[Annual review of progress in research on chronic obstructive pulmonary disease(2022-2023)].

Chronic obstructive pulmonary disease (COPD) is the most common chronic airway disease, with a high prevalence and high disease burden. Clinical questions have driven advances in clinical research that continue to deepen our understanding of COPD. At the same time, new perspectives, evidence, and strategies have emerged. Studies since 2022 have increased knowledge of the impact of risk factors, such as low-to-moderate income and ambient ozone, on the prevalence of COPD. The effect of preterm birth on obstructive lung function deficits and COPD in the sixth decade of life was investigated for the first time. Screening studies for COPD in developed and low- and middle-income countries suggest the importance of tailoring screening strategies to local conditions. Developments in artificial intelligence provide a general framework for using machine-learning-based methods and medical record-based labels to improve disease prediction. New perspectives on endotypes/phenotypes and prognostic assessment of COPD were provided by lifetime spirometry patterns of obstruction and limitation, sensitisation to recombinant Aspergillus fumigatus allergens, airway-occluding mucus plugs and exacerbation history in COPD group A and B patients. Clinical trials focusing on inflammatory mediators, comorbidity treatment, non-pharmacological treatments, and environmental interventions shed light on some crucial and long-debated issues. Further research is needed for individualised diagnosis and treatment of COPD.

[Clinical research progress in non-invasive positive pressure ventilation in 2023].

Non-invasive positive pressure ventilation (NPPV) is a widely used method of providing respiratory support in a variety of clinical settings, including emergency departments, general wards, and intensive care units. The relevant research articles on NPPV published between 1st October 2022 and 30th September 2023 were retrieved from Medline and reviewed. In the management of acute respiratory failure (ARF) associated with COVID-19, studies have highlighted the significant influence of regional economic status on the choice of respiratory support strategies. It has been observed that NPPV is more suitable for patients with mild to moderate acute respiratory distress syndrome (ARDS) than for those with severe ARDS, as the latter group has an increased risk of delayed intubation. In addition, patients with severe dyspnea tended to benefit more from NPPV compared with high flow nasal cannula (HFNC) and conventional oxygen therapy, with a reduced risk of self-induced lung injury. For non-COVID-19-related ARF, research shows no significant differences in mortality and intubation rates between HFNC and NPPV in patients with hypercapnic ARF. The updated HACOR score and ROX score have been validated to have a high predictive value for clinical outcomes in patients receiving NPPV for hypoxemic ARF. With regard to weaning from invasive mechanical ventilation, immediate application of NPPV after extubation showed a lower mortality rate compared to continued invasive weaning. Moreover, NPPV with active humidification significantly decreased the reintubation rate within 7 days after extubation compared with HFNC. The choice between using NPPV and HFNC should be based on the specific etiology of the patient's condition. The potential effect of noninvasive high-frequency oscillatory ventilation on CO2 clearance was also investigated.

[Investigation on cognition, diagnosis and treatment status of chest tightness variant asthma among Chinese pediatricians].

Objective: To evaluate the awareness, diagnosis and treatment of chest tightness variant asthma (CTVA) among pediatricians in China. Methods: The survey was conducted by convenient sampling method. Pediatricians with professional title of attending physician and above from different grades hospitals in 30 provinces were invited to conduct online questionnaire surveys through WeChat, pediatricians scan QR codes to complete electronic questionnaires in the mini program from January 16th to February 4th, 2021. The contents of questionnaire included the awareness, diagnosis and treatment of CTVA, and comparing the differences between pediatricians in secondary hospitals and tertiary hospitals. Results: A total of 1 529 pediatricians participated in the survey, and 1 484 (97.06%) pediatricians completed the questionnaire and included in the analysis, including 420 males (28.30%). The awareness rate of CTVA among pediatricians was 77.83 % (1 155/1 484). Pediatricians in tertiary hospitals had higher rates of awareness of CTVA than pediatricians in secondary hospitals [81.86% (898/1 097) vs 66.41% (257/387), P<0.001] and had better execution of the guidelines [89.15% (978/1 097) vs 79.59% (308/387), P<0.001]. A total of 93.06 % (1 381/1 484) of pediatricians' first-line treatment included inhaled corticosteroids (ICS) for CTVA. Among them, a higher proportion of pediatricians in tertiary hospitals used ICS included regimens for first-line treatment of CTVA compared with pediatricians in secondary hospitals [94.90% (1 041/1 097) vs 87.86% (340/387), P<0.001]. The reported well control rate of CTVA was 32.08% (476/1 484), which was significantly lower in secondary hospitals than that in tertiary hospitals [17.31% (67/387) vs 37.28% (409/1 097), P<0.001]. Conclusion: Most pediatricians are well aware of CTVA, among which there is a certain gap in clinical practice between pediatricians in secondary hospitals and tertiary hospitals in terms of understanding, diagnosis, and treatment of CTVA.

[Clinical update in non-invasive positive pressure ventilation for respiratory failure in 2022].

