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Latest Research on Emphysema/COPD
     
Am J Med. 2008 Jan;121(1):3-9.
Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment.
Köhnlein T, Welte T.
Hannover Medical School, Department of Respiratory Medicine, Hannover, Germany. thomas.koehnlein@web.de

Alpha-1 antitrypsin deficiency is an inherited disease affecting the lung and liver. The typical pulmonary manifestation is chronic obstructive pulmonary disease and emphysema. Severe chronic obstructive pulmonary disease may occur in young adulthood, and terminal respiratory insufficiency causes premature death in many patients. In the liver, alpha-1 antitrypsin deficiency may manifest as benign neonatal hepatitis syndrome; a small percentage of adults develop liver fibrosis, with progression to cirrhosis and hepatocellular carcinoma. The alpha-1 antitrypsin molecule is a serine protease inhibitor that is predominantly produced in the liver. Its most important physiologic functions are the protection of pulmonary tissue from aggressive proteolytic enzymes and regulation of pulmonary immune processes. Diagnosis of alpha-1 antitrypsin deficiency can be established by measurement of the serum alpha-1 antitrypsin concentration or by genetic analysis. Treatment is similar to the usual treatment for patients with chronic obstructive pulmonary disease. A further option is substitution therapy with human alpha-1 antitrypsin. The targets of treatment are the prevention of the accelerated decline of pulmonary function, reduction of lung infections, and improvements in exercise capacity.

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Am J Respir Crit Care Med. 2008 Jan 15;177(2):164-9. Epub 2007 Oct 25. Comment in: Am J Respir Crit Care Med. 2008 Jan 15;177(2):130-1.
The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations.
Washko GR, Fan VS, Ramsey SD, Mohsenifar Z, Martinez F, Make BJ, Sciurba FC, Criner GJ, Minai O, Decamp MM, Reilly JJ; for the National Emphysema Treatment Trial Research Group.
Pulmonary and Critical Care Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. gwashko@partners.org

RATIONALE: Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known. OBJECTIVES: To examine the effect, and mechanism of potential benefit, of LVRS on COPD exacerbations by comparing the medical and surgical cohorts of the National Emphysema Treatment Trial (NETT). METHODS: A COPD exacerbation was defined using Centers for Medicare and Medicaid Services data and International Classification of Diseases, Ninth Revision, discharge diagnosis. MEASUREMENTS AND MAIN RESULTS: There was no difference in exacerbation rate or time to first exacerbation between the medical and surgical cohorts during the year before study randomization (P = 0.58 and 0.85, respectively). Postrandomization, the surgical cohort experienced an approximate 30% reduction in exacerbation frequency (P = 0.0005). This effect was greatest in those subjects with the largest postoperative improvement in FEV(1) (P = 0.04) when controlling for changes in other spirometric measures of lung function, lung capacities, and room air arterial blood gas tensions. Finally, LVRS increased the time to first exacerbation in both those subjects with and those without a prior history of exacerbations (P = 0.0002 and P < 0.0001, respectively). CONCLUSIONS: LVRS reduces the frequency of COPD exacerbations and increases the time to first exacerbation. One explanation for this benefit may be the postoperative improvement in lung function.

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Transplant Proc. 2007 Dec;39(10):3317-22.
Factors related to postoperative mortality in lung transplantation for emphysema.
Ferrer J, Rodriguez E, Roman A, Bravo C, Roldan J, Hermosilla E, Canela M.
Respiratory Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.

BACKGROUND: Chronic obstructive pulmonary disease is the primary indication for lung transplantation worldwide. In this study, we analyzed the early outcomes of patients with emphysema undergoing bilateral lung transplantation at our center. METHODS: This retrospective analysis included 79 consecutive bilateral lung transplantation performed due to emphysema (8 with alpha-1 antitrypsin [AAT] deficiency) between 1993 and 2005. We analyzed variety of demographic, clinical, respiratory function, and surgical variables. Early mortality was defined as death occurring in the first month after lung transplantation. Statistical analysis included Student t test and Fisher exact test. RESULTS: Seventy-nine patients with emphysema, 74 men and 5 women, with a mean FEV1 of 21.1%+/-6.3%, underwent bilateral lung transplantation. Fourteen patients (17.7%) died in the first month after surgery. Compared with survivors, patients who died in the first month, had longer ischemic times (365+/-60
vs 295+/-55 minutes; P=.01), needed more cardiopulmonary bypass (69.2% vs 6.2%; P<.0001), and had a greater incidence of hemothorax (46.2% vs 10.9%; P=.007). Patients with ischemic time longer than 6 hours had a greater 1-month mortality rate (38.5%) than those with shorter ischemic times (12.9%; P=.03). No preoperative variable was related to 1-month mortality after bilateral lung transplantation. CONCLUSIONS: In our experience, 1-month mortality after bilateral lung transplantation in emphysema was higher among patients with more than 6 hours of ischemic time, those undergoing cardiopulmonary bypass, and those developing posttransplantation hemothorax.

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Med Klin (Munich). 2007 Nov 15;102(11):904-12.
[Clinical Year in Review - advanced COPD]
[Article in German]
Köhler D.
Abteilung für Pneumologie I, Fachkrankenhaus Kloster Grafschaft, Schmallenberg-Grafschaft, Germany. d.koehler@fkkg.de

COPD is a frequent disease, affecting approximately one in four smokers. In older patients > 70 years of age, the proportion of individuals who never have smoked increases up to one in three individuals. Severe disease is present in 10%, and the limitation of performance is usually caused by airway obstruction, in a smaller portion of patients by the loss of alveolar surface (emphysema). After medical treatment with antiobstructive and anti-inflammatory drugs, oxygen remains a major therapy option. With it, hypercapnic patients benefit most from long-term therapy. Patients with predominant emphysema benefit most from high-flow (6-8 l/min) oxygen therapy during exercise. Permanent yellow or greenish sputum decoloration is suggestive of chronic bacterial colonization. This group of patients may benefit from a permanent inhalative therapy with antibiotics (mainly aminoglycosides). There is growing evidence from current literature to support this concept. If dyspnea is severe, especially during mild exercise, a subset of patients might benefit from the use of long-acting morphium. Goal of this therapy is to downregulate breathing control. Predominantly "pink puffers" seem to respond. A dose of 10-20 mg will usually be sufficient. Life-threatening hypercapnia is usually not observed with this form of therapy. Noninvasive ventilation is an option for patients with severe hypercapnia. Thereby, ventilatory pressure or inspiratory volume should be selected to effectively unload the respiratory muscles. This will increase quality of life. Life span is likely to be prolonged, however, comparative data where patients were effectively ventilated (as seen on the reduction of hypercapnia) are missing. A multicenter trial addressing this topic is currently being conducted in Germany. Independent of the severity of COPD, patients in general benefit from physical training with alternation of endurance and interval training being most effective. This will decrease
the number of hospital admissions and probably mortality as well. Lung volume reduction surgery virtually treats lung hyperinflation. Bullectomy is still considered effective for isolated bullous emphysema as well as lobectomy, if this portion of the lung is without function. Shaving procedures are still associated with high rates of complications and should only be performed in selected cases. Effectiveness of endoscopic lung volume reduction surgery by implantation of plugs or valves cannot be assessed yet. First data are rather disappointing. Ultimate alternative remains lung transplantation with life expectancy ranging between 5-6 years independent of age. Indeed, consequent application of previously described measures might preserve a stable state over many years.

