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.

Lung volumes before and after lung volume reduction surgery: quantitative CT analysis.

The volume and severity of pulmonary emphysema in individual lungs were measured by means of quantitative computed tomography (CT) studies in 28 patients (14 women, 14 men, median age 65 yr) who underwent either bilateral (n = 15) or unilateral (n = 13) lung volume reduction surgery (LVRS). Spirometric, total body plethysmographic, and CT data (at TLC and RV) were correlated before and after LVRS. Lung volumes determined by CT correlated well with volumes obtained by total body plethysmography (p < 0.0001). For individual lungs after LVRS, CT-derived mean lung capacity decreased 13% and residual volume 20% (p < 0.00001 for each), while mean total functional lung volume (TFLV, defined as the volume of lung with CT attenuation greater than -910 Hounsfield units) increased 9% (p < 0.01), and the mean ratio of the air space to tissue space volume (V(AS)/V(TS)) decreased more at RV (23%) than at TLC (14%) (p < 0.0005 for each). In contrast, unilateral LVRS did not affect exhalation from the unoperated lung (2% reduction in RV, p = NS). The magnitude of the postoperative response (CT-derived TLC, RV, TFLV, V(AS)/V(TS)) of each operated lung was comparable for unilateral and bilateral LVRS. Thus, a lung's response to LVRS was independent from that of the contralateral lung. Moreover, postoperative alterations in TFLV and FEV1 correlated significantly (r = 0.80, p < 0.0001), which suggests that the expansion of functioning tissue may contribute to the mechanism by which LVRS palliates airway obstruction.

Lung reduction operation and resection of pulmonary nodules in patients with severe emphysema.

BACKGROUND: Severe pulmonary dysfunction has been considered a relative contraindication to surgical resection in patients with solitary pulmonary nodules. We report our initial experience with the combined use of lung volume reduction operation and tumor resection in this patient population. METHODS AND PATIENTS: Between January 1995 and July 1996, 14 patients underwent combined lung volume reduction operation and pulmonary nodule resection. Ten (71%) patients were oxygen dependent, 5 (36%) had a room air partial pressure of carbon dioxide > or = 45, and 5 (36%) were steroid dependent preoperatively. Mean preoperative pulmonary function tests included a forced expiratory volume in 1 second of 680 +/- 98 mL (24% +/- 5% predicted), forced vital capacity of 54% +/- 5% predicted, and a forced expiratory volume in 1 second to vital capacity ratio of 37% +/- 2% predicted. RESULTS: Sixteen lesions were resected in the 14 patients and included 9 non-small cell carcinomas. There was one postoperative death. All other patients are alive and well through a mean follow-up of 22.6 +/- 2.3 months (12 to 35 months). At 6-month follow-up improvements were noted in dyspnea index, forced expiratory volume in 1 second forced vital capacity, and 6-minute walk distance. Mediastinal recurrence at 12-month follow-up developed in 1 patient with two separate bronchioalveolar carcinomas. CONCLUSIONS: Simultaneous lung volume reduction operation and tumor resection should be considered in patients with emphysema with marginal reserve in the hope of maximizing postoperative lung function.

Association between right ventricular function and perfusion abnormalities in hemodynamically stable patients with acute pulmonary embolism.

