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Biomedical subjects

A Boehler

Publications and source records attributed to A Boehler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Obliterative bronchiolitis after lung transplantation.

Despite marked improvements in early survival, long-term outcome after lung transplantation is still threatened by obliterative bronchiolitis (OB). Thought to be a manifestation of chronic allograft rejection, OB affects up to 65% of patients at 5 years after surgery and produces a relentless airflow obstruction. Early and late acute rejection are the primary risk factors for OB, but cytomegalovirus infection and airway ischemia may also play a role. In most patients, OB responds poorly to augmented immunosuppression and eventually leads to infectious complications and terminal respiratory failure. Because early diagnosis is associated with better prognosis, every effort should be made to detect OB in a preclinical stage. This may be best achieved by combining several techniques, such as surveillance transbronchial biopsy and bronchoalveolar lavage, measurements of ventilation distribution and exhaled nitric oxide, and expiratory computed tomography.

Anti-Inflammatory Agents↗
PubMed1999

Extracorporeal photochemotherapy for Epstein-Barr virus-associated lymphoma after lung transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication after transplantation of solid organs. Highest incidence rates have been reported for lung transplant recipients. With the current treatment strategy for early onset PTLD, a reduction of immunosuppressive drugs, mortality of lung transplant recipients with PTLD remains high, due to both, incomplete control of PTLD and transplant rejection. We present a lung transplant recipient with a history of acute rejection and Epstein Barr virus-associated posttransplantation malignant non-Hodgkin's lymphoma. Extracorporeal photochemotherapy, in combination with a moderate reduction of immunosuppressive therapy, resulted in complete disappearance of PTLD. After a first year of follow-up, no further rejection and no recurrence of PTLD have occurred. Treatment with ECP, with its beneficial effects on both, rejection after organ transplantation and malignant lymphoma, may be a particularly valuable approach for the treatment of PTLD in patients after lung transplantation, with its increased risk for transplant rejection.

Adolescent↗
PubMed1999

Efficacy and cost effectiveness of oral ganciclovir in the prevention of cytomegalovirus disease after lung transplantation.

BACKGROUND: Cytomegalovirus is the single most frequent pulmonary pathogen in lung transplant recipients who survive at least 2 weeks. Patients at increased risk are either seropositive or have received an allograft from a donor with latent infection. Morbidity and mortality caused by cytomegalovirus disease is still considerably high. METHODS: In an open, comparative study, we evaluated the efficacy, tolerance, and cost effectiveness of postoperative ganciclovir prophylaxis: intravenous dose of 2x5 mg/kg/day for 14 days, followed by either intravenous doses of 5 mg/kg]day (five patients), or oral doses of 3x 1000 mg (nine patients) up to 90 days. Oral ganciclovir was continued until prednisone was tapered below 15 mg/day. Prophylaxed groups were compared with a historical control (eight patients) in respect to cytomegalovirus disease, in-hospital stay, overall costs, and survival. Follow-up times and the net state of immunosuppressive therapy between groups were comparable. RESULTS: Six (75%) of the non-prophylaxed patients developed cytomegalovirus disease compared to none in the intravenous and one in the oral ganciclovir group (P=0.013). The non-prophylaxed patients had a longer cytomegalovirus-related in-hospital stay (P=0.018) and nonsignificantly higher cytomegalovirus-related costs. Bronchiolitis obliterans syndrome was less frequent with prophylaxis (P=0.039), and survival tended to be better (P=0.072). The only adverse effect was a subclavian vein thrombosis in the intravenous ganciclovir group. CONCLUSIONS: In lung transplant recipients, ganciclovir prophylaxis, either intravenous or oral, is safe, well tolerated, and effective in preventing cytomegalovirus disease. Moreover, ganciclovir prophylaxis seems likely to reduce the incidence of bronchiolitis obliterans syndrome. The oral formulation might be preferable because its convenience and possibly lower costs.

Administration, Oral↗
PubMed1999

Transgene expression after adenovirus-mediated retransfection of rat lungs is increased and prolonged by transplant immunosuppression.

