Validation of a standardized version of the Asthma Quality of Life Questionnaire.

BACKGROUND: In the original 32-item Asthma Quality of Life Questionnaire (AQLQ), five activity questions are selected by patients themselves. However, for long-term studies and large clinical trials, generic activities may be more appropriate. METHODS: For the standardized version of the AQLQ, the AQLQ(S), we formulated five generic activities (strenuous exercise, moderate exercise, work-related activities, social activities, and sleep) to replace the five patient-specific activities in the AQLQ. In a 9-week observational study, we compared the AQLQ with the AQLQ(S) and examined their measurement properties. Forty symptomatic adult asthma patients completed the AQLQ(S), the AQLQ, the Medical Outcomes Survey Short Form 36, the Asthma Control Questionnaire, and spirometry at baseline, 1, 5, and 9 weeks. RESULTS: Activity domain scores (mean +/- SD) were lower with the AQLQ (5.7 +/- 0.9) than with the AQLQ(S) (5.9 +/- 0.8; p = 0.0003) and correlation between the two was moderate (r = 0.77). However, for overall scores, there was minimal difference (AQLQ, 5.4 +/- 0.8; AQLQ(S), 5.5 +/- 0.8; r = 0.99). Reliability (AQLQ intraclass correlation coefficient, 0.95; AQLQ(S) intraclass correlation coefficient, 0.96) and responsiveness (AQLQ, p < 0.0001; AQLQ(S), p < 0.0001) were similar for the two instruments. Construct validity (correlation with other measures of health status and clinical asthma) was also similar for the two instruments. CONCLUSIONS: The AQLQ(S) has strong measurement properties and is valid for measuring health-related quality of life in asthma. The choice of instrument should depend on the task at hand.     

Anti-inflammatory and analgesic effects of Daphne retusa Hemsl

Daphne retusa Hemsl. belongs to the genus Daphne, a member of Thymelaeaceae family. The barks and stems of Daphne retusa are used as a folkloric medicine 'Zhu Shi Ma' in Western China because of its effects of detumescence and acesodyne. In this paper, we investigate the anti-inflammatory and analgesic effects of the 75% ethanol extract of the stems and barks of Daphne retusa and different fractions partitioned with petroleum ether, methylene chloride, ethyl acetate and n-butanol, respectively. The anti-inflammatory effects were evaluated using xylene-induced ear oedema in mice and carrageenan-induced paw oedema in rats, while the acetic acid-induced writhing test and hot-plate test as models for evaluating the centrally and peripherally analgesic activity. The results showed the plant has significant anti-inflammatory and analgesic effects (P<0.05-0.01). Meanwhile, the result of the acute toxicity test at which the MTD was above 5g/kg indicates that the plant extract is relatively safe in, and/or non-toxic to, mice. The findings of these experimental animal studies indicate that the Daphne retusa ethanol extract possesses anti-inflammatory and analgesic properties, and thus provide pharmacological support to folkloric, ethnomedical uses of 'Zhu shima' in the treatment and/of management of anti-inflammatory and painful conditions in China.     

