Background: Cold exposure can trigger asthma attacks. However, the underlying mechanism is yet to be elucidated. We hypothesize that low temperature reduces occludin expression and compromises airway epithelial barrier function, which, in turn, results in asthma exacerbation. Methods: We examined occludin expression in Beas-2B cells exposed to either 29 °C or 37 °C. The following drugs were administered prior to cold treatment: MG132 (a proteasome inhibitor), cycloheximide (a protein synthesis inhibitor), HC-067047 plus GSK2193874 (transient receptor potential vanilloid 4 [TRPV4] antagonists), or C4-ceramide (an SGK1 activator). siNedd4-2 was transfected into Beas-2B cells to investigate the role of Nedd4-2 in mediating cold-induced occludin instability. In animal experiments, we treated ovalbumin (OVA)-induced asthmatic mice with either a thermoneutral temperature of 30 °C or repeated cold stress (10 °C, 6 h/day) for 2 weeks. Either GSK2193874 or C4-ceramide was administered during the cold treatment. After a final OVA challenge, pulmonary permeability, serum IgE levels, and lung inflammation were assessed. Results: Treatment at 29 °C for 1−9 h significantly reduced Beas-2B cell occludin expression, which was rescued upon treatment with MG132, HC-067047 plus GSK2193874, C4-ceramide, or the Nedd4-2 knockdown. Notably, low temperatures affected occludin stability through SGK1/Nedd4-2-dependent proteolysis. In vivo analyses revealed that repeated cold exposure compromised the airway epithelial barrier function and exacerbated lung inflammation in mice, which was partially attenuated by the GSK2193874 or C4-ceramide injection. Conclusions: We identified a new mechanism underlying cold-induced asthma exacerbation that may involve SGK1/Nedd4-2-mediated occludin proteolysis, resulting in epithelial barrier dysfunction.

Background: Growing evidence from observational studies suggests a link between Allergic [rhinitis](https://www.sciencedirect.com/topics/neuroscience/rhinitis) (AR) and psychiatric disorders; whether these associations represent causal relationships remains uncertain. Methods: We performed bi-directional two-sample mendelian randomization (MR) using summary statistics from European genome-wide association studies to examine evidence of causality, specificity and direction of association of AR with 11 different psychiatric disorders or relevant traits. MR was conducted using the inverse-variance weighted method (IVW), MR-Egger and weighted median methods. Sensitivity analyses included the MR-Egger regression and MR pleiotropy residual sum and outlier test. Results: AR from 2 different GWAS data was positively associated with bipolar disorder (OR=1.649, 95% CI: 1.077-2.526; P=0.021; OR=1.599; 95%CI 1.058-2.417; P=0.026). AR was also associated with major depressive disorder (OR=1.539; 95%CI 1.007-2.353; P=0.047). There were no significant association between AR and other 9 psychiatric disorders. Bidirectional analyses showed that bipolar disorder is negatively associated with AR (OR=0.964; 95%CI: 0.936-0.993; P=0.015). There was no evidence for potential causal schizophrenia and effects of attention deficit/hyperactivity disorder on risk of AR by MR method, but, MR pleiotropy residual outlier test suggested that attention deficit/hyperactivity disorder is negatively associated with AR after outlier correction (OR=0.976, 95%CI: 0.958-0.995, P=0.012). Conclusions: This MR study indicated that AR was a causal risk factor for bipolar disorder and major depressive disorder, but not for other psychiatric disorders. Bipolar disorder and attention deficit/hyperactivity disorder may be a protective factor for AR. Further studies could be carried out to leverage these new found insight into better clinical and experimental research in AR and psychiatric disorders.

Background and Purpose As of 5 March 2021, coronavirus disease 2019 (COVID-19) has infected more than 116 million people worldwide, with over 91 million convalescent patients. A decrease in function of multiple organs has been reported in recovering patients. In China, traditional Chinese medicine (TCM) is recommended to treat patients in the rehabilitation period; however, its efficacy and safety still need to be confirmed. Experimental Approach We conducted a multicentre, double-blind, randomised controlled trial that recruited patients with COVID-19 during the rehabilitation period. In total, 131 patients were randomly divided into two groups: 66 in the Bufei Huoxue capsules (BFHX)-treated group and 65 in the control group. BFHX was administered orally three times a day (1.4g/dose) for 90 days, and the control group was administered placebo for 90 days. The primary endpoint was to evaluate improvements in fatigue symptoms and exercise tolerance. Key Results After three months of treatment, the six-minute walk distance (6MWD) of the BFHX-treated group was significantly longer than that of the control group, compared to baseline. The Fatigue Assessment Inventory (FAI) was lower in the BFHX-treated group than in the control group. Adverse event rates were higher in the BFHX-treated group, but there was no statistical difference between groups. Conclusions and Implications BFHX may have strong rehabilitative effects on patients recovering from COVID-19 in terms of improvements in physiological activities, such as fatigue symptoms and exercise tolerance. The drug has proven to have favourable safety and effectiveness profiles.

Background Understanding asthmatic airway structural changes and the bronchodilator responses may help unravel targets for intervention. However, structural abnormalities of asthmatic airways with different disease severity and the major anatomical site of bronchodilator responses have not been well elucidated. We aim to evaluate the airway remodeling characteristics and the bronchodilator responses in medium-sized and small airways of asthma. Methods We recruited 104 asthmatic patients and 31 non-smoking control subjects to compare the airway inner area (Ai) and airway wall area percentage (Aw%) with endobronchial optical coherence tomography. We also enrolled 32 patients with moderate-to-severe asthma to dynamically assess the airway morphological changes after salbutamol inhalation. Results More prominent airway structural abnormalities correlated with greater asthma severity, evidenced by the decreased Ai and greater Aw% in medium-sized and small airways. Patients with mild asthma yielded comparable Ai but greater Aw% than control subjects. Salbutamol inhalation led to a rapid dilatation of both medium-sized and small airways, the lung function improvement correlated significantly with the increase in Ai of the medium-sized, but not small, airways at 15 min. Conclusion Luminal narrowing and airway wall thickening of the medium-sized and small airways are present in mild asthma and reflect asthma severity, lending support to the use of anti-imflammatory intervention in mild asthma. The medium-sized airways are the crucial site of the bronchodilator responses, providing the scientific rationale for future development of more effective delivery of inhaled medications for asthma.

Changes in sensitization rates in patients with asthma and/or rhinitis in China between 2008 and 2018: a national cross-sectional studyWanjun Wang1*, Jianhong Wang2*, Guihua Song3*, Hua Xie4*, Xiaoping Lin4*, Ruonan Chai4*, Rongfei Zhu5*, Yong He6*, Jun Tang7*, Junge Wang8*, Jinghua Yang9*, Lili Zhi10*, Lin Wu11*, Yan Jiang12*, Xiaoqin Zhou13*, Dongming Huang14*, Ning Wang15*, Rui Xu16*, Yuan Gao17*, Zhimin Chen18*, Jinling Liu18*, Xiaoli Han19*, Guolin Tan20*, Jinzhun Wu21*, Deyu Zhao22*, Jianjun Chen23*, Xiwei Zhang24*, Mengrong Li24*, Yuemei Sun25*, Yi Jiang26*, Weitian Zhang27*, Qianhui Qiu28*, Chuanhe Liu29*, Jie Yin30*, Guodong Hao31*, Huabin Li32*, Yongsheng Xu33*, Shaohua Chen34*, Hua Zhang35, Shi Chen36, Juan Meng37, Dan Zeng38, Wei Tang39, Chuangli Hao40, Jing Li1†, Nanshan Zhong1†, for the China Alliance of Research on Respiratory Allergic Disease*Contributed equally†Joint corresponding authors1 National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University;2 The First People’s Hospital of Yibin, Sichuan;3 The First Affiliated Hospital of Henan University of Traditional Chinese Medicine;4 General Hospital of Northern Theater Command;5 Tongji Hospital, Tongji Medical College, Huazhong University of Science&Technology;6 The Affiliated Hospital of Medical School, Ningbo University;7 Foshan First people’s hospital;8 Beijing Hospital of Traditional Chinese Medicine;9 GuangDong Provincial Hospital of Chinese Medicine;10 The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases;11 Hangzhou Hospital of Traditional Chinese;12 The Affiliated Hospital of Qingdao University;13 Hubei Province Maternal and Child Health Hospital;14 Boai Hospital of Zhongshan City;15 Xi’an Children’s Hospital;16 The First Affiliated Hospital of Sun-Yat University;17 The First Affiliated Hospital of Zhengzhou University;18 Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health;19 Hebei General Hospital;20 Third Xiangya Hospital of Central South University;21 The Women and Children’s Hospital affiliated to Xiamen University;22 Children’s Hospital of Nanjing Medical University;23 Union hospital of Tongji medical college;24 The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University;25 Yu Huang Ding Hospital;26 The First Hospital of Shanxi Medical University;27 Shanghai Jiao Tong University Affiliated Sixth People’s Hospital;28 Zhujiang Hospital of Southern Medical University;29 Children’s Hospital Capital Institute of Pediatrics;30 Chengdu First People’s Hospital;31 Tangshan Gongren Hospital;32 ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University;33 Children’s Hospital of Tianjin University;34 Guangdong Provincial People’s Hospital;35 The First Affiliated Hospital of Xinjiang Medical University;36 Hainan provincial people’s Hospital;37 West China Hospital of Sichuan University;38 Chongqing General Hospital, University of Chinese Academy of Sciences;39 Ruijin Hospital of Shanghai Jiaotong University;40 Children’s Hospital of Soochow University.

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increase in pulmonary artery pressure, which eventually develops to right heart failure and death. Though newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, the fact that limited types of effective and economical drugs for PH is available still makes it as a life-threatening disease. Some drugs from Chinese Materia Medica are traditionally applied in treating lung diseases. Accumulating evidence suggests the active pharmaceutical ingredients (APIs) derived from those medicines have brought prospective future for prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which is potent in treating PH, aiming at bringing new ideas in initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

Abstract: Background: The diagnosis of COVID-19 relies mainly on viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis. SARS-CoV-2-specific antibody detection is convenient, safe, and highly sensitive. IgM and IgG are commonly used to serologically diagnose COVID-19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS-CoV-2-specific IgM, IgA, and IgG antibodies, identify changes in them based on COVID-19 severity, and establish the significance of combined antibody detection. Methods: COVID-19 patients, divided into a severe & critical group and a moderate group, and non-COVID-19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS-CoV-2-specific IgM, IgA, and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results, and other data were recorded for all patients. Results: Compared to the traditional IgM–IgG combined antibodies, IgA–IgG combined antibodies are better for diagnosing COVID-19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID-19 patients than in non-COVID-19 patients. IgA and IgG were also higher for severe & critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Conclusions: Detection of SARS-CoV-2-specific combined IgA–IgG antibodies is advantageous in diagnosing COVID-19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity.