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A 30-year-old woman with blunt chest trauma after falling from a horse appeared to have a haematothorax. Bronchoscopy showed a bronchial rupture of the posterior segment of the right upper lobe. As her condition was stable, a policy of expectant management was instigated. She recovered without problems. A 73-year-old woman with an ileus of the small intestine had, after several intubations, a tracheal rupture. Due to her poor condition a policy of conservative management was followed. The rupture healed in 2 months. The patient died due to her abdominal problems. Tracheo-bronchial ruptures are rare, mostly caused by blunt chest trauma or iatrogenic due to complicated intubations. Acute therapy involves the optimalization of ventilation. In certain selected cases following a policy of expectant management may be successful.

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Patients with bronchiectasis usually have chronic pulmonary infection with secondary obstructive airway disease. This disease has to be distinguished from chronic obstructive pulmonary disease (COPD). The diagnosis is established with the help of high resolution CT scan of the thorax. Further diagnostic evaluation is necessary to identify aetiologic factors. The treatment is complicated and involves many aspects: treatment of underlying conditions, recognition of exacerbations, boosting of tracheobronchial clearance, treatment of haemoptysis, surgical resection of affected lung segments and antibiotic therapy. Antibiotic therapy can focus on treatment of exacerbations but chronic suppressive antibiotic therapy is also used. Favourable results have been reported for maintenance treatment with macrolids as well as anti-inflammatory therapy.

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A 66-year-old man was hospitalised because of pneumonia and chronic obstructive pulmonary disease. He suffered from facial burns when he tested a cigarette lighter whilst on oxygen therapy by nasal prongs.

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Three patients, men aged 21, 57 and 53 years, presented with variable non-specific symptoms such as general malaise, weight loss, elevated temperature, abdominal pain, cough, pulmonary crepitations and elevated liver enzymes. Diffuse fine nodular infiltration was seen on chest radiography in the last two cases. The first patient refused to be tentatively treated with tuberculostatics and died. Mycobacterium tuberculosis complex grew on Löwenstein medium a week later. The two other patients received tuberculostatic treatment. The second patient recovered, while the third patient suffered a cerebrovascular accident on top of emaciation and respiratory insufficiency and died. In the Netherlands, currently more than one hundred patients with tuberculosis disease die each year. The disease is mostly seen in people from the high-risk groups for tuberculosis such as asylum seekers and immigrants. Even after extensive diagnostic procedures it can be difficult to obtain rapid bacteriological confirmation. When miliary tuberculosis is suspected it is important to carry out the complete range of tests (Ziehl Neelsen microscopy, PCR, Löwenstein cultivation) and to start therapy immediately and not to await the results of the diagnostic tests. However, in many cases this may still be too late, with an estimated mortality of 20%.

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The aim of the present study was to perform a proof of principle study with a new colistin dry powder inhalation system in six healthy volunteers and five patients with cystic fibrosis. All subjects were asked to inhale 25 mg colistin sulfate dry powder. The patients were also asked to nebulize 160 mg colistin sulfomethate as a solution. Colistin serum concentrations were determined as an indirect parameter to compare both forms of administration. Pulmonary function tests were performed. Peak serum colistin concentrations ranged from 14 to 59 microg/l in volunteers after inhalation of 25 mg as dry powder. In patients, peak concentrations ranged from 18 to 64 microg/l after nebulization of 160 mg colistin sulfomethate solution and from 77 to 159 microg/l after inhalation of 25 mg colistin sulfate dry powder. Pulmonary function tests were not significantly different after inhalation of the dry powder by the volunteers nor after nebulization of the solution by the patients. In some patients a decrease in pulmonary function and moderate to severe cough was observed after inhalation of the dry powder. The new colistin inhaler provides an attractive alternative for nebulized colistin and was highly appreciated by the patients. The decrease in pulmonary function and cough in patients is a drawback, which may be overcome by dose reduction and a further improvement of the new dosage form.

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Data on the pharmacokinetics of antibiotics after inhalation are limited. The aim of this pilot study was to assess the pharmacokinetics of tobramycin under optimalized and standardized aerosol circumstances and, furthermore, to be able to consider possible treatment of exacerbations with inhalation therapy. Six patients were studied after inhalation of 600 mg tobramycin. A jet nebulizer loaded with a 10% solution of tobramycin in water was used. The percentage of the dose that was systemically absorbed ranged from 1.0% to 16.6%. The maximum serum levels of tobramycin ranged from 0.77 mg/L to 3.63 mg/L (mean 1.70 +/- 1.01). The pharmacokinetic data were best described by a two-compartment model. Compared to intravenous administration, the long terminal half-life (mean 9.47 h +/- 3.28 h) could be explained by the slow absorption of tobramycin from the site of administration (flip-flop model). Despite standardized aerosol conditions, considerable interpatient variability was observed. However, the relatively low serum levels allow a further increase of the dose.

