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PubMed1992

Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema.

Transgenic mice were generated that expressed a human collagenase transgene in their lungs under the direction of the haptoglobin promoter. Histological analysis demonstrated disruption of the alveolar walls and coalescence of the alveolar spaces with no evidence of fibrosis or inflammation. This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process. Although elastase has been proposed as the primary enzyme responsible for emphysematous lung damage, this study provides evidence that other extracellular matrix proteases could play a role in emphysema. In addition, these transgenic mice are a defined genetic animal model system to study the pathogenesis of emphysema.

Animals↗
PubMed1989

Use of laboratory animal models in investigating emphysema and cigarette smoking in humans.

To increase our understanding of biological systems, the first step is to make an observation at the level of organization that we wish to understand. It has yet to be conclusively shown that any laboratory animal has contracted emphysema solely as a result of exposure to cigarette smoke. Available mechanism-of-response studies at the tissue, cellular, or biochemical level of organization are not useful in elucidating the relationship between emphysema and exposure to cigarette smoke without an animal model for the disease. If progress in understanding the etiology of emphysema from cigarette smoking is judged to be important to the scientific and regulatory communities, the highest priority should be given to discovering a suitable animal model.

Animals↗
PubMed1994

Spontaneous subcutaneous emphysema.

Subcutaneous emphysema is an unusual complication of bronchiolitis. The investigators describe a patient with bronchiolitis who developed extensive subcutaneous emphysema. Despite an alarming appearance, the patient recovered with symptomatic care and observation. Review of the literature shows a multitude of causes of subcutaneous emphysema. The vast majority of cases resolve without intervention.

Bronchiolitis↗
PubMed2006

Lung volume reduction surgery allows esophageal tumor resection in selected esophageal carcinoma with severe emphysema.

BACKGROUND: Esophageal carcinoma patients with coexisting severe emphysema are high risk surgical candidates. We hypothesize that simultaneous unilateral lung volume reduction surgery (LVRS) allows us to offer esophageal tumor resection to patients previously considered inoperable. METHODS: Twenty-one patients with esophageal carcinoma were recruited. All patients had severe emphysema with impaired respiratory function and health-related quality of life (HRQL). Esophageal tumor resection with gastroesophagostomy in the thorax and then unilateral LVRS were performed at the same anesthesia. Dyspnea index, exercise capacity, pulmonary function, and HRQL were assessed at baseline and every three months up to one year postoperatively. RESULTS: There was no perioperative death or significant morbidity. Clinical improvements were observed at 3, 6, and 12 months, in terms of dyspnea index, forced expiratory volume in 1 second, residual volume, partial pressure of oxygen, arterial, partial pressure of carbon dioxide, arterial, 6-minute walking distance, dysphagia, and odynophagia (p < 0.01 or p < 0.05). The Karnofsky Performance Status score improved from baseline 36 +/- 3 to 53 +/- 3 at 3 months, 67 +/- 5 at 6 months, and 63 +/- 8 at 12 months (p < 0.01). Significant improvement was seen in all the Short-Form 36-item Health Survey HRQL domains at 3 months (p < 0.01 or p < 0.05). These improvements remained significant for up to 6 months, and for up to 12 months for physical functioning and general health. The Psychosocial Adjustment to Illness Scale score and all the scales were improved after surgery (p < 0.01). CONCLUSIONS: Our study shows that in selected patients with esophageal carcinoma who suffer from severe emphysema, simultaneous unilateral LVRS renders esophageal tumor resection safe and effective. Also, these patients may experience early improvement in pulmonary function and HRQL.

Aged↗
PubMed2006

Bronchoscopic procedures for emphysema treatment.

Emphysema is a debilitating lung disease continuing to be a major source of morbidity and mortality in the developed countries. Medical treatment is the mainstay of therapy and consists of smoking cessation, pulmonary rehabilitation, administration of bronchodilators and, when indicated, steroids and supplemental oxygen. Various surgical procedures have been promoted in the past to relieve dyspnoea and improve quality of life in patients with advanced emphysema; whilst early results were often encouraging, a sustained objective functional improvement was rarely achieved and most of those procedures were progressively abandoned. Despite controversies, LVRS has been shown to be beneficial to selected patients with end-stage emphysema when medical therapy has failed. There is no doubt that LVRS allows a significative functional improvement in a selected group of patients; however, it still carries a substantial morbidity, even if mortality is low at the centres with the larger experience. Patients with a most advanced functional deterioration show a higher surgical mortality and less impressive functional results, suggesting that LVRS should be considered more carefully in these situations. Bronchoscopic alternatives to the surgical approach have been recently proposed and some of them may play an important role in the future; in particular, the airway bypass and bronchoscopic lung volume reduction with one-way valves are certainly one step beyond on their way to clinical application. We hereby report the initial experimental and clinical experience with these new treatment options.

