Biomedical subjects

G H Koëter

Publications and source records attributed to G H Koëter.

At least 19 recordsLinked to original sources

PubMed2001

Long-term outcome of lung transplantation is predicted by the number of HLA-DR mismatches.

BACKGROUND: The importance of HLA mismatch in determining long-term outcome in lung transplantation remains largely uncertain. METHODS: A retrospective analysis of 102 consecutive primary lung transplants was performed to identify risk factors for poor long-term outcome after lung transplantation defined as graft survival and bronchiolitis obliterans syndrome (BOS) stage I and II. Variables included were patient characteristics (age, sex, prior diagnosis), the number of HLA mismatches between donor and recipient, cold ischemic time, cytomegalovirus serologic concordance, number of acute rejections, and time to first rejection. Variables carrying significance in a univariate analysis were subjected to a proportional hazard regression analysis. RESULTS: In the multivariate analysis, an increased number of acute rejections correlated positively with decreased graft survival (risk ratio [RR] = 1.25; 95% confidence interval [CI], 1.05-1.5; P = 0.011), development of BOS stage I (RR = 1.36/episode; 95% CI, 1.16-1.58;P < 0.001), and BOS stage II (RR = 1.42/episode; 95% CI, 1.2-1.67; P < 0.001). An increased time to rejection correlated positively with reduced graft survival (RR = 1.03/day; 95% CI, 1.01-1.06; P = 0.02), and BOS stage I and II (both RR = 1.04/day; 95% CI, 1.01-1.07; P < 0.005). Compared with 2 HLA-DR mismatches, 0 or 1 mismatch was associated with improved graft survival (RR = 0.43; 95% CI, 0.19-0.98; P = 0.045) and protected against development of BOS stage I (RR = 0.47; 95% CI, 0.23-0.98; P = 0.044) and BOS stage II (RR = 0.35; 95% CI, 0.15-0.83; P = 0.017). CONCLUSIONS: HLA-DR mismatching appears to be a risk factor for the development of BOS and graft loss. Improved outcome after lung transplantation might be achieved with prospective matching for HLA-DR. Alternatively, the amount and type of immunosuppressive drugs may be guided by the degree of HLA-DR (mis)matching.

Adolescent↗

PubMed2001

Inspiratory muscle training in patients with cystic fibrosis.

Little information is available about the effects of inspiratory muscle training in patients with cystic fibrosis (CF). In this study the effects of inspiratory-threshold loading in patients with CF on strength and endurance of the inspiratory muscles, pulmonary function, exercise capacity, dyspnoea and fatigue were evaluated. Sixteen patients were assigned to one of two groups using the minimization method: eight patients in the training group and eight patients in the control group. The training was performed using an inspiratory-threshold loading device. Patients were instructed to use the threshold trainer 20 min a day, 5 days a week for 6 weeks. Patients in the training group trained at inspiratory threshold loads up to 40% of maximal static inspiratory pressure (Pimax) and patients in the control group got 'sham' training at a load of 10% of Pimax. No significant differences were found among the two groups in gender, age, weight, height, pulmonary function, exercise capacity, inspiratory-muscle strength and inspiratory-muscle endurance before starting the training programme. Mean (SD) age in the control group was 19 (5.5) years, mean (SD) age in the training group was 17 (5.2) years. Mean FEV1 in both groups was 70% predicted, mean inspiratory-muscle strength in both groups was above 100% predicted. All patients except one, assigned to the training group, completed the programme. After 6 weeks of training, mean inspiratory-muscle endurance (% Pimax) in the control group increased from 50% to 54% (P = 0.197); in the training group mean inspiratory muscle endurance (% Pimax) increased from 49% to 66% (P = 0.003). Statistical analysis showed that the change in inspiratory-muscle endurance (% Pimax) in the training group was significantly higher than in the control group (P = 0.012). After training, in the training group there was a tendency of improvement in Pimax with an increase from 105 to 123% predicted, which just fell short of statistical significance (P = 0.064). After training no significant differences were found in changes from baseline in pulmonary function, exercise capacity, dyspnoea and fatigue. It is concluded that low-intensity inspiratory-threshold loading at 40% of Pimax was sufficient to elicit an increased inspiratory-muscle endurance in patients with CF.