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The majority of patients with cystic fibrosis (CF) will grow into adulthood. Despite this improvement in survival, the disease is progressive, especially with respect to the decline in pulmonary function, which in turn may have an impact on a patient's quality of life. In this study we evaluated the quality of life in CF adults and examined the relationship between quality of life and pulmonary function, exercise capacity, and dyspnea. We assessed in 15 patients in stable clinical condition their forced expired volume in the first second (FEV1) inspiratory vital capacity (IVC), cycle exercise capacity (Wmax), and subjective degrees of dyspnea during daily living (MRC dyspnea scale). Quality of life was assessed with the Sickness Impact Profile (SIP). A sample of 100 healthy individuals, ranging in age from 18 to 30 years, served as the control group. Mean (SD) age of the patients was 25.9 (7.3) years, FEV1 was 38 (16)% predicted, IVC was 65 (17)% predicted, FEV1 IVC ratio was 46 (10)%, and Wmax was 90 (54) W. The overall SIP and physical SIP scores in CF patients were significantly higher than in the controls, indicating more impairment in overall and physical functioning in the patients than in the control group (P < 0.001). The psychosocial SIP score did not differ significantly between the two groups. Overall SIP score correlated poorly with FEV1 % predicted (r = -0.33; n.s) and IVC % predicted (r = -0.36; n.s.) but showed a better and significant relationship to the maximal exercise capacity (r = -0.57; P < 0.05). MRC dyspnea scores showed a strong correlation with overall SIP scores (r = 0.75; P < 0.001). These results show that CF affects quality of life in adults primarily due to a limitation in physical functioning. Psychosocial functioning did not differ from that of healthy controls. Exercise capacity and dyspnea scores were related to the impairment in the quality of life. Therefore, the effects of programs aimed to improve exercise capacity and reduce dyspnea on CF patients' quality of life need to be evaluated.

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The median age of survival in patients with cystic fibrosis (CF) has improved considerably. Despite this improvement, deterioration of pulmonary function and decrease in exercise capacity are still the main problems for many patients. Although dyspnoea is a common complaint in CF patients, relatively little regard has been paid to this symptom. This study examined the relationship between dyspnoea, bicycle exercise capacity and pulmonary function in patients with CF. In 14 patients in a stable clinical condition, pulmonary function [forced expiratory volume in 1 s (FEV1), inspiratory vital capacity (IVC)], bicycle exercise capacity [maximum exercise capacity (Wmax)], subjective degree of dyspnoea during daily living [Medical Research Council (MRC) dyspnoea scale], and during exercise (Borg scale) were assessed. The mean (SD) age of the patients was 25 (6.8) years, FEV1 was 41 (19)% predicted, IVC was 63 (17)% predicted and FEV1/IVC ratio was 47 (10)%; median (range) Wmax was 55 (0-79)% predicted. Bicycle exercise test performance appeared to be mainly determined by pulmonary function and MRC dyspnoea grade; multiple regression equation containing FEV1 and dyspnoea accounted for 76% of the variance in Wmax (% predicted) (Wmax = -7.9 dysp + 1.1 FEV1, +24). Exercise dyspnoea, assessed by the Borg scale, showed a significant linear correlation with minute ventilation. (VE), maximal voluntary ventilation (MVV) (%) (r = 0.76; P < 0.001). Medical Research Council dyspnoea score correlated relatively poorly with FEV1 (% predicted) (r = -0.17; n.s.) and IVC (% predicted) (r = -0.48; n.s.). Borg score at maximal exercise did not correlate with MRC dyspnoea score (r = -0.07). Borg50% score correlated significantly with MRC dyspnoea score (r = 0.61; P < 0.05). These results show that dyspnoea has an influence on exercise capacity. Dyspnoea score showed a large inter-individual variation, not strongly related to pulmonary function. It is concluded that dyspnoea deserves more attention in CF patients and needs to be assessed in rehabilitation programmes and other intervention studies in these patients.

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A woman aged 30 and a man aged 40, both with a bad general condition due to cystic fibrosis, showed a clear clinical improvement after they were treated in a cystic fibrosis centre, while in a young adult male patient the diagnosis of cystic fibrosis could be rejected. In the Netherlands there are approximately 1000 patients with cystic fibrosis. As a consequence most doctors have hardly any experience of the treatment of such patients. To optimize the treatment of patients with cystic fibrosis, it would seem wise to concentrate experience and knowledge in several cystic fibrosis centres.