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Expert Opin Pharmacother. 2007 Oct;8(15):2609-14.
Aralast: an alpha 1-protease inhibitor for the treatment of alpha-antitrypsin deficiency.
Mordwinkin NM, Louie SG.
University of Southern California School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA. mordwink@usc.edu

Alpha-antitrypsin (AAT) is a serine protease inhibitor, which inhibits the proteolytic enzyme elastase. Individuals with a deficiency of AAT may develop clinical manifestations that include a decline in lung function. Deficiency of AAT can lead to many clinical manifestations, most commonly chronic obstructive pulmonary disease in the form of emphysema. However, patients with this genetic disorder may also develop dysfunctions of other organs such as the liver and/or skin. There are approximately 100 alleles associated with the gene encoding for AAT, where the estimated prevalence of this disorder is approximately as common as cystic fibrosis; however, misdiagnosis continues to be a problem. Augmentation therapy using intravenous AAT has been shown to reduce the forced expiratory volume in one second decline, associated with AAT deficiency. Restoration of serum AAT concentrations above 11 microM have correlated with a reduced level of disease progression. The normal dosing regimen of intravenous AAT is 60 mg/kg given every week. Although a dosage consolidation of 250 mg/kg given every 28 days has been explored, long-term efficacy has not been determined. Aralast is one of three approved human plasma-derived treatment options used to prevent the progression of emphysema associated with AAT deficiency disorder.

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Clin Chest Med. 2007 Sep;28(3):639-53, vii.
Update in surgical therapy for chronic obstructive pulmonary disease.
Lederer DJ, Arcasoy SM.
Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, Lung Transplantation Program, PH-14 East, Room 104, New York, NY 10032, USA.

Bullectomy for giant bullae, lung volume reduction surgery, and lung transplantation are three surgical therapies that may benefit highly selected patients with advanced chronic obstructive pulmonary disease. In this article, each procedure is reviewed, with an emphasis on guidelines for patient selection and clinical outcomes for the practicing pulmonologist. Recent results from the National Emphysema Treatment Trial, updated International Society for Heart and Lung Transplantation Registry data, and revised guidelines for patient selection for lung transplantation are discussed.

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COPD. 2007 Sep;4(3):273-8.
Activity Limitation and Quality of life In COPD.
Jones PW.
St. George's, University of London, London, United Kingdom.

Limitation of activity and impaired quality of life are important outcomes of COPD. There is an association between measures of self-reported physical activity and overall health status, and they appear to change together spontaneously over time and in response to treatment. The relationship between symptoms and activity limitation is complex, because activity can be limited entirely by symptoms, or impaired by symptoms so that it requires greater effort or causes discomfort. The patient has the choice of whether to restrict their activity or maintain it at the cost of having symptoms. In theory, this may make it difficult to produce reliable standardized assessments of activity limitation because it may not be clear exactly what is being measured. Analysis of items in the St George's Respiratory Questionnaire (SGRQ) concerned with activities that are either not possible due to breathlessness, or are a cause of breathlessness, show that they contribute to a unidimensional model of activity limitation in daily life and a unidimensional model of overall COPD-related health status. The items lie distributed evenly along the same severity continuum, from very mild to very severe, along with other items concerned with symptoms and the psycho-social impact of the disease. This suggests that self-reported limitation of activity may form a reliable construct, and may also provide a good surrogate marker of health status in COPD.

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COPD. 2007 Sep;4(3):283-7.
COPD and Exercise: What's Really Important? A Nursing Perspective.
Reardon JZ.
Department of Medicine, Acute Care Nurse Practitioner, Hartford Hospital, Hartford, Connecticut.

Numerous studies demonstrate the importance of exercise training to improve endurance in patients with chronic obstructive pulmonary disease (COPD) and its positive effect on activities of daily living and quality of life. However, successful care of the individual with COPD also relies on recognizing that this person requires individualized care and non-pharmacologic modalities specific to their needs in order to cope with the various aspects of their disease. It is also important to note that improvement in quality of life is not necessarily related to improvement in exercise endurance alone. Comprehensive and effective pulmonary rehabilitation for the COPD patient needs to encompass several components to provide benefit for the spectrum of symptoms of COPD beyond exercise tolerance and dyspnea to ultimately improve quality of life.

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J Adv Nurs. 2007 Sep;59(6):559-68.
Smoking cessation interventions in chronic obstructive pulmonary disease and the role of the family: a systematic literature review.
Luker KA, Chalmers KI, Caress AL, Salmon MP.
School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK.

Aim. This paper is a report of a systematic review to assess the effectiveness of family-focused smoking cessation interventions for people with chronic obstructive pulmonary disease and to determine what data on families are documented in studies of smoking cessation interventions. Background. Chronic obstructive pulmonary disease is a major public health problem and cigarette smoking is the most important factor contributing to its development and progression. However, smoking cessation rates are low and relapse is common. The role of families in smoking cessation efforts has received little attention. Methods. All studies were included in the review that (i) addressed an evaluation of a psycho-social/educational smoking cessation intervention for people with chronic obstructive pulmonary disease, (ii) addressed some information on the family (i.e. living arrangements, marital status, smoking history of family members, support for quitting) and/or included the family as part of the intervention and (iii) were published between 1990 and 2006. Electronic data sources, existing systematic reviews of smoking cessation interventions and the grey literature were reviewed. Results. Seven studies were included. Six studies (11 papers) included data on marital status, smoking status of household members, support for quitting smoking and related variables. In two of the studies, the variable on the family was used to analyse smoking cessation outcomes. One additional study met the inclusion criterion of an evaluation of a smoking cessation intervention, which also included a family focus in the intervention. Conclusion. No conclusions about the effectiveness of a family-focused smoking cessation intervention could be drawn from this review. Further research is needed to determine if a more family-focused intervention, in conjunction with pharmacological and counselling approaches, would lead to improved smoking cessation outcomes.