OBJECTIVES: Adenovirus-mediated gene therapy has been proposed as a potential treatment modality in lung transplantation. However, to date its utility has been limited by an inflammatory host immune response that not only limits the amount and duration of transgene expression but also obviates successful retransfection. Having previously shown that by administering triple-immunosuppression, as is routine in lung transplantation, we could increase and prolong transgene expression after initial transfection, we hypothesized that transgene expression after retransfection could also be increased and prolonged. METHODS: Lewis rats underwent intratracheal adenovirus-mediated transfection with the beta-galactosidase gene and were randomized to either the immunosuppression group, receiving daily cyclosporine (INN: ciclosporin), azathioprine, and methylprednisolone, or the control group (no immunosuppression). Five weeks later, rats were similarly retransfected and transgene expression and post-transfection inflammation were evaluated 1, 7, and 14 days after retransfection. RESULTS: After retransfection, immunosuppressed rats had significantly higher levels of transgene expression (P <.001), whereas control rats had virtually no detectable levels. On histologic sections of the lungs, immunosuppressed rats had overall lesser grades of post-transfection inflammation. CONCLUSIONS: Transplant immunosuppression attenuates the severe immune response to gene transfer and permits increased, prolonged, and repeated transfection. Retransfection is now achievable in the immunosuppressed lung transplant setting to allow for chronic, repeated administration of gene therapy.

Adenoviridae↗
PubMed1999

Donor and recipient treatment with the Lazaroid U-74006F do not improve post-transplant lung function in swine.

OBJECTIVE: U-74006F is the only Lazaroid which is currently in clinical use. A number of experimental studies demonstrate that Lazaroids reduce ischemia/reperfusion injury in various organ systems. We evaluated the effect of U-74006F on reperfusion injury in a large animal model of lung allo-transplantation. METHODS: Two different treatment modalities were evaluated and compared with corresponding control groups. Unilateral left lung transplantation was performed in 21 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.51 cold (1 degrees C) LPD solution and preserved for 20 h. In group I (n = 5), donor animals were pretreated with U-74006F (10 mg/ kg i.v.) 20 min before harvest. In addition U-74006F was added to the flush solution (10 mg/l). In group III (n = 6), the Lazaroid was given to the donor before flush and to the recipient before reperfusion (3 mg/kg i.v.). Group II and IV (n = 5) served as control. One hour after reperfusion, the recipient contralateral right pulmonary artery and bronchus were ligated to assess graft function only. Extravascular lung water index (EVLWI), mean pulmonary artery pressure, cardiac output, and gas exchange were assessed during a 5 h observation period. Lipid peroxidation (TBARS) and neutrophil migration (MPO activity) were measured at the end of the assessment in lung allograft tissue. RESULTS: A significant change of TBARS concentration was shown in group III (group III 78.7+/-4.6 pmol/g vs. group IV 120.8+/-7.2 pmol/g (P = 0.0065) normal lung tissue 41.3+/-4.2 pmol/g). MPO activity was reduced in group III 3.74+/-0.25 deltaOD/mg per min vs. group IV 4.97+/-0.26 deltaOD/mg per min (P = 0.027), normal lung tissue 1.04+/-0.27 deltaOD/mg per min). Pulmonary hemodynamics and gas exchange after reperfusion did not differ between groups. In group I and III, a tendency towards a reduced EVLWI was noted. CONCLUSION: We conclude that combined treatment of donor and recipient with U-74006F reduces free radical mediated injury in the allograft. However, this intervention did not result in a significant reduction of post-transplant lung edema or improvement of pulmonary hemodynamics. Donor pretreatment alone did not improve lung allograft reperfusion injury. These results indicate that the benefit of U-74006F is too small to consider clinical application in lung transplantation.

Animals↗
PubMed1999

Complications in the native lung after single lung transplantation.

OBJECTIVES: Single lung transplantation is a viable option for patients with end-stage pulmonary disease; despite encouraging results, we observed serious complications arising in the native lung. We retrospectively reviewed 36 single lung transplants to evaluate the incidence of complications arising in the native lung, their treatment and outcome. METHODS: Between 1991 and 1997, 35 patients received 36 single lung transplants for emphysema (16), pulmonary fibrosis (14), lymphangioleiomyomatosis (4), primary pulmonary hypertension (1) and bronchiolitis obliterans (1). The clinical records were reviewed and the complications related to the native lung were divided into early (up to 6 weeks after the transplant) and late complications. RESULTS: Nineteen complications occurred in 18 patients (50%), leading to death in nine (25%). Early complications (within 6 weeks from the transplant) were bacterial pneumonia (1), overinflation (3), retention of secretions with bronchial obstruction and atelectasis (1), hemothorax (1), pneumothorax (1) and invasive aspergillosis (3); one patient showed active tuberculosis at the time of transplantation. Two patients developed bacterial pneumonia and invasive aspergillosis leading to sepsis and death. The other complications were treated with separate lung ventilation (1), bronchoscopic clearance (1), chest tube drainage (1) and wedge resection and pleurodesis (mechanical) by VATS (1). One patient with hyperinflation of the native lung eventually required pneumonectomy and died of sepsis. The patient with active tuberculosis is alive and well after 9 months of medical treatment. Late complications were recurrent pneumothorax (4), progressive overinflation with functional deterioration (2), aspergillosis (1) and pulmonary nocardiosis (1). Recurrent pneumothorax was treated with chest tube drainage alone (1), thoracoscopic wedge resection and/or pleurodesis (2) and pneumonectomy (1); hyperinflation was treated with thoracoscopic lung volume reduction in both cases; both patients with late infectious complications died. CONCLUSIONS: After single lung transplantation, the native lung can be the source of serious problems. Early and late infectious complications generally result in a fatal outcome; the other complications can be successfully treated in most cases, even if surgery is required.