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OBJECTIVE: To determine whether quantification of specific antifungal antibody responses in serum can provide supplemental information for the diagnosis of Aspergillus fumigatus infections and the monitoring of antifungal treatment in patients after lung transplantation. DESIGN: Retrospective study. SETTING: Center for lung transplantation, University Hospital Groningen, the Netherlands. PATIENTS: 4 patients with proven A. fumigatus infections after lung transplantation and fatal outcome. MEASUREMENTS: The IgG antibody response specific for A. fumigatus antigens was measured by enzyme-linked immunosorbent assay and was compared with radiographic features, cytologic findings, microbiological cultures, and clinical diagnosis. RESULTS: Increasing IgG antibody responses specific for A. fumigatus antigens closely paralleled cytologic or microbiological identification of A. fumigatus from bronchoalveolar lavage fluid and decrease of lung function. Increasing specific IgG antibody responses were found to precede radiographic identification of lung cavitation by 1 to 2 weeks, precede the diagnosis of aspergillosis by 2 to 20 weeks, and detect fungal reinfection. In most cases, successful antifungal treatment decreased specific IgG antibody response. A decrease in specific IgG antibody response correlated with the inability to culture or identify A. fumigatus in bronchoalveolar lavage fluid and with radiographic and clinical improvement. CONCLUSIONS: Specific IgG antibody responses in serum correlate with radiographic, cytologic, and microbiological findings and with the clinical diagnosis of A. fumigatus infections in patients who have had lung transplantation. Increased IgG antibody responses in serum may provide important information that is helpful in the diagnosis and early treatment of pulmonary fungal infections and in monitoring antifungal treatment.

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OBJECTIVE: To describe the development of the lung transplantation programme in Groningen, and the results of single and bilateral lung transplantations in the first 75 consecutive patients, up to December 1995. DESIGN: Retrospective. SETTING: Academic Hospital Groningen, the Netherlands. METHODS: The results of the lung transplantation programme were evaluated retrospectively. RESULTS: In November 1990 the first unilateral lung transplantation was performed in Groningen in a patient with pulmonary fibrosis. In February 1991 a national lung transplantation programme for the Netherlands was instituted in Groningen by the government. Of 500 patients referred from all over the Netherlands from 1990 to December 1995, 75 were transplanted, 16 unilaterally and 59 bilaterally. The actuarial survival for all patients was 85% after 1 year and 72% after 2 years. After transplantation 16 patients died (21%) after 15 months follow-up (median). Early mortality (5%) was caused by graft failure, late mortality (16%) by chronic rejection and lymphoproliferative disease. The mean time on the transplantation waiting list was 9.3 months; it increased during the programme. The limiting factor for further expansion of the programme was caused by donor scarcity. The lungs from only 16% of the multiorgan donors reported by Eurotransplant to our centre could be transplanted. CONCLUSION: The results of the lung transplantation programme in Groningen are good but with an increasing number of lung transplantation centres in the Eurotransplant region the further development of lung transplantation in the Netherlands will depend mainly on the availability of lung donors from the Netherlands.

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Renal function impairment is common after solid organ transplantation, due to the nephrotoxicity of cyclosporine. Moreover, in patients with severe respiratory failure, renal function is often impaired. This renal function impairment may predispose patients to further renal function impairment after lung transplantation. Therefore, renal hemodynamics were measured in 44 patients before lung transplantation and 1, 6, 12, 18, 24, and 30 months after transplantation. After transplantation, a decline in renal function occurred, with a progressive fall in glomerular filtration rate (GFR) of 33 +/- 4% at 12 months and 42 +/- 9% at 30 months. Effective renal blood flow fell by 22 +/- 5% at 12 months and remained stable thereafter. Changes in effective renal plasma flow (ERPF) were less pronounced than those of effective renal blood flow, due to a fall in hematocrit after transplantation. Blood pressure and renal vascular resistance increased significantly, consistent with the effects of cyclosporine. Prior to transplantation, renal function impairment with intense renal vasoconstriction had been found in a subset of the patients. Remarkably, the decrease in renal function after transplantation was less pronounced in patients with renal function impairment prior to transplantation, as indicated by significant negative correlations between pretransplantation GFR and the percentage change in GFR after transplantation, and pretransplantation ERPF and the percentage change in ERPF after transplantation. This suggests that the net course of renal hemodynamics after lung transplantation is the result of the opposed effects of cyclosporine nephrotoxicity and the favorable effects of the normalization of respiratory status. In conclusion, after lung transplantation a decline in renal function occurs that is less pronounced in patients with renal function impairment and intense renal vasoconstriction prior to transplantation. Such a renal function impairment, therefore, should not be considered a contraindication to lung transplantation.

