Profile of the ProAxsis active neutrophil elastase immunoassay for precision medicine in chronic respiratory disease

Introduction: Neutrophil elastase (NE) is a 29kDa serine protease released from the azurophilic granules of neutrophils. It may be directly involved in the pathogenesis and disease progression in cystic fibrosis, bronchiectasis and COPD through the degradation of airway elastin and by impairing host defence.

Areas covered: Measurement of NE activity has emerged as a promising biomarker strategy in inflammatory lung disease. The authors review studies where NE activity has been linked with clinical outcomes such as lung function decline, exacerbation frequency or other cross-sectional and longitudinal markers of disease severity. In this article the evidence for NE measurement, and the strengths and weaknesses of a commercially available immunoassay which can specifically detect NE activity in human biological samples such as sputum and bronchoalveolar lavage are reviewed.

Expert commentary: NE is a promising biomarker for stratifying severity disease. NE also appears to be responsive to antibiotic and other treatments, potentially therefore allowing it to be used as an indicator of treatment response in clinical trials.     

Activation of polymorphonuclear neutrophils by immune complex: possible involvement in development of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a serious side-effect of transfusion. We presumed that immune complex (IC)-activated polymorphonuclear neutrophils (PMNs) are involved in the development of TRALI. The aim of this study is to examine the various effects of ICs on normal human PMNs. ICs used here were artificially formed by combining soluble human leucocyte antigen (HLA) class II-positive serum and anti-HLA class II antiserum. The abilities of ICs to trigger PMNs and induce the production of soluble mediators and the involvement of the Fc receptor (FcR) in the activation of PMNs by ICs were investigated. Moreover, the ability of the culture supernatant of PMNs incubated with ICs regarded to induce the apoptosis of lung microvascular endothelial (LME) cells was examined. The results proved that PMNs are triggered by ICs resulting in the acceleration of the production of tumour necrosis factor-alpha (TNF-alpha), perforin and Fas ligand, in which FcR on PMNs appears to be involved. Furthermore, the culture supernatants of PMNs cultured with ICs were revealed to induce the apoptosis of LME cells. In conclusion, the ICs used here were proved to induce PMNs to release cytotoxic factors upon activation. These results suggest that ICs are mediators of the development of TRALI.     

Early postnatal dexamethasone for the prevention of chronic lung disease in high-risk preterm infants

Objective: The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease (CLD) in high risk preterm infants and to evaluate the side effects of the early steroid administration. Design: Randomised clinical trial. Setting: Neonatal intensive care unit. Patients: 50 infants at high risk of CLD were randomly assigned after 72 h of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg per day for the first 3 days, 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day). The control group received no steroid treatment. Results: The incidence of CLD at 28 days of life and at 36 weeks' postconceptional age was significantly lower in the dexamethasone group than in the control group (p < 0.001). Moreover, infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group (p < 0.001). Hyperglycaemia, hypertension, growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration. Conclusions: Early dexamethasone administration may be useful in preventing CLD, but its use should prudently be restricted to preterm infants at high risk of CLD. Received: 31 December 1998 Accepted: 19 April 1999     

脉冲振荡法测定慢性阻塞性肺病呼吸阻抗的应用价值探讨

目的：探讨呼吸阻抗对慢性阻塞性肺病的诊断价值。方法：185例健康人和446例慢性阻塞性肺病患者进行脉冲振荡肺功能测定，并与常规肺通气功能比较。结果：慢性阻塞性肺病患者与健康人相比，呼吸总阻抗、周边阻力、共振频率、总气道阻力、周边气道阻力均显著增高，电抗明显降低，仅电抗随慢性阻塞性肺病严重程度增加而降低。慢性阻塞性肺病患者呼吸总阻抗、周边阻力、共振频率、总气道阻力、周边气道阻力与肺通气功能呈负相关，电抗呈正相关，共振频率的相关性最为密切。以共振频率〉15Hz为标准诊断慢性阻塞性肺病时，其灵敏度、特异度综合判断为最好的脉冲振荡肺功能指标。R实测值／预计值（％）〉150％者灵敏度高。结论：脉冲振荡肺功能测定可用于慢性阻塞性肺病的诊断，共振频率为诊断慢性阻塞性肺病气流受限最敏感的指标，电抗是判断慢性阻塞性肺病严重程度的最好指标。     

广汉市慢性代谢性疾病与慢性肾脏病患病情况调查

目的调查广汉市18岁以上慢性代谢性疾病与慢性肾脏病（chronickidnerydisease,CKD）的患病情况。方法抽取广汉市18岁以上常住居民1650人,通过问卷调查、实验室检查等了解CKD、代谢综合征（metabolicsyndrome,Ms）及其相应组分的患病情况。结果在资料完善的1514名调查对象中,CKD患病率为25．1％,高血压患病率为15．35％,糖尿病患病率为6．75％,高脂血症患病率为55．85％,高尿酸血症11．56％,肥胖症患病率为10．48％,MS患病率为8．84％。结论广汉市慢性代谢性疾病及CKD有较高的患病率,应提高相应的筛查及防范工作。     

Plasminogen receptors and their role in the pathogenesis of inflammatory,autoimmune and malignant disease

Summary. Plasminogen is the proenzyme of plasmin, the key protease of the fibrinolytic system, but its role is not limited to fibrinolysis regulation. Plasminogen binds not only to fibrin, but also to different receptors on cell surfaces, including the heterotetrameric complex Annexin A2‐S100A10, enolase‐1, histone H2B and the plasminogen receptor Plg‐R_KT. These receptors localize plasmin generation to the cell surface and provide a broad spectrum of reactions including proteolytic activity, cell migration and recruitment as well as signaling pathway activation. These plasminogen‐binding proteins are involved in both physiologic and pathologic processes such as inflammation, thrombosis and cancer. Thus, plasminogen is at the center of a complex tightly controlled and regulated system where plasminogen‐binding proteins have a crucial role, suggesting new therapeutic and diagnostic strategies. This review will discuss currently available information on plasminogen receptors, particularly their mechanisms of action and their roles in inflammatory, autoimmune and malignant disease.     

The effects of home-based pulmonary rehabilitation in patients with chronic lung disease

The purpose of this study was to examine the effects of a home-based pulmonary rehabilitation program on lung function, dyspnea, exercise tolerance, and quality of life in 23 Koreans with moderate to severe chronic lung disease. The outcome measures were forced expiratory volume in 1 s (FEV₁, % predicted), Borg score, 6 min walking distance (6 MWD), and chronic respiratory disease questionnaire (CRDQ). Experimental group (n=15) performed the 8-week home-based pulmonary rehabilitation program, composed of inspiratory muscle training, upper and lower extremity exercise, relaxation, and telephone visit. Patients in control group (n=8) were only given educational advice. The experimental group showed a lower level of exertional dyspnea, more exercise tolerance, and greater improvement in health-related quality of life than the control group (p<0.05). Lung function was not statistically different. This study yielded evidence for the beneficial effects of home-based pulmonary rehabilitation program.     

Management of chronic lung disease infants in the community

The aim of this study is to review the current home oxygen weaning programme used in the past 6 years by the Community Neonatal Nurses, in order to improve or maintain current practice. The study was done retrospectively, by reviewing data of infants discharged from the neonatal unit based in London, United Kingdom and weaned off oxygen by the Community Neonatal Nurses. At least 65/108 (60%) infants were weaned off home oxygen within the 1st year of life.     