In this article, we searched the research literatures related to clinical investigation of non-invasive positive pressure ventilation (NPPV) in acute respiratory failure(ARF)/chronic respiratory failure(CRF) between 1st October 2021 and 30th September 2022 through Medline, and reviewed the important advances. Three prospective randomized controlled studies related to the efficacy and safety of NPPV and/or high-flow nasal cannula oxygen therapy (HFNC) on patients with COVID-19 with ARF were reported, showing that NPPV (including continuous positive airway pressure and bilevel positive airway pressure) was able to reduce the intubation rate, but the efficacy of HFNC was contradictory. In addition, progress has been made in outcome prediction models for ARF treated with NPPV, NPPV-related cardiac arrest, and the impact of human-machine interface on NPPV treatment outcomes. The effects of NPPV as preoxygenation method before intubation was reported to be able to reduce severe desaturation during intubation, especially in obese population. The use of NPPV in extubated patients resulting in reduced reintubation rate was also studied. With regard to long-term home application of NPPV, five indicators of successful initiation were proposed, but the success rate was low in clinical practice. Some reports showed that psychological support could improve the adherence to NPPV. The results of these studies contributed to the rational selection and optimal application of NPPV in clinical practice.

[MiR-340 mediates the involvement of high mobility group box 1 in the pathogenesis of liver fibrosis].

Objective: To explore the pathogenic mechanism of the miR-340/high mobility group box 1 (HMGB1) axis in the formation of liver fibrosis. Methods: A rat liver fibrosis model was established by injecting CCl(4) intraperitoneally. miRNAs targeting and validating HMGB1 were selected with gene microarrays after screening the differentially expressed miRNAs in rats with normal and hepatic fibrosis. The effect of miRNA expressional changes on HMGB1 levels was detected by qPCR. Dual luciferase gene reporter assays (LUC) was used to verify the targeting relationship between miR-340 and HMGB1. The proliferative activity of the hepatic stellate cell line HSC-T6 was detected by thiazolyl blue tetrazolium bromide (MTT) assay after co-transfection of miRNA mimics and HMGB1 overexpression vector, and the expression of extracellular matrix (ECM) proteins type I collagen and α-smooth muscle actin (SMA) was detected by western blot. Statistical analysis was performed by analysis of variance and the LSD-t test. Results: Hematoxylin-eosin and Masson staining results showed that the rat model of liver fibrosis was successfully established. Gene microarray analysis and bioinformatics prediction had detected eight miRNAs possibly targeting HMGB1, and animal model validation had detected miR-340. qPCR detection results showed that miR-340 had inhibited the expression of HMGB1, and a luciferase complementation assay suggested that miR-340 had targeted HMGB1. Functional experiments results showed that HMGB1 overexpression had enhanced cell proliferation activity and the expression of type I collagen and α-SMA, while miR-340 mimics had not only inhibited cell proliferation activity and the expression of HMGB1, type I collagen, and α-SMA, but also partially reversed the promoting effect of HMGB1 on cell proliferation and ECM synthesis. Conclusion: miR-340 targets HMGB1 to inhibit the proliferation and ECM deposition in hepatic stellate cells and plays a protective role during the process of liver fibrosis.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

[Two families with Birt-Hogg-Dubé syndrome:case report and literature review].

Objective: To improve the awareness of Birt-Hogg-Dubé syndrome. Methods: We performed a retrospective analysis with two families of Birt-Hogg-Dubé syndrome (BHD syndrome) diagnosed in Department of Respiratory and Critical Care Medicine, Shenzhen People's Hospital from 2020 to 2021. Clinical manifestations, imaging features, diagnosis and gene detection results were summarized. Relative literatures were reviewed in Wanfang Database and PubMed from 2015 to 2021 by using the search terms of "BHD syndrome" "Birt-Hogg-Dubé" "Birt-Hogg-Dubé syndrome", respectively. Results: The probands of both families were female, aged 37 and 34 years respectively. The onset manifestation was pulmonary bullae combined with pneumothorax. Chest computed tomography (CT) imaging showed multiple pulmonary cysts in both lobes, and no skin lesions or renal tumors were found in either case. History of pneumothorax was present in Family 1 while absent in Family 2. The FLCN gene of the two probands and their relatives showed the same mutation site. Totally 12 Chinese literatures and 394 English literatures were retrieved, among which 96 reported lung involvement only. A total of 10 literatures about Chinese population were screened out from the English literatures, and 115 patients, 31 males and 84 females, were included. The incidence of spontaneous pneumothorax was 66.95% (77/115), while a family history of pneumothorax was 88.31%(68/77). The onset age of spontaneous pneumothorax was between 30 and 44 years. The most common mutation site of FLCN was c.1285dup. Conclusions: BHD syndrome in Asian population may only have lung involvement. Patients with pneumothorax and pulmonary cystic lesions should be inquired of the family history. We speculate that there are many underdiagnosed cases in clinical practice.

[Hyper-IgE syndrome in adults characterized by disseminated mixed infection: a case report and literature review].