Adolescent↗
PubMed1999

[Lung transplantation in advanced pulmonary emphysema].

Over the last 15 years lung transplantation developed from an experimental technique to a valid therapy for patients with end-stage pulmonary emphysema. The main reason for this progress are better defined selection criteria, improved operative technique and organ preservation, optimized peri- and postoperative management, and a more precise immunosuppressive and anti-infective therapy. Indications, technique, treatment and results of lung transplantation in emphysema patients are discussed.

Aged↗
PubMed1999

Upregulation of T-helper 1 cytokines and chemokine expression in post-transplant airway obliteration.

The major obstacle to long-term survival after lung transplantation is chronic graft dysfunction manifest as bronchiolitis obliterans. Since the early stages are characterized by proliferation of itinerant cells (lymphocytes and macrophages), we hypothesized that cytokines and chemokines may play a role in the development of the fibroproliferative process. In a heterotopic rat tracheal transplant model, we studied isografts and allografts 3, 7, and 21 d after transplantation as representative time points for the triphasic time course in the evolution of allograft airway obliteration. Using a semiquantitative RT-PCR technique, intragraft gene expression of T-helper 1 (Th1)- and Th2-type cytokines and of C-C and C-X-C chemokines was examined. The results of our study show a distinct pattern of cytokine and chemokine gene expression in the development of post-transplant airway obliteration. Allografts, in contrast to isografts, showed a strong and persistent Th1-type response (expression of interleukin-2 and interferon-gamma genes), even after fibrous airway obliteration was complete, suggesting an ongoing allo-immune process until late in the fibroproliferative stage. RANTES and MCP-1 were also upregulated late after transplantation, whereas MIP-2 upregulation occurred early post-transplant and was not restricted to allografts alone, which might reflect alloantigen-independent processes after transplantation that are present in both allografts and isografts.

Animals↗
PubMed1998

Adenovirus-mediated interleukin-10 gene transfer inhibits post-transplant fibrous airway obliteration in an animal model of bronchiolitis obliterans.

Bronchiolitis obliterans, a form of chronic allograft rejection characterized by progressive fibrous obliteration of the airways, is the major obstacle limiting prolonged survival of lung transplant recipients. To date, no effective therapy against this fatal complication exists. Interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine, inhibits various T cell and antigen-presenting cell functions. We examined the effect of IL-10 in an animal model for bronchiolitis obliterans. A heterotopic tracheal transplant model was used. IL-10 was administered to the recipient either in its recombinant form by osmotic minipump or by adenoviral-mediated IL-10 gene transfer (Ad5E1mIL-10). Successful gene transfection and expression was confirmed by measuring circulating IL-10 protein. Tracheal allografts were assessed histologically based on a scoring system. IL-10 administration (in recombinant form or by gene transfer) inhibited the development of fibrous airway obliteration 3 weeks after transplantation in comparison to untreated controls (p < 0.05). This was demonstrated only if the delivery was initiated 5 days after transplantation and not if it was started at the time of transplantation. A single administration of the gene construct was sufficient to achieve the desired effect. We have shown that IL-10 can prevent the development of airway fibro-obliteration in this model. Gene transfection at a site distant from a graft can be used to produce a desired effect on the graft. IL-10 may be of major importance in the control of post-transplant bronchiolitis obliterans. The timing of its administration is critical and further studies are required to determine the mechanisms underlying the observed effects of IL-10.

Adenoviruses, Human↗
PubMed1997

Salvage therapy with mycophenolate mofetil for lung transplant bronchiolitis obliterans: importance of dosage.