Cryosurgery for malignant endobronchial tumors: analysis of outcome

STUDY OBJECTIVES: More than 80% of patients with lung cancer are unsuitable for curative surgical treatment. Palliative relief of symptoms, often caused by airway obstruction, is very important. Endobronchial cryosurgery is used for destruction of intraluminal tumors. This study analyzes the effects of cryosurgery on patients with obstructive endobronchial carcinoma. DESIGN: Retrospective analysis of data extracted from a prospective computerized database. SETTING: Tertiary referral thoracic surgical center. PATIENTS: Data of the 172 patients who underwent at least two sessions of endobronchial cryosurgery (group A) were compared with 157 patients who underwent one session of cryosurgery (group B) for malignant primary or metastatic obstructive lung carcinoma over a 5-year period. INTERVENTION: Endobronchial cryosurgery is performed under general anesthesia. A nitrous oxide cryoprobe is inserted through a rigid bronchoscope. The probe achieves a temperature of - 70 degrees C at its tip and is applied to the tumor for two 3-min periods. Statistical analysis assessed the effects of cryosurgery on symptoms, lung function, Karnofsky performance score, and survival. RESULTS: Symptoms of dyspnea, cough, and hemoptysis were significantly reduced in both groups after cryosurgery (p < 0.001), although group A benefited more than group B. Lung function test results improved significantly in group A. The mean Karnofsky performance score (+/- SD) increased from 67 +/- 9 to 74 +/- 10 (group A) and from 67 +/- 10 to 73 +/- 11 (group B). The mean survival was 15 months (median, 11 months) for group A and 8.3 months (median, 6 months) for group B (p = 0.006). Univariate regression analysis showed that no particular patient or tumor characteristic was associated with reduction of symptoms. Patients who had cryosurgery and external beam radiotherapy showed longer survival (p < 0.01). Females and patients with stage IIIa and IIIb tumors achieved significantly improved Karnofsky scores (p < 0.02). Female sex was also a factor for increase in FEV at 1 min (p = 0.003) and FVC (p < 0.001). CONCLUSIONS: Cryosurgery is a safe method for palliation of endobronchial malignancies causing airway obstruction. Statistical analysis showed improvement of dyspnea, cough, and hemoptysis. Cryosurgery can be considered in patients with inoperable obstructive endobronchial carcinoma.     

小剂量舒利迭联合罗红霉素治疗支气管哮喘疗效观察

目的 观察小剂量舒利遮联合罗红霉素治疗支气管哮喘的临床疗效.方法 将符合诊断标准的98例患者分为观察组(n=49)和对照组(n=49).对照组应用综合疗法和吸入小剂量舒利迭(丙酸氟替卡松/沙美特罗干粉剂TM50μg/100μg),观察组在此基础上加用罗红霉素(5mg/(kg·d)).     

Variability in asthma severity in pediatric subjects with asthma previously receiving short-acting beta2-agonists

OBJECTIVE: An analysis of 5 double-blinded, randomized, 12-week asthma trials was undertaken to evaluate pediatric subjects (4 to 11 years; n=276) who were previously receiving short-acting beta2-agonists alone and subsequently received treatment with placebo. At baseline, all subjects met National Asthma Education and Prevention Program criteria for moderate/severe asthma. STUDY DESIGN: Asthma severity was categorized individually for symptoms, albuterol use, and morning peak expiratory flow and then overall taking into account all three parameters. RESULTS: Subjects spent the majority of weeks (55%) in the moderate/severe category. Subjects spent approximately 48%, 31%, and 22% of weeks in intermittent, mild, and moderate/severe categories and 57%, 27%, and 15% of weeks, respectively, based on asthma symptoms and albuterol use. Subjects spent approximately 62%, 31%, and 8% of weeks in intermittent/mild, moderate, and severe categories, based on peak expiratory flow; however, >35% of subjects exhibited >or=15 changes in asthma severity classification, based on peak expiratory flow. CONCLUSIONS: Asthma is a disease with varying symptomatology, and pediatric subjects frequently move between severity categories, especially in children with inadequate asthma control. These data also emphasize that asthma severity cannot be determined in many pediatric subjects by discrete, point-in-time assessments of lung function, albuterol use, or asthma symptoms. Failure to recognize this problem may contribute to underestimation of disease severity in pediatric subjects.     

Targeting airway inflammation in asthma: current and future therapies

Asthma is a chronic inflammatory disease of the airway that requires long-term antiinflammatory therapy. Inhaled corticosteroids (ICSs) are recommended for first-line treatment of persistent disease, but not all patients achieve asthma control even when these agents are used in high doses and in combination with other medications, including a long-acting beta(2)-agonist or a leukotriene modifier. Such patients may require additional therapy. As information about asthma pathophysiology and inflammatory phenotypes continues to increase, and additional antiinflammatory options become available, it may be possible to target antiinflammatory therapy to various aspects of the disease and consequently to improve the treatment of patients with inadequate responses to standard ICS-based therapy. Several novel antiinflammatory therapies are in different stages of clinical development. The most clinically advanced of these is omalizumab, a recombinant humanized monoclonal antibody that specifically targets IgE and is indicated for patients with moderate-to-severe asthma caused by allergies. Omalizumab has demonstrated efficacy in patients with moderate-to-severe asthma and documented evidence of allergen sensitivity. Other key therapy options in clinical development either target proinflammatory cytokines (eg, interleukin-4 and tumor necrosis factor-alpha) or inflammatory cells (eg, T-helper type 2 cells and eosinophils). This review provides an overview of the current and future approaches targeting airway inflammation in patients with asthma.     