Objective: To improve the awareness of hyper-IgE syndrome (HIES) characterized by disseminated infection. Methods: We retrospectively analyzed a patient with HIES characterized by Talaromyces marneffei and Staphylococcus aureus mixed disseminated infection in Shenzhen People's Hospital. The clinical manifestations, results of laboratory tests/genetic examinations, therapeutic strategies and prognosis were summarized. The keywords "hyper-lgE syndrome" were used to search and review the literature in Wanfang databases and Pubmed database. Results: In February 2021, an 18-year-old male patient was admitted to our hospital with backache for over 3 weeks and fever for 4 days. Physical examination revealed deciduous teeth in the oral cavity, bilateral renal pain on percussion, and interphalangeal joint hyperextension. Laboratory studies demonstrated increased blood eosinophils and serum level of total IgE. Bacterial culture from bronchoscopic secretions, bronchial mucosa, and necrotic tissue from the left upper arm showed Talaromyces marneffei. Bacterial culture from alveolar lavage fluid, left upper arm necrotic tissue, puncture fluid of right retroauricular abscess and renal drainage fluid suggested methicillin-sensitive Staphylococcus aureus. The chest and abdominal CT revealed diffuse patchy and nodular lesions in bilateral lungs, cavitary lesions in the upper lobe of the left lung, multiple enlarged lymph nodes in the mediastinum, and infectious lesions within both kidneys and perirenal space. Furthermore, the patients was identified with STAT3 mutations by whole exome sequencing, which confirmed the diagnosis of HIES. Nineteen literature articles were retrieved, involving 27 adult patients with a median age of diagnosis of 23 years. The most common manifestations included: skin infection (16/27), eczema (15/27), elevated IgE (26/27) and eosinophils (17/27), as well as positive STAT3 mutation (11/27). Conclusion: Clinicians should be alert to the possibility of hyper-IgE syndrome in patients with severe or disseminated intracellular bacterial infections.

[Clinical research progress in non-invasive positive pressure ventilation from 2020 to 2021].

Non-invasive positive pressure ventilation (NPPV), an essential respiratory support method, is widely used in acute/chronic respiratory failure and assisting rehabilitation in patients with chronic obstructive pulmonary disease (COPD). We searched the relevant research articles about NPPV published from 1st October 2020 to 30th September 2021 through Medline. Researches focusing on the clinical application and viral transmission protection during high-flow nasal cannula oxygen and NPPV in COVID-19, were mainly retrospective and of small sample size. It demonstrated that high-flow nasal cannula oxygen and NPPV might reduce intubation rates when treating patients with mild-to-moderate respiratory failure, but the risk of delayed intubation should draw particular precaution. When using NPPV in non-COVID-19-related de novo acute respiratory failure, diaphragm thickening fraction and tidal change of esophageal pressure were validated to predict the treatment outcome. In addition, some studies explored the compliance and related influencing factors associated with the treatment effects of early NPPV initiation on amyotrophic lateral sclerosis patients and the effects of NPPV on dynamic hyperinflation during exercise in COPD patients. Furthermore, the effectiveness of neurally adjusted ventilatory assist ventilation and a novel communication device optimizing the use of NPPV were also investigated and outlined.

[Effect of closed extension tube on preventing airway leakage during artificial airway clearance].

