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Anaemia (haemoglobin 10.7 g/dl) and small spotty infiltrates in both lungs were found in an 18-year-old man who had increasing haemoptysis over the preceding 3 weeks. Bronchoscopy revealed diffuse bilateral pulmonary haemorrhage. Further diagnostic measures provided no evidence of involvement of other organs, in particular the kidneys. The demonstration of anti-basement membrane antibodies confirmed the diagnosis of a disease within the group of immune-induced alveolar haemorrhage. The radiological signs in the lungs regressed over 3 weeks of administering prednisone, initially 100 mg daily, then 60 mg daily, and the patient was discharged. While being treated as an out-patient, with reduction of prednisone to 10 mg daily, the haemoptysis recurred so that a single dose of cyclophosphamide, 1.5 g, was added to the immunosuppressive treatment. There was no further haemoptysis and the prednisone was discontinued after having been given for 15 months. The patient has now been in complete clinical remission for 3 years and anti-basement membrane antibodies are no longer demonstrable. At no time was there any evidence of renal involvement in the sense of the classical Goodpasture's syndrome.

Objective: Experiments were designed to compare large animal models for lung ischemia-reperfusion injury using either 90 minutes' warm or 24 hours' cold ischemia. Methods: In 6 pigs, the left lung was perfused in situ with cold LPD solution. Reperfusion was started after 90 min of warm ischemia. The left lung of 6 donor pigs was perfused with LPD solution and the lung transplanted after 24 hours of cold storage into 6 recipient pigs. In both groups the right pulmonary artery and main bronchus were clamped after reperfusion of the left lung. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h of reperfusion. Hemodynamic and respiratory parameters were monitored. Surfactant activity was determined from the BAL in a pulsating bubble surfactometer. Results: Moderate lung injury was evident after reperfusion, but without any significant differences between groups. Surfactant composition and function were mildly impaired after reperfusion in both groups. Conclusions: Our results suggest that short periods of warm ischemia might be accepted as an accelerated model for ischemia-reperfusion injury of the lung after cold storage.

Obliterative bronchiolitis is commonly interpreted as chronic rejection and involves the bronchial and bronchiolar epithelium. Upregulation of major histocompatibility complex (MHC) II on bronchial epithelial cells (BEC) had been hypothesised to be an important trigger of a bronchus directed rejection response. More recently, the additional expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on antigen presenting cells were found to play an important role in the activation of T-lymphocytes in transplant rejection. The role of the expression of these molecules by BEC is unclear. BEC obtained by bronchial brushing and bronchoalveolar lavage fluid (BALF) cells from lung transplant recipients were studied and evaluated for messenger ribonucleic acid (mRNA) expression of B7-1 and B7-2 by semi-quantitative reverse transcriptase-polymerase chain reaction. Significantly elevated B7-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios were found in BEC from patients examined during the first 3 months after lung transplantation. Interestingly, in a small group of patients with bronchiolitis obliterans syndrome the B7-1/GAPDH and B7-2/GAPDH ratios were significantly elevated for BEC, whereas no differences were found for the BALF cells. In summary, B7 messenger ribonucleic acid expression by bronchial epithelial cells may play a role in (chronic) lung allograft rejection.

BACKGROUND: Pulmonary preservation with high potassium/low oncotic pressure Euro-Collins (EC) solution is associated with endothelial dysfunction and reduced surfactant function. We compared two low potassium solutions, histidine-tryptophane-ketoglutarate (HTK) and Celsior, to EC in lung ischemia-reperfusion injury. METHODS: In 19 minipigs, the left lung was perfused in situ with cold preservation solution (EC, n=6; HTK, n=6; Celsior, n=7). Reperfusion was started after 90 min of warm ischemia. The right pulmonary artery and main bronchus were clamped. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h of reperfusion. Surfactant activity was determined from the BAL in a pulsating bubble surfactometer. RESULTS: Animals in the EC group survived 3.7+/-1.4 h. Six Celsior and five HTK treated animals survived the observation period of 7 h (P

OBJECTIVE: Surfactant function was shown to be impaired in clinical and experimental lung transplantation. This study was designed to define the impact of retrograde flush perfusion on graft and surfactant function after an extended period of ischemia. METHODS: Left lung transplantation was performed after 24 hours of graft ischemia in 12 pigs. In half of the grafts antegrade cold flush perfusion (Perfadex) was used for preservation. In the second group grafts were flushed in a retrograde fashion via the left atrium. Graft function was monitored for 7 hours after transplantation. Before transplantation (basal) and after 2 hours of reperfusion, bronchoalveolar lavage fluid was obtained. Minimal surface tension of bronchoalveolar lavage fluid was determined and the ratio of small and large surfactant aggregates was calculated. Lung water content was analyzed online in the reperfusion period. RESULTS: Right-sided heart failure developed in 2 animals of group 1 (antegrade perfusion) within 2 and 4.5 hours of reperfusion, respectively. All other pigs survived the observation period. PO(2)/FIO(2) (P =.001) and dynamic lung compliance (P =.001) were superior in retrogradely flushed grafts. A comparable increase of minimal surface tension was found after reperfusion in both groups. Small/large surfactant aggregate ratio after reperfusion (P =.03), as well as extravascular lung water content, was higher in the antegrade perfusion group. CONCLUSION: Retrograde flush perfusion for 24-hour lung preservation with low-potassium dextran (Perfadex) solution led to better initial graft function than the standard antegrade perfusion technique. A moderate impairment of surfactant function was found in both groups, which was more pronounced in the antegrade perfusion group.

