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Biomedical subjects

G H Koëter

Publications and source records attributed to G H Koëter.

At least 19 recordsLinked to original sources
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

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↗
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↗
PubMed1999

Markers of nitric oxide metabolism in sputum and exhaled air are not increased in chronic obstructive pulmonary disease.

BACKGROUND: Nitric oxide (NO) is involved in inflammation and host defence of the lung. It has been found in increased concentrations in the airways in asthmatic subjects but its levels in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. A study was undertaken to determine whether markers of NO metabolism (NO in exhaled air, iNOS expression in sputum cells, and nitrite + nitrate (NO2-/NO3-) in sputum supernatant) are increased in subjects with COPD, and whether they correlate with inflammatory indices in induced sputum. The associations of these markers with smoking were also assessed. METHODS: Sixteen subjects with COPD (median age 66 years, median forced expiratory volume in one second (FEV1) 63% predicted, eight current smokers) and 16 healthy subjects (median age 63 years, median FEV1 113% predicted, eight current smokers) participated in the study. NO was measured during tidal breathing and sputum was induced by inhalation of hypertonic saline. RESULTS: No differences were observed between subjects with COPD and healthy controls in exhaled NO excretion rate (median 5.15 and 6.25 nmol/min), sputum macrophage iNOS expression (14% and 12%), and sputum supernatant NO2-/NO3- (46 and 73 microM). NO in exhaled air correlated with the percentage of sputum eosinophils in patients with COPD (rho = 0.65, p = 0.009) but not in healthy individuals. Exhaled NO and supernatant NO2-/NO3- levels were lower in healthy smokers than in healthy non/ex-smokers. CONCLUSIONS: Our findings indicate that NO metabolism is not increased in patients with stable COPD. The close association between exhaled NO levels and sputum eosinophils suggests a role for NO in airway inflammation in COPD. Studies performed during exacerbations may clarify this role.

Aged↗
PubMed1999

Risk factors from childhood to adulthood for bronchial responsiveness at age 32-42 yr.

UNLABELLED: Bronchial responsiveness (BR) is an important risk factor for the development and outcome of asthma. This study assessed childhood risk factors for both the severity of BR in adulthood and either improvement or worsening of BR over time. Finally, we studied cross-sectional risk factors of BR in adulthood. Between 1966 and 1969, 119 allergic asthmatic children (5-14 yr of age) were studied. Of these, 101 (85%) subjects were reinvestigated at age 22-32 yr (visit 2), and at age 32-42 yr (visit 3). Spirometry, PC10 histamine, skin tests, blood eosinophils, and serum total IgE were measured and a questionnaire was used. Higher FEV1 values in childhood were associated with less severe BR at age 32-42 yr independent of other potential risk factors. Larger increases in FEV1 values both from visit 1 to 2 and from visit 2 to 3, a longer time interval from visit 1 to 3, and having pets in childhood were associated with less severe BR at age 32-42 yr. The same factors were found to be associated with less deterioration of BR from visit 2 to 3. In nonsmokers a higher IgE level at visit 2 was a risk factor for an increase in BR. At age 32-42 yr, a low level of lung function and the presence of asthma symptoms were associated with more severe BR, and older age and having pets were associated with less severe BR. IgE was related to more severe BR only in nonsmokers. CONCLUSIONS: A lower lung function in childhood and less improvement in FEV1 over time were associated with more severe BR in adulthood.

Adolescent↗
PubMed1999

Risk factors for growth and decline of lung function in asthmatic individuals up to age 42 years. A 30-year follow-up study.

Little is known about factors determining the outcome of childhood asthma. The purpose of this longitudinal study was to assess the factors in childhood that determine the level of FEV(1) in early adulthood in asthmatic individuals, and to examine factors associated with decline in FEV(1) during adulthood. Between 1966 and 1969, 119 allergic asthmatic subjects aged 5 to 14 yr were studied (Visit 1). Of these subjects, 101 (85%) were reinvestigated at ages 22 to 32 yr (Visit 2) and 32 to 42 yr (Visit 3). At the first survey and during follow-up, a standardized questionnaire was used, serum total IgE and peripheral blood eosinophils were measured, and physical examination, skin tests, lung function tests, and histamine challenge (provocative concentration causing a 10% decline in FEV(1); PC(10)) tests were performed according to the same protocol. Multiple linear regression analyses were performed with FEV(1) at Visit 2 and with the change of FEV(1) from Visit 2 to Visit 3 as outcome variables. A low FEV(1)% predicted at Visit 1 and PC(10) </= 16 mg/ml at Visit 1 were significantly associated with a lower level of FEV(1) at Visit 2. Subjects who quit smoking and subjects who continued to use inhaled corticosteroids had a significantly smaller annual decline in FEV(1) from Visit 2 to Visit 3, adjusted for attained level of FEV(1) at Visit 2. In conclusion, bronchial hyperresponsiveness and a low level of lung function in childhood are independent risk factors for a low level of FEV(1) in early adulthood. A smaller decline in FEV(1) after