Objective: To explore the role of closed extension tube in preventing airway leakage during artificial airway clearance. Methods: The test lung was connected with a ventilator for mechanical ventilation. The pressure parameters were set as 16/5, 20/6, 24/7, 28/8, 32/9 and 36/10 cmH2O(1 cmH2O=0.098 kPa), respectively. The circuit was connected with an open extension tube or a closed extension tube. The ventilator was set with different pressure parameters to observe the changes of airway pressure and tidal volume during airway clearance. Results: (1) The pressure parameters were set as 16/5, 20/6, 24/7, 28/8, 32/9 and 36/10 cmH2O, and the airway pressures (in cmH2O) of circuit connected with open extension tube were (15.94±0.27)/(4.81±0.04), (20.09±0.23)/(6.05±0.16), (23.89±0.41)/(6.94±0.06), (27.90±0.22)/(7.71±0.18), (31.92±0.13)/(8.74±0.12)and(35.65±0.31)/(9.72±0.07), respectively.Under the same ventilator pressure parameters, the airway pressures (in cmH2O) of circuit connected with close extension tube were (16.36±0.06)/(4.85±0.04), (20.54±0.26)/(6.44±0.12), (24.36±0.24)/(7.01±0.33), (28.69±0.25)/(8.07±0.08), (32.97±0.33)/(8.93±0.09), (37.34±0.29)/(9.75±0.08), respectively. The airway pressure of circuit connected with open extension tube was lower than that connected with closed extension tube(P<0.05);with the increase of the pressure setting of the ventilator, the difference of the airway pressure between the two extended tubes gradually increased. When the maximum inspiratory pressure of the ventilator was set 36 cmH2O, the difference reached 1.69 cmH2O. (2) The airway pressures (in cmH2O) dropped from (15.94±0.27)/(4.81±0.04), (20.09±0.23)/(6.05±0.16), (23.89±0.41)/(6.94±0.06), (27.90±0.22)/(7.71±0.18), (31.92±0.13)/(8.74±0.12), (35.65±0.31)/(9.72±0.07) to (13.42±0.4)/(3.15±0.14), (16.81±0.6)/(4.30±0.14), (20.22±0.5)/(5.48±0.45), (23.73±1.4)/(6.25±0.22), (24.78±0.7)/(7.13±0.21), (20.83±0.4)/(6.61±0.19)when the suction port of the open extension tube was opened (P<0.05);and the tidal volume (in L) also decreased from 0.328±0.004, 0.580±0.012, 0.621±0.003, 0.626±0.003, 0.615±0.003, 0.603±0.002 to 0.272±0.008, 0.416±0.051, 0.487±0.047, 0.396±0.116, 0.507±0.022, 0.508±0.079, respectively (P<0.05). The decrease of airway pressure and tidal volume gradually increased with the increase of ventilator setting pressure. When the ventilator setting parameter was 36/10 cmH2O, the decrease of airway inspiratory pressure was (14.82±0.51) cmH2O and the maximum reduction of tidal volume was (0.164±0.021)L. (3)The airway pressure (in cmH2O) was increased to(15.70±0.23)/(4.80±0.33), (19.01±0.81)/(5.71±0.34), (22.27±0.62)/(6.85±0.44), (25.35±2.09)/(7.94±0.16), (28.38±0.46)/(8.96±0.23), (33.34±0.71)/(9.71±0.25) when the suction tube was inserted from the suction port of the open extension tube in the open state, and the tidal volume (in L) was increased to 0.340±0.016, 0.563±0.020, 0.571±0.030, 0.556±0.026, 0.514±0.021, 0.512±0.031 as well.The airway pressure and tidal volume of the ventilation circuit were higher than those in the open state, but still lower than those in the closed state. Compared with the closed state of the suction port, the maximum pressure drop and tidal volume decrease were (3.53±0.46) cmH2O and (0.101±0.011) L, respectively. (4) The pressure of the ventilator was set between 16/5 cmH2O to 36/10 cmH2O. The airway pressure (in cmH2O) was decreased from (16.26±0.04)/(4.85±0.04), (20.74±0.15)/(6.42±0.11), (25.09±0.31)/(7.10±0.13), (29.38±0.24)/(8.17±0.09), (33.80±0.16)/(9.02±0.17), (37.89±0.19)/(9.83±0.07) to(16.36±0.06)/(4.85±0.04), (20.54±0.26)/(6.44±0.12), (24.36±0.24)/(7.01±0.33), (28.69±0.25)/(8.07±0.08), (32.97±0.33)/(8.93±0.09), (37.34±0.29)/(9.75±0.08), respectively during the insertion of the suction tube from the suction port of the closed extension tube, and the tidal volume (in L) was decreased from0.361±0.005, 0.592±0.003, 0.631±0.001, 0.642±0.007, 0.633±0.007, 0.626±0.08 to 0.335±0.005, 0.588±0.008, 0.631±0.002, 0.638±0.004, 0.628±0.004, 0.618±0.005.The maximum pressure change of the ventilation circuit was (0.83±0.27) cm H2O and the maximum tidal volume change was (0.008±0.006)L. The changes of airway pressure and tidal volume were significantly lower than those of ventilation circuit connected with open extension tube under the same pressure parameters. Conclusion: The connection of closed extension tube in mechanical ventilation circuit can reduce the airway leakage during artificial airway clearance, which is worthy of clinical recommendation.

[Correlation between aspiration and long-term survival of inpatients with chronic obstructive pulmonary disease].

Objective: To retrospectively analyze the high risk factors of death in patients with chronic obstructive pulmonary disease (COPD) and to explore the influence of aspiration on the long-term survival rate of COPD patients. Methods: A retrospective analysis of clinical data of inpatients, who were admitted to the First Affiliated Hospital of Guangzhou Medical University from April 2012 to December 2013 due to COPD exacerbations and had radionuclide aspiration test, was conducted. Meanwhile, we phoned the patients' family members, whose phone numbers were recorded in the electronic patient record system, to follow up the patients' survival status, and learn the causes of death from their death records if patients died during follow-up period. Inquired the resident administration patients belonging to according to their original address to get patient's current contact information if changed. Besides, if family members of patients failed to provide death record, we should look up information concerned from the medical records room of the hospital where they died. Results: The follow-up for the last patient was performed on February 20, 2017.The time span of this study is 58 months, starting from the radionuclide aspiration test for the first patient and ending with the follow-up for the last patient. 16 of the 53 patients(16/53, 30.2%)were tested positive whose average age was slightly higher than patients without aspiration (76.0±6.8 vs 70.9±9.9), but there was no significant difference between them(P=0.064). The aspiration rates among patients over and under the age of seventy were 14/35 and 2/18 respectively, and there was a significant difference between them(P = 0.03). Compared to the aspiration-negative patients, the aspiration-positive patients had higher incidence rate of pneumonia in COPD exacerbations (11/16 vs 9/37, χ²= 9.383, P = 0.002).The major cause of death in the patients with and without aspiration were respectively severe pneumonia and pulmonary encephalopathy(P<0.05 in both cases).Among COPD patients who took radionuclide aspiration test, the median survival time of the patients with and without aspiration were about 3 and 5 years respectively. The high-risk factors influencing long-term survival of the COPD patients with aspiration included ICU-involved medical history and accompanying pneumonia. Conclusions: The incidence rate of aspiration is relatively high in COPD patients over 70 years old. Compared to COPD patients without aspiration, COPD patients with aspiration have higher incidence rate of pneumonia and shorter median survival time. ICU-involved medical history and severe pneumonia are the two high-risk factors influencing long-term survival of COPD patients with aspiration.To improve the survival time of COPD patients with aspiration, we need to attach importance to the prevention and treatment of aspiration.