Non‐isothermal Crystallization Kinetics of Biobased Poly(ethylene 2,5‐furandicarboxylate) Synthesized via the Direct Esterification Process

Poly(ethylene 2,5‐furandicarboxylate) (PEF) is an emergent biobased polyester whose chemical structure is analogous to poly(ethylene terephthalate). Pilot‐scale PEF is synthesized through the direct esterification process from 2,5‐furandicarboxylic acid and bio‐ethylene glycol. Wide‐angle X‐ray diffraction (WAXD) measurements reveal similar crystallinities and unit cell structures for melt‐crystallized and glass‐crystallized samples. The non‐isothermal crystallization of PEF sample is investigated by means of DSC experiments both from the glass and the melt. The temperature dependence of the effective activation energy of the growth rate is obtained from these data, and the results show that the glass and early stage of the melt crystallization share common dynamics. Hoffman–Lauritzen parameters and the temperature at maximum crystallization rate are evaluated. It is found that the melt‐crystallization kinetics undergo a transition from regime I to II; however, the crystal growth rate from the melt shows an atypical depression at T < 171 °C compared with the predicted Hoffman–Lauritzen theory.

     

清开灵注射液联合亚胺培南西司他丁钠治疗老年重症肺炎的临床研究

目的 基于网络药理学的方法探索银翘解毒软胶囊治疗新型冠状病毒肺炎（COVID-19）的作用机制。方法 将银翘解毒软胶囊所含1 418个化合物与48个COVID-19炎症相关靶蛋白进行分子对接,构建药物-靶蛋白网络,阐明银翘解毒软胶囊的关键活性成分和潜在作用靶点。结果 通过网络分析获得银翘解毒软胶囊的活性成分有50个,主要为黄酮类和三萜类化合物;潜在作用靶点37个,主要为MTOR、JAK3、ACE、ACE2、PIK3CA、TNF、AKT2和MAP2K1等炎症靶点。分子对接结果显示连翘酯苷及牡荆素-2″-O-鼠李糖苷与新型冠状病毒（SARS-CoV-2）3CL水解酶具有较好的亲和力,甘草酸与血管紧张素转化酶II（ACE2）具有较好的亲和力。结论 银翘解毒软胶囊通过干扰SARS-CoV-2病毒复制、调节炎症信号通路表达及炎症因子分泌发挥治疗COVID-19作用。     

Accelerated reactivity of blood granulocytes in patients with atopic bronchial asthma out of exacerbation

Reactive oxygen species (ROS) are important in bronchial asthma (BA) pathogenesis owing to accumulation of activated granulocytes in the lungs. But the ROS-producing activity of the cells is insufficiently understood in the blood of BA patients. This study analyzes the kinetics of phagocyte respiratory burst in the blood to improve the methods of BA patients monitoring. Patients with atopic BA out of exacerbation (n = 60) and healthy controls (n = 43) were recruited. The time-course of respiratory response to opsonized zymosan (OZ) was recorded in the whole blood using luminol-dependent chemiluminescence (CL), and its activation kinetics (lag-time, rate, amplitude, ROS production) was calculated. The discriminative power of ROS generation kinetics was defined by Receiver Operating Characteristic (ROC) curve analysis. Standard physiological respiratory parameters of patients did not differ from the controls. More rapid response to OZ was recorded in BA patient samples versus the controls. The primed state of phagocytes in the blood of BA patients was corroborated by significant weakening formyl peptide priming effect. The adhesion of granulocytes to cultured human endothelial cells was two-fold higher in BA patients versus controls. ROC curve analysis exhibited good discriminative effectiveness of the CL kinetics to compare BA individuals with the controls. The highest power (86% sensitivity and 90% specificity) was achieved at a linear combination of the parameters. We assume that the assessment of phagocyte reactivity based on the analysis of the response kinetic profile is a good test for monitoring of the state in BA patients.