Adolescent↗

PubMed2001

PC(20) adenosine 5'-monophosphate is more closely associated with airway inflammation in asthma than PC(20) methacholine.

Inhalation of a direct stimulus such as histamine or methacholine is generally used to measure bronchial hyperresponsiveness (BHR). Provocation with adenosine 5'-monophosphate (AMP), an indirect airway challenge, has been suggested to be a better marker of airway inflammation than direct challenges. However, so far little information on this subject is available. The aim of our study was to assess whether the concentration of AMP causing the FEV(1) to drop by 20% (PC(20)) is more closely associated with inflammatory parameters in asthma than PC(20) methacholine. In 120 patients with atopic asthma (median FEV(1) 81% predicted [pred], median age 27 yr), PC(20) methacholine and PC(20) AMP as well as sputum induction, blood sampling, and measurement of nitric oxide in exhaled air were performed. PC(20) methacholine was predominantly predicted by FEV(1) %pred (explained variance [ev] = 18%) with the percentage of peripheral blood monocytes being a weak additional independent predictor (total ev = 23%). By contrast, PC(20) AMP was predominantly predicted by the percentage of eosinophils in sputum (ev = 25%), while FEV(1) %pred was only an additional independent predictor (total ev = 36%). PC(20) AMP reflects more closely the extent of airway inflammation due to asthma than PC(20) methacholine.

Adenosine Monophosphate↗

PubMed2000

Preoperative staging of non-small-cell lung cancer with positron-emission tomography.

BACKGROUND: Determining the stage of non-small-cell lung cancer often requires multiple preoperative tests and invasive procedures. Whole-body positron-emission tomography (PET) may simplify and improve the evaluation of patients with this tumor. METHODS: We prospectively compared the ability of a standard approach to staging (computed tomography [CT], ultrasonography, bone scanning, and, when indicated, needle biopsies) and one involving PET to detect metastases in mediastinal lymph nodes and at distant sites in 102 patients with resectable non-small-cell lung cancer. The presence of mediastinal metastatic disease was confirmed histopathologically. Distant metastases that were detected by PET were further evaluated by standard imaging tests and biopsies. Patients were followed postoperatively for six months by standard methods to detect occult metastases. Logistic-regression analysis was used to evaluate the ability of PET and CT to identify malignant mediastinal lymph nodes. RESULTS: The sensitivity and specificity of PET for the detection of mediastinal metastases were 91 percent (95 percent confidence interval, 81 to 100 percent) and 86 percent (95 percent confidence interval, 78 to 94 percent), respectively. The corresponding values for CT were 75 percent (95 percent confidence interval, 60 to 90 percent) and 66 percent (95 percent confidence interval, 55 to 77 percent). When the results of PET and CT were adjusted for each other, only PET results were positively correlated with the histopathological findings in mediastinal lymph nodes (P<0.001). PET identified distant metastases that had not been found by standard methods in 11 of 102 patients. The sensitivity and specificity of PET for the detection of both mediastinal and distant metastatic disease were 95 percent (95 percent confidence interval, 88 to 100 percent) and 83 percent (95 percent confidence interval, 74 to 92 percent), respectively. The use of PET to identify the stage of the disease resulted in a different stage from the one determined by standard methods in 62 patients: the stage was lowered in 20 and raised in 42. CONCLUSIONS: PET improves the rate of detection of local and distant metastases in patients with non-small-cell lung cancer.

Adult↗

PubMed2000

Cyclosporine, FK506, mycophenolate mofetil, and prednisolone differentially modulate cytokine gene expression in human airway-derived epithelial cells.

BACKGROUND: The immunosuppressive effects of cyclosporine (CsA), tacrolimus (FK506), mycophenolate mofetil (MMF), and prednisolone in cells from the immunological compartment are well documented. In contrast, limited information is available with respect to the effects of these immunosuppressive drugs on airway-epithelial cells, although these cells may contribute to the development of obliterative bronchiolitis (OB) through the production of interleukin (IL)-6 and IL-8. METHODS: We studied the production of IL-6 and IL-8 proteins by airway-derived epithelial cell lines and primary epithelial cell cultures obtained from lung brushings. Transcriptional mechanisms were detected by transient transfections. RESULTS: We demonstrate that CsA dose dependently induces the production of the proinflammatory cytokines IL-6 and IL-8 in both cell lines and primary epithelial cells. FK506 and MMF were also able to upregulate IL-8, although the effect was less dramatic than observed for CsA. Low concentrations of prednisolone (0.01 and 0.001 microg/ml) enhanced IL-6 and IL-8 secretion, whereas concentrations > or =0.01 microg/ml significantly diminished IL-6 secretion. Furthermore, we showed that CsA and prednisolone mediate their effects at the transcriptional level. CONCLUSIONS: The data provide evidence that relevant concentrations of CsA and MMF in vivo may enhance the inflammatory processes in the lower airways of patients after lung transplantation.