[A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China].

Objective: To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China. Methods: A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals. The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture, antigen detection and histopathology were enrolled in the study. The clinical data of enrolled patients were collected and analyzed. Results: A total of 457 cases of pulmonary cryptococcosis were enrolled, among which 3.28% (15/457) were disseminated infections. The case fatality rate was 0.88% (4/457). The majority of the cases were diagnosed by histopathological examinations (74.40%, 340/457) and cryptococcus antigen detection (37.64%, 172/457). Patients with pulmonary cryptococcosis accounted for 2.04‰ (457/223 748) of the total hospitalized patients in the Department of Respiratory Diseases during the same period, and the ratio was the highest in south and east China. Meanwhile, 70.24% (321/457) of the patients had no underlying diseases, while 87.75% (401/457) were found to have immunocompetent status. Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis. However, 25.16% (115/457) of the patients had no clinical symptom or physical signs. In terms of imaging features on pulmonary CT, multiple pulmonary lesions were more common than isolated lesions, and there were more subpleural lesions than perihilar or medial lesions. Morphologically, most of the lesions were middle-sized nodules (1-5 cm) or small-sized nodules (3 mm to 1 cm). The sensitivity of serum cryptococcus antigen test was 71.99% (203/282). Moreover, antigen-positive patients differed from antigen-negative patients in terms of basic immune status, clinical symptoms, imaging features and infection types. Meanwhile, immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms, physical signs, infection-related inflammation indicator levels, imaging features, serum cryptococcus antigen positive rate and prognosis. Conclusions: The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status, and the overrall prognosis was favorable. However, early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.

[The effect of a breathing trainer on relieving airway pressure caused by active cough in patients with mechanical ventilation].

Objective: To explore the effect of a breathing trainer on relieving the peak airway pressure caused by forced exhalation at the end of deep inspiration, gentle coughing at the end of calm inspiration and forced coughing at the end of deep inspiration in patients undergoing mechanical ventilation. Methods: From July to September 2018, 15 patients undergoing mechanical ventilation were selected from the First Affiliated Hospital of Guangzhou Medical University, including 5 patients with invasive ventilation (3 with tracheotomy and 2 with endotracheal intubation), and 10 patients with non-invasive ventilation through mask. The patients included 14 males and 1 female, aging 48-79 years, with an average age of (68±10) years. A Breathing Trainer developed by both Dongguan Yongsheng Medical Products Co., Ltd. and Guangzhou Institute of Respiratory Health was used to relieve the peak airway pressure. A one-way expiratory valve connected with a spring at the expiratory end of the Breathing Trainer was not opened until the pressure inside the airway was higher than 20 cmH(2)O (1 cmH(2)O=0.098 kPa), and opened completely when the pressure was higher than 35 cmH(2)O. Both before and after the Breathing Trainer was connected to the respiratory circuit, the patients were asked to exhale hard at the end of deep inspiration, to cough gently at the end of calm inspiration and to cough forcefully at the end of deep inspiration and the airway pressure were measured respectively. Each action was tested 3 times, and the interval time of each test was 1 min, and the interval of each action was 10 min. Results: Among the patients with tracheotomy or endotracheal intubation for invasive mechanical ventilation, when the patients exhaled hard at the end of deep inspiration,coughed gently at the end of gentle inspiration and coughed forcefully at the end of deep inspiration, the peak airway pressure measured before the ventilation circuit was connected to the Breathing Trainer was (30.0±4.5), (31.4±5.0) and (34.9±5.0)cmH(2)O, respectively, which was significantly higher than that after the ventilation circuit was connected to the Breathing Trainer(26.3±2.9), (26.7±3.5) and (29.0±4.1) cmH(2)O (all P<0.01). Among the patients with non-invasive mechanical ventilation wearing face masks, when the patients exhaled hard at the end of deep inspiration, coughed gently at the end of gentle inspiration and coughed forcefully at the end of deep inspiration, the peak airway pressure was (17.7±1.9), (16.6±2.5) and (18.9±2.5) respectively, before the ventilation circuit was connected to the Breathing Trainer, and was (18.9±2.5), (16.3±1.9) and (18.8±2.0) cmH(2)O respectively, after the ventilation circuit was connected to the Breathing Trainer. There was no significant difference between them (P>0.05). Conclusion: The application of Breathing Trainer in the mechanical ventilation circuit of tracheotomy or endotracheal intubation could significantly reduce the peak airway pressure caused by hard exhalation and cough. It could be used as an active cough assist device for mechanical ventilation patients to prevent high airway pressure.