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Clin Chest Med. 2007 Sep;28(3):639-653.
Update in Surgical Therapy for Chronic Obstructive Pulmonary Disease.
Lederer DJ, Arcasoy SM.
Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, Lung Transplantation Program, PH-14 East, Room 104, New York, NY 10032, USA; New York Presbyterian Hospital of Columbia and Cornell University, 622 West 168th Street, New York, NY 10032, USA.

Bullectomy for giant bullae, lung volume reduction surgery, and lung transplantation are three surgical therapies that may benefit highly selected patients with advanced chronic obstructive pulmonary disease. In this article, each procedure is reviewed, with an emphasis on guidelines for patient selection and clinical outcomes for the practicing pulmonologist. Recent results from the National Emphysema Treatment Trial, updated International Society for Heart and Lung Transplantation Registry data, and revised guidelines for patient selection for lung transplantation are discussed.

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Clin Chest Med. 2007 Sep;28(3):589-607.
Update on the pharmacologic therapy for chronic obstructive pulmonary disease.
Hanania NA, Sharafkhaneh A.
Asthma Clinical Research Center, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, 1504 Taub Loop, Houston, TX 77030, USA.

Chronic obstructive pulmonary disease is a treatable disease characterized by progressive airflow limitation. Prevention of disease progression; improvement of symptoms, exercise tolerance, and health status; and decrease in exacerbations and mortality are the goals of management. Inhaled short-acting bronchodilators are recommended for symptoms in mild disease, whereas inhaled long-acting bronchodilators are recommended for maintenance therapy of daily symptoms. When symptoms are not controlled using one bronchodilator, combining bronchodilators may be more effective. Combining a long-acting beta-agonist with an inhaled corticosteroid is more effective than either agent alone. Several novel therapies are in different stages of development.

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J Thorac Cardiovasc Surg. 2007 Jun;133(6):1434-8. Comment in: J Thorac Cardiovasc Surg. 2007 Jun;133(6):1412-3.
Lung-volume reduction surgery for pulmonary emphysema: Improvement in body mass index, airflow obstruction, dyspnea, and exercise capacity index after 1 year.
Lederer DJ, Thomashow BM, Ginsburg ME, Austin JH, Bartels MN, Yip CK, Jellen PA, Brogan FL, Kawut SM, Maxfield RA, DiMango AM, Simonelli PF, Gorenstein LA, Pearson GD, Sonett JR.
New York Presbyterian Lung Volume Reduction Surgery Program, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

OBJECTIVES: We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index, a multidimensional predictor of survival in chronic obstructive pulmonary disease. We also aimed to identify preoperative predictors of improvement in the BODE index. METHODS: In a prospective cohort study of patients undergoing lung-volume reduction surgery at our center, with the methodology of the National Emphysema Treatment Trial, we compared clinical characteristics before and 1 year after surgery with the Wilcoxon signed rank test. Changes in the BODE index were correlated with preoperative variables with the Spearman correlation coefficient. RESULTS: Twenty-three patients with predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction surgery (14 by video-assisted thoracoscopic surgery, 9 by median sternotomy). There were no postoperative or follow-up deaths. The BODE index improved from a median of 5 (interquartile range 4-5) before surgery to 3 (interquartile range 2-4) 1 year after surgery (P < .0001). Improvements were seen in the lung function and dyspnea components of the BODE index. Lower preoperative 6-minute walk distance and lower postwalk Borg fatigue scores were each associated with greater improvement in the BODE index after 1 year. CONCLUSION: Lung-volume reduction surgery for pulmonary emphysema improved the BODE index in patients with predominantly upper-lobe disease. Lower preoperative 6-minute walk distance correlated with greater improvement in the BODE index.

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Presse Med. 2007 Jun;36(6 Pt 2):936-44. Epub 2007 Apr 18.
[Combined pulmonary fibrosis and emphysema]
[Article in French]
Cottin V, Brillet PY, Nunes H, Cordier JF; Groupe d'étude et de recherche sur les maladies "orphelines" pulmonaires (GERM"O"P).
Service de pneumologie, Centre de référence des maladies orphelines pulmonaires, Hôpital Louis Pradel, Lyon, France. vincent.cottin@chu-lyon.fr

A syndrome including upper-lobe emphysema and pulmonary fibrosis of the lower lungs was recently characterized. It is found most often in men who are smokers or ex-smokers of more than 40 pack-years; their mean age is 65 years. Exertional dyspnea is always present. There are basal crackles. The disease has no known cause; the only certain risk factor is smoking. Pulmonary function tests show respiratory volumes and flows that are often normal or subnormal, while carbon monoxide transfer is substantially reduced and exercise hypoxemia is present. Diagnosis is based on findings from millimeter-slices of computed tomography of the chest, which show either centrilobular emphysema or upper-zone bullous emphysema, associated in 90% of cases with very suggestive paraseptal emphysema and diffuse infiltrating fibrosing lung disease at the bases (subpleural reticular opacities, honeycomb images, traction bronchiectasis), with more frequent ground glass opacities than in idiopathic pulmonary fibrosis. Pulmonary hypertension is present in almost half of all patients and represents the principal negative prognostic factor for this condition, which has a median survival of 6 years.

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Mo Med. 2007 May-Jun;104(3):255-9.
An overview of alpha-1 antitrypsin deficiency.
Hericks AJ, Bhat A.
University of Missouri-Kansas City School of Medicine and Truman Medical Center, USA. aehericks@comcast.net

Alpha-1 Antitrypsin Deficiency is a common hereditary disorder that results from abnormal Alpha Antitrypsin production. This predisposes patients to early onset emphysema especially when exposed to tobacco smoke. Early recognition is important. Smoking cessation and augmentation therapy are currently the only treatments available to slow the disease process. Surgical intervention may be palliative when medical and rehabilitation efforts have failed. This paper summarizes the current literature and presents an overview of AATD.

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Drugs Aging. 2007;24(8):615-28.
Is Combination Therapy with Inhaled Anticholinergics and beta(2)-Adrenoceptor Agonists Justified for Chronic Obstructive Pulmonary Disease?
Reddy CB, Kanner RE.
Department of Medicine, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.

Chronic obstructive pulmonary disease (COPD) is a debilitating condition characterised by progressive, irreversible airflow limitation. The economic and social burden of the disease is enormous. The treatment of COPD is guided by the stage of the disease and is aimed primarily at control of symptoms. Bronchodilators are the cornerstone of pharmacological management of COPD. Short-acting bronchodilators (beta(2)-adrenoceptor agonists and anticholinergics) have been available for many years and have been extensively studied as individual agents and in combination. When administered in combination, short-acting bronchodilators provide superior bronchodilation compared with individual agents given alone. However, the improvement in bronchodilation does not translate into an improvement in quality-of-life (QOL) indices. More recently, long-acting beta(2)-adrenoceptor agonists (LABAs) and anticholinergics have been introduced, and current guidelines recommend regular use of these agents in COPD of Global initiative for chronic Obstructive Lung Disease (GOLD) stage II or more. Combining short-acting anticholinergics with LABAs for daily use has been evaluated, but this combination does not confer any advantage in terms of subjective improvement or prevention of exacerbations. Combining the long-acting anticholinergic tiotropium bromide with formoterol given once or twice daily improves airway obstruction and hyperinflation. However, the effects of combinations of long-acting bronchodilators on patients' symptom scores, QOL and exacerbations remain to be studied. Ultra-LABAs, which are in development, may enable use of a combination of long-acting bronchodilators in a single inhaler for once-daily use, thus simplifying the regimen.This article discusses the results of various clinical trials comparing the efficacy of bronchodilators given alone or in combination to patients with COPD, with emphasis on the effects of these agents on bronchodilation, symptomatic and objective improvements in QOL and prevention of exacerbations.

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Acta Anaesthesiol Scand. 2007 May;51(5):559-64.
Low concentrations of inhaled nitric oxide do not improve oxygenation in patients with very severe chronic obstructive pulmonary disease.
Melsom MN, Flatebo T, Nicolaysen G.
The Glittre Clinic, Hakadal, Norway.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway narrowing that is most frequently inhomogeneously distributed. Ventilation/perfusion (V/Q) mismatch may explain much of the hypoxemia in patients with advanced disease. A potential treatment strategy would be to redistribute blood flow to well-ventilated lung regions in order to decrease V/Q mismatch. It has been suggested that inhaled nitric oxide (iNO) in physiologic concentrations ( approximately 100 p.p.b.) could act as a local vasodilating agent in well-ventilated lung regions. To test this, we included 10 volunteer patients with very severe COPD in this study. Methods: NO was mixed with O(2) and N(2) and administered through a face mask. The partial pressure of inspired oxygen (P(i)o(2)) did not change by more than +/- 0.5 kPa from the room air value. NO was given in 15-min periods at concentrations of approximately 0, approximately 40, approximately 400, approximately 4000 and approximately 40,000 p.p.b. (random order). During each NO exposure, arterial blood gases, methemoglobin and systemic blood pressure were measured every fifth minute. Results: None of the patients reported subjective effects of the different gas mixtures. The partial pressure of oxygen in arterial blood (P(a)o(2)) did not change by more than +/- 1.2 kPa from the baseline value, and there was no correlation between the change in P(a)o(2) and iNO concentration. No significant changes were found in blood pressure or methemoglobin during iNO. Conclusion: No significant effect of iNO at concentrations up to 40,000 p.p.b. in inspired gas was found on arterial blood gases. This indicates that neither low nor high concentrations of iNO improve oxygenation in patients with very severe COPD.

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Chest. 2007 Apr;131(4):1108-13.
Biological lung volume reduction: a new bronchoscopic therapy for advanced emphysema.
Reilly J, Washko G, Pinto-Plata V, Velez E, Kenney L, Berger R, Celli B.
Brigham and Women's Hospital, Pulmonary/Critical Care Medicine, 75 Francis St, Boston, MA 02115-6110, USA. jreilly@partners.org

BACKGROUND: Biological lung volume reduction (BLVR) using biological reagents to remodel and shrink damaged regions of lung has previously been accomplished in sheep with experimental pulmonary emphysema. This report summarizes the initial clinical experience including a 3-month follow-up using this technique in humans. METHODS: An open-label phase 1 trial designed to evaluate the safety of BLVR in patients with advanced heterogeneous emphysema enrolled six patients. Of these, three patients received unilateral treatment at two pulmonary subsegments (group 1) and three patients received unilateral treatment at four pulmonary subsegments (group 2). The incidence of adverse events and changes in pulmonary function test results, symptoms, and exercise capacity were evaluated. RESULTS: The mean (+/- SD) age of the six men enrolled in the study was 66 +/- 5.7 years (age range, 57 to 73 years). BLVR was well tolerated in both treatment groups and was not associated with any serious complications. All patients were discharged from the hospital on posttreatment day 1. Although the primary purpose of the study was to examine safety, improvements were observed in mean vital capacity (+7.2 +/- 9.5%; range, -2% to + 19%), mean residual volume (RV) [-7.8 +/- 8.5%; range, + 1% to -22%], mean RV/total lung capacity ratio (-6.6 +/- 4.7%; range, -1% to -15%), mean 6-min walk distance (+14.5 +/- 18.5%; range, 0 to + 51%), and in mean dyspnea score. On average, group 2 patients experienced greater benefit from BLVR than group 1 patients, suggesting a dose-response pattern. CONCLUSIONS: Preliminary results indicate that BLVR can be safe and may produce benefits in appropriately selected patients with advanced heterogeneous emphysema.

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Chest. 2007 Apr;131(4):1068-74.
Effects of a walking aid in COPD patients receiving oxygen therapy.
Crisafulli E, Costi S, De Blasio F, Biscione G, Americi F, Penza S, Eutropio E, Pasqua F, Fabbri LM, Clini EM.
University of Modena-Reggio Emilia, Department of Pulmonary Rehabilitation, Ospedale Villa Pineta, Italy, Via Gaiato 127, 41026 Pavullo n/F (MO), USA.

STUDY OBJECTIVES: To elucidate whether a simple walking aid may improve physical performance in COPD patients with chronic respiratory insufficiency who usually carry their own heavy oxygen canister. DESIGN: Randomized crossover trial. SETTING: Physiopathology laboratory of three rehabilitation centers. PATIENTS AND INTERVENTIONS: We studied 60 stable COPD patients (mean age, 70.6 +/- 7.9 years; FEV(1), 44.8 +/- 14.3% of predicted [+/- SD]) with chronic respiratory insufficiency who randomly performed, on 2 consecutive days, a standardized 6-min walking test using two different modalities: a full-weight oxygen canister transported using a small wheeled cart and pulled by the patient (Aid modality) or full-weight oxygen canister carried on the patient's shoulder (No-Aid modality). MEASUREMENTS AND RESULTS: The distance walked, peak effort dyspnea, and leg fatigue scores as primary outcomes, and other cardiorespiratory parameters as secondary outcomes were recorded during both tests. A significant difference (p < 0.05) between the two tests occurred for all the measured outcomes in favor of the Aid modality. Most importantly, significant changes for distance (+ 43 m, p < 0.001), peak effort dyspnea (- 2.0 points, p < 0.001), leg fatigue (- 1.4 points, p < 0.001), as well as for mean and nadir oxygen saturation and heart rate with the Aid modality (but not with the No-Aid modality) were recorded in the subgroup of patients walking < 300 m at baseline. CONCLUSIONS: This study suggests that a simple walking aid may be helpful in COPD patients receiving long-term oxygen therapy, particularly in those with lower residual exercise capacity.

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Am J Respir Crit Care Med. 2007 Apr 19; [Epub ahead of print]
Effect of Oxygen on Health Quality of Life in COPD Patients with Transient Exertional Hypoxemia.
Nonoyama ML, Brooks D, Guyatt GH, Goldstein RS.
Graduate Department of Rehabilitation Sciences, University of Toronto, Toronto, Ontario, Canada; Department of Respiratory Medicine, West Park Healthcare Centre, Toronto, Ontario, Canada.

RATIONALE: Ambulatory oxygen improves acute exercise performance in people with Chronic Obstructive Pulmonary Disease (COPD). This improvement may not translate into symptomatic benefit for patients, during activities of daily living. OBJECTIVES: We undertook a series of individual randomized controlled trials (N-of-1 RCTs) to measure the effect of oxygen in patients with COPD who do not meet criteria for mortality reduction with long-term oxygen therapy (LTOT). METHODS: Twenty-seven patients completed blinded N-of-1 RCTs, each comprising 3 pairs of 2-week home treatment periods, with oxygen provided during one period of each pair and a placebo mixture during the other. MEASUREMENTS: Patients completed the Chronic Respiratory Questionnaire (CRQ), the St. George's Respiratory Questionnaire (SGRQ), and a home 5 minute walk test (5MWT) at the end of each period. We defined a positive response as a CRQ dyspnea score greater (less dyspnea) on oxygen than placebo during all 3 pairs, with a difference >/=0.5 in at least 2 pairs. RESULTS: Oxygen significantly increased the 5MWT (427 versus 412 steps, p=0.04). Two of 27 patients met the responder criteria. Among the whole group, neither the CRQ nor the SGRQ showed any statistical or clinical differences between oxygen and placebo. CONCLUSIONS: This study does not support the general application of long-term ambulatory oxygen therapy for patients with COPD who do not meet criteria for mortality reduction with LTOT. N-of-1 RCTs can identify patients who may benefit.

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Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005372.
Oxygen therapy during exercise training in chronic obstructive pulmonary disease.
Nonoyama M, Brooks D, Lacasse Y, Guyatt G, Goldstein R.

BACKGROUND: Exercise training within the context of pulmonary rehabilitation improves outcomes of exercise capacity, dyspnea and health-related quality of life in individuals with chronic obstructive pulmonary disease (COPD). Supplemental oxygen in comparison to placebo increases exercise capacity in patients performing single-assessment exercise tests. The addition of supplemental oxygen during exercise training may enable individuals with COPD to tolerate higher levels of activity with less exertional symptoms, ultimately improving quality of life. OBJECTIVES: To determine how supplemental oxygen in comparison to control (compressed air or room air) during the exercise-training component of a pulmonary rehabilitation program affects exercise capacity, dyspnea and health-related quality of life in individuals with COPD. SEARCH STRATEGY: All records in the Cochrane Airways Group Specialized Register of trials coded as 'COPD' were searched using the following terms: (oxygen* or O2*) AND (exercis* or train* or rehabilitat* or fitness* or physical* or activ* or endur* or exert* or walk* or cycle*). Searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE and CINAHL databases identified studies. The last search was carried out in June 2006. SELECTION CRITERIA: Only randomized controlled trials (RCTs) comparing oxygen-supplemented exercise training to non-supplemented exercise training (control group) were considered for inclusion. Participants were 18 years or older, diagnosed with COPD and did not meet criteria for long-term oxygen therapy. No studies with mixed populations (pulmonary fibrosis, cystic fibrosis, etc) were included. Exercise training was greater than or equal to three weeks in duration and included a minimum of two sessions a week. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review and extracted data. Weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated using a random-effects model. Missing data were requested from authors of primary studies. MAIN RESULTS: Five RCTs met the inclusion criteria. The maximum number of studies compared in the meta-analysis was three (31 on oxygen versus 32 control participants), because all included studies did not measure the same outcomes. When two studies were pooled, statistically significant improvements of oxygen-supplemented exercise training were found in constant power exercise time, WMD 2.68 minutes (95% CI 0.07 to 5.28 minutes). Supplemental oxygen increased the average exercise time from 6 to 14 minutes; the control intervention increased average exercise time from 6 to 12 minutes. Constant power exercise end-of-test Borg score (on a scale from 1 to 10) also showed statistically significant improvements with oxygen-supplemented exercise training, WMD -1.22 units (95% CI -2.39 to -0.06). One study showed a significant improvement in the change of Borg score after the shuttle walk test, by -1.46 units (95% CI -2.72 to -0.19). There were no significant differences in maximal exercise outcomes, functional exercise outcomes (six-minute walk test), shuttle walk distance, health-related quality of life or oxygenation status. According to the GRADE system most outcomes were rated as low quality because they were limited by study quality. AUTHORS' CONCLUSIONS: This review provides little support for oxygen supplementation during exercise training for individuals with COPD, but the evidence is very limited. Studies with larger number of participants and strong design are required to permit strong conclusions, especially for functional outcomes such as symptom alleviation, health-related quality of life and ambulation.

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Cochrane Database Syst Rev. 2007 Apr 18;(2):CD002991.
Inhaled corticosteroids for stable chronic obstructive pulmonary disease.
Yang Ia, Fong K, Sim E, Black P, Lasserson T.