Cells, Cultured↗

PubMed2000

Changes in peak expiratory flow indices as a proxy for changes in bronchial hyperresponsiveness. Dutch Chronic Non-Specific Lung Disease study group.

Guidelines for asthma management advocate home peak expiratory flow (PEF) monitoring. It is commonly stated that PEF variability is a good proxy of bronchial hyperresponsiveness (BHR), a hallmark of asthma. However, this has hardly been tested longitudinally, as required to monitor asthma. This study assesses which PEF index correlates best with BHR longitudinally and whether the correlation improves when correcting PEF values for the known nonlinearity of mini-Wright PEF meters. Every 6 months, for a period of 2 yrs, PEF diary cards were filled in and BHR to histamine was tested in 104 patients with BHR and reversible airways obstruction, who started treatment with bronchodilators with (n=33) or without (n=71) inhaled corticosteroids. Within each subject, PEF indices and BHR were correlated longitudinally. The highest median correlation coefficients were obtained in the group of patients using inhaled corticosteroids. The PEF indices providing the best correlation with BHR were: mean PEF bronchodilator response (rho=-0.50) and within-day variation (% mean or % maximum) (with postbronchodilator values, rho=-0.50; without postbronchodilator values, rho=-0.40). Using PEF data corrected for the nonlinearity of the PEF meters did not result in higher correlation coefficients. Since current guidelines on asthma management recommend only bronchodilators on demand, the most useful peak expiratory flow index for reflecting bronchial hyperresponsiveness longitudinally is mean within-day peak expiratory flow variation (% mean or % maximum) (without postbronchodilator values). Since the correlation coefficients are not very strong, the authors suggest that peak expiratory flow measurements are not used as a proxy for bronchial hyperresponsiveness longitudinally but as a measurement in its own right. The use of corrections of peak expiratory flows for the nonlinearity of mini-Wright peak expiratory flow meters does not improve the correlation between peak expiratory flow and bronchial hyperresponsiveness.

Administration, Inhalation↗

PubMed2000

Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension.

The transfer factor of the lung for carbon monoxide (TL,CO) is decreased in patients with pulmonary hypertension. The pulmonary membrane diffusion capacity (Dm) and pulmonary capillary blood volume (Vc), were studied to establish: 1) the relative contribution of the components of the transfer factor to the decrease in TL,CO; 2) whether differences exist between primary pulmonary hypertension (PPH) and chronic thromboembolic pulmonary hypertension (CTEPH); and 3) the relationship between these parameters and haemodynamic parameters. Dm and Vc were determined in 19 patients with PPH and in eight patients with CTEPH. The patients had been referred for consideration for lung transplantation. Haemodynamic parameters were assessed by heart catheterization. In the PPH group, Vc was reduced in 12 of 19 patients (mean+/-SD Vc 72+/-14% of the predicted value) and Dm in 17 of 19 patients (60+/-22% pred). In the CTEPH group, Vc was reduced in six of eight patients and Dm in seven of eight patients. The mean TL,CO Dm and Vc values were similar to those in the PPH group. The reduction in pulmonary membrane diffusion capacity was significantly greater than that in pulmonary capillary blood volume. No differences in pulmonary and cardiovascular functional values were found between the groups. Right atrial pressure showed a significant negative correlation with pulmonary capillary blood volume and an increased pulmonary vascular resistance was associated with a decrease in pulmonary membrane diffusion capacity. These results suggest pronounced functional impairment of the alveolocapillary membrane in these patients.

