Motavizumab for the prevention of respiratory syncytial virus infection in infants

Background: Respiratory syncytial virus (RSV) is the most important respiratory viral pathogen of infancy. The only unequivocally effective pharmacological compound for the management of RSV infection is palivizumab, a monoclonal antibody against the fusion protein of RSV. Recently, motavizumab, a similar but more potent monoclonal antibody, has been developed and tested against palivizumab. Objective: In this review, we summarize data comparing the safety and efficacy of the two monoclonal antibodies in prevention of RSV infection. Other therapeutic options also are discussed. Methods: We reviewed all published articles listing motavizumab or palivizumab in the title or keywords. Results/conclusion: In a large comparative clinical trial for which peer review is pending, motavizumab proved noninferior to palivizumab for prevention of RSV-related hospital admission in infants with underlying conditions placing them at high risk for hospitalization after RSV infection. In this trial, motavizumab in comparison to palivizumab significantly reduced the severity of illness among those infants hospitalized with RSV infection, as well as the number of outpatient lower respiratory infections caused by RSV. Safety profiles of each of the two compounds were excellent. Based on these data, motavizumab should eventually replace palivizumab in the prevention of RSV infection.     

Palivizumab in the prophylaxis of respiratory syncytial virus infection

Respiratory syncytial virus infection continues to be one of the most important health problems in infancy. Active prophylaxis against this infection (i.e., vaccination) is not available. Therefore, protection of high-risk infants is possible only by passive prophylaxis with specific antibodies. Palivizumab (Synagis®) and respiratory syncytial virus intravenous immune globulin are licensed by the US Food and Drug Administration for the prevention of severe lower respiratory tract infections caused by respiratory syncytial virus in infants with bronchopulmonary dysplasia, infants with a history of premature birth (≤35 weeks gestational age) and children with hemodynamically significant congenital heart disease. Palivizumab is a humanized monoclonal antibody produced by recombinant DNA technology, directed to an epitope in the A antigenic side of the F-protein of the respiratory syncytial virus. This review discusses the characteristics of this drug in detail.     

Nitrogen monoxide and carbon monoxide transfer interpretation: state of the art

Just a few clinicians routinely measure the subcomponents of the lung diffusing capacity for Carbone monoxide (DL_CO). This is because the measurement of membrane and blood conductances for CO (Dm_CO and Db_CO = θ_CO × V_c, respectively) by the classic Roughton and Forster method is complicated and time consuming. In addition, it mistakenly assumes a close relationship between alveolar oxygen partial pressure (PAO₂) and mean intracapillary oxygen partial pressure (PcapO₂) which is the true determinant of specific conductance of haemoglobin for CO (θ_CO). Besides that, the critical multistep oxygenation method along with different linear equations relating 1/θ_CO to PcapO₂ gave highly scattered Dm_CO and V_c values. The Dm and V_c can also be derived from a simultaneous measurement of DL_NO and DL_CO with the blood resistance for NO assumed to be negligible. However, recent in vitro and in vivo experiments point towards a finite value of θ_NO (about 4·5 ml_NO × ml_blood^?1 × min^?1 × mmHg^?1). Putting together the arguments and our clinical data allows us to report here the state of the art in partitioning the CO diffusing capacity into its constitutive components, with the goal to encourage further studies examining the sensitivity of Dm_CO and V_c to alterations observed in parenchymal diseases.     

Detection of chronic rejection by quantitative ventilation scintigrams in lung-transplanted patients: a pilot study

The suspicion of chronic rejection [bronchiolithis obliterans syndrome (BOS)] is usually based on deteriorating forced expired volume in 1 s. It is however, desirable to develop more sensitive methods as increased anti-inflammatory therapy is thought to stop progression of the rejection. The aim of the present study was to develop quantitative tools based on ventilation scintigrams, to diagnose BOS. Sixteen double-lung-transplanted patients participated, six developing BOS and 10 who did not develop BOS. They were investigated with planar posterior-anterior (99m)Tc-Technegas (Tetley Manufacturing Ltd, Sydney, Australia) ventilation scintigraphy at baseline, 6 months to 1 year post-transplantation, and at a follow-up examination 3-4-year post-transplant or in the BOS patients close to the time of the diagnosis. An automatic region of interest (ROI) was drawn on each lung in the scintigraphic image at baseline and also applied to the follow-up investigation. The area inside the ROI was subdivided into stripes 10.8 mm high and squares 10.8 x 10.8 mm wide. Corresponding stripes and squares in baseline and follow-up were analysed regarding differences in relative retention. The results show that the square analysis is superior. Applying chosen cut-off values for square element differences, 6/6 right and 5/6 left BOS lungs were identified and one left and one right lung of patients not developing BOS were misclassified. We conclude that the square element difference appears to be a promising method to diagnose BOS.     