Subdural haematoma mimics.

A subdural haematoma (SDH) is a frequently encountered pathology seen on an emergency room computed tomography (CT) head scan. An extra-axial crescentic density along the convexity of the brain or within the interhemispheric fissure is generally thought to represent a SDH; however, SDH mimics are known to occur in nature, and can be broadly classified under the subcategories of normal anatomy, artefacts, tumour, inflammation, infection, ischaemia, trauma, and iatrogenic. Understanding the typical characteristics of a SDH, knowledge of normal anatomy, close inspection of the morphology of the subdural process, changes to the adjacent structures, and rigorous attention to clinical details may reveal subtle clues that distinguish a true SDH from a mimic. This is crucial in appropriately directing clinical management. This review amalgamates most of the rare subdural processes that have been reported to mimic SDH, and discusses the imaging and clinical features that help to differentiate between them. This topic is highly valuable for radiology trainees, general radiologists, and emergency room physicians, and may serve as a refresher for the practising neuroradiologist.

[Respiratory pathogen spectrum in pulmonary exacerbation of bronchiectasis in adults and its association with disease severity].

Objective: To determine the pattern of respiratory pathogens at bronchiectasis exacerbation and its associations with disease severity. Methods: A total of 119 steady-state bronchiectasis patients [42 males, 77 females, age range 19 to 74 years, mean age (45±14)years], diagnosed by a compatible history combined with evidence of bronchial dilatation on high-resolution computed tomography (HRCT), were recruited prospectively from out-patient clinics in the First Affiliated Hospital of Guangzhou Medical University between September 2012 and March 2013. A comprehensive history taking, radiologic appearance, spirometry, sputum bacterial culture and 16 respiratory viruses in nasopharyngeal swabs and sputum samples by PCR assays were collected at steady-state bronchiectasis. All bronchiectasis patients were followed up one year and assessed for bacteriology, virology and systemic inflammatory indices [including white blood cell, C-reactive protein (CRP), interleukin-6, 8 and tumor necrosis factor-α] during bronchiectasis exacerbation. Results: Fifty-eight bronchiectasis patients [20 males, 38 females, age range 19 to 74 years, mean age (44±14) years] reported 100 exacerbations (1 to 5 exacerbation events per patient) during one year follow-up. Respiratory viruses were found more frequently in sputum and nasal swab during exacerbation [35.0% (35/100) and 39% (39/100)] than those during steady-state in bronchiectasis [sputum: 13.8% (8/58), nasal swab: 8.6% (5/58)] (χ(2)=8.33,χ(2)=13.51; respectively, all P<0.05). The rate of bacterial detection during exacerbation in sputum was 56% (56/100), which was not significantly different compared with those at steady-state (35/58, 60.3%;χ(2)=0.284, P=0.59). Of these respiratory infections, viral-bacterial co-infection accounted for 30% exacerbation events. The most common bacteria and viruses during exacerbation in mild bronchiectasis (n=18, with 25 exacerbation events) were Haemophilus parainfluenzae (4 cases) in sputum and influenza A in nasal swab or sputum (4 cases), respectively. In patients with moderate (n=17, with 29 exacerbation events)-severe bronchiectasis (n=23, with 46 exacerbation events), pseudomonas aeruginosa was the most common bacteria in sputum (35 cases), and the most common respiratory viruses were rhinovirus in nasal swab or sputum (11 cases). In these 100 exacerbation events, patients with bacterial and viral co-infection, pure bacteria infection, pure virus infection, no bacteria and virus infection accounted for 30, 29, 16 and 25 exacerbation events, respectively. And patients with co-infection had higher serum CRP (45±23) mg/L and IL-8 [9.0 (4.4-15.5) ng/L] (F=23.32, F=9.81,respectively; all P<0.05), and increased risk of hospitalization (30% vs. 0] compared with those in non-infectious group(χ(2)=9.0, P=0.003). Conclusions: Pseudomonas aeruginosa, rhinovirus and influenza A were common causative agents of exacerbation in bronchiectasis.In patients with moderate-severe bronchiectasis, pseudomonas aeruginosa was the most common bacterium in sputum, and the most common respiratory virus was rhinovirus in nasal swab or sputum, compared to Haemophilus parainfluenzae in sputum and influenza A in nasal swab or sputum in mild bronchiectasis. Patients with co-infection had more severe systemic inflammatory response and higher risk of hospitalization during exacerbation.