Adult↗

PubMed2000

Airway inflammation and hyperresponsiveness to adenosine 5'-monophosphate in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation. OBJECTIVE: To investigate the role of airway inflammation in hyperresponsiveness to adenosine 5'-monophosphate (AMP) in COPD. METHODS: We investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean +/- SD, age 63 +/- 8 years, FEV1% predicted 56 +/- 13%), six without BHR (age 60 +/- 6 years, FEV1% predicted 65 +/- 11%) and 11 healthy nonatopic controls without BHR (age 58 +/- 8 years, FEV1% predicted 104 +/- 11%) participated in the study. RESULTS: Subjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm2; range, 30-1340 vs 280 cells/mm2; range, 110-450, P = 0.045; and median, 2.7%; range, 0.5-8.5 vs 0.6%; range, 0-0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid. CONCLUSION: We conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.

Adenosine Monophosphate↗

PubMed2000

Ongoing airway inflammation in patients with COPD who do not currently smoke.

BACKGROUND: Inflammatory changes in the airways in chronic obstructive pulmonary disease (COPD) are largely attributed to smoking, yet they may be present even if patients do not currently smoke. The differences in inflammatory cells and the factors contributing to these differences were examined in the airways of patients with COPD who do not currently smoke. METHODS: Eighteen non-atopic subjects with COPD (14 men) of mean (SD) age 62 (8) years and forced expiratory volume in one second (FEV(1)) 59 (13)% predicted and 11 non-atopic healthy subjects (eight men) of mean (SD) age 58 (8) years, FEV(1) 104 (11)% predicted were studied. Sputum induction and bronchoscopy with bronchoalveolar lavage (BAL) and biopsies were performed. RESULTS: Patients with COPD had more mucosal EG2+ cells (eosinophils) (median (range) 40 (0-190) versus 5 (0-40) cells/mm(2), p = 0.049) and CD68+ cells (1115 (330-2920) versus 590 (450-1580) cells/mm(2), p = 0.03), and a tendency towards more CD4+ but not CD8+ lymphocytes than healthy controls. Furthermore, patients with COPD had higher percentages of sputum neutrophils (77 (29-94) versus 36 (18-60)%, p = 0.001) and eosinophils (1.2 (0-8.5) versus 0.2 (0-3.1)%, p = 0.008), BAL fluid eosinophils (0.4 (0-1.7) versus 0.2 (0-0.5)%, p = 0.03), and higher concentrations of sputum eosinophilic cationic protein (ECP) (838 (115-23 760) versus 121 (35-218) ng/ml, p<0.001). Concentrations of ECP expressed per eosinophil were not higher. Patients with COPD with high mucosal EG2+ cell numbers also had high mucosal CD4+ cell numbers. Sputum eosinophilia was associated with a decrease in FEV(1)/VC and BAL fluid eosinophilia with a decrease in mucosal NP57+ cells (neutrophils). CONCLUSIONS: Subjects with COPD who do not currently smoke have increased numbers of inflammatory cells. Eosinophils are increased in number in the airways in COPD but do not seem to be activated. The increased eosinophil numbers are probably due to recruitment as a result of ongoing inflammation. Macrophages and lymphocytes may play a part in this inflammation.

Biopsy↗

PubMed2000

Bronchiolitis obliterans syndrome after lung transplantation and health-related quality of life.

The present study was undertaken to assess the relationship between health-related quality of life (HRQOL) and bronchiolitis obliterans syndrome (BOS), as both represent important parameters of outcome after lung transplantation. HRQOL was measured both cross-sectionally and longitudinally by standardized patient self-administered questionnaires, including the Nottingham Health Profile, the State-trait Anxiety Inventory, the Zung Self-Rating Depression Scale, and the Index of Well-Being. Data were collected at 4 and 7 mo, and every 6 mo afterwards for as long as 49 mo post-transplantation. The number of patients who completed the questionnaires varied from 72 at 4 mo, to 27 at 49 mo after transplantation. Cross-sectionally, the patients with BOS reported persistently statistically significantly more restrictions on the dimensions energy and physical mobility of the Nottingham Health Profile compared with patients without BOS. Other domains, i.e., pain, sleep, social interaction, and emotional reactions, were not affected. Additionally, patients with BOS reported statistically significantly more depressive symptoms and anxiety 1 and 2 yr after transplantation. Results from the longitudinal analysis support these findings, although no change in depressive symptoms could be found after onset of BOS. This study suggests that all lung transplant recipients improve in HRQOL. The development of BOS, however, is associated with a significantly reduced HRQOL.