Animals↗
PubMed2007

Is there a role for therapeutic lobectomy for emphysema?

OBJECTIVE: The feasibility of performing a standard lobectomy in patients with non-small cell lung cancer (NSCLC) and severe heterogeneous emphysema whose respiratory reserve is outside standard operability guidelines has been described [Edwards JG, Duthie DJR, Waller DA. Lobar volume reduction surgery: a method of increasing the lung cancer resection rate in patients with emphysema. Thorax 2001;56:791-5; Korst RJ, Ginsberg RJ, Ailawadi M, Bains MS, Downey RJ, Rusch V, Stover D. Lobectomy improves ventilatory function in selected patients with severe COPD. Ann Thorac Surg 1998;66:898-902; Carretta A, Zannini P, Puglisi A, Chiesa G, Vanzulli A, Bianchi A, Fumagalli A, Bianco S. Improvement in pulmonary function after lobectomy for non-small cell lung cancer in emphysematous patients. Eur J Cardiothorac Surg 1999;15(5):602-7]. Postoperative lung function was better than predicted, attributable to the therapeutic benefit of deflation of the hemithorax. Our aim was to determine whether the physiological benefits of this approach were superior to conventional non-anatomical lung volume reduction surgery (LVRS) in similar patients. METHODS: A retrospective review of a single surgeon's experience identified 34 consecutive patients who underwent upper lobectomy for completely resected stage I-II NSCLC, and who had severe heterogeneous emphysema of apical distribution with a predicted postoperative FEV1 of less than 40%. Their perioperative characteristics, postoperative spirometry and survival of these cases were compared to 46 similar patients who underwent unilateral upper lobe LVRS during the same period. RESULTS: Data expressed as median (range). LVRS patients were significantly younger (59 years [39-70] vs 67 years [48-79] p<0.001), with more severe airflow obstruction (FEV(1) %pred 24 [12-60] vs 44 [17-54] p<0.001) and more heterogenous disease ('Q' score 4 [0.5-11.5] vs 7 [1-13] p=0.001) than the lobectomy group. No significant difference was found in median survival (88 vs 53 months, p=0.06). Lobectomy patients had a shorter air leak duration (5 days [2-36] vs 9 days [1-40], p=0.02) and hospital stay (8 days [3-63] vs 13 days [6-90] p=0.01). A significant correlation was found between pre-operative Q score and percentage improvement in FEV1 (r=-0.33, p=0.02). CONCLUSIONS: Lobectomy for lung cancer in patients in severe heterogenous chronic obstructive pulmonary disease is associated with similar improvement in airflow obstruction as conventional LVRS, but is associated with a shorter postoperative course. Lobectomy may therefore offer a therapeutic alternative to conventional LVRS in a selected population.

Adult↗
PubMed2004

Lung cancer resection combined with lung volume reduction in patients with severe emphysema.

OBJECTIVE: Certain patients with resectable lung cancer and severe respiratory limitation due to emphysema may have a suitable operative risk by combining cancer resection with lung volume reduction surgery. The purpose of this study is to review our experience with such patients. METHODS: A review was conducted on 21 patients with lung cancer in the setting of severe emphysema who underwent an operation designed to provide complete cancer resection and volume reduction effect. RESULTS: In the 21 patients, the mean preoperative forced expiratory volume in 1 second was 0.7 +/- 0.2 L (29% predicted), residual volume was 5.5 +/- 1.0 L (271%), and diffusing capacity for carbon monoxide was 8.0 +/- 2.2 mL/min/mm Hg (34% predicted). In 9 patients, the cancer was located in a severely emphysematous lobe and the lung volume reduction surgery component of the procedure was accomplished with lobectomy alone. In the remaining 12 patients, the cancer resection lobectomy (n = 9) and wedge resection (n = 3) were supplemented with lung volume reduction surgery. Final pathologic staging was stage I in 16 patients, stage II in 2 patients, and stage III in 2 patients. One patient was found to have stage IV disease due to multifocal tumors in separate lobes. There were no hospital deaths. Postoperative complications included prolonged air leak in 11 patients, atrial fibrillation in 6 patients, and reintubation for ventilatory assistance in 2 patients. All patients showed improved lung function postoperatively. Survival was 100% and 62.7% at 1 and 5 years, respectively. CONCLUSIONS: Patients with severe emphysema and resectable lung cancer who have a favorable anatomy for lung volume reduction surgery may undergo a combined cancer resection and lung volume reduction surgery with an acceptable risk and good long-term survival.