[Effect of connecting airbag in different filling state at the front end of piezometric tube in noninvasive ventilation circuit on man-machine synchronization].

Objective: To investigate the effect of connecting airbag in different filling state at the front end of piezometric tube in the noninvasive ventilation circuit on pressure transmission and human-machine synchronization. Method: In test 1, the airbag was connected to a piezometric tube which was placed in a closed container, the filling state of the airbag was regulated, and the pressure inside the container was changed to observe the corresponding pressure change in the piezometric tube. In test 2, the airbag in different filling state was connected at the front end of piezometric tube in noninvasive ventilation circuit. Twelve subjects were connected to the ventilator such that dynamic changes in the pressure inside the mask (Pmask) and piezometric tube (Ptube) could be measured. Data with normal distribution was analyzed by t test, while data with abnormal distribution was analyzed by K-W test. Results: In test 1, the pressure inside the container changed between 0 and 50 cmH(2)O(1 cmH(2)O=0.098 kPa), when the big airbag was filled at 1/5, 2/5, 3/5, 4/5, the medium-sized airbag was filled at 3/5, 4/5, 5/5, and the small airbag was filled at 4/5, the pressure inside the piezometric tube changed synchronously with the pressure inside the container with no statistically significant difference(P>0.05). In a state of no filling in the small airbag and the medium-sized airbag, and filled at 1/5 in the small airbag, the pressure inside the piezometric tube no longer changed with the pressure in the container when the pressure reached a certain level .When the small airbag was filled at 1/5, 2/5, 3/5, 5/5, the medium-sized airbag at 1/5, 2/5, and the big airbag at 5/5, and all the airbags were in the state of no filling , the difference in the pressure between the piezometric tube and the container was statistically significant. In test 2, respiratory ventilation parameters were set on 10/4 cmH(2)O-30/14 cmH(2)O , and the connecting airbag at the front end of piezometric tube in noninvasive ventilation circuit. The platform pressure in the mask was slightly higher than that in the piezometer tube, and the baseline pressure in the mask was slightly lower than that of the piezometer tube. When the big airbag was filled at 1/5, 2/5, 3/5, 4/5 and medium-sized airbag at 2/5, 3/5, 4/5, the pressure difference between Pmask and Ptube was less than 0.5 cmH(2)O, which was acceptable clinically. When the big airbag was filled at 1/5, 2/5, 3/5 and the medium-sized airbag at 2/5, 3/5, there was no significant difference in trigger work before and after connecting the airbag at the front end of the piezometric tube(P>0.05). Conclusion: Connecting the airbag at the front end of the piezometric tube could avoid the forming of condensate in piezometric tube. The airbag showed good properties of pressure conductivity under ideal size and filling state.

[Clinical analysis of 3 cases of eosinophilic granulomatosis with polyangiitis].

Objective: To improve the clinical recognition of eosinophilic granulomatosis with polyangiitis(EGPA) in clinical manifestations, diagnosis and treatment. Methods: The clinical manifestations, pathological characteristic, imaging manifestations, diagnosis and the therapy of three patients with EGPA were presented. Results: These 3 patients had asthma-like symptoms and extrapulmonary manifestations of systemic vasculitis. They were 20, 40 and 44 years old. All of them were female.They denied exposure or contact. Chest radiographic examination showed that the most common features were nodule shadow and tree-in-bud in the lung. The pathological manifestation was characterized by hypereosinophilia, high total IgE(over 300 KU/L) and high CRP(over 14.1mg/L). The FeNO of 2 patients was over 100ppb. The ANCA of these 3 patients was negative. The pulmonary pathology was observed had eosinophil infiltration in the alveolar, interstitial and vessel for 3 cases. The clinical manifestations were nonspecific. All patients were treated by glucocorticoid and immune-inhibitor(alkylating agents or purine synthesis inhibitors) therapy. Because patients were complicated with other organs involved, they needed long-time treatment. Conclusions: This disease is diverse and complex, with a lack of pathognomonic symptoms. We should highly suspect eosinophilic granulomatosis with polyangiitis, when the patients present severe asthma and eosinophilia. Early detection, early treatment, and the prognosis could be better.

Usefulness of albumin-bilirubin grade for evaluation of long-term prognosis for hepatitis B-related cirrhosis.