Effects of Bupivacaine Versus Levobupivacaine on Pulmonary Function in Patients With Chronic Obstructive Pulmonary Disease Undergoing Urologic Surgery: A Randomized, Double-Blind, Controlled Trial

Background

There are limited data to determine the impact of subarachnoid blockade with local anesthetics on perioperative pulmonary function. The effects of local anesthetics used in spinal anesthesia are very important in terms of respiratory function in patients with chronic obstructive pulmonary disease (COPD).

Objective

The aim of this study was to evaluate the effects of bupivacaine versus levobupivacaine on pulmonary function in patients with COPD undergoing urologic surgery.

Methods

Patients were randomized into 2 groups: group B (n = 25) received 3 mL of hyperbaric 0.5% bupivacaine; group L (n = 25) received 3 mL of isobaric 0.5% levobupivacaine. Both agents were administered intrathecally. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), peak expiratory flow rate (PEFR), vital capacity (VC), and FEV₁/FVC ratio were measured using spirometry 10 and 30 minutes after spinal anesthesia and 30 minutes after completion of the operation. An arterial blood gas test was performed before and after spinal anesthesia.

Results

Fifty male patients aged 40 to 80 years completed the study. There were no differences in the results of preoperative and postoperative FVC, FEV₁, PEFR, VC, FEV₁/FVC ratio, and arterial blood gas between the bupivacaine (n = 25) and levobupivacaine (n = 25) groups. However, patients who took bupivacaine showed a significant decrease in intraoperative PEFR at 30 minutes compared with baseline, a result not seen in patients who took levobupivacaine (P = 0.036 and P = 0.282, respectively).

Conclusions

In 50 patients with moderate COPD undergoing urologic surgery, hyperbaric bupivacaine caused a decrease in intraoperative PEFR compared with baseline because of higher level block; however, the effects of hyperbaric bupivacaine and isobaric levobupivacaine on pulmonary function in these patients showed equally effective potencies for spinal anesthesia.     

Changes in transfer factor of the lung in response to bronchodilatation

Measurement of the transfer factor for carbon monoxide (T_LCO) is a widely used clinical lung function test. Although it is frequently applied in patients with bronchial obstruction, there is little information on the effects of bronchodilatation on the test. We therefore measured T_LCO in 40 patients before and after inhalation of terbutaline. T_LCO was measured with the single‐breath technique in 20 patients and with the intra‐breath technique in 20 patients. T_LCO was also measured in 20 healthy subjects with the single‐breath technique. Forced expiratory volume (FEV₁) increased from 2·9 ± 1·1 to 3·2 ± 1·2 l in patients with bronchial obstruction in response to terbutaline inhalation. T_LCO increased from 8·2 ± 2·6 to 8·6 ± 2·7 mmol min^–1 kPa^–1 (P< 0·001) and alveolar volume (V_A) from 5·74 ± 1·21 to 5·90 ± 1·21 l (P<0·001). There was no difference between the single‐breath and the intra‐breath techniques. There was little change in FEV₁ in the healthy subjects in response to terbutaline. T_LCO increased from 10·2 ± 2·1 to 10·5 ± 2·2 mmol min^–1 kPa^–1 (P< 0·01), but there was no change in V_A. The increase in T_LCO in patients may partly be explained by improved distribution of the inhaled gas. In healthy subjects, terbutaline may increase pulmonary capillary volume. We conclude that bronchodilatation results in a small increase in T_LCO in patients with light to moderate bronchoconstriction as well as in healthy subjects. The effect is small and should in most cases be simple to account for in the interpretation of pulmonary function tests, provided the patient’s treatment is known.     

Prevalence of Bordetella pertussis and Bordetella parapertussis in Infants Presenting to the Emergency Department with Bronchiolitis

Background: The clinical presentation of Bordetella pertussis can overlap with that of respiratory syncytial virus (RSV), and coinfection does occur, but management differs. Hypothesis: The prevalence of B. pertussis is < 2% among Emergency Department (ED) patients with bronchiolitis. Our secondary hypothesis was that the prevalence of Bordetella parapertussis is also < 2% among these patients. Methods: Nasal washings were obtained from children up to 18 months of age (inclusive) who presented to a county hospital ED with a clinical diagnosis of bronchiolitis. These washings were frozen to −70°C before testing for B. pertussis and B. parapertussis using species-specific real-time polymerase chain reaction (PCR) assays. The assays were optimized to target conserved regions within a complement gene and the CarB gene, respectively. A Bordetella spp. genus-specific real-time PCR assay was designed to detect the Bhur gene of B. pertussis, B. parapertussis, and B. bronchiseptica. RSV antigen detection was also performed. Results: There were 227 patients enrolled. After exclusions, 204 remained in the analysis. RSV antigen testing was positive in 109/186 (59%) of the patients in whom it was performed. All samples were tested for B. pertussis. B. parapertussis testing could not be completed on 23 samples. No cases (0/204; 95% confidence interval [CI] 0–1.8%) tested positive for B. pertussis or B. parapertussis (0/181; 95% CI 0–2%). Conclusion: The prevalence of B. pertussis in children presenting to the ED with bronchiolitis was < 2%.     