Aged↗
PubMed2006

A multicenter trial of an intrabronchial valve for treatment of severe emphysema.

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.

Adult↗
PubMed2006

Longitudinal changes in hyperinflation parameters and exercise capacity after giant bullous emphysema surgery.

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.

Aged↗
PubMed2006

Dynamic lung mechanics in late-stage emphysema before and after lung volume reduction surgery.

This study evaluated the effects of lung volume reduction surgery (LVRS) on the heterogeneity of lung function in awake, late-stage emphysema patients with measurements taken before and after full recovery from LVRS. We assessed standard clinical measures of lung function and functional heterogeneity in six awake, late-stage emphysema patients before and 6 months after LVRS. Functional heterogeneity was quantified by measuring dynamic inspiratory resistance (R(L)(insp)) and elastance (E(L)(insp)) over a frequency range that included normal breathing ( approximately 0.33-8 Hz). Since LVRS involves targeted resection of emphysematous regions of the lung, we hypothesized that emphysema patients would be functionally more homogeneous post-LVRS. We also compared our measures of functional heterogeneity with indices of anatomic heterogeneity and severity using high-resolution computed tomography (HRCT). After LVRS, 6 min walk distance increased by 22% (940+/-91 versus 1158+/-299, p=0.031) and recoil pressure at TLC increased (9.0+/-2.0 versus 14+/-5, p=0.031), but changes in R(L)(insp) and E(L)(insp) varied greatly between subjects. A measure of anatomic severity quantified using HRCT positively correlated with airway resistance (r(s)=0.89, p=0.048). These results suggest that subjects with more severe disease as assessed by HRCT criteria had reduced overall effective airway caliber consequent to active airway constriction, reduced parenchymal tethering, and/or loss of parallel lung units. Furthermore, LVRS may not necessarily improve lung function via a substantial reduction in mechanical heterogeneity.

Adolescent↗
PubMed2005

Repeated cadmium nebulizations induce pulmonary MMP-2 and MMP-9 production and emphysema in rats.

This study describes induction of pulmonary inflammation, production of matrix metalloprotease of type 2 (MMP-2) and type 9 (MMP-9), and emphysema in cadmium (Cd)-exposed rats. Sprague-Dawley rats were randomly distributed into two groups: one placebo-exposed group undergoing saline (NaCl 0.9%) inhalation (n=30) and one Cd-exposed group undergoing cadmium (CdCl(2) 0.1%) inhalation (n=30). The animals of the placebo- and Cd-exposed groups were divided in five subgroups (n=6). Subgroups underwent either a single exposure of 1h or repeated exposures three times weekly for 1h during 3 weeks (3W), 5 weeks (5W), 5 weeks followed by 2 weeks without exposure (5W+2) or 5 weeks followed by 4 weeks without exposure (5W+4). Each animal underwent determination of enhanced pause (Penh) as index of airflow limitation prior to the first exposure as well as before sacrifice. The animals were sacrificed the day after their last exposure. The left lung was fixed for histomorphometric analysis (determination of median interwall distance (MIWD)), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. BALF was analyzed cytologically, and MMP-2 and MMP-9 levels were determined by gelatine zymography. Twelve rats previously instilled with pancreatic elastase were used as positive emphysema controls and underwent the same investigations. Cd-exposure induced a significant increase of BALF macrophages, neutrophils and MMP-9 up to 5W+4, whereas MMP-2 gelatinolytic activity returned to baseline levels within 5W. MIWD was significantly increased in all repeatedly Cd-exposed groups and elastase-treated rats. Penh was increased in Cd-exposed rats after a single exposure and after 3W. MMP gelatinolytic activity was significantly correlated with macrophages, neutrophils and Penh. In repeatedly exposed rats, MIWD was positively and significantly correlated with MMP gelatinolytic activity, suggesting that increased MMP-2 and MMP-9 production favours the development of emphysema.

Administration, Inhalation↗
PubMed2006

Perioperative complications of lung transplantation in patients with emphysema and fibrosis: experience from 1992-2002.