Long-term prognosis varies widely among patients with hepatitis B virus (HBV)-related liver cirrhosis. Our study aimed to investigate the applicability of albumin-bilirubin (ALBI), Child-Pugh and model for end-stage liver disease (MELD) scores to the long-term prognosis prediction of HBV-related cirrhosis. Patients diagnosed with HBV-associated cirrhosis from the First Affiliated Hospital of Wenzhou Medical University between January 2010 and December 2015 were enrolled in this study. The patients were followed up every 3 months. The prognostic performance of ALBI in long-term outcome prediction for HBV-related cirrhosis was compared with Child-Pugh and MELD scores using time-dependent receiver operating characteristic curve (tdROC) and decision curve analysis. A total of 806 patients were included in our study with 275 (34.1%) deceased during the follow-up. Multivariate Cox regression analysis showed that ALBI grade was an independent predictor associated with mortality. The tdROC analysis showed that ALBI score (0.787, 0.830 and 0.833) was superior to MELD (0.693, P=.003; 0.717, P<.001; 0.744, P<.001) and Child-Pugh score (0.641, P<.001; 0.649, P<.001; 0.657, P<.001) for predicting 1-year, 2-year and 3-year mortality. Additionally, decision curves also got the similar results. In addition, patients with lower ALBI score had a longer life expectancy, even among patients within the same Child-Pugh class. Thus, ALBI score was effective in predicting the long-term prognosis for patients with HBV-related cirrhosis and more accurate than Child-Pugh and MELD scores.

A diagnostic algorithm for assessment of liver fibrosis by liver stiffness measurement in patients with chronic hepatitis B.

Steatosis could affect liver stiffness measurement in patients with nonalcoholic fatty liver disease and chronic hepatitis C. In this study, we aimed to investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)-infected patients and develop a diagnostic algorithm for prediction of liver fibrosis by liver stiffness based on the controlled attenuation parameter. A total of 488 HBV-infected patients who underwent clinical examination, Fibroscan and liver biopsy were prospectively enrolled. The best liver stiffness measurement (kPa) cut-offs for significant fibrosis (S≥3) and advanced fibrosis (S≥4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter cut-off for severe steatosis (≥30%) was 287 dB/m. Among patients with low-grade fibrosis (S0-S2/S0-S3), mean liver stiffness values were significantly higher in subjects with severe steatosis or controlled attenuation parameter ≥287 dB/m compared with those without. Moreover, in subjects with low-grade fibrosis, a higher rate of false-positive rate was observed in patients with severe steatosis than those in patients without (F0-F2: 28.2% vs 9.7%; F0-F3: 17.0% vs 5.3%), and in patients with CAP≥287 dB/m compared with their counterpart (F0-F2: 23.7% vs 9.2%; F0-F3: 14.1% vs 4.8%). Low-grade fibrosis was accurately identified by γ-glutamyl transpeptidase-to-platelet ratio (GPR) with a cut-off value of 0.17. In patients with GPR<0.17, similar results were observed. The presence of steatosis may lead to overestimation of fibrosis assessed by liver stiffness measurement in patient with chronic hepatitis B. A diagnostic algorithm for assessing fibrosis using liver stiffness was developed by combining both controlled attenuation parameter and GPR values.

[Effects of noninvasive proportional assist vs pressure support ventilation on respiratory work in chronic obstructive pulmonary disease patients with hypercapnia].

Objective: To investigate the effect of noninvasive proportional assist ventilation (PAV) on respiratory work in chronic obstructive pulmonary disease(COPD) patients, in comparison to noninvasive pressure support ventilation(PSV). Methods: Ten severe COPD patients with hypercapnia during acute exacerbation were examined. The baseline inspiratory pressure of PSV (PS) and the assistance level of PAV(PA) were titrated by patients' tolerance. In addition to the baseline PS and PA, an additional decrease by 25% (PS-=75% PS, PA-=75% PA) or increase by 25% (PS+ =125% PS, PA+ =125% PA) of the assist level were applied to the patients. After the assessment of unassisted spontaneous breathing (SB), the patient was placed on the 6 levels of noninvasive-PSV and noninvasive-PAV in random sequence. Each level lasted at least 20 minutes. Respiratory rate (RR), tidal volume (Vt), and respiratory work(Wex, Wip and Wv) were measured. Asynchrony index (AI) was calculated. Results: During ventilation, Vt was significantly higher with each assist level than with SB. The Vt was significant increased with PS+ than with PA+ . An increase in expiratory work(Wex) and decrease in inspiratory work(Wip) were observed respectively, with the increasing assist level. The inspiratory muscles assessed by Wip were more unloaded at PS compared with PA [PS: (1.59±1.27) J/min vs PA: (4.99±3.48) J/min P<0.01]. However, the Wex was significantly higher with PS+ than with PA+ [PS+ : (1.17±0.54) J/min vs PA+ : (0.49±0.56)J/min, P<0.01]. The AI was increased with the increasing assist level of PSV [PS-: (0.46±0.57)%, PS: (1.36±1.24)% PS+ : (5.26±4.77)]. No asynchrony events were observed at PA- and PA. "Runaway" (expiratory asynchrony) was observed during PA+ [AI: (2.62±2.72)%]. Conclusions: Noninvasive-PAV can increase the Vt and decrease the Wip of the COPD patients with hypercapnia and avoid the over-assistance. The "Runaway" will occur at assist level higher than that set by tolerance. Physiological data can monitor the patient's responses and the ventilator-patient interaction, which may provide objective criteria for ventilator setting.