day mortality (+) patients was significantly higher than that in 30-day mortality (-) patients. According to the logistic regression analysis, NLR, cTnI (+), and NT-proBNP (+) correlated with RVD. The formula for the RVD risk score is 0.072 × NLR+1.460 × NT-proBNP (+)+2.113 × cTnI (+), and the area under the curve (AUC) = 0.890 (95% CI: 0.839-0.941, P = .001). The formula for the 30-day mortality risk score is 0.115 × NLR + 2.046 × NT-proBNP (+) + 1.946 × cTnI (+) -0.016 × PLR, and the AUC = 0.903 (95% CI: 0.829-0.976, P = .001). CONCLUSIONS: The rapid on-site evaluation of routine biochemical parameters, including NLR, cTnI, and NT-proBNP levels, and the formula developed using these parameters are valuable for predicting RVD and 30-day mortality in patients with APE.

Cycle ergometer and inspiratory muscle training offer modest benefit compared with cycle ergometer alone: a comprehensive assessment in stable COPD patients.

BACKGROUND: Cycle ergometer training (CET) has been shown to improve exercise performance of the quadriceps muscles in patients with COPD, and inspiratory muscle training (IMT) may improve the pressure-generating capacity of the inspiratory muscles. However, the effects of combined CET and IMT remain unclear and there is a lack of comprehensive assessment. MATERIALS AND METHODS: Eighty-one patients with COPD were randomly allocated to three groups: 28 received 8 weeks of CET + IMT (combined training group), 27 received 8 weeks of CET alone (CET group), and 26 only received 8 weeks of free walking (control group). Comprehensive assessment including respiratory muscle strength, exercise capacity, pulmonary function, dyspnea, quality of life, emotional status, nutritional status, and body mass index, airflow obstruction, and exercise capacity index were measured before and after the pulmonary rehabilitation program. RESULTS: Respiratory muscle strength, exercise capacity, inspiratory capacity, dyspnea, quality of life, depression and anxiety, and nutritional status were all improved in the combined training and CET groups when compared with that in the control group (P<0.05) after pulmonary rehabilitation program. Inspiratory muscle strength increased significantly in the combined training group when compared with that in the CET group (ΔPImax [maximal inspiratory pressure] 5.20±0.89 cmH2O vs 1.32±0.91 cmH2O; P<0.05). However, there were no significant differences in the other indices between the two groups (P>0.05). Patients with weakened respiratory muscles in the combined training group derived no greater benefit than those without respiratory muscle weakness (P>0.05). There were no significant differences in these indices between the patients with malnutrition and normal nutrition after pulmonary rehabilitation program (P>0.05). CONCLUSION: Combined training is more effective than CET alone for increasing inspiratory muscle strength. IMT may not be useful when combined with CET in patients with weakened inspiratory muscles. Nutritional status had slight impact on the effects of pulmonary rehabilitation. A comprehensive assessment approach can be more objective to evaluate the effects of combined CET and IMT.

Food allergy and related risk factors in 2540 preschool children: an epidemiological survey in Guangdong Province, southern China.

BACKGROUND: Although the number of studies on allergic diseases in the general population of southern China is increasing, only a few have addressed food allergy (FA) in children in this region. The present study aimed to investigate the prevalence, clinical manifestations, spectrum of allergens, and related risk factors of FA in preschool children in Guangdong Province, southern China. METHODS: A random cluster-sampling method was used to select 24 kindergartens from 12 cities in Guangdong Province. The parents or guardians of the children were requested to complete a questionnaire on general information and data regarding FA diagnosis and symptoms in the children and their first-degree relatives. Thereafter, the Chi-square test, multivariate regression analysis, and Spearman's rank-order correlation coefficient analysis were performed to identify statistically significant differences. RESULTS: Analysis of 2540 valid questionnaires revealed an FA prevalence rate of 4%. Adverse food reactions were due to the consumption of shrimp (4.4%), crab (3.2%), mango (2.3%), cow's milk and dairy products (1.9%), and eggs (1.4%). Logistic regression analysis indicated that a history of FA and a history of allergic rhinitis in the first-degree relatives were the major factors leading to FA in children. CONCLUSIONS: The incidence of FA in children in Guangdong Province is higher than that commonly believed. An individual's genetic background is an important risk factor for FA. Hence, mitigation of the impact of lifestyle and environmental factors should be carefully considered to reduce the incidence of childhood FA.