Treatment of respiratory failure using minitracheotomy and intratracheal oxygenation in selected patients with chronic lung disease

Objective To evaluate the efficacy of minitracheotomy (MT) insertion for intratracheal oxygen insufflation (ITO₂) on arterial blood gases and survival in patients with respiratory failure from chronic lung disease.Design Open, prospective clinical study.Setting A 12-bed medical intensive care unit in a non-university hospital.Patients 20 patients (14 males and 6 females, mean age 74.8±2.6 years), admitted for respiratory failure and denied mechanical ventilation.Intervention Percutaneous insertion of an MT for ITO₂ Arterial blood gases were drawn just prior to, then 3, 24, 48 h and 1 week after MT insertion. Data are evaluated with a two-way analysis of variance for distribution-free data (Friedman's rank sums test).Measurments and results Three hours after starting ITO₂, the partial pressure of oxygen in arterial blood (PaO₂) and the arterial oxygen saturation (SaO₂) both increased from 51.7±2.8 to 85.4±5.6 mmHg and from 79.7±3.1 to 93.7±0.9%, respectively (p<0.001 for both), along with a slight worsening in the partial pressure of carbon dioxide in arterial blood (PaCO₂), from 59.6±2.5 to 63.5±3.0 mmHg (p<0.05). At 1 week, improvements in PaO₂ and SaO₂ were maintained in all patients, while PaCO₂ decreased in 14 patients (mean decrease 8.3 mmHg) and increased in the remaining patients (mean 12.5 mmHg), when compared to pre-ITO₂ values. Seven patients died during follow-up, leading to a success rate of 65%. Eight and 4 patients were discharged home and to a nursing home, respectively, 9 still receiving ITO₂ via MT as chronic oxygen therapy.Conclusion Our results suggest that MT insertion for ITO₂ may be a therapeutic option in selected patients with respiratory failure from CLD.     

慢性阻塞性肺疾病稳定期病人的肺功能康复护理进展

总结有关慢性阻塞性肺疾病稳定期肺功能康复护理方面的进展，对康复评定、主要措施及健康教育进行重点阐述。     

慢性阻塞性肺疾病稳定期病人的肺功能康复护理进展

总结有关慢性阻塞性肺疾病稳定期肺功能康复护理方面的进展,对康复评定、主要措施及健康教育进行重点阐述。     

甲泼尼龙对慢性阻塞性肺疾病患者C-反应蛋白和肺功能的影响

目的研究甲泼尼龙对慢性阻塞性肺疾病患者C-反应蛋白（CRP）和肺功能影响。方法慢性阻塞性肺疾病急性发作期患者随机分为两组,治疗组加用甲泼尼龙治疗,观察治疗前后肺功能和血清CRP变化。结果两组治疗后均能降低血清CPR,改善患者肺功能指标,且治疗组优于对照组。结论甲泼尼龙可显著抑制慢性阻塞性肺疾病急性发作期患者气道炎性反应,并显著改善肺功能。     

肺超声联合超声弹性成像技术评价结缔组织病相关间质性肺疾病研究进展

结缔组织病相关间质性肺病（CTD-ILD）发病率和死亡率均高，早发现、早治疗是控制CTD-ILD进展的关键。目前，肺超声（LUS）及超声弹性成像（UE）用于临床评估CTD-ILD，其中常规灰阶超声可观察B线、胸膜不规则等异常改变，UE可发现肺表面组织的弹性改变。本文对LUS及UE在CTD-ILD中的应用价值及研究进展进行综述。     

Glucocorticoid modulation of muscarinic and β-adrenergic receptors in guinea pig lung