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In November 1990, a lung transplantation program began at the University Hospital in Groningen, the Netherlands. As of April 1994, 300 patients were referred for lung transplantation and we investigated the decisions that have been made concerning these referrals up to January 1, 1995. The patients were evaluated according to a stepwise procedure. In stage 1, written information about the referred patients was discussed during the weekly, multidisciplinary lung transplantation meeting. In this stage, 14% of the patients were rejected and 2% were postponed. If no major objections for transplantation were identified, the patient was invited for a visit to the outpatient clinic, stage 2. The newly acquired information from that visit was discussed again at the transplantation meeting. In this stage, 11% of the patients were rejected and 18% postponed. The remaining patients underwent an (partial or complete) inpatient evaluation, stage 3. From all patients about whom a decision was made in this stage, only 5% were rejected, respectively 35% after partial evaluation and only 1.5% after complete evaluation. A total of 110 patients (37% of all referred patients) were listed for lung transplantation, stage 4. Of the listed patients, 20% died while awaiting an appropriate donor. The group of patients with COPD/emphysema had by far the lowest death rate on the waiting list. Patients with short stature (< or = 1.65 m) had a much higher risk to die on the waiting list compared with patients with longer stature, 42% vs 13%. As of January 1, 1995, 55 patients have undergone transplantation, which is 50% of all patients on the waiting list and 18% of all referred patients. The stepwise selection procedure identifies patients with potential contraindications at an early stage. In this way, unrealistic expectations and unnecessary examinations, expense, and/or hospital admissions may be prevented. Donor shortage, and thus waiting list problems, still remains a significant drawback in the further development of lung transplantation.

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Spontaneous pneumopericardium occurred in a patient almost 4 weeks after bilateral lung transplantation for cystic fibrosis. The patient had no specific complaints and was in stable haemodynamic condition. We suggest that this pneumopericardium was related to a concomitant active cytomegalovirus (CMV) infection. After treatment of the CMV infection, the pneumopericardium resolved spontaneously.

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BACKGROUND: Opportunistic fungal infections are an important cause of morbidity and mortality in solid organ transplant recipients. Conventional therapy with amphotericin B is often restricted by toxicity. However, side effects and toxicity of liposomal amphotericin B are reported to be limited. METHODS: Three lung transplant recipients with proven infections with Aspergillus fumigatus were treated with liposomal amphotericin B. RESULTS: Therapy with liposomal amphotericin B in our patients showed more side effects and (nephro)toxicity than suggested by previous reports. However, it did not result in cessation of treatment prematurely, and patients were able to complete the antifungal therapy with good clinical success. CONCLUSIONS: Treatment with liposomal amphotericin B represents an advance from conventional amphotericin B therapy.

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Worldwide more than 600 heart-lung or lung transplantations have been performed in patients with cystic fibrosis and end-stage respiratory disease. At the University Hospital in Groningen 10 patients with cystic fibrosis underwent bilateral sequential lung transplantation until April 1994. The 1-year survival was 76%, which is similar to that of lung transplant recipients with other diseases. Postoperative problems were mainly related to acute rejection, chronic graft dysfunction and infection. The main problem for further extension of the lung transplantation program is the persistent shortage of usable donor-organs for cystic fibrosis patients, especially of small-sized donors.

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Intravenous antibiotics and enteral tube feeding at home for the treatment of pulmonary exacerbations and underweight condition in cystic fibrosis (CF) patients have become tools that are used in many cystic fibrosis centres. The experience with home care programmes from different countries is quite conclusive. If the necessary preparations are made, such as training of staff and patients, and financial support is arranged, home care is easy to put into practice. Optimal patient compliance is also necessary. Home care is as effective as hospital treatment for selected patients, and less expensive. Experience has increased during many treatment periods in different cystic fibrosis centres, and only a few adverse events have been recorded, indicating that home care is safe. However, the most important gain for cystic fibrosis patients is the reduction of hospital admission time, which means a definite improvement in the quality of life.

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OBJECTIVE: Medical technology assessment of lung transplant programme in Groningen, the Netherlands. DESIGN: Descriptive evaluation study. SETTING: University Hospital Groningen. METHOD: Description of the patient route through the treatment process of the transplantation programme. RESULTS: From mid-1990 to 1-1-1994, 257 patients (M/F ratio approximately 1, median age 43 years) were evaluated. The most frequent diagnoses were: COPD/emphysema, cystic fibrosis, pulmonary hypertension and lung fibrosis. In 1991 relatively more patients came from the northern provinces, but in 1993 there was no difference from the rest of the Netherlands. Until 1-1-1994, 116 patients were excluded from the programme: 58 patients were denied transplantation in the early phase of the programme, 47 died, 6 withdrew and 5 were lost in follow-up. Until 1-1-94, 77 patients were placed on a waiting list and 35 of these underwent unilateral (n = 12) or bilateral transplantation (n = 23). One patient had a retransplantation. The 1-year survival rate was 84%. The mean time between admission and transplantation was 15 months. CONCLUSION: The results of the lung transplantation programme in Groningen are promising.

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