BACKGROUND: Bronchiolitis obliterans (BO) is the most important long-term complication of lung transplantation. Treatment of this condition is often unsuccessful. METHODS: A patient presented with early BO. Despite OKT3 and the addition of methotrexate, the patient needed persistently high doses of prednisone to maintain lung function at a moderate level. Only the substitution of azathioprine by mycophenolate mofetil (MMF, 3 g/day) made it possible to reduce the dose of prednisone. RESULTS: Reduction of the dose of MMF to 2 g/day resulted in a deterioration of lung function, which improved impressively after MMF was increased again to 3 g/day. CONCLUSIONS: MMF may be a valuable therapy for lung transplant BO. However, the use of a high dose, i.e., 3 g/day, may be crucial.

Adult↗
PubMed1997

Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat model of bronchiolitis obliterans.

BACKGROUND: Bronchiolitis obliterans is the most significant complication adversely affecting prolonged survival of lung allograft recipients. The evolution from the initial insult to the final pathologic entity is largely unknown. The aim of this study was to characterize the evolution of transplant-induced fibrous airway obliteration in a rat tracheal transplant model of bronchiolitis obliterans. METHODS: Tracheal segments were transplanted from Brown Norway rats to Brown Norway rats (isografts) or to Lewis rats (allografts). Grafts were implanted into a subcutaneous pouch and an abdominal omental wrap. They were harvested at 14 different time points (from 1 day to 1 year after transplantation) and assessed histologically. RESULTS: The fibrous airway obliteration developed only in allografts showing a triphasic time course: an initial ischemic phase (observed in both isografts and allografts) was followed by a marked lymphocytic infiltrative phase with complete epithelial loss (observed only in allografts, P<0.01), and finally by an obliterative phase with fibrous obliteration of the allograft airway lumen (P<0.01). CONCLUSIONS: This animal model shows a distinct and reproducible triphasic time course in the development of obliterative airway lesions in allografts. It confirms that the mechanism leading to airway obliteration is immune mediated as only allografts showed this lesion and that lymphocytic infiltration is a precursor of the lesion in this model. The insights into the different phases demonstrated may lead to novel approaches regarding the type and timing of therapeutic interventions.

Animals↗
PubMed1997

A case report of a double-blind, randomized trial of inhaled steroids in a patient with lung transplant bronchiolitis obliterans.

Lung transplant bronchiolitis obliterans syndrome (BOS) is the most significant long-term cause of morbidity and mortality after lung transplantation. Although augmented immunosuppression is used by most centers, reported on treatment to reverse BOS are largely anecdotal. We performed a double-blind, randomized, controlled trial (RCT) with ten treatment pairs of 2 weeks duration each comparing inhaled fluticasone propionate (2 x 1,000 micrograms/day) with placebo in a patient with BOS grade 2 who previously showed an improvement in lung function after inhaled steroids. The Baseline Dyspnea Index and the Modified Medical Research Council Dyspnea Scale showed a significant improvement during fluticasone treatment compared with the placebo period (2.7 +/- 0.2 vs. 2.0 +/- 0.3; p = 0.043; and 1.7 +/- 0.2 vs. 2.4 +/- 0.2; p = 0.043). The patient correctly identified fluticasone and placebo, respectively, in eight of ten trial pairs (p = 0.016). The values of forced expiratory volume in 1 s were significantly higher during the fluticasone period (1,207 +/- 10 ml; 95% confidence interval, CI, 1,187-1,227 ml) compared to the placebo period (1,150 +/- 6 ml; 95% CI 1,138-1,162 ml; p = 0.0012). In conclusion, this n-of-1 RCT suggests the efficacy of high-dose inhaled fluticasone in our patient with lung transplant BOS. We propose to conduct a multicenter RCT of high-dose inhaled steroids. Until further data are available, this treatment modality should be offered to patients with lung transplant BOS.

Administration, Inhalation↗
PubMed1997

Bronchial anastomotic complications following lung transplantation: still a major cause of morbidity?

The frequency of bronchial anastomotic complications following lung transplantation has decreased in recent years, but continues to be a potential cause of morbidity and mortality. We have, therefore, reviewed the results of 67 consecutive bronchial anastomoses at risk in 43 patients surviving more than 7 days following lung transplantation. The bronchial anastomoses were performed using a standardized technique, without direct or indirect revascularization. Regular triple immunosuppressive therapy was given, including prednisone (0.5 mg x kg(-1) daily) starting on the day of surgery. Bronchial healing was graded using the Couraud classification. The median follow-up time was 14 months (range 1-45 months). No major airway complications occurred. On 236 serial bronchoscopic examinations, no anastomotic stenoses were observed. One anastomosis showed limited focal necrosis (2 mm) (Couraud 3a), and two anastomoses had partial primary mucosal healing without necrosis (Couraud 2a). In all other anastomoses, primary mucosal healing (Couraud 1) was observed. Carefully performed bronchial anastomosis according to the technique described enables reliable bronchial healing and yields a low complication rate. Additional measures, such as direct revascularization, forced telescoping, omentum wrap and interruption of steroid therapy, are not necessary.