Activities of Daily Living↗

PubMed2000

Eosinophilic granulocytes and interleukin-6 level in bronchoalveolar lavage fluid are associated with the development of obliterative bronchiolitis after lung transplantation.

In a prospective cohort study, we assessed whether changes in total cell counts and differentiation and interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) concentrations in bronchoalveolar lavage fluid (BALF) are associated with a higher risk to develop obliterative bronchiolitis (OB). We investigated 60 lung transplant patients (follow-up of 2 to 8 yr) with either histologic evidence of OB within 1 yr after lung transplantation (n = 19) or no pathology, good outcome (GO) for at least 24 mo and well-preserved lung function, i.e., FEV > or = 80% of baseline (n = 41). Median time between lung transplantation and the first BAL was 42 d for the GO group and 41 d for the OB group (p > 0.05). In the bronchial fraction, median total cell counts (0.06 x 10(3)/ml versus 0.04 x 10(3)/ml), lymphocyte (9 x 10(3)/ml versus 2 x 10(3)/ml), and eosinophilic granulocyte counts (1 x 10(3)/ml versus 0) were significantly higher in the OB group than in the GO group (p < 0.05). In the alveolar fraction, this was the case for the median value of neutrophilic granulocyte counts (19 x 10(3)/ml versus 4 x 10(3)/ml), respectively. Median values of IL-6 and IL-8 concentrations in both bronchial (IL-6: 23 versus 6 pg/ml, IL-8: 744 versus 102 pg/ml) and alveolar fractions (IL-6: 13 versus 3 pg/ml, IL-8: 110 versus 30 pg/ml) of the BALF were significantly higher in the OB group than in the GO group. By means of logistic regression, we showed that higher total cell, neutrophilic granulocyte, and lymphocyte counts, the presence of eosinophilic granulocytes, and higher concentrations of IL-6 and IL-8 were significantly associated with an increased risk to develop OB. We conclude that monitoring cell counts, neutrophilic and eosinophilic granulocytes, IL-6, and IL-8 in BALF within 2 mo after lung transplantation in addition to the transbronchial lung biopsy (TBB) pathology will contribute to a better identification and management of the group of patients at risk for developing OB within a year.

Adult↗

PubMed2000

Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD.

It is unclear how cellular and soluble inflammatory markers in induced sputum relate to markers in lavage fluid and biopsies in chronic obstructive pulmonary disease (COPD). This was investigated and also the possible differences between subjects with COPD and healthy controls assessed. Eighteen nonatopic subjects with COPD and 11 healthy controls were studied. Sputum was induced by inhalation of hypertonic saline. The airways were lavaged, using the first 50 mL for bronchial wash (BW) and the subsequent 150 mL for bronchoalveolar lavage (BAL), and biopsies were taken from subsegmental carinae. Neutrophils were the predominant cell type in sputum in COPD (median 77.3%) but not in BW (5.5%) and BAL fluid (1.7%). Differential cell counts in sputum did not correlate with the counts in BW or BAL fluid or biopsies, whereas sputum eosinophil cationic protein (ECP) levels correlated with BW fluid ECP levels (p=0.66, p=0.007) and sputum interleukin-8 (IL-8) concentration with BAL fluid IL-8 concentration (p= 0.52, p=0.026). Subjects with COPD had a higher percentage of sputum neutrophils and eosinophils and higher concentrations of ECP and IL-8 than healthy controls. The higher percentages of eosinophils and concentrations of ECP were also seen in BW and BAL fluid. Finally, higher numbers of macrophages and eosinophils were found in biopsies. In conclusion, induced sputum is derived from a different compartment from BW and BAL fluid and biopsies. Induced sputum may be useful for studying the contribution of luminal neutrophils and eosinophils in chronic obstructive pulmonary disease.

Adult↗

PubMed2000

Bronchiolitis obliterans syndrome and additional costs of lung transplantation.