BACKGROUND: The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much controversy. Major international guidelines recommend selective use of ICS. Recently published meta-analyses have reported conflicting findings on the effects of inhaled steroid therapy in COPD. OBJECTIVES: The objective of the review is to determine the efficacy of regular use of inhaled corticosteroids in patients with stable COPD. SEARCH STRATEGY: A pre-defined search strategy was used to search the Cochrane Airways Group specialised register for relevant literature. Searches are current as of October 2006. SELECTION CRITERIA: We selected randomised trials comparing any dose of any type of inhaled steroid with a placebo control in patients with COPD. Acute bronchodilator reversibility to short term beta2-agonists and bronchial hyperresponsiveness were not exclusion criteria. The a priori primary outcome was change in lung function. Data on mortality, exacerbations, quality of life and symptoms, rescue bronchodilator use, exercise capacity, biomarkers and safety were also analysed. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Forty-seven primary studies with 13,139 participants met the inclusion criteria. Medium term use of ICS (> two months and up to six months) resulted in a small improvement in FEV1 in some studies. Long term use of ICS (> six months) did not significantly reduce the rate of decline in FEV1 in COPD patients (weighted mean difference (WMD) 5.80 ml/year with ICS over placebo, 95% CI -0.28 to 11.88, 2333 participants). There was no statistically significant effect on mortality in COPD patients (OR 0.98, 95% CI 0.83 to 1.16, 8390 participants). Long term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (WMD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (WMD -1.22 units/year, 95% CI -1.83 to -0.60, 2507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.49, 95% CI 1.78 to 3.49, 4380 participants) and hoarseness. The few long term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over 3 years. AUTHORS' CONCLUSIONS: Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life), against the known increase in local side effects (oropharyngeal candidiasis and hoarseness). The risk of long term adverse effects is unknown.

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Crit Care. 2007 Mar 26;11(2):210 [Epub ahead of print]
Clinical review: Long-term noninvasive ventilation.
Robert D, Argaud L.
Emergency and Medical Intensive Care Department, Edouard Herriot Hospital, Place d'Arsonval, Lyon, F-69008, France. laurent.argaud@chu-lyon.fr.

ABSTRACT: Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected to improve patient outcomes, reduce ICU admission, enhance patient comfort, and increase the efficiency of health care resource utilization. Current literature indicates that noninvasive ventilation improves and stabilizes the clinical course of many patients with chronic ventilatory failure. Noninvasive ventilation also permits long-term mechanical ventilation to be an acceptable option for patients who otherwise would not have been treated if tracheostomy were the only alternative. Nevertheless, these results appear to be better in patients with neuromuscular/-parietal disorders than in chronic obstructive pulmonary disease. This clinical review will address the use of noninvasive ventilation (not including continuous positive airway pressure) mainly in diseases responsible for chronic hypoventilation (that is, restrictive disorders, including neuromuscular disease and lung disease) and incidentally in others such as obstructive sleep apnea or problems of central drive.

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Thorac Cardiovasc Surg. 2007 Feb;55(1):48-52.
Quantitative lung perfusion following single lung transplantation.
Starobin D, Shitrit D, Steinmetz A, Fink G, Hardoff R, Kramer MR.
Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petach-Tikva and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

BACKGROUND: Following successful lung transplantation, most of the lung perfusion, as well as ventilation, is shifted towards the transplanted lung. We investigated the changes in perfusion during exercise in lung transplant recipients. PATIENTS AND METHODS: Twelve patients were included in the study. Six patients had emphysema and 6 patients had idiopathic pulmonary fibrosis (IPF). Patients underwent two upright lung perfusion scans: the first at rest and the second during a maximal cardiopulmonary exercise test. Lung perfusion was assessed in each lung and regionally. RESULTS: At rest, patients with emphysema had 83.3 +/- 8 % of total perfusion to the transplanted side and 16.7 +/- 8 % to the native lung, while in the IPF patients, it was 68.7 +/- 12 and 32.7 +/- 10 %, respectively ( P = 0.028). At peak exercise, perfusion shifted from the transplanted lung to the native lung ( P = 0.0095) both in emphysema and IPF patients. CONCLUSIONS: Following successful lung transplantation, most of the perfusion is directed towards the transplanted lung. During exercise, there was a small but significant shift towards the native lung. These findings highlighted the important role of the native lung during maximal exercise.

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Drugs Aging. 2007;24(4):303-24.
Management of acute exacerbations of chronic obstructive pulmonary disease in the elderly : an appraisal of published evidence.
Kunisaki KM, Rice KL, Niewoehner DE.
University of Minnesota, Minneapolis, Minnesota, USA.

Chronic obstructive pulmonary disease (COPD) is a debilitating disease with rising worldwide prevalence. Exacerbations of COPD cause significant morbidity and become more common with advancing age. Healthcare providers caring for elderly patients should therefore be familiar with effective treatments for exacerbations of COPD. An extensive body of literature has identified several effective drug therapies for exacerbations. These drugs include inhaled bronchodilators, systemic corticosteroids and antibacterials. The two main classes of inhaled bronchodilators are beta-adrenoceptor agonists and anticholinergics. These drugs optimise lung function during exacerbations, with neither class demonstrating clear superiority over the other. Systemic corticosteroids are effective when used either for inpatient or outpatient treatment of exacerbations. They hasten recovery from exacerbations and reduce relapse rates. Antibacterials decrease morbidity from exacerbations and may decrease mortality in the more severe exacerbations. Other effective therapies for the treatment of acute exacerbations of COPD include oxygen and non-invasive ventilation. Oxygen can be safely administered in acute exacerbations associated with hypoxaemia, with titration of oxygen delivery to a goal oxygen saturation of 90%. Non-invasive ventilation reduces the morbidity and mortality associated with acute exacerbations complicated by hypercapnic respiratory failure. Strategies to prevent COPD exacerbations include smoking cessation, long-acting inhaled beta-adrenoceptor agonists, inhaled long-acting anticholinergics, inhaled corticosteroids and vaccination. Mucolytic agents, pulmonary rehabilitation, and case management programmes may also reduce exacerbation risk, but the current evidence supporting these interventions is weaker.

