Survival effect of lung transplantation among patients with cystic fibrosis.

CONTEXT: Patients with cystic fibrosis (CF) are the second largest group of lung transplant recipients in the United States. The survival effect of transplantation on a general CF population has not previously been measured. OBJECTIVE: To determine the impact of bilateral lung transplantation on survival in patients with CF. DESIGN, SETTING, AND PATIENTS: Retrospective observational cohort study of 11 630 CF patients who did not undergo lung transplantation (controls) and 468 transplant recipients with CF from 115 CF centers in the United States, 1992-1998. Patients were stratified into 5 groups based on a 5-year survival prediction model (survival group 1: <30%; survival group 2: 30 to <50%; survival groups 3-5: 50 to <100%.) MAIN OUTCOME MEASURE: Five-year survival from date of transplantation in 1992-1997 in the transplant group and from January 1, 1993, in the control group. RESULTS: Lung transplantation increased 5-year survival of CF patients in survival group 1. Survival group 2 had equivocal survival effects, and groups 3-5 had negative survival effects from transplantation. From 1994-1997, there was a mean annual prevalence of 238 patients in survival group 1 and mean annual incidence of 154 patients entering the group, approximately 1.5 times the number of lung transplantations performed each year in CF patients (mean, 104). Use of the criterion of forced expiratory volume in 1 second of less than 30% resulted in an equivocal survival benefit and identified 1458 potential candidates for transplantation in 1993. CONCLUSIONS: Cystic fibrosis patients in group 1 have improved 5-year survival after lung transplantation. The majority of patients with CF have equivocal or negative survival effects from the procedure. Selection of patients with CF for transplantation based on group 1 survival predictions maximizes survival benefits to individuals and may reduce the demand for scarce donor organs.

Prevention of bone loss and fracture after lung transplantation: a pilot study.

BACKGROUND: Osteoporotic fracture is a significant source of morbidity after lung transplantation. Therapies to prevent posttransplant fracture are largely untested among lung transplant recipients. METHODS: In this prospective uncontrolled study, lung transplant referrals were assessed for bone health with metabolic, radiographic, and bone mineral density measurements. Transplant recipients were treated with an antiresorptive regimen that included a bisphosphonate starting before or after transplantation. One year after transplantation, the fracture rate and bone density of patients in each group were reassessed and compared to historical controls. Between January 1996 and August 1999, 45/50 (90%) lung transplant referrals underwent bone health assessment. Transplant candidates received calcium, vitamin D, and hormone replacement therapy as indicated for hypogonadism. After July 1998, bisphosphonate therapy was added for candidates with osteopenia or osteoporosis (T score <1). After transplantation, all patients received 90 mg of pamidronate i.v. every 12 weeks, regardless of pretransplant bone density. Radiologic evaluation was performed for clinical suspicion of fracture. Bone density was remeasured 1 year after transplantation. RESULTS: Most transplant referrals suffered from osteopenia or osteoporosis, and 29% of transplant referrals had prevalent vertebral compression fractures. Hypogonadism was untreated in 50% of men and 20% of women, and 15% of patients had hypovitaminosis D. Of the 21 patients assessed 1 year after transplantation, new fractures occurred in 4% of these patients. Lateral lumbar spine and hip bone density remained stable or improved in 65% and 86% of patients, respectively. Most of those who lost bone density had started bisphosphonate therapy after transplantation. CONCLUSIONS: Antiresorptive therapy with a bisphosphonate decreases the fracture rate and preserves bone mass 1 year after lung transplantation. In end-stage lung disease patients with osteopenia or osteoporosis, bisphosphonate therapy should be initiated before transplant surgery is contemplated.

Predictive 5-year survivorship model of cystic fibrosis.