STUDY OBJECTIVES: The influence of bronchiolitis obliterans syndrome (BOS) on costs after lung transplantation was investigated by comparing the costs of patients with and without this condition. DESIGN: Follow-up costs were prospectively investigated in a medical technology assessment of the Dutch Lung Transplant Program, in relation to the development of the BOS. First, average follow-up costs per week per patient were compared between patients who did or did not develop BOS. Second, in the BOS group, these costs were compared before and after the onset of BOS. SETTING: Dutch Lung Transplant Program, University Hospital of Groningen. RESULTS: Data on 53 patients (37 patients without BOS and 16 with BOS) who underwent transplantation between November 1990 and April 1995 were available. The average follow-up time of these 53 patients was 1.5 years. The follow-up costs amounted to an average (in Dutch guilders [Dfl]) of 1,774/wk for non-BOS patients, compared to 3,072/wk for BOS patients (+ 73%; p = 0.002; one Dfl = 50 cents US currency). This difference in costs was largely accounted for by an increase in used health-care resources, in particular hospitalization and medication. For the BOS patients, the average costs per week before and after the onset of BOS were 1,941 Dfl and 2,422 Dfl, respectively. CONCLUSION: BOS is associated with substantial extra costs. These findings reemphasize the need to focus efforts on prevention of BOS to enhance the cost-effectiveness of lung transplantation.

Adult↗

PubMed2000

Home-based rehabilitation for patients with COPD: organization, effects and financial implications.

Rehabilitation in patients with chronic obstructive pulmonary disease (COPD) has been shown to be an effective treatment and can be carried out in different settings, i.e. inpatient, outpatient or home-based. This review focuses on home-based rehabilitation and four important issues are discussed. 1) Which patients should received home-based rehabilitation? 2) How should home-based rehabilitation be organized? 3) What are the effects of home-based rehabilitation? 4) What are the financial implications. Home-based rehabilitation is an attractive approach for most patients with COPD. However, there is some evidence that patients who are severely disabled due to dyspnoea do not gain benefit from home-based rehabilitation. This might not be the appropriate setting for this group, and these patients are probably better candidates for an inpatient or outpatient multidisciplinary approach. After initial evaluation of the patient by a pulmonary physician, home-based rehabilitation can be set up in two different ways. Firstly, the patients can receive their instructions at the hospital: a detailed exercise programme can be developed that the patients can perform unsupervised at home with regular follow-up at the outpatient clinic. Second, home rehabilitation can be fully addressed at home with instruction and regular supervision by a local team. At this moment, it is not clear which disciplines, i.e. what kinds of intervention, are needed in a home rehabilitation team. Nevertheless, the key element of home-based rehabilitation is exercise training, which is the same for the other settings. Short-term studies with a maximum duration of 12 weeks showed increased exercise tolerance, decreased dyspnoea and improved quality of life. Conversely, the effects of long-term home-based rehabilitation are not clearly established. The need for long-term supervision is still open to debate: contradictory results have been shown regarding dyspnoea and exercise tolerance. Cost/benefit analysis showed positive trends in reduction in hospitalization rate and reduction of total costs; however, these results came from uncontrolled studies.

Cost-Benefit Analysis↗

PubMed1999

[Survival and impact of bronchiolitis obliterans syndrome after lung transplantation at the Academic Hospital Groningen, 1990/'98].

OBJECTIVE: To describe the results of the lung transplantation programme in Groningen in relation to the bronchiolitis obliterans syndrome (BOS), in the first 118 consecutive patients. DESIGN: Retrospective. METHOD: Data were collected on the 118 patients subjected to lung transplantation in November 1990 to June 1998 in the University Hospital Groningen, the Netherlands, regarding the prevalence of chronic transplant dysfunction (BOS) and survival. RESULTS: 117 lung transplantations (95 bilateral lung transplantations including 2 retransplants, and 22 single lung transplantations) and 1 heart-lung transplantation had been performed. The patients were 70 males and 48 females with a mean age of 42 years (range: 9-64). The mean (SD) survival at 1, 2, 3 and 5 years post transplantation was 83% (3), 70% (4), 66% (5) and 61% (5) respectively. The median survival amounted to 2447 days. The mean (SD) prevalence of BOS at respectively 1, 2, 3 and 5 years post transplantation was 32% (5), 36% (5), 44% (5) en 54% (6). After a diagnosis of BOS stage I the median survival was 649 days. CONCLUSION: The survival of the lung transplant programme of the University Hospital Groningen is considered to compare favourably with other centres. The prevalence of BOS is considerable, and comparable with the prevalence of BOS reported by other programmes. BOS is associated with a decreased life expectancy.