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J Thorac Cardiovasc Surg. 2007 Jan;133(1):65-73. Epub 2006 Dec 1.
A multicenter trial of an intrabronchial valve for treatment of severe emphysema.
Wood DE, McKenna RJ Jr, Yusen RD, Sterman DH, Ost DE, Springmeyer SC, Gonzalez HX, Mulligan MS, Gildea T, Houck WV, Machuzak M, Mehta AC.
Division of Cardiothoracic Surgery, the University of Washington, Seattle, Wash 98195-6310, USA. dewood@u.washington.edu

OBJECTIVES: Minimally invasive endoscopic treatment of emphysema could provide palliation with less risk than lung volume reduction surgery and offer therapy to patients currently not considered for lung volume reduction surgery. The Intrabronchial Valve is used to block bronchial airflow in the most emphysematous areas of lung. METHODS: Patients with severe chronic obstructive pulmonary disease and heterogeneous upper lobe-predominant emphysema were eligible. Patients underwent flexible bronchoscopic placement of valves into segmental or subsegmental airways in both upper lobes. Outcomes assessed over a minimum of 6 months of follow-up included the safety, feasibility, tolerance, and success of valve placement; health-related quality of life; exercise capacity; pulmonary function; and gas exchange. RESULTS: Five centers treated 30 patients. Patient follow-up ranged from 1 to 12 months. A mean of 6.1 valves were placed per patient. Valves were positioned by means of flexible bronchoscopy in 99% of desired airways, and the procedure duration ranged from 15 to 125 minutes (mean, 65 minutes). Hospital discharge occurred within 2 days in 27 of 30 patients. There were no deaths or episodes of valve migration, tissue erosion, or significant bleeding. Eighty-three percent of patients had no adverse events judged probably or definitely related to the device. Patients experienced significant improvement in health-related quality of life, although the physiologic and exercise outcomes did not show statistically significant improvements. CONCLUSIONS: These first multicenter results with the Intrabronchial Valve demonstrate significant improvements in health-related quality of life and acceptable safety, ease of use, and procedural complication rates. The valve might be a safer and less-invasive alternative to surgical therapy for patients with severe emphysema.

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Ann Thorac Surg. 2007 Jan;83(1):241-51.
Lung volume reduction surgery in patients with emphysema and alpha-1 antitrypsin deficiency.
Stoller JK, Gildea TR, Ries AL, Meli YM, Karafa MT; National Emphysema Treatment Trial Research Group.
Division of Medicine, Section of Respiratory Therapy, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. stollej@ccf.org

BACKGROUND: The role of lung volume reduction surgery (LVRS) for individuals with alpha-1 antitrypsin (AAT) deficiency is unclear. METHODS: To assess the role of LVRS in individuals with severe deficiency of AAT, outcomes within the National Emphysema Treatment Trial were analyzed. RESULTS: Of 1218 randomized subjects, 16 (1.3%) had severe AAT deficiency (serum level < 80 mg/dL) and a consistent phenotype (when available). Characteristics of these 16 patients include 87.5% male; median serum AAT level, 55.5 mg/dL; age, 66 years; forced expiratory volume in 1 second (FEV1), 27% predicted; and 50% had upper-lobe-predominant emphysema. All 10 subjects randomized to LVRS underwent the procedure. Although the small number of subjects hampered statistical analysis, 2-year mortality was higher with surgery (20% versus 0%) than with medical treatment. Comparison of outcomes between the 10 AAT-deficient and the 554 AAT-replete subjects undergoing LVRS showed a greater increase in exercise capacity at 6 months in replete subjects and a trend toward lower and shorter duration FEV1 rise in deficient individuals. CONCLUSIONS: This study extends to 49 cases the published experience of LVRS in severe AAT deficiency. Although the small number of subjects precludes firm conclusions, trends of lower magnitude and duration of FEV1 rise after surgery in AAT-deficient versus AAT-replete subjects and higher mortality in deficient individuals randomized to surgery versus medical treatment suggest caution in recommending LVRS in AAT deficiency.

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Arch Bronconeumol. 2006 Dec;42(Supl.2):32-37.
Endoscopic treatment of emphysema.
[Article in English, Spanish]
Sauleda Roig J.
Servei de Pneumologia. Hospital Son Dureta. Palma de Mallorca. Fundacio Caubet-CIMERA. Bunyola. Illes Balears. Espana. jsauleda@hsd.es.

Severe pulmonary emphysema causes substantial morbidity and mortality. This disease can be treated with lung volume reduction surgery (LVRS) but only a subgroup of patients will derive a benefit and the procedure is not free of severe adverse effects. Bronchoscopic lung volume reduction (BLVR) is a minimally invasive procedure without the adverse effects of LVRS. Due to its ease of use and effectiveness, the most commonly employed method is endobronchial valve placement through fiberoptic bronchoscopy under local anesthetic. Nevertheless, a subgroup of patients will not improve due to an increase in collateral ventilation. These patients may be suitable for BLVR using other techniques such as airway bypass through bronchial fenestration. Although studies performed with valves are encouraging, the results of two controlled multicenter studies should be known before this technique is implemented in clinical practice.

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J Thorac Cardiovasc Surg. 2006 Nov;132(5):1203-7.
Longitudinal changes in hyperinflation parameters and exercise capacity after giant bullous emphysema surgery.
Neviere R, Catto M, Bautin N, Robin S, Porte H, Desbordes J, Matran R.
Explorations Fonctionnelles Respiratoires, Hopital Calmette, CRHU Lille, France. rneviere@univ-lille2.fr

OBJECTIVE: Although resection of giant bullae for the purpose of improving the function of underlying compressed lung is an accepted form of surgery for emphysema, there is only limited information regarding long-term improvement in dynamic hyperinflation and exercise tolerance. Our major goal was to investigate the effects of lung resection for giant bullae on pulmonary function, dynamic hyperinflation, and exercise capacity in patients with chronic obstructive pulmonary disease characterized by emphysema. METHODS: Pulmonary function and exercise testing were assessed prospectively before and 3, 6, 12, 24, and 48 months after surgery in 12 patients who had chronic obstructive pulmonary disease with emphysema who underwent lung resection of giant bullae. RESULTS: Forced expiratory volume, diffusing capacity for carbon monoxide, arterial partial pressure of oxygen, and exercise capacity were significantly increased after resection of surgical bullae. Dynamic hyperinflation, as assessed by reduction in inspiratory capacity and dyspnea Borg scale, were significantly decreased during exercise. Improvement in baseline and exercise functional capacity slightly decreased over time, remaining, however, far above the value before surgery. CONCLUSION: Altogether, these findings suggest that surgery for resection of giant bullae is an effective procedure for improving airflow, limiting gas exchange, and limiting exercise dynamic hyperinflation over time.