Adult↗
PubMed1996

Lung transplantation for lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis is a rare disease of unknown origin that usually leads to progressive deterioration of lung function and eventual death from respiratory failure. It occurs in women of reproductive age and people with tuberous sclerosis. Lung transplantation is a recent therapeutic approach. METHODS: We conducted a retrospective study by questionnaire of 34 patients, treated at 16 transplantation centers, who underwent lung transplantation for end-stage lymphangioleiomyomatosis between 1983 and 1995. RESULTS: Of the 34 patients, 27 received single-lung transplants; 6, bilateral transplants; and 1, a heart-lung transplant. As of August 31, 1995, the actuarial survival calculated by the Kaplan-Meier method was 69 percent after one year and 58 percent after two years. Eighteen patients were alive 33 +/- 20 months (range, 3 to 74) after transplantation. Forced expiratory volume in one second increased from 24 +/- 12 percent of the predicted value before transplantation to 48 +/- 16 percent six months after transplantation. Five early deaths (within one month) were due to hemorrhage (in one patient), acute lung injury (in three), and dehiscence of the bronchial anastomosis (in one). Eleven late deaths (after one month) were due to infections (in eight patients), bronchiolitis obliterans (in two), and metastatic nephroblastoma (in one). Disease-associated problems were extensive pleural adhesions in 18 patients, leading to moderate-to-severe intraoperative hemorrhage in 4; pneumothorax in the native lung after single-lung transplantation in 6 patients; postoperative chylothorax in 3; and recurrent lymphangioleiomyomatosis in the allograft in 1 patient, who died of disseminated aspergillosis. CONCLUSIONS: Although disease-related complications are frequent, lung transplantation can be a valuable therapy for patients with end-stage lymphangioleiomyomatosis.

Adult↗
PubMed1996

Prospective study of the value of transbronchial lung biopsy after lung transplantation.

Transbronchial lung biopsy (TBB) has become the gold standard for the diagnosis of acute rejection and cytomegalovirus (CMV) pneumonia in lung transplant recipients. The aim of this study was to assess the value of regular surveillance TBB in stable asymptomatic patients and to establish the role of TBB as a follow-up procedure 1 month after a previous pathological biopsy result. We prospectively evaluated 76 TBBs performed in 17 lung transplant recipients. A definite pathological results was found in 14 of 15 TBBs performed for clinical indications: CMV pneumonia (5), acute rejection grade > or = A2 according to the criteria of the International Society for Heart and Lung Transplantation (ISHLT) (4), bronchiolitis obliterans (3), and desquamative interstitial pneumonitis (2). Fifteen of 45 surveillance TBBs performed in asymptomatic patients revealed significant abnormalities. Ten episodes of acute rejection ISHLT grade > or = A2 and three episodes of CMV pneumonia detected by TBB had direct therapeutic consequences. Nine of 16 follow-up TBBs performed 1 month after a pathological biopsy result again showed relevant pathological findings. With the exception of one severe haemorrhage, no life-threatening complications occurred. Our results suggest that transbronchial lung biopsies performed on a regular basis after lung transplantation are important for the detection of asymptomatic and/or persistent acute rejection or injection. In the long-term, this strategy might be the most effective tool in reducing the incidence of bronchiolitis obliterans, which is still the main obstacle for further improvement of long-term survival after lung transplantation.

Aspergillosis↗
PubMed1996

Bronchiolitis obliterans in a patient with localized scleroderma treated with D-penicillamine.

D-penicillamine-associated bronchiolitis obliterans (BO) is a rare but well-known pulmonary complication in patients with rheumatoid arthritis or progressive systemic sclerosis. It has been assumed that in most, if not all cases, BO is a complication of the underlying disease rather than a side-effect of treatment. We report the case of a 46 year old man with scleroderma localized to his lower legs (morphea), who received a daily dose of 750 mg D-penicillamine. During the treatment of 1 yr duration, he developed progressive shortness of breath due to a worsening obstructive ventilatory defect suggesting BO, which was confirmed by surgical lung biopsy (constrictive BO). Bronchial obstruction progressed over the next 5 yrs and did not respond to corticosteroids. The patient finally underwent a successful single left lung transplantation. The histological features of constrictive BO were confirmed in the explanted lung. This observation suggests that D-penicillamine may induce bronchiolitis obliterans in the absence of a systemic connective tissue disease.

Antirheumatic Agents↗