Summary— We investigated the effect of the in vivo treatment of guinea pigs with methylprednisolone, 10 mg/kg daily, on lung muscarinic and β-adrenergic receptors. Receptor densities were assessed by saturation experiments of tritiated N-methylscopolamine and dihydroalprenolol binding to lung membranes. After 3 h of treatment, methylprednisolone induced a decrease of 19.2% ( P < 0.05) of muscarinic receptors but was without effect on β-adrenergic receptor density. After 24 h, an increase of 39.7% ( P < 0.01) and 16.9% ( P < 0.05) was observed for muscarinic and β-adrenergic receptors, respectively. For muscarinic receptors, this increase reached 53.4% ( P < 0.01) within 48 h and stayed at this level until 96 h. The increase of β-adrenergic receptors was maximal (24.9%) after 72 h and returned to the control value after 96 h. The dissociation constant (K_d) values of both ligands were not affected by the glucocorticoid treatment. Functional studies showed that the 96 h treatment did not affect the contractile response of guinea pig lung parenchymal strips to carbachol since the 50% concentration value (EC₅₀) and the maximal contraction value (E_max) were not significatively different from control values. These data show that glucocorticoids control the expression of both muscarinic and β-adrenergic receptors in guinea pig lung but with different time courses and to a larger extent for muscarinic receptors. The glucocorticoid treament did not modify the contractile response of lung strips to carbachol, confirming the absence of effect on the affinity of muscarinic receptors and suggesting that the receptor reserve exceed the increase of their density by the steroid.     

Prevalence,impact and specialised treatment of urinary incontinence in women with chronic lung disease

Objectives

To determine in women with clinically stable chronic lung disease (CLD) and healthy women; (1) prevalence of urinary incontinence; (2) risk factors for urinary incontinence; (3) effects of a standard course of specialised physiotherapy treatment (PT) in women with CLD.

Toll样受体在慢性阻塞性肺疾病发病机制中的作用

慢性阻塞性肺疾病(COPD)是一种以气道炎症为主要标志的慢性呼吸系统疾病。而COPD气道炎症的启动、激发和炎性信号级联放大机制尚不甚明了。近年来研究表明模式识别受体(PRRs)在COPD慢性炎症的启动和维持过程中扮演着重要角色。其中,尤以Toll样受体(TLRs)与COPD发病关系最为密切。吸烟、有害气体、微生物及损伤相关分子模式(DAMPs)与TLRs相互作用,通过NF-κB信号转导通路完成跨膜信号转导,最终调节炎症基因的转录和翻译,产生大量炎症介质并趋化大量炎症细胞参与气道炎症反应的启动及维持。本文结合近年来国内外的最新相关研究成果,对TLRs及下游信号转导通路在COPD发病机制中的重要作用综述如下。     

A scoring system to predict the evolution of respiratory distress syndrome into chronic lung disease in preterm infants

Objective: The purpose of this study was to develop and validate an empirical scoring system to predict the evolution of neonatal respiratory distress syndrome (RDS) into chronic lung disease (CLD) in preterm infants, by comparing it with a more complicated logistic regression model. Design: Clinical study. Setting: Neonatal intensive care unit. Patients: The retrospective analysis of a 3-year experience showed that a gestational age (GA) of less than 30 weeks, a birth weight (BW) of less than 1000 g, the diagnosis of hyaline membrane disease (HMD) and pulmonary interstitial emphysema (PIE) during the first 72 h of life, the peak inspiratory pressure (PIP) and the fraction of inspired oxygen (FIO₂) were the highest relative risk factors correlated with the evolution of CLD. On this basis an empirical and a statistical scoring system were defined and prospectively applied at 3 and 5 days of life to 228 neonates with BW less than 1250 g. The results obtained with both scoring systems were then compared. Results: Of the 149 infants surviving at 28 days of life, 67 (GA: 29.9 ± 2.3 weeks; BW: 1058 ± 143 g) were normal and 82 (GA: 27.5 ± 3.9 weeks; BW: 838 ± 200 g) had CLD. Using a cut-off value of 4.0, the empirical scoring system showed a specificity of 97.0 % and a sensitivity of 92.7 % on the 3rd day of life; on the 5th day of life the specificity was still 95.5 %, while sensitivity remained 92.7 %. The areas under the ROC curves plotted with both scoring systems tested were similar. Conclusions: The proposed empirical scoring system is easy to use and is highly reliable. The application of this scoring system provides the opportunity to direct aggressive treatment for CLD toward only very high risk patients between the 3rd and 5th days of life. Received: 21 August 1997 Accepted: 10 March 1998