Treatment Of Emphysema Research Articles

Surgical treatment of cystic disease and emphysema in young children.

Surgical treatment of cystic disease and emphysema in young children.

Surgical treatment of pulmonary emphysema

Chronic obstructive pulmonary disease is an umbrella term for a range of conditions affecting the small airways (e.g. emphysema, chronic bronchitis, asthma). These are characterized by progressive, irreversible limitation of airflow, and evidence of an abnormal inflammatory response associated with inhalation of noxious gases or particles. Typically, this causes destruction of the alveolar wall, reduced elasticity, dilation of the units distal to the terminal bronchiole (resulting in hyperinflation of the chest wall), diaphragm flattening, gas trapping, and poor alveolar gas exchange compounded by a V:Q mismatch. This results in pulmonary hypertension with consequent right ventricular dysfunction in 40% of patients. Surgical procedures for emphysema were first developed more than 100 years ago, but only three have endured: bullectomy, lung-volume reduction surgery, and transplantation. This review discusses bullectomy (elective and for spontaneous secondary pneumothorax) and lung-volume reduction surgery. The indications and contraindications of surgery, technical aspects of the surgical approach, and timing of surgery are discussed. The future of surgical treatment for emphysema is considered, together with the evolving evidence base for existing treatments.

CASE OF HEMOPTYSIS ONE MONTH AFTER ENDOBRONCHIAL VALVE PLACEMENT FOR LUNG VOLUME REDUCTION

INTRODUCTION: Bronchoscopic valve placement is currently under investigation as a non-surgical means of lung volume reduction for the treatment of emphysema. This is a case of hemoptysis one month after 5 valves were placed to exclude the right lower lobe.

Perfil radiológico do candidato ideal à cirurgia redutora de volume pulmonar no enfisema: uma revisão sistemática

INTRODUÇÃO: A cirurgia redutora de volume pulmonar é uma alternativa terapêutica para o enfisema pulmonar avançado. A avaliação radiológica do tipo e distribuição do enfisema parece ser o principal critério de indicação cirúrgica, além da função pulmonar. OBJETIVO: Determinar o nível de evidência científica referente ao padrão radiológico do candidato ideal à cirurgia redutora de volume pulmonar. MÉTODO: Revisão sistemática da literatura entre janeiro de 1994 e janeiro de 2004, utilizando as bases de dados: MEDLINE, EMbase, LILACS, The Cochrane Library e EBM Reviews. RESULTADOS: Foram identificados 208 artigos e 16 deles preenchiam os critérios do estudo. Destes, dois eram randomizados (um multicêntrico, denominado National Emphysema Treatment Trial, envolvendo 1.218 pacientes; e outro que, embora randomizado, com apenas 30 pacientes). Os 14 remanescentes eram estudos observacionais. O National Emphysema Treatment Trial identificou um subgrupo de pacientes de prognóstico favorável, quando submetidos à cirurgia redutora de volume pulmonar, formado por portadores de enfisema pulmonar avançado e heterogêneo, com predomínio nos lobos superiores, na presença de hiperdistensão pulmonar difusa e baixa capacidade para exercícios físicos. O padrão dos resultados dos demais estudos foi consistente na análise individual, apesar de sua heterogeneidade. Benefício cirúrgico, taxas de mortalidade e qualidade de vida também foram mensurados nos estudos observacionais. CONCLUSÃO: O perfil radiológico caracterizado pelo tipo de enfisema, sua heterogeneidade, distribuição e presença de hiperdistensão difusa, ao lado do nível de gravidade, representa o principal fator preditor de bom resultado cirúrgico. Esta recomendação tem o nível de evidência B, pela escassez de trabalhos na literatura.

AEROSOLIZED HYALURONAN LIMITS AIRSPACE ENLARGEMENT IN A MOUSE MODEL OF CIGARETTE SMOKE–INDUCED PULMONARY EMPHYSEMA

This study was designed to determine if aerosolized hyaluronan (HA) could prevent airspace enlargement and elastic fiber injury in a mouse model of cigarette smoke–induced pulmonary emphysema. Compared to untreated/smoked controls, HA-treated animals showed statistically significant reductions in mean linear intercept (54 versus 65 μm; P < .001) and elastic fiber breakdown products (desmosine and isodesmosine) in bronchoalveolar lavage fluid (0.3 versus 7.0 ng/mL; P < .05). As in previous studies, the aerosolized HA showed preferential binding to elastic fibers, suggesting that it may protect them from injury. These findings support further investigation of the potential use of HA as a treatment for pulmonary emphysema.