Academic Medical Centers↗

PubMed1999

Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5'-monophosphate-induced bronchoconstriction in patients with COPD.

BACKGROUND: Inhalation of adenosine 5'-monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP-induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC20AMP. OBJECTIVE: To investigate the mechanism of AMP-induced bronchoconstriction in COPD. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover trial. Forty-four nonatopic hyperresponsive smokers with COPD (mean age +/- SD: 60+/-7 years, FEV1 61+/-12% of predicted and FEV1/VC 51+/-8%, geometric mean [GM] PC20methacholine 0.62 mg/mL and GM PC20AMP 6.77 mg/mL) participated. PC20methacholine and PC20AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 microg of inhaled ipratropium bromide, or placebo. RESULTS: GM PC20AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P<0.0001) after terfenadine and decreasing 0.3 doubling concentration after ipratropium bromide (NS). GM PC20methacholine was 0.75 mg/mL after placebo, increasing 0.4 doubling concentration after terfenadine (NS) and 3 doubling concentrations after ipratropium bromide (P<0.0001). CONCLUSION: These findings indicate that histamine release is important in the pathophysiology of AMP-induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.

Adenosine Monophosphate↗

PubMed1999

Proteases from Aspergillus fumigatus induce interleukin (IL)-6 and IL-8 production in airway epithelial cell lines by transcriptional mechanisms.

Proteases secreted by Aspergillus fumigatus induce the production of cytokines by epithelial cells, including interleukin (IL)-6 and IL-8. In the present study, we focused on the mechanism(s) by which A. fumigatus-derived proteases elicit cytokine production in epithelial cells. In the epithelial cell line A549, IL-6 and IL-8 mRNA levels were enhanced by proteases as a result of transcriptional induction of the respective genes. Transcriptional induction of both genes coincided with enhanced DNA binding of nuclear factor (NF)-kappaB and NF-IL6, whereas activator protein-1 was unlikely to be involved. The enhanced transcriptional activity could be inhibited by the addition of chymostatin, showing serine protease dependency. Posttranscriptional mechanisms affecting the stability of IL-6 and IL-8 mRNAs were not involved in protease-induced IL-6 and IL-8 production. These data show that after exposure to A. fumigatus-derived proteases, IL-6 and IL-8 gene expressions are up-regulated as a result of transcriptional mechanisms.

Aspergillus fumigatus↗

PubMed1999

Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma.

BACKGROUND: Guidelines state that oral and inhaled corticosteroids are the cornerstone of asthma treatment. The effect of both types of treatment can be assessed by measuring lung and systemic parameters. Treatment for two weeks with either oral prednisolone (30 mg/day), high dose fluticasone propionate (2000 microg/day, FP2000), or lower dose FP (500 microg/day, FP500), both given by a dry powder inhaler, were compared. METHODS: One hundred and twenty patients with asthma were treated for two weeks in a double blind parallel group design. Lung function, asthma symptoms, airway hyperresponsiveness (PC(20) methacholine and adenosine-5'-monophosphate), sputum eosinophil and eosinophilic cationic protein (ECP) levels were measured as lung parameters. In addition, morning serum blood cortisol, blood eosinophil, and serum ECP levels were measured as systemic parameters. RESULTS: PC(20) methacholine and adenosine-5'-monophosphate showed significantly greater improvement with FP2000 (1.99 and 4.04 doubling concentrations (DC), respectively) than prednisolone (0.90 DC, p = 0.02; 2.15 DC, p = 0. 05) and marginally more than with FP500 (1.69 and 3.54 DC). Changes in sputum eosinophil and ECP concentrations showed similar trends; the decrease in ECP was significantly greater with FP2000 than with FP500. In contrast, the systemic parameters of steroid activity (cortisol, peripheral blood eosinophils, and serum ECP) decreased to a similar extent with FP2000 and prednisolone but significantly less with FP500. CONCLUSIONS: Oral prednisolone (30 mg/day) was inferior to FP2000 in improving airway hyperresponsiveness to both methacholine and AMP, with similar trends in forced expiratory volume in one second (FEV(1)), sputum eosinophil and ECP concentrations. Systemic effects were similar with prednisolone and FP2000 and less with FP500.

Administration, Inhalation↗