BACKGROUND/OBJECTIVES: Patients presenting with acute pulmonary embolism associated with hemodynamic compromise exhibit right ventricular enlargement and dysfunction on transthoracic echocardiogram. However, the degree of echocardiographic abnormalities among hemodynamically stable patients without preexisting cardiopulmonary disease during the acute stage of pulmonary embolism, and following treatment, is unknown. Therefore, this study was designed to assess the extent of right ventricular abnormalities detected on transthoracic echocardiogram in patients following acute pulmonary embolism and during treatment with anticoagulation or vena caval interruption. The extent of pulmonary vascular obstruction and complication rate on follow-up were also assessed. DESIGN/INTERVENTIONS: Sixty-four consecutive hemodynamically stable patients without preexisting known cardiopulmonary disorder presenting with acute pulmonary embolism and undergoing treatment with anticoagulation or inferior vena caval interruption were studied. All subjects underwent a two-dimensional transthoracic echocardiogram within 24 h of diagnosis. The degree of perfusion abnormality on lung scan was quantified. Twenty-six patients underwent follow-up echocardiogram and lung scan at 6 weeks. The echocardiographic findings were compared with those obtained from a group of normal control subjects matched for gender and age. RESULTS: Although the mean right ventricular end-diastolic areas did not differ (21.9+/-5.2 cm2 vs 20.1+/-2.9 cm2 for control subjects; p=not significant), the right ventricular end-systolic area was larger in comparison to our series of control subjects (14.6+/-5.1 cm2 vs 11.7+/-2.0 cm2; p=0.025). Fractional right ventricular area change was reduced in the patient group compared with the control subjects (34.3+/-9.0% vs 41.3+/-7.0%; p=0.003). The extent of right ventricular end-systolic area enlargement and decrease in fractional area change did not correlate with the degree of pulmonary vascular obstruction. Patients who were restudied at 6 weeks showed minimal improvement in echocardiographic findings, despite almost complete resolution of perfusion defects on lung scan. CONCLUSIONS: The extent of right ventricular dysfunction in hemodynamically stable, previously normal patients with acute pulmonary embolism does not reflect the extent of the perfusion abnormalities. Further, right ventricular enlargement and systolic dysfunction are present and persistent despite treatment with heparin and warfarin therapy or vena caval interruption.

Functional comparison of unilateral versus bilateral lung volume reduction surgery.

BACKGROUND: Lung volume reduction surgery (LVRS) has shown early promise as a palliative therapy in severe emphysema. A number of patients, however, are not candidates for a bilateral operation, or exhibit a predominantly unilateral disease distribution. METHODS: Over 20 months, we performed LVRS in 92 patients selected on the basis of severe hyperinflation with air trapping, diaphragmatic dysfunction, and disease heterogeneity. Twenty-eight patients underwent unilateral LVRS on the basis of asymmetric disease distribution, prior thoracic operation, or concomitant tumor resection. RESULTS: Unilateral LVRS resulted in comparable improvements in exercise capacity and dyspnea as the bilateral procedure, with a similar perioperative mortality and actuarial survival to 24 months. Improvements in spirometric indices of pulmonary function, however, were less in patients undergoing unilateral than bilateral LVRS. CONCLUSIONS: In properly selected patients, unilateral LVRS provides functional and subjective benefits of comparable magnitude to those associated with a bilateral operation. Unilateral LVRS is therefore an option in the therapy of end-stage emphysema in patients with asymmetric disease distribution, a prior thoracic operation, or contraindications to sternotomy, and may have a role as a bridge to transplantation in selected cases.

Relation between patent foramen ovale and perfusion abnormalities in acute pulmonary embolism.

The frequency of right-to-left shunt through a patent foramen ovale is increased in hemodynamically stable patients without preexisting cardiopulmonary disease with acute pulmonary embolism. This is associated with a greater degree of perfusion abnormalities as quantified by perfusion scan and the presence of tricuspid regurgitation.

Extended indications for lung volume reduction surgery in advanced emphysema.

BACKGROUND: Lung volume reduction surgery has shown early promise as a palliative therapy in severe emphysema. Selection of potential candidates has been based on certain functional and anatomic criteria, and a variety of operative contraindications have been proposed. METHODS: Over 15 months, we performed lung volume reduction surgery in 85 patients selected on the basis of severe hyperinflation with air trapping, diaphragmatic dysfunction, and disease heterogeneity. Patients were not excluded on the basis of severe hypercapnia, steroid dependence, profound pulmonary dysfunction, or inability to complete preoperative rehabilitation. RESULTS: We observed significant improvements in pulmonary function, exercise capacity, and dyspnea, with an acceptable 30-day perioperative mortality of 7% and actuarial survival of 90% and 83% at 6 and 12 months, respectively. In each "high-risk" group, perioperative mortality, actuarial survival to 1 year, and functional results were equivalent, and in some cases superior, to those in the corresponding "low-risk" patients. CONCLUSIONS: Severe hypercapnia, steroid dependence, profound pulmonary dysfunction, and inability to complete preoperative rehabilitation do not preclude successful lung volume reduction surgery and should not be regarded as absolute exclusionary criteria.