Allergy-related evidences in relation to serum IgE: data from the China state key laboratory of respiratory disease, 2008-2013.

OBJECTIVE: To investigate the serum total IgE (tIgE) and specific IgE (sIgE) to common allergens among allergic patients in Guangzhou, China. METHODS: 7 085 patients were examined for tIgE and sIgE to 15 allergens, based on the protocols of reversed enzyme allergosorbent test and the sandwich enzyme-linked immunosorbent assay. RESULTS: 3 758 (53.04%) patients tested positive for tIgE, and 4 640 (65.49%) for sIgE. Der pteronyssinus, Der farinae, eggs, and cow's milk were the most common allergens leading to higher positive rates of sIgE responses. Several peaks of sensitization were: Der pteronyssinus, Der farinae, and Blomia tropicalis at age 10-12; cow's milk at age below 3; eggs at age 4-6. The mean level and positive rate of tIgE tended to increase in subjects sensitized to more allergens. Sensitization to Der pteronyssinus (OR, 1.6; P<0.05), Der farinae (OR, 1.5; P<0.05), Blomia tropicalis (OR, 1.4; P<0.05), Blattella germanica (OR, 1.5; P<0.05), cow's milk (OR, 1.3; P<0.05), and soy beans (OR, 2.0; P<0.05) were independently correlated with allergy-related conditions in preliminary diagnosis. CONCLUSION: The major allergens in Guangzhou include Der pteronyssinus, Der farinae, cow's milk, and eggs. Sensitization to these allergens appears to be predictors of allergy-related disorder.

Prevalence of allergen sensitization among patients with allergic diseases in Guangzhou, Southern China: a four-year observational study.

BACKGROUND: The distribution of allergens may vary with different geographic areas, suggesting the importance of local epidemiological data to support evidence-based prevention and management of allergic diseases. We investigated the distribution of common allergens in allergic patients in Guangzhou, southern China. METHODS: 7,047 patients with allergic symptoms were examined for serum sIgE to 15 common allergens in this region, based on the protocol of reversed enzyme allergosorbent test. RESULTS: 4,869 (69.09%) of the subjects tested positive for sIgE to at least one of the 15 common allergens. There was no statistical difference in the overall rate of positive sIgE detection between males (3128/4523, 69.16%) and females (1741/2524, 68.98%). Der pteronyssinus and Der farinae were the most common aeroallergens, while eggs and cow's milk the most common food allergens, responsible for higher positive rates of sIgE responses. A good correlation in positive sIgE response was found between Der pteronyssinus and Der farinae. By age-group analysis, we noted several peaks of sensitization to certain allergens: Der pteronyssinus, Der farinae, and Blomiatropicalis at age between 9 and 12; Blattellagermanica and mosquito at age between 15 and 18, cow's milk before age 3; eggs and flour at age between 3 and 6; crabs and shrimps at age between 12 and 15. Along with older age, there was an ascending tendency in the overall positive rate of sIgE response to house dust mites among subjects who tested positive for sIgE to eggs or cow's milk. CONCLUSIONS: Der pteronyssinus, Der farinae, cow's milk, and eggs are major allergens in Guangzhou. Sensitization to eggs and cow's milk is more common at younger age, and then gives place to the increasing prevalence of sensitization to Der pteronyssinus and Der farinae at older age. Such a sequence of events may be a result of allergy march. Knowledge on the prevalence of allergen sensitization in different age groups would help early diagnosis and intervention of allergic diseases in this large geographical region.