高脂低糖膳食对慢性阻塞性肺疾病机械通气患者呼吸功能状况影响的meta分析

目的 系统评价高脂低糖膳食对慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）机械通气患者呼吸功能状况的影响。方法 计算机检索中国知网（CNKI）、维普数据库（VIP）、万方数据库、PubMed、EMbase等中英文数据库。搜集2019年10月前发表的有关高脂低糖膳食和COPD机械通气的中英文随机对照试验（RCTs）,检索时间自2009年1月至2019年10月。由2位研究员分别独立的筛选符合纳入和排除标准的文献后汇总意见并提取资料,采用Cochrane偏倚风险评估工具对文献质量进行评价。结果 共纳入15个RCTs,包括1 146例患者。Meta分析结果显示,COPD机械通气患者每分钟通气量（VE）［MD=-1.4, Z=8.23, P＜0.01, 95%CI -1.74,-1.07), 每分钟二氧化碳产生量（VCO2）(MD=-42.61, Z=8.65, P＜0.01, 95%CI -52.26, -32.96), 每分钟耗氧量（VO2） (MD=-30.16, Z=7.37, P＜0.01, 95%CI -38.18, -22.14), 呼吸商（RQ）(MD=-0.08, Z=19.3, P＜0.01, 95%CI -0.08,-0.07), 动脉血二氧化碳分压（PaCO2）(MD=-1.13, Z=5.93, P＜0.01, 95%CI -1.5, -0.76), 动脉氧分压（PaO2）(MD=1.24, Z=8.02, P＜0.01, 95%CI 0.94, 1.54),应用高脂低糖组均优于对照组。结论 高脂低糖膳食有助于改善COPD机械通气患者的通气状况,减少CO2的产生,降低PaCO2,提高PaO2,纠正呼吸衰竭。     

Accuracy of the dynamic signal analysis approach in respiratory mechanics during noninvasive pressure support ventilation: a bench study

ObjectiveTo evaluate the accuracy of respiratory mechanics using dynamic signal analysis during noninvasive pressure support ventilation (PSV).MethodsA Respironics V60 ventilator was connected to an active lung simulator to model normal, restrictive, obstructive, and mixed obstructive and restrictive profiles. The PSV was adjusted to maintain tidal volumes (V_T) that achieved 5.0, 7.0, and 10.0 mL/kg body weight, and the positive end-expiration pressure (PEEP) was set to 5 cmH₂O. Ventilator performance was evaluated by measuring the flow, airway pressure, and volume. The system compliance (C_rs) and airway resistance (inspiratory and expiratory resistance, R_insp and R_exp, respectively) were calculated.ResultsUnder active breathing conditions, the C_rs was overestimated in the normal and restrictive models, and it decreased with an increasing pressure support (PS) level. The R_insp calculated error was approximately 10% at 10.0 mL/kg of V_T, and similar results were obtained for the calculated R_exp at 7.0 mL/kg of V_T.ConclusionUsing dynamic signal analysis, appropriate tidal volume was beneficial for R_rs, especially for estimating R_exp during assisted ventilation. The C_rs measurement was also relatively accurate in obstructive conditions.     

Experimental studies on the adult respiratory distress syndrome: effects of induced DIC; granulocytes and elastase in mini pigs

The potential role of granulocyte proteinases on experimentally induced ARDS was evaluated. In order to investigate the acute effects on lung function, elastase (330 U kg-1h-1) or thrombin (75-150 U kg-1 h-1) was continuously infused into anaesthetized and mechanically ventilated mini pigs. Both elastase as well as thrombin induced a progressive respiratory failure with prompt increase in pulmonary vascular resistance, and decrease of cardiac output, further a pulmonary leukostasis, and a disturbance of blood coagulation leading to hypocoagulability. High proteolytic activity selectively in the lung indicates a possible role of proteinases released from sequestered polymorphonuclear neutrophils. Similar results following elastase infusion were however obtained in leukopenic animals pretreated with a single dose of dimethylmyleran (5 mg kg-1) which depleted the granulocytes totally. These results offer the possibility that elastase itself may cause respiratory failure and lung tissue damage. On the other hand the digestion pattern of phosphorylase kinase by lung tissue homogenates of thrombin- or elastase-infused mini pigs clearly indicates that elastase is only one of several mediators which may cause experimentally induced ARDS even in the absence of granulocytes.