Bronchoscopic Lung Volume Reduction in Patients with Severe Emphysema: Anesthetic Management

Bronchoscopic lung volume reduction is a novel approach to the treatment of severe emphysema. Its objective is to achieve the same improvements in lung function and exercise tolerance as lung volume reduction surgery while avoiding the surgical morbidity and mortality. We describe the anesthetic experience in a series of seven patients who underwent a total of eight procedures (one patient underwent a second procedure on the contralateral side). The technique used was one of total IV anesthesia using remifentanil and propofol, with a ventilatory strategy aimed at avoiding gas trapping and dynamic hyperinflation. To achieve this pressure, limited ventilation with a prolonged expiratory phase was provided by a Draeger Evita 2 ventilator. This technique resulted in intraoperative hypercapnia (Paco(2) 6.75 kPa) compared with baseline values (median Paco(2) 5.1 kPa; P < 0.05), but 2 h postoperatively the arterial partial pressure of CO(2) was returning to baseline (median Paco(2) 5.6 kPa; P < 0.01 compared with intraoperative data). There were no deaths or admissions to the intensive care unit after the procedure. One patient developed a pneumothorax that required drainage, three patients had acute exacerbations of chronic obstructive pulmonary disease, and one patient developed a cough that resolved spontaneously. Total hospital stay did not exceed 5 days for any of these patients.

Infection Risk During Chronic Implantation of Intra-bronchial Valves to Produce Lung Volume Reduction in an Ovine Model

PURPOSE: Intrabronchial valves are being evaluated in patients for palliative treatment of advanced emphysema. Any object placed in the airway increases the risk of infection. One-year implants of Intra-bronchial Valves (IBV, Spiration Inc.) in a canine model showed no evidence of pulmonary infection and insignificant bacterial culture yields. A sheep model with greater sensitivity was used to challenge the IBV and evaluate the incidence of pulmonary bacterial colonization and infections.

Endobronchial Volume Reduction: A Myth or a Marvel?

Recently, several techniques and devices have been suggested for achieving endobronchial volume reduction in patients with emphysema. The proposed devices include bronchial blockers, bronchial valves, glues, biomodulators, and stents for bronchial fenestration; all could be positioned only with flexible bronchoscopy. The current available evidence on safety and efficacy for these methods is based on animal studies and patient case series at best; therefore, all the results should be seen with caution. However, the preliminary work reviewed here suggests that most of the proposed techniques can work, and seem to be safer than surgical volume reduction. We do not yet have a proven, widely applicable endobronchial palliative treatment for severe emphysema, but we have a rapidly growing area of new research in interventional pneumology with preliminary results that challenge traditional medical thinking.

Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

Chirurgie de réduction de volume pulmonaire pour emphysème : approche uni- ou bilatérale ?

Lung Volume reduction surgery (LVRS) is a recognized therapeutic option for patients presenting with severe and disabling pulmonary emphysema. Case selection is based upon clinical, morphological and functional criteria. LVRS has shown promising results, with improvements in exercise capacity, pulmonary function and quality of life, in selected patients with severe and disabling emphysema. A variety of surgical techniques have been described. The procedure may be unilateral or bilateral, through a sternotomy or by a video-assisted thoracoscopic (VATS) technique. The controversial aspects of the surgical technique will be analysed and discussed in the following review. A bilateral approach clearly offers a better functional improvement when compared to a unilateral procedure, however, the postoperative functional decline appears greater and more rapid after a bilateral procedure. A unilateral approach, with often less postoperative morbidity, allows the option to perform a future contra-lateral procedure in the event of further clinical or functional deterioration. In selected cases LVRS is an effective treatment for severe pulmonary emphysema. Different surgical techniques have been described. Nowadays VATS is considered to be the technique of choice, with the option to carry out a future unilateral or bilateral procedure.

Comparison of computer-aided calculation of emphysema volumetry with manual quantification using CT images

Emphysema is a common lung disease causing shortness of breath and affecting a large proportion of the human population. Quantitative analysis of emphysema is important to determine the nature, history and extent of the disease. Quantification of emphysema is also very important in planning the surgical treatments for emphysema. This paper compares the results of a computer-aided method of emphysema quantification to the manual method. The results of the comparison show a very close correlation between the manual and automated methods. The computer-aided method is reliable, easy and reproducible as compared to the manual method. It may provide the users with a fast and accurate estimation of emphysema helping in planning the treatment and therapy procedures for emphysema patients.

Chirurgie de l’emphysème : progrès récents

The treatment of chronic obstructive pulmonary disease has progressed considerably over the past 40 Years but, for most patients with advanced disease, medical management does not often produce more than limited benefits, particularly in terms of quality of life. Over the last decade the surgical treatment of emphysema, which was previously limited to bullectomy, has seen important developments: for carefully selected patients lung Volume reduction surgery and lung transplantation now offer the possibility of real symptomatic improvement and even prolonged survival. Thanks to the thousands of patients who have received these treatments our understanding of the pathophysiological mechanisms, surgical techniques, risks and benefits, medium and long-term results, and selection criteria has improved considerably. This review summarises the most important aspects of these developments and discusses the role of Volume reduction and lung transplantation in the treatment of advanced emphysema.

Bronchoscopic Lung Volume Reduction in a Sheep Model of Heterogeneous Emphysema

We have previously described the use of bronchoscopic lung volume reduction (BLVR), a novel, tissue engineering-based, minimally invasive technique, in experimental homogeneous pulmonary emphysema in sheep. In this report, we describe the use of CT-guided, site-directed BLVR in the treatment of experimental heterogeneous emphysema. Nine sheep were treated with localized papain instillations and nebulized papain to generate heterogeneous emphysema. Six animals subsequently underwent BLVR while the remaining 3 served as controls. The procedure was safe and well tolerated. BLVR reduced gas trapping (26.7%) as measured by RV-to-TLC ratio, improved diffusing capacity, and reduced a bullous lesion seen by CT scan.

Can Exogenously Administered Hyaluronan Improve Respiratory Function in Patients With Pulmonary Emphysema?

While most attempts at developing a treatment for pulmonary emphysema have focused on the use of elastase inhibitors to reduce elastic fiber damage and the loss of alveoli, this laboratory has developed a method of preventing such injury by the intratracheal administration of hyaluronan (HA). Animals treated with HA prior to the induction of experimental emphysema develop significantly less disease than untreated controls. The protective effect of HA may be related to its ability to bind to lung elastic fibers, thereby preventing their breakdown by elastases. Although clinical trials involving nebulized HA are not expected to yield a measurable treatment effect for at least several years, it is proposed that the special ability of this polysaccharide to retain water may increase the elasticity of lung elastic fibers, producing a relatively rapid improvement in pulmonary mechanics. Such an outcome might speed the development of this potential treatment for pulmonary emphysema.

Emphysema: the challenge of the remodelled lung.

Emphysema is recognized as the component of chronic obstructive airways disease that is responsible for airways obstruction. Different patterns of emphysema are, however, recognized, suggesting possible different pathogenetic processes within the lung. This, coupled with the associated idea of susceptibility factors to the development of emphysema, has led to studies of genes that may be involved in the defence of the lung from proteolytic and oxidative damage. These studies have been driven by the goal of finding a treatment for emphysema, but appear to have lost sight of the fundamental remodelling of the lung that has occurred in patients with emphysema and the fact that it is not a single morphological entity.

Anaesthesia for lung volume reduction surgery.

Lung volume reduction surgery is a surgical treatment for severe emphysema that is increasing in popularity. The aim is to reverse the hyperexpansion of the lungs that leads to expiratory airflow limitation, compromises the diaphragm and chest wall mechanics, and tamponades the right ventricle. Optimal patient selection has not yet been established, but it has become clear that those patients with the most severe disease have an unacceptably high surgical mortality. The anaesthetic management of patients undergoing lung volume reduction surgery requires a good understanding of both the pathophysiology of the disease and the surgical procedure. It is important for the anaesthetist and the surgeon to work closely, supported by a large multidisciplinary team. Excellent analgesia is essential to a successful outcome; whether this is best provided by thoracic epidural is as yet unclear.

Lung volume reduction surgery (LVRS): criteria for selecting patient in Antonio Pedro Hospital, Federal Fluminense University, Niter i city, Rio de Janeiro, Brazil

Chronic Obstructive Pulmonary Disease (CPOD) is an important problem in Brazil and other countries. The clinical treatment of ambulatory patients is now reasonably standardized. Lung volume reduction surgery (LVRS) is an alternative of surgical treatment of emphysema (aside from lung transplantation). The aim of this study was to analyse patient selection criteria for LVRS. This study was carried out using a sample of 31 patients referred to and given assistance to at the Smoking and Chronic Obstructive Pulmonary Disease Outpatient Ward Antonio Pedro Hospital, who were evaluated to check whether or not they could be eligible for LVRS. Aiming at evaluating the major criteria for eligibility for LVRS, the patients underwent a protocol including standardized anamnesis and physical examination, spirometry with maximum inspiratory and expiratory flow volume curves associated with post-bronchodilatator test, room air arterial blood gases, a six-minute walking test, plain chest roentgenograms and left lateral chest roentgenograms, high-resolution chest computed tomographic scans and lung perfusion scans. Statistical analysis was conducted with description of data proportions. Contraindications to surgery included chronic bronchitis (29% or nine patients), forced expiratory volume in one second (FEV 1) more than 80 percent predicted (13% or four patients), negative consent for surgery (10% or three patients), fibrosis pattern, severe depression and bronchiectasis (two patients each one), solitary pulmonary nodule, severe obesity, severe bullous emphysema, pulmonary hipertension, pulmonary resection history, current cigarette smoking, diffuse emphysema with alpha-1-antitrypsin deficiency and severe cardiac disease (one patient each). Indication. One selected patient with severe symptoms of emphysema met criteria for LVRS (bilateral superior lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan). Chronic bronchitis was the major isolated factor to contraindicate LVRS. Most patients who fit the criteria for the surgery performance refused to undergo the LVRS for fear of the surgery and after pulmonary rehabilitation. The most important criteria for LVRS is bilateral superior lobe heterogeneous pattern of emphysema.

A Novel Orally Active Inhibitor of HLE.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Alpha-1-Antitrypsin ameliorates cigarette smoke-induced emphysema in the mouse.

Serine elastase inhibitors have been proposed as a treatment for cigarette smoke-induced emphysema, but little is known about whether such agents actually are effective. We recently reported that a synthetic serine elastase inhibitor, ZD0892, provided some protection against emphysema in a guinea pig model. For these experiments, we used transgenic mice that expressed extremely low levels of human alpha-1-antitrypsin (A1AT) but were tolerant of exogenous human A1AT. Mice were exposed to daily cigarette smoke for up to 6 months; some animals received 20 mg of human A1AT (Prolastin) every 48 hours. Treatment with A1AT produced an approximate twofold increase in serum A1AT levels and elastase inhibitory capacity and abolished smoke-induced elevations in lavage neutrophils and matrix breakdown products (desmosine and hydroxyproline) measured from 2 to 30 days of smoke exposure. A1AT oxidized to remove antiproteolytic activity did not increase serum elastase inhibitory capacity but did prevent neutrophil influx. Treatment with A1AT for 6 months provided 63% protection against increased airspace size (emphysema) and abolished smoke-mediated increases in plasma tumor necrosis factor-alpha. We conclude that A1AT therapy ameliorates smoke-induced inflammation and matrix breakdown, possibly via an antiinflammatory mechanism related to tumor necrosis factor-alpha suppression, and provides partial protection against emphysema.

A novel orally active inhibitor of HLE

Human leukocyte elastase (HLE) is a serine proteinase, capable of degrading a variety of structural matrix proteins. SSR69071 2-[(4-isopropyl-6-methoxy-1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3 H)-yl)methoxy]-9-(2-piperidin-1-ylethoxy)-4 H-pyrido[1,2- a]pyrimidin-4-one was selected as a novel orally active HLE inhibitor for treatment of chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis and several inflammatory diseases (WO 01/44245 A1) (J. Pharm. Exp. Ther., submitted for publication).