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Ann Thorac Surg. 2006 Aug;82(2):431-43. Comment in: Ann Thorac Surg. 2006 Aug;82(2):385-7.
Long-term follow-up of patients receiving lung-volume-reduction surgery versus medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group.
Naunheim KS, Wood DE, Mohsenifar Z, Sternberg AL, Criner GJ, DeCamp MM, Deschamps CC, Martinez FJ, Sciurba FC, Tonascia J, Fishman AP; National Emphysema Treatment Trial Research Group.
St. Louis University, 3635 Vista Blvd, St. Louis, MO 63110-0250, USA. naunheim@slu.edu

BACKGROUND: The National Emphysema Treatment Trial defined subgroups of patients with severe emphysema in whom lung-volume-reduction surgery (LVRS) improved survival and function at 2 years. Two additional years of follow-up provide valuable information regarding durability. METHODS: A total of 1218 patients with severe emphysema were randomized to receive LVRS or medical treatment. We present updated analyses (4.3 versus 2.4 years median follow-up), including 40% more patients with functional measures 2 years after randomization. RESULTS: The intention-to-treat analysis of 1218 randomized patients demonstrates an overall survival advantage for LVRS, with a 5-year risk ratio (RR) for death of 0.86 (p = 0.02). Improvement was more likely in the LVRS than in the medical group for maximal exercise through 3 years and for health-related quality of life (St. George's Respiratory Questionnaire [SGRQ]) through 4 years. Updated comparisons of survival and functional improvement were consistent with initial results for four clinical subgroups of non-high-risk patients defined by upper-lobe predominance and exercise capacity. After LVRS, the upper-lobe patients with low exercise capacity demonstrated improved survival (5-year RR, 0.67; p = 0.003), exercise throughout 3 years (p < 0.001), and symptoms (SGRQ) through 5 years (p < 0.001 years 1 to 3, p = 0.01 year 5). Upper-lobe-predominant and high-exercise-capacity LVRS patients obtained no survival advantage but were likely to improve exercise capacity (p < 0.01 years 1 to 3) and SGRQ (p < 0.01 years 1 to 4). CONCLUSIONS: Effects of LVRS are durable, and it can be recommended for upper-lobe-predominant emphysema patients with low exercise capacity and should be considered for palliation in patients with upper-lobe emphysema and high exercise capacity.

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Chest. 2006 Jul;130(1):190-9.
Transbronchoscopic pulmonary emphysema treatment: 1-month to 24-month endoscopic follow-up.
de Oliveira HG, Macedo-Neto AV, John AB, Jungblut S, Prolla JC, Menna-Barreto SS, Fortis EA.
Department of Thoracic Surgery, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Sala 2050 MI CEP, 90035-004 Porto Alegre, RS, Brazil. hugo@oliveira.com

OBJECTIVE: Describe the results of a 1- to 24-month follow-up of individuals undergoing transbronchoscopic placement of one-way valves. DESIGN: Longitudinal, noncomparative study. SETTING: University hospital. PATIENTS: Nineteen heterogeneous emphysema patients. MEASUREMENTS AND RESULTS: Pulmonary function testing, imaging examination, and videobronchoscopy were performed at 1, 3, 6, 12, and 24 months after the insertion of one-way valves. Mean age was 67.63 +/- 8.71 years, mean body mass index (BMI) was 24.02 +/- 2.65, and mean exposure to smoking was 65.32 +/- 27.46 pack-years (+/- SD). Baseline BODE index (BMI, degree of airflow obstruction and dyspnea, exercise capacity as measured by the 6-min walk test [6MWT]) was 7 to 10 in 10 patients (estimated 4-year mortality, 80%) and 5 to 6 in 9 patients (estimated 4-year mortality, 40%). Sixty-four valves were inserted. There was no procedure-related mortality. Nonsustained atelectasis was observed within 48 h in 2 of 12 patients with right upper lobe occlusion. Fifty-six bronchoscopic examinations were performed in 24 months. Granulomas not requiring treatment were the main complication. Mucus clogging the valve, mainly at 1 month, was easily cleaned. Eighteen patients completed the 1- and 3-month follow-ups, 14 patients completed the 6-month follow-up, 11 patients completed the 12-month follow-up, and 5 patients completed the 24-month follow-up. Improvement was observed in the 6MWT after 1 month (p = 0.028) and in the BODE index at 3 months (p = 0.002). FEV1 or FVC improvement > or = 12% or > or = 150 mL was observed, respectively, in 4 of 18 patients and 8 of 18 patients at 1 month, 4 of 18 patients and 7 of 18 patients at 3 months, and in 3 of 14 patients and 5 of 14 patients at 6 months. After 24 months, one of five patients and three of five patients, respectively, retained an FEV1 and FVC change > or = 12% or > or = 150 mL. Significant improvement (decrease > or = 4%) in the St. George Respiratory Questionnaire was observed at 3 months and 6 months in three of four domains. CONCLUSION: Endobronchial valves are safe, but the criteria to measure improvement and to select patients should be refined. Atelectasis should be reconsidered as primary treatment goal.

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Ann Thorac Surg. 2006 Jul;82(1):208-13; discussion 213.
Lung-volume reduction surgery as an alternative or bridging procedure to lung transplantation.
Tutic M, Lardinois D, Imfeld S, Korom S, Boehler A, Speich R, Bloch KE, Russi EW, Weder W.
Department of Thoracic Surgery, and Division of Pulmonary Medicine, University Hospital, Zurich, Switzerland.

BACKGROUND: In this study, we prospectively analyzed the functional outcome and the survival after lung-volume reduction surgery (LVRS) in patients with end-stage emphysema who were initially potential candidates for lung transplantation (LTX), and investigated the impact of LVRS on posttransplant course in patients who underwent LTX after LVRS. METHODS: Of the 216 patients who underwent LVRS between 1994 and 2005, 58 were potential candidates for LTX at the time of LVRS (age 65 years or younger, forced expiratory volume in 1 second 25% of predicted or less; LVRS/LTX group). Lung-volume reduction surgery was performed by means of video-assisted, bilateral stapled resection of target areas. During the same period, 31 patients underwent primary LTX for end-stage emphysema (LTX group). Spirometry, plethysmography, carbon monoxide diffusing capacity, 6-minute walking distance, and dyspnea score were assessed preoperatively and at predetermined times after operation. Survival analysis was performed by use of the Kaplan-Meier method. RESULTS: All the functional variables significantly improved after LVRS and peaked within the first year. Subjective improvement was observed for up to 5 years after LVRS, and 53% (31 of 58) of the patients were still alive and had not undergone transplantation after a median follow-up of 44 months. Fourteen percent (8 of 58) of the patients underwent secondary LTX because of progressive worsening of the respiratory function after a median bridging time between LVRS and LTX of 33 months. Postoperative recovery after transplantation and median survival time were comparable between the 8 patients of the LVRS/LTX group and the 31 patients of the LTX group (96.5 months versus 118.5 months, p = 0.9). CONCLUSIONS: Lung-volume reduction surgery can significantly improve symptoms and lung function in selected patients who are initially potential candidates for LTX. Lung-volume reduction surgery can allow the postponement of LTX for up to 4 to 5 years and does not impair the chances for a subsequent successful LTX.
 

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