The objective of this study was to create a 5-year survivorship model to identify key clinical features of cystic fibrosis. Such a model could help researchers and clinicians to evaluate therapies, improve the design of prospective studies, monitor practice patterns, counsel individual patients, and determine the best candidates for lung transplantation. The authors used information from the Cystic Fibrosis Foundation Patient Registry (CFFPR), which has collected longitudinal data on approximately 90% of cystic fibrosis patients diagnosed in the United States since 1986. They developed multivariate logistic regression models by using data on 5,820 patients randomly selected from 11,630 in the CFFPR in 1993. Models were tested for goodness of fit and were validated for the remaining 5,810 patients for 1993. The validated 5-year survivorship model included age, forced expiratory volume in 1 second as a percentage of predicted normal, gender, weight-for-age z score, pancreatic sufficiency, diabetes mellitus, Staphylococcus aureus infection, Burkerholderia cepacia infection, and annual number of acute pulmonary exacerbations. The model provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research.

Aspergillus airway colonization and invasive disease after lung transplantation.

BACKGROUND: Invasive Aspergillus is an important cause of morbidity and mortality among lung transplant recipients. The diagnosis can be difficult and treatment is often unsuccessful so many centers preemptively treat all Aspergillus airway isolates to prevent invasive disease. This approach is untested as little is known about the relationship between Aspergillus airway colonization and invasive disease. This study was undertaken to evaluate the incidence of Aspergillus airway colonization after lung transplantation and the risk of invasive disease after colonization. DESIGN: All cultures and histologic specimens obtained from a consecutive series of 151 lung transplant cases were reviewed for the presence of Aspergillus and compared with clinical data. RESULTS: Aspergillus was isolated from the airway in 69 (46%) of 151 transplant recipients. Invasive disease occurred in five cases and was uniformly fatal, accounting for 13% of all posttransplant deaths. Results of cytologic examination of BAL fluid were normal in all cases of invasive disease and cultures were positive in only one of five patients prior to invasion. Invasive disease occurred exclusively in patients who died or were colonized with Aspergillus fumigatus within the first 6 months posttransplant. Patients growing A. fumigatus from the airway during the first 6 months were 11 times more likely to develop invasive disease relative to those not colonized. CONCLUSION: Aspergillus airway colonization after lung transplantation is common and in most cases, transient. In contrast, invasive Aspergillus disease is less common, but fatal. Bronchoscopy with cytologic examination and fungal culture are not sensitive or timely predictors of invasive disease. Invasive Aspergillus occurred only in patients initially colonized with A. fumigatus within the first 6 months posttransplant. A trial of empiric anti-Aspergillus therapy limited to the first 6 months posttransplant may be warranted.

Methotrexate for lung transplant recipients with steroid-resistant acute rejection.

BACKGROUND: Steroid-resistant or recurrent acute rejection is a risk factor for the development of chronic graft failure in lung transplant recipients. The best treatment for these patients is not known. Methotrexate has been used successfully in heart transplant recipients with persistent or recurrent acute rejection. This study was performed to evaluate the efficacy of methotrexate in lung transplant recipients with steroid-resistant acute rejection. METHODS: From January 1991 to December 1995, 12 patients with steroid-resistant acute rejection were treated with methotrexate given weekly for 6 weeks and dose-adjusted according to laboratory data and clinical side effects. After completion of therapy, all patients underwent transbronchial biopsy to evaluate the efficacy of methotrexate treatment. RESULTS: Twelve patients underwent treatment with methotrexate for steroid-resistant acute rejection. Acute rejection resolved in all patients completing at least 4 weeks of therapy; 10 of 12 patients (83%) had no further episodes of acute rejection during a mean follow-up period of 12.5 months (range 1 to 42 months). Acute rejection recurred in two patients 6 and 16 months after methotrexate therapy. Both resolved with high-dose corticosteroid therapy. One patient had asymptomatic cytomegalovirus shedding 8 weeks after completion of methotrexate therapy. One patient had aseptic meningitis after her fourth dose of methotrexate. Neither infectious complication was associated with neutropenia. One patient had bone marrow suppression and neutropenic fevers after augmentation of her methotrexate dose. Two patients received shortened methotrexate courses because of gastrointestinal side effects. CONCLUSIONS: Methotrexate is efficacious in the treatment of lung transplant recipients with steroid-resistant acute rejection. Patients must be monitored for side effects during therapy and dosing must be individualized based on laboratory and clinical parameters.

Massive hemoptysis. Assessment and management.