Submaximal exercise in emphysema and malnutrition at two levels of carbohydrate and fat intake.

Eight malnourished patients with emphysema (EMPH) and eight malnourished patients without evidence of lung disease (MLAN) received an infusion of 5% dextrose plus electrolytes (D5W) for 48 h and were then randomly assigned to a hypercaloric diet with either 53% of the calories as carbohydrate (CB) or with 55% as fat (FB) for the 1st wk, maintaining a constant protein intake. The alternate diet was given the following week. Ventilation and gas exchange were measured during supine cycle ergometry at 0, 12, and 25 W during the D5W, CB, and FB diet periods. At each exercise intensity, the EMPH group demonstrated a 12-15% greater O2 consumption, a lower respiratory quotient, and an O2 debt larger than that of the MALN group. Resting ventilation was higher during the CB than FB regimen in both groups of patients, but during the CB diet the EMPH group had a more exaggerated ventilatory response than the MALN group. The results demonstrate that EMPH patients have an unusual metabolic pattern during hypercaloric feeding and exercise. Furthermore in EMPH patients a FB regimen does not appear to create the additional stress on the respiratory system during exercise that is generated with a CB regimen.

Nitrogen and energy relationships in malnourished patients with emphysema.

The purpose of this study was to examine the impact of nutritional support on nitrogen-energy relationships and functional parameters in malnourished patients with emphysema. Malnourished patients without lung disease served as the control group. Ten ambulatory, stable patients with emphysema and six patients without lung disease received an infusion of 5% dextrose (baseline) plus electrolytes (D5W) for two days, which was followed by an enteral or a parenteral infusion of either a carbohydrate-based (CB, 53% carbohydrate) or a fat-based diet (FB, 55% fat) for 1 wk each, in a randomized cross-over design. All patients had greater than 10% weight loss. Caloric intake was set at 1.7 times the resting energy expenditure (REE) as measured during the baseline period. The REE of patients with emphysema was 23 and 27% above that of the control group during baseline and refeeding periods, respectively. The increased REE was met primarily by an increased carbohydrate oxidation. During the infusion of D5W, N balance was lower in patients with emphysema, but during repletion N balance was similar in both groups of patients. Two weeks of nutritional support with either a CB or a FB diet increased body weight, N balance, and arm muscle area and improved maximal inspiratory pressure, skeletal muscle strength, and endurance-strength (using quadriceps, hamstring, and handgrip) to a similar degree in malnourished patients with and without lung disease. In other stress states, such as infection, it has been shown that hypermetabolism, hypercatabolism, and preferential fat oxidation occur concomitantly. Patients with emphysema are unusual because, although they are hypermetabolic, they are not hypercatabolic and do not demonstrate preferential fat oxidation.

Intravenous fat emulsions and lung function: a review.

Numerous studies have reported varying degrees of apparent pulmonary dysfunction when iv fat emulsions (IVFE) are given. These changes have generally not been of sufficient magnitude to carry clinical significance. The lung dysfunction observed has been attributed to an associated hyperlipemia. Recent studies, however, suggest that the associated impairment in lung function is due to alterations in pulmonary vascular tone (which results in ventilation/perfusion inequalities) caused by an IVFE-related increase in prostaglandin (PG) production. The polyunsaturated fatty acids in the IVFE serve as precursors to the PGs. Due to the varied effects of PGs on inflammation and pulmonary vasomotor tone, infusion of IVFE could have profound physiologic and pharmacologic actions aside from the provision of lipid calories. In some circumstances, IVFE may, in fact, be beneficial to the lung via alterations in

Energy expenditure in patients with chronic obstructive pulmonary disease.