UNLABELLED: Our objective was to describe the incidence of perioperative complications of lung transplantation among patients with emphysema and fibrosis and the morbidity and mortality risk factors. MATERIALS AND METHODS: We performed a retrospective study of 111 lung transplant patients engrafted from 1992 to 2002 for emphysema (n = 65) or lung fibrosis (n = 46). This descriptive study included the most frequent complications during the perioperative period in the intensive care unit. RESULTS: The most frequent intraoperative complications were reperfusion syndrome, hemodynamic instability, and cardiac arrhythmias. Among patients with emphysema, the follow-up of postoperative complications proved statistically significant on univariate analysis for an association of patient mortality with prolonged intubation (P = .005), rejection (P = .0001), hemorrhage (P = .0001), sepsis (P = .0001), renal failure (P = .001), and implantation response (P = .014). Mortality among these patients was 16.9%. Mechanical ventilation for over 48 hours and postoperative hemorrhage were the variables with the greatest predictive value for mortality in the postoperative period. Among patients with fibrosis, the complication-related mortality were reperfusion syndrome (P = .039), implantation response (P = .039), renal failure (P = .013), rejection (P = .016), and sepsis (P < .001). The mortality rate was 23.9% with sepsis (P = .000) being the most frequent cause of death in the immediate postoperative period. CONCLUSIONS: The most frequent intraoperative complications were reperfusion syndrome and hemodynamic instability. The most frequent postoperative complications were implantation response, sepsis, prolonged intubation, hemorrhage, and renal failure.

Emphysema↗
PubMed1999

Bilateral orbital emphysema from compressed air injury.

PURPOSE: To describe a patient who developed bilateral subconjunctival and orbital emphysema after an automobile tire explosion. METHOD: Case report. RESULTS: A 60-year-old man sustained bilateral ocular injury after a tire explosion. Ophthalmic examination disclosed bilateral subconjunctival air, with no visible conjunctival laceration. Computed tomography showed orbital emphysema, with no evidence of orbital fracture. Follow-up examination 2 weeks after the injury disclosed resolution of the subconjunctival air. Best-corrected visual acuity in the right eye was decreased after the explosion but improved to the baseline level of 20/40 2 weeks after the injury. CONCLUSION: Subconjunctival and orbital emphysema can occur from high-pressure air injury in the absence of an obvious entry site.

Air↗
PubMed2000

Expression of Egr-1 in late stage emphysema.

The transcription factor early growth response (Egr)-1 is an immediate-early gene product rapidly and transiently expressed after acute tissue injury. In contrast, in this report we demonstrate that lung tissue from patients undergoing lung reduction surgery for advanced emphysema, without clinical or anatomical evidence of acute infection, displays a selective and apparently sustained increase in Egr-1 transcripts and antigen, compared with a broad survey of other genes, including the transcription factor Sp1, whose levels were not significantly altered. Enhanced Egr-1 expression was especially evident in smooth muscle cells of bronchial and vascular walls, in alveolar macrophages, and some vascular endothelium. Gel shift analysis with (32)P-labeled Egr probe showed a band with nuclear extracts from emphysematous lung which was supershifted with antibody to Egr-1. Egr-1 has the capacity to regulate genes relevant to the pathophysiology of emphysema, namely those related to extracellular matrix formation and remodeling, thrombogenesis, and those encoding cytokines/chemokines and growth factors. Thus, we propose that further analysis of Egr-1, which appears to be up-regulated in a sustained fashion in patients with late stage emphysema, may provide insights into the pathogenesis of this destructive pulmonary disease, as well as a new facet in the biology of Egr-1.

Aged↗
PubMed2001

Economic analysis of lung volume reduction surgery as part of the National Emphysema Treatment Trial. NETT Research Group.

BACKGROUND: In today's cost-conscious health care environment, obtaining timely and accurate economic information regarding new medical technologies has become extremely important. The National Emphysema Treatment Trial, a multicenter, randomized controlled trial of lung volume reduction surgery (LVRS) plus medical therapy, versus medical therapy for patients with severe emphysema, includes a parallel cost-effectiveness analysis. METHODS: The analysis is designed to determine the cost-effectiveness of LVRS versus medical therapy for those who are eligible for the procedure. After describing theoretical foundations of cost-effectiveness analysis as they apply to this study, we describe the economic and quality of life data that are being collected alongside the clinical trial, methods of analysis, and approach to presenting the results. RESULTS: The cost-effectiveness of LVRS relative to medical therapy will be presented as costs per quality-adjusted life years gained. CONCLUSIONS: This analysis will provide timely economic data that can be considered alongside the clinical results of the National Emphysema Treatment Trial. As one of the largest clinical trials to include a parallel, prospective cost-effectiveness analyses, this study will also provide valuable practical information about conducting an economic analysis alongside a multicenter clinical trial.

Cost-Benefit Analysis↗
PubMed2003

Quality of life after tailored combined surgery for stage I non-small-cell lung cancer and severe emphysema.

BACKGROUND: We analyzed the early and long-term quality of life changes occurring in 16 patients undergoing tailored combined surgery for stage I non-small-cell lung cancer (NSCLC) and severe emphysema. METHODS: Mean age was 65 +/- 5 years. All patients had severe emphysema with severely impaired respiratory function and quality of life. Tumor resection was performed with sole lung volume reduction (LVR) in 5 patients, separate wedge resection in 3 patients, segmentectomy in 2 patients, and lobectomy in 6 patients. A bilateral LVR was performed in 5 patients. Quality of life was assessed at baseline and every 6 months postoperatively by the Short-form 36 (SF-36) item questionnaire. RESULTS: Mean follow-up was 44 +/- 21 months. All tumors were pathologic stage I. There was no hospital mortality nor major morbidity. Significant improvements occurred for up to 36 months in the general health (p = 0.02) domain and for up to 24 months in physical functioning (p = 0.02), role physical (p = 0.005), and general health (p = 0.01) SF-36 domains. Associated improvements regarded dyspnea index (-1.3 +/- 0.6) forced expiratory volume in one second (+0.28 +/- 0.2L), residual volume (-1.18 +/- 0.5L) and 6-minute-walking test distance (+86 +/- 67 m). Actuarial 5-year survival was similar to that of patients with no cancer undergoing LVRS during the same period (68% vs 82%, p = not significant). CONCLUSIONS: Our study suggests that selected patients with stage I NSCLC and severe emphysema may significantly benefit from tailored combined surgery in terms of long-term quality of life and survival.

Aged↗
PubMed1999

Compliance and functional residual capacity after staple versus combined staple/holmium laser lung volume reduction surgery in a rabbit emphysema model.

BACKGROUND: There is some evidence to suggest that laser exposure, when added to standard staple reduction techniques, may result in improved physiologic response to lung volume reduction surgery (LVRS). In this study, we compared physiologic responses of staple LVRS with combined staple/laser in a rabbit emphysema model. METHODS: Ninety-three New Zealand White rabbits underwent emphysema induction with aerosolized elastase 4 weeks before surgery and were killed 1 week after surgery. Treatment groups were bilateral moderate volume staple LVRS (< or =3 g, n = 39), combined moderate volume staple (< or =3 g)/holmium laser LVRS (n = 18), large-volume staple LVRS (> or =3 g, n = 27), or sham surgery (n = 9). RESULTS: Decrease in postoperative static respiratory system compliance by combined moderate-volume staple/laser treatment (1.22 cc/cm H2O) was similar to large-volume staple resection (1.40 cc/cm H2O, p = 0.39), and superior to moderate staple resection (0.82 cc/cm H2O, p = 0.01) or sham surgery (0.09 cc/cm H2O, p = 0.0001). Functional residual capacity decrease was greater after combined moderate staple/laser resection (6.46 cc) than large-volume staple resection (4.52 cc, p = 0.33), moderate-volume staple resection (4.59 cc, p = 0.43), or sham surgery (4.10 cc, p = 0.29). Perioperative mortality was highest after laser/staple LVRS (22%, 4/18). CONCLUSIONS: In this rabbit model, combined staple/ holmium laser reduction for emphysema results in significant improvement in compliance and trends toward improvement in functional residual capacity above staple reduction alone, but with higher mortality.

Animals↗
PubMed1987

Interstitial emphysema of the stomach due to perforated appendicitis.

There are three recognised variations of gas within the wall of the stomach (interstitial emphysema, cystic pneumatosis and emphysematous gastritis). Only 26 cases of interstitial emphysema have been described, with an overall mortality of 42%, and we report the first known case of this rare phenomenon associated with acute appendicitis. A description of the clinical and radiological features of these three types of intramural stomach gas is presented and the literature pertinent to interstitial emphysema is reviewed.

Appendicitis↗