The first priorities in treating the patient with massive hemoptysis are to maintain the airway, optimize oxygenation, and stabilize the hemodynamic status. The major question to be answered is whether or not the patient should be intubated for better gas exchange, suctioning, and protection from sudden cardiorespiratory arrest. If the bleeding site is known, the patient should be placed with the bleeding lung in the dependent position. Once stabilization is accomplished, diagnostic and therapeutic interventions should be promptly performed because recurrent bleeding occurs unpredictably. Early bronchoscopy, preferably during active bleeding, should be performed with three goals in mind: to lateralize the bleeding side, localize the specific site, and identify the cause of the bleeding. In those patients with lateralized or localized persistent bleeding, immediate control of the airway may be obtained during the procedure with topical therapy, endobronchial tamponade, or unilateral intubation of the nonbleeding lung. If bleeding continues but the side of origin is uncertain, lung isolation or use of a double-lumen tube is reasonable, provided that the staff is skilled in this procedure. If the bleeding cannot be localized because the rate of hemorrhage makes it impossible to visualize the airway, emergent rigid bronchoscopy or emergent arteriography is indicated. Arteriography and embolization should be used emergently for both diagnosis and therapy in those patients who continue to bleed despite endobronchial therapy. Emergent surgical intervention should be considered in operative candidates with unilateral bleeding when embolization is not available or not feasible, when bleeding continues despite embolization, or when bleeding is associated with persistent hemodynamic and respiratory compromise. For patients in whom bleeding has ceased or is decreased, emergent intervention may not be necessary. If the bleeding site has been localized or lateralized with early bronchoscopy, recurrent bleeding can be managed more confidently and rapidly. The cause of bleeding can be determined at bronchoscopy in patients with endobronchial adenomas, carcinomas, foreign bodies, or broncholiths. If no diagnosis is obtained at bronchoscopy, elective angiography of the bronchial and, if necessary, the pulmonary vasculature is reasonable. The precise timing and nature of the further evaluation are dictated by the suspected underlying pathologic process and the clinical condition of the patient. Surgery is the most definitive form of therapy for patients with hemoptysis because it removes the source of bleeding. Whether to proceed with elective surgery in patients with a major bleed that stops or one that is controlled angiographically is a difficult decision. Little data are available to assist in this decision, even for specific diseases, such as bronchiectasis. Similarly, the long-term course of patients treated with endobronchial tamponade or topical therapy is unknown. For patients with inoperable disease, limited reserve, or bilateral progressive disease, embolization frequently controls bleeding for prolonged periods.(ABSTRACT TRUNCATED AT 400 WORDS)

Tracheobronchial obstruction due to silicosis.

Broncholithiasis can result in airway obstruction through the erosion of calcified lymph nodes into the bronchial lumen or by extrinsic compression of the tracheobronchial tree. We report an unusual case of broncholithiasis in a patient with silicosis who developed airway obstruction from endobronchial polypoid masses of granulation tissue adjacent to calcified mediastinal lymph nodes. The production of granulation tissue may have been the result of broncholiths in the early stages of erosion into the tracheobronchial tree. Efforts to ablate the endobronchial polyps using YAG laser phototherapy were only temporarily successful and surgical removal of the calcified mediastinal lymph nodes was required to halt further polyp growth. Surgical specimens grew Mycobacterium avium-intracellulare (MAI), a common pathogen in patients with silicosis. MAI may have contributed to the local inflammatory milieu provoking the exuberant tissue response.

Combined laser phototherapy and growth factor treatment of bronchial obstruction after lung transplantation.

Lung transplantation has resulted in dramatic functional improvement in patients with end-stage pulmonary diseases. Among the complications of lung transplantation are dehiscence and stenosis at the site of the bronchial or tracheal anastomosis. In this case report, we describe a single lung transplant recipient in whom partial bronchial dehiscence, followed by exuberant growth of granulation tissue, resulted in obstruction of the bronchial lumen. After mechanical dilation failed to produce lasting relief of bronchial obstruction, a novel approach to this problem was successfully employed: YAG laser phototherapy was used to remove obstructing granulation tissue, followed by application of a preparation derived from autologous blood platelets to promote epithelialization of the bronchial anastomosis. The bronchus remains patent and fully epithelialized six months after therapy.