Energy expenditure was studied in ten patients with chronic obstructive pulmonary disease (COPD) and weight loss, and in five malnourished patients without clinical evidence of COPD (control group) prior to and after a two-week refeeding regimen. Patients received 5 percent dextrose solution (plus electrolytes) for 36 hours to establish standard baseline conditions and were then randomly assigned to either a carbohydrate-based (CB; 53 percent of calories) or fat-based (FB; 55 percent of calories) diet for the first week. The alternate diet was given the following week. Total calorie intake was set at 70 percent above the energy expenditure measured prior to institution of nutritional support. During energy repletion, energy expenditure was greater than predicted (116 percent) in patients with COPD and less than predicted (90 percent) in the control patients. Thermic effect of nutrients during administration of either regimen was significantly greater (p less than .05) in patients with COPD than in those without COPD during both diets. The difference between the two groups was enhanced during the CB regimen. These observations suggest that malnourished patients with COPD have an elevated resting energy expenditure, and an enhanced thermic response to nutrients as compared to malnourished patients without COPD. Increased diet-induced thermogenesis may contribute to weight loss in patients with COPD, in addition to factors previously described such as decreased caloric intake and increased resting energy expenditure.

Functional changes during nutritional repletion in patients with lung disease.

In conclusion, the weight loss in COPD is associated with hypermetabolism. Under these circumstances, caloric intake may be insufficient to meet increased metabolic demands, thereby contributing to progressive weight loss. This is in contrast to depleted surgical patients who have energy expenditures 5% below predicted. There is an increased VE in patients receiving a high-carbohydrate diet, secondary to an increased VCO2 that is similar to that seen in patients with neither COPD nor weight loss. Neither diet composition, whether high-carbohydrate or high-fat, nor refeeding have any effect on PaCO2. However, ventilatory drive does appear to be influenced by nutritional repletion. There was an increased sensitivity to PaCO2, independent of diet composition, during a high caloric intake. Respiratory and skeletal muscle function increased, particularly strength, endurance, and work efficiency, indicating that the increased metabolic demand can be well tolerated. It should be noted, however, that refeeding the COPD patient must be done as a preventive measure at the start of weight loss. Patients with long-term weight loss and end-stage COPD appear unable to tolerate any increase in metabolic demand; consequently, they cannot improve respiratory and skeletal muscle function through refeeding.

Complete transection of the intrathoracic trachea due to blunt trauma.

A 24-year-old man was transferred to Columbia-Presbyterian Medical Center from a local hospital 24 hours after a car crash. Bronchoscopy at the local hospital revealed transection with discontinuity of the trachea just above the carina. At Columbia-Presbyterian Medical Center, following cautious intubation without positive airway pressure, a right posterolateral thoracotomy was performed, and the bronchi were intubated with sterile endotracheal tubes for initial airway control. A 6-cm tracheal disruption was repaired. Early care was complicated by chest wall instability and pulmonary contusions, but the patient was discharged breathing comfortably on the tenth postoperative day. Subsequent to discharge, flow-volume loops revealed the development of a tracheal stricture. Three months after the initial procedure, tracheal resection for stenosis was completed. To date, the patient is asymptomatic.

Diffuse intrapulmonary hemorrhage, renal failure and a systemic vasculitis. A case report and review of the literature.

A 63 year old women was hospitalized with massive hemoptysis, anemia and renal failure. Despite intensive supportive care, she died soon after admission. Autopsy revealed diffuse necrotizing alveolitis, rapidly progressive glomerulonephritis and a systemic vasculitis. Massive intrapulmonary hemorrhage with hemoptysis is an unusual complication of a systemic vasculitis. The case is discussed and the literature reviewed.