Pulmonary artery catheterization (PAC) is widely used for monitoring and optimization of hemodynamic therapy in critically ill patients. Despite its widespread use there is no clear evidence that morbidity and mortality can be reduced by this approach. In contrast, it has been suggested that PAC might increase mortality. Available data do not allow the definitive omission of PAC in medical intensive care, nor do they justify its widespread use. Possible reasons that might affect outcome are catheter-related complications and often misinterpretation due to insufficient knowledge about PAC. Open questions on the influence of PAC on outcome variables in critically ill patients have to be answered by conducting randomized controlled trials. Beforehand, knowledge about PAC has to be improved. As a consequence, PAC should be performed whenever a specific hemodynamic question arises that cannot be answered by clinical judgement or by less invasive means. It is important that the investigator be experienced in catheter placement and data interpretation to avoid harm to these critically ill patients.

We reviewed our experience with various forms of lung transplantation (heart-lung [HLTx], bilateral lung [BLTx] and single lung [SLTx]) from December 1987 to September 1998 at Hannover University.In 258 patients 282 procedures (46 HLTx, 142 BLTx and 94 SLTx) were performed. Major indications were pulmonary fibrosis (n = 73), obstructive lung disease (n = 55), cystic fibrosis (n = 48), primary pulmonary hypertension (PPHT, n = 36), secondary pulmonary hypertension (n = 30) and retransplantation (n = 24).The 1-, 3- and 5-year survival rates in all 258 recipients were 77%, 70% and 63% respectively. Significantly better 1-year survival was noted in patients with cystic fibrosis (90%), pulmonary fibrosis (81%), obstructive lung disease (71%) and secondary pulmonary hypertension (83%) when compared to patients with primary pulmonary hypertension (58%). There was no significant difference in actuarial 1-year survival rates between the different procedures (HLTx 78%, BLTx 77%, SLTx 77%). Bronchiolitis obliterans syndrome (BOS) proved to be the major obstacle for long term survival. Actuarial freedom from BOS was 80% at 1 year and only 45% at 5 years. Various treatment strategies including augmentation of immunosuppression could only temporarily halt the deterioration of lung function in the majority of patients with BOS.Lung transplantation provides a true therapeutic option for patients with endstage lung disease. However, improved long term outlook will depend on a better understanding and treatment of bronchiolitis obliterans.

Fibrin glue pleurodesis has proven effective in the management of malignant pleural effusions. In a first study we compared two agents in 20 selected patients who provided optimal preconditions for this procedure. All patients had a complete drainage of the pleural space and a total expansion of the lung following pleural drainage. Tetracycline and fibrin glue were installed in four different positions of the patient body. This technique resulted in a complete obliteration of the pleural space in 80%–90% of the patients. A consecutive study with 22 unselected patients who were treated with fibrin glue in the same technique did not confirm these good results. In this group only 71% had a successful pleurodesis; however, in the majority of patients (45%) only a partial obliteration of the pleural space was achieved. Retrospective analysis of our data reveals that essential requirements for successful pleurodesis are a complete drainage of pleural effusion, total reexpansion of the lung, and diaphragmai location of the catheter tip. In patients with suboptimal preconditions we therefore prefer different agents such as tetracycline for pleurodesis.

The diagnosis of the obliterative bronchiolitis syndrome in lung transplantation is presently best established by evaluation of postoperative lung function tests. Unfortunately the decline in lung function occurs only when obliteration has progressed significantly and is therefore not an early predictive indicator. To distinguish patients at increased risk for the development of obliterative bronchiolitis, we regularly assessed the chemiluminescence response of polymorphonuclear leukocytes, opsonic capacity, and plasma elastase/beta-N-acetylglucosaminidase in 52 outpatients (25 women and 27 men; mean age 45 +/- 12 years) who underwent transplantation between January 1991 and January 1992. Recent onset bronchiolitis within the described observation period occurred in 16 patients (group obliterative bronchiolitis). A matched cohort of 16 patients was formed according to type of procedure, age and follow-up (control) from the remaining 36 patients. Data obtained from a period 6 months before clinical onset of the syndrome showed a significant drop of the opsonic capacity (group obliterative bronchiolitis = 87% +/- 7%; control = 100% +/- 9%; p0.023) and rise of the N-acetyl-D-glucosaminidase (group obliterative bronchiolitis = 7.5 +/- 2 U/L; control = 5.8 +/- 1.8 U/L; p0.04). No correlation was found between the number of infectious events or rejection episodes and the incidence of obliterative bronchiolitis. According to these results, it can be concluded that a decrease in the plasma opsonic capacity and a rise in beta-N-acetylglucosaminidase may be early markers before clinical onset of obliterative bronchiolitis. The nonspecific immune system may therefore play an important role in the development of obliterative bronchiolitis.