Effects of nebulized high-dose budesonide on moderate-to-severe acute exacerbation of asthma in children: a randomized, double-blind, placebo-controlled study.

BACKGROUND AND OBJECTIVE: The efficacy of inhaled corticosteroids (ICS) in asthma exacerbation are yet to be clarified. The aim of this study was to investigate the efficacy of nebulized ICS in children with moderate-to-severe acute exacerbation of asthma in an emergency room setting in order to elucidate the potential use of ICS as the first-line therapy in the management of acute exacerbation of asthma. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study. Paediatric patients with moderate-to-severe acute exacerbation of asthma in emergency room were randomized to receive nebulized salbutamol and ipratropium bromide, with the addition of nebulized high-dose budesonide (BUD group, n = 60) or normal saline (control group, n = 58), three doses in the first hour. RESULTS: The improvement in forced expiratory volume in 1 s was similar in both groups at 0 h after three doses of nebulization, but there was significantly further improvement at 1 and 2 h in the BUD group (0.095 ± 0.062 L and 0.100 ± 0.120 L, respectively) compared with the control group (0.059 ± 0.082 L and 0.021 ± 0.128 L, respectively), P = 0.013 and 0.001, respectively. Complete remission rate was significantly higher (84.7% vs 46.3%, P = 0.004) and need for oral corticosteroids was significantly lower (16.9% vs 46.3%, P = 0.011) in BUD group than in control group. CONCLUSION: On the basis of nebulized short-acting bronchodilators, addition of nebulized high-dose budesonide resulted in clinical improvement in children with moderate-to-severe acute exacerbation of asthma, suggesting that nebulized high-dose ICS can be used as first-line therapy for non-life-threatening acute exacerbation of asthma in children.

Single intraperitoneal injection of monocrotaline as a novel large animal model of chronic pulmonary hypertension in Tibet minipigs.

OBJECTIVE: The purpose of this study was to establish an animal model of chronic pulmonary hypertension with a single-dose intraperitoneal injection of monocrotaline (MCT) in young Tibet minipigs, so as to enable both invasive and noninvasive measurements and hence facilitate future studies. METHODS: Twenty-four minipigs (8-week-old) were randomized to receive single-dose injection of 12.0 mg/kg MCT (MCT group, n = 12) or placebo (control group, n = 12 each). On day 42, all animals were evaluated for pulmonary hypertension with conventional transthoracic echocardiography, right heart catheterization (RHC), and pathological changes. Findings of these studies were compared between the two groups. RESULTS: At echocardiography, the MCT group showed significantly higher pulmonary arterial mean pressure (PAMP) compared with the controls (P<0.001). The pulmonary valve curve showed v-shaped signals with reduction of a-waves in minipigs treated with MCT. In addition, the MCT group had longer pulmonary artery pre-ejection phases, and shorter acceleration time and ejection time. RHC revealed higher mean pulmonary arterial pressure (mPAP) in the MCT group than in the control group (P<0.01). A significant and positive correlation between the mPAP values and the PAMP values (R = 0.974, P<0.0001), and a negative correlation between the mPAP and ejection time (R = 0.680, P<0.0001) was noted. Pathology demonstrated evidence of pulmonary vascular remodeling and higer index of right ventricular hypertrophy in MCT-treated minipigs. CONCLUSION: A chronic pulmonary hypertension model can be successfully established in young minipigs at six weeks after MCT injection. These minipig models exhibited features of pulmonary arterial hypertension that can be evaluated by both invasive (RHC) and noninvasive (echocardiography) measurements, and may be used as an easy and stable tool for future studies on pulmonary hypertension.

Visualization of peripheral pulmonary artery red thrombi utilizing optical coherence tomography.

Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images and has been used in interventional cardiology. However, an application of OCT in pulmonary arteries had seldom been documented. In this case, OCT imaging is performed in peripheral pulmonary arteries and shows mural red thrombi. Subsequently, the red thrombi are aspirated and confirmed by a histological examination. These findings suggest that OCT may be a useful tool to depict peripheral pulmonary artery thrombi.

Reference values of induced sputum cytology in healthy children in guangzhou, southern china.

OBJECTIVE: To establish normal reference values of induced sputum cytology in healthy children in southern China. METHODS: During a period from January 2010 to December 2011, a total of 580 healthy children (5-16 years of age) were approached. A total of 266 children (137 boys and 129 girls) participated in the study. Sputum induction was carried out by using 5% hypertonic saline. Cell types in the sputum were examined by using routine methods. RESULTS: Sputum induction was completed in 175 of the 266 subjects (65.79%), but 16 sputum samples were disqualified. The overall success rate was 59.77% (159/266). Macrophages and neutrophils were the predominant cell types: macrophages: median, 76.14%; interquartile range (IQR), 32.68%; and 2.5% to 97.5% percentile, 1.00% to 94.50%; neutrophils: median, 20.67%; IQR, 33.0%; and 2.5% to 97.5% percentile, 4.00% to 92.75%; eosinophils: median, 0.39%; IQR, 1.93%; and 2.5% to 97.5% percentile, 0.00% to 6.50%; and lymphocytes: median, 1.22%; IQR, 2.04%; and 2.5% to 97.5% percentile, 0.00% to 5.00%. The cell types did not differ among different age, gender, and passive smoking groups. Adverse events occurred in 4.4% (7/159) of the participants who completed the procedures but required no specific treatment to dissipate. Peak expiratory flow did not differ between those who completed the procedures compared with those who did not, suggesting that the procedure is safe and feasible in children. CONCLUSIONS: The current study represents the first attempt to develop normal reference values of induced sputum cytology in Chinese children, and could be used as a control for future studies.

Using optical coherence tomography to detect peripheral pulmonary thrombi.

BACKGROUND: Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images of small vessels and has been widely used in interventional cardiology. However, application of OCT in peripheral pulmonary arteries in patients has been seldom documented. METHODS: Three patients who were highly suspected peripheral pulmonary arteries thrombi and had undergone CT pulmonary angiography but tested negative for thrombi in peripheral pulmonary arteries were enrolled. Subsequently, OCT imaging was performed in peripheral pulmonary arteries. The patients received more than three-month anticoagulative treatment if thrombi were detected by OCT. Thereafter, OCT re-evaluation of the thrombolized blood vessels detected earlier was performed. The changes of thrombi before and after anticoagulative treatment were compared. RESULTS: Three patients underwent OCT imaging of peripheral pulmonary arteries. Thrombi were found in most of imaged vessels in these patients. Red and white thrombi can be differentiated, according to features of the thrombus on OCT images. After anticoagulation treatment, these patients' symptoms and hypoxemia improved. Repeated OCT imaging showed that most thrombi disappeared or became smaller. CONCLUSION: OCT may be used as a potential tool for detecting peripheral pulmonary artery thrombi and differentiating red thrombi from white ones.

Pandemic planning in China: applying lessons from severe acute respiratory syndrome.

There were three events of severe acute respiratory syndrome (SARS) in China from 2003 to 2004. Starting from 2002, we are also aware of the increasing alert of an avian flu pandemic. Epidemics of SARS and avian flu have posed huge threats to social stability, economic prosperity and human health in this country. What we have experienced during SARS outbreaks has great implications for the protection of people against a resurgence of SARS and potential attacks of high-pathogenic avian flu viruses. To that end, China has been preparing to contain future pandemics by applying lessons learnt from SARS.

Evaluation by indirect immunofluorescent assay and enzyme linked immunosorbent assay of the dynamic changes of serum antibody responses against severe acute respiratory syndrome coronavirus.

BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emerging virus that gives rise to SARS patients with high rates of infectivity and fatality. To study the humoral immune responses to SARS-CoV, the authors evaluated IgG and IgM specific antibodies in patients' sera. METHODS: Two methods, enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescent assay (IFA), were used to detect specific serum IgG and IgM against SARS-CoV in 98 SARS patients and 250 controls consisting of patients with pneumonia, health-care professionals and healthy subjects. The serum antibody profiles were investigated at different times over one and a half years in 18 of the SARS patients. RESULTS: The sensitivity and specificity of ELISA for detecting IgG against SARS-CoV were 100.0% and 97.2% and for IgM 89.8% and 97.6% respectively; the figures using IFA for IgG were 100.0% and 100.0% and for IgM 81.8% and 100.0% respectively. During the first seven days of the antibodies trace test, no IgG and IgM were detected, but on day 15, IgG response increased dramatically, reaching a peak on day 60, remaining high up to day 180 and decreasing gradually until day 540. On day 15, IgM was detected, rapidly reached a peak, then declined gradually until day 180 when IgM was undetectable. CONCLUSION: The detection of antibodies against SARS virus is helpful in the clinical diagnosis of SARS.

Chemokine-like factor 1, a novel cytokine, contributes to airway damage, remodeling and pulmonary fibrosis.

BACKGROUND: Chemokine-like factor 1 (CKLF1) was recently identified as a novel cytokine. The full-length CKLF1 cDNA contains 530 bp encoding 99 amino acid residues with a CC motif similar to that of other CC family chemokines. Recombinant CKLF1 exhibits chemotactic activity on leucocytes and stimulates proliferation of murine skeletal muscle cells. We questioned whether CKLF1 could be involved in the pathogenesis of inflammation and proliferation in the lung. Therefore we used efficient in vivo gene delivery method to investigate the biological effect of CKLF1 in the murine lung. METHODS: CKLF1-expressing plasmid, pCDI-CKLF1, was constructed and injected into the skeletal muscles followed by electroporation. Lung tissues were obtained at the end of week 1, 2, 3 and 4 respectively after injection. The pathological changes in the lungs were observed by light microscope. RESULTS: A single intramuscular injection of CKLF1 plasmid DNA into BALB/c mice caused dramatic pathological changes in the lungs of treated mice. These changes included peribronchial leukocyte infiltration, epithelial shedding, collagen deposition, proliferation of bronchial smooth muscle cells and fibrosis of the lung. CONCLUSIONS: The sustained morphological abnormalities of the bronchial and bronchiolar wall, the acute pneumonitis and interstitial pulmonary fibrosis induced by CKLF1 were similar to phenomena observed in chronic persistent asthma, acute respiratory distress syndrome and severe acute respiratory syndrome. These data suggest that CKLF1 may play an important role in the pathogenesis of these important diseases and the study also implies that gene electro-transfer in vivo could serve as a valuable approach for evaluating the function of a novel gene in animals.

[Protective effect of specific antibody in serum of convalescent patient with SARS].

OBJECTIVE: To investigate inhibitory effect of serum severe acute respiratory syndrome (SARS) -specific antibodies from convalescent patients after half an year of onset on SARS-CoV-mediated cytopathic response. METHODS: SARS-CoV immunoglobulin G (IgG) antibody was determined by enzyme linked immunoadsorbent assay (ELISA). Twelve serum samples from convalescent patients, diluted by 1:8 with maintenance medium, were mixed with the three dilution supernatants of SARS-CoV. SARS-CoV were isolated, cultured and identified by the Guangzhou Institute of Respiratory Disease, and cultured with Vero E6 cell suspension. The extent of cytopathic response was observed. RESULTS: The absorbance (A) value of SARS-CoV IgG antibody ranged from 0.81 to 2.06 in patients after half an year of SARS onset, and form 0.79 to 2.01 in patients before half an year of SARS onset. The extent of cytopathic response was decreased by more than 25% in all 12 convalescent patients, as compared with control serum. CONCLUSION: The A value of SARS-CoV IgG antibody in serum of convalescent patients tended to elevate in half an year after SARS onset. SARS-CoV IgG antibody could inhibit SARS-CoV-mediated cytopathic response, indicating it might be one of protective antibodies.