Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19

BackgroundEffective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. MethodIn this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. ResultsA total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. ConclusionsAlthough randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating 102 the COVID-19 pandemic.

Effects of triptolide on serum cytokine levels, symptoms and pulmonary function in patients with steroid- resistant asthma / 中国病理生理杂志

AIM: To evaluate the influences of triptolide on serum cytokines, symptoms and pulmonary function in patients with steroid - resistant asthma, so as to investigate if there is therapeutic effect of triptolide on these patients. METHODS: Sixteen patients with steroid - resistant asthma were randomly divided into two groups (A and B, n =8 for each group). All of the patients took procaterol (50 - 100 μg/d) and theophylline (400 mg/d) orally as baseline treatment. Additionally, triptolide was prescribed for group A (33 μg, orally, three times per day for 4 weeks). Asthmatic symptom score calculation, serum cytokines ( interferon - γ, IFN - γ; interleukin - 4, IL - 4; and interleukin - 5, IL - 5)determination and pulmonary function test (FVC%, FEV1%, PEF%, V50% and V25% ) were undertaken before and at the end of the study. RESULTS: At baseline, no significant difference was found between group A and group B with respect to the above mentioned indices. Following the administration of triptolide, group A had significantly increased serum IFN -γlevel, FVC%, FEV1%, PEF%, V50% and V25%, and significantly decreased asthmatic symptom score and serum IL-4, IL-5 levels (P＜0.01 compared with baseline in the same group, and P＜0.05 compared with group B at the end of the study). Compared with baseline, no significant change was observed for group B regarding all the indices at the end of the study. CONCLUSION: Triptolide in combination with procaterol and theophylline may be a novel and effective strategy for the treatment of steroid - resistant asthma.

Pulmonary function in patients with type 2 diabetes mellitus / 中国病理生理杂志

AIM: To evaluate the pulmonary function in patients with type 2 diabetes mellitus in order to identify whether the lung is a target organ of chronic pathologic changes in diabetes mellitus. METHODS: Pulmonary ventilation function and diffusion capacity were studied in 107 patients with type 2 diabetes mellitus and 61 healthy subjects matched for age and sex. Glycosylated hemoglobin (HbA1c), urine albumin excretion rate (AER), fundus examination and nerve conduction velocity were included as parameters of glycemic control and diabetic microangiopathies. RESULTS: Pulmonary ventilation function was similar in type 2 diabetic group and the control. Compared with the control, carbon monoxide diffusion capacity (DLCO) and DLCO corrected by alveolar volume (DLCO/VA) were significantly lower in type 2 diabetic group (P<0.05). DLCO and DLCO/VA were inversely correlated with microangiopathy score (r: -0.291, -0.324, respectively, P<0.01). Furthermore, DLCO/VA was negatively correlated with age and duration of diabetes mellitus (r: -0.269, -0.236, respectively, P<0.05). CONCLUSIONS: Pulmonary ventilation function is normal in patients with type 2 diabetes mellitus, but their diffusion capacity is impaired. It suggests that the lung may also be the target organ of the chronic pathologic changes of diabetes mellitus.

Digestive system manifestations in patients with severe acute respiratory syndrome / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To explore digestive system manifestations in patients with severe acute respiratory syndrome (SARS).</p><p><b>METHOD</b>The clinical data of 96 cases with SARS admitted into our hospital from February 6, 2003 to March 28, 2003 were retrospectively analyzed.</p><p><b>RESULTS</b>Among the 96 cases, 26 cases (27%) had diarrhea, 17 (18%) had nausea, 6 (6%) had vomiting, 16 (17%) had bellyache, and 8 (8%) had ALT elevation.</p><p><b>CONCLUSIONS</b>Patients with SARS may have digestive system manifestations; diarrhea is the most common symptom.</p>

Ventilation of wards and nosocomial outbreak of severe acute respiratory syndrome among healthcare workers / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To identify valid measures for preventing outbreaks of severe acute respiratory syndrome (SARS) among protected healthcare workers in isolation units.</p><p><b>METHODS</b>Architectural factors, admitted SARS cases and infection of healthcare workers in different isolation wards between January 30 and March 30, 2003 were analyzed.</p><p><b>RESULTS</b>Four types of isolation wards were analyzed, including the ward where the thirty-first bed was located on the twelfth floor, the laminar flow ward in the Intensive Care Unit where the tenth bed was located on the fifteenth floor, the ward where the twenty-seventh bed was located on the thirteenth floor of the Lingnan Building, and thirty wards on the fourteenth to eighteenth floors of the Zhongshan Building. The ratios (m(2)/m(3)) of the area of the ventilation windows to the volume of the rooms were 0, 0, 1:95 and 1:40, respectively. Numbers of SARS cases in the wards mentioned above were 1, 1, 1 and 96, respectively. Total times of hospitalization were 43, 168, 110 and 1272 hours, respectively. The infection rates of the healthcare workers in the areas mentioned above were 73.2%, 32.1%, 27.5% and 1.7%, respectively. The difference in the infection rates was of statistical significance.</p><p><b>CONCLUSIONS</b>Isolating SARS cases in wards with good ventilation could reduce the viral load of the ward and might be the key to preventing outbreaks of SARS among healthcare workers along with strict personal protection measures in isolation units.</p>

A hospital outbreak of severe acute respiratory syndrome in Guangzhou, China / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To describe a hospital outbreak of severe acute respiratory syndrome (SARS) and summarize its clinical features and therapeutic approaches.</p><p><b>METHODS</b>The outbreak started with a SARS patient from the community, and a total of 96 people (76 women and 20 men, mean age (29.5 +/- 10.3) years, 93.8% of whom were health care workers) who had exposure to this source patient became infected in a short time. Clinical data in this cohort were collected prospectively as they were identified.</p><p><b>RESULTS</b>(1) The incubation period ranged from 1 to 20 (mean: 5.9 +/- 3.5) days. The duration of hospitalization was (17.2 +/- 8.0) days. (2) The initial temperature was (38.3 +/- 0.6) degrees C, while the highest was (39.2 +/- 0.6) degrees C (P < 0.001), with fever duration of (9.0 +/- 4.2) days. (3) Other most common symptoms included fatigue (93.8%), cough (85.4%), mild sputum production (66.7%), chills (55.2%), headache (39.6%), general malaise (35.4%) and myalgia (21.9%). (4) The radiographic changes were predominantly bilateral in the middle or lower lung zones. The number of affected lung fields was 1.2 +/- 0.8 on presentation, which increased to 2.9 +/- 1.4 after admission (P < 0.001). The interval from the beginning of fever to the onset of abnormal chest radiographs was (3.5 +/- 2.3) days, which increased in size, extent, and severity to the maximum (6.7 +/- 3.5) days later. The time before the lung opacities were basically absorbed was (14.9 +/- 7.8) days. (5) Leukopenia was observed in 67.7% of this cohort. The time between the onset of fever and leukopenia was (4.4 +/- 2.3) days, with the lowest white blood cell count of (2.80 +/- 0.72) x 10(9)/L. (6) The lowest arterial oxygen saturation was (94.8 +/- 3.1)% with supplementary oxygen. (7) Antibiotical therapies included tetracyclines (91.0%), aminoglycosides (83.3%), quinolones (79.2%); 18.8% of the patients received a combination of tetracyclines and aminoglycosides, while 11.5% received a combination of tetracyclines and quinolones, and 63.5% received a combination of tetracyclines, aminoglycosides and quinolones. Vancomycin was used in 13.5% of the patients. (8) 68.8% of the patients were treated with methylprednisolones for a mean interval of (4.9 +/- 2.4) days. The initial dose was (67.3 +/- 28.2) mg/d and the maximal dose was (82.4 +/- 30.5) mg/d. (9) Human gamma-globulin, interferon-alpha, antiviral drugs (oral ribavirin or oseltamivir) were used respectively in 68.6%, 46.9% and 92.7% of the patients. (10) Ninety-five patients (99.0%) had a complete clinical recovery, and only 1 patient (1.0%) died.</p><p><b>CONCLUSIONS</b>SARS appears to be quickly infectious and potentially lethal among health care workers, characterized by acute onset and rapid progression, and mostly bilateral lung involvement on chest radiographs. Proper administration of glucocorticosteroids seems to be of some benefits. Antibiotics, human gamma-globulin, interferon-alpha, and antiviral drugs, although empirically, might be useful to shorten the clinical course.</p>

Correlation between intracellular magnesium and expression of beta 2-adrenergic receptor mRNA in the lung of C57BL/6 asthmatic mice / 中国病理生理杂志

0.05,respectively).Plasma Mg2+,intracellular Mg2+,the beta 2-AR mRNA and protein in lung tissue in group C at 21st d and 34th d were significantly higher than those in group A at 21st d and 34th d 21st d:(0.84?0.09)mmol/L vs 0.57?0.10)mmol/L,(2.39?0.14)mmol/L vs(2.11?0.08)mmol/L,(0.75?0.09)pmol/g vs(0.59?0.06)pmol/g,(88.50?8.50)pmol/g vs(60.10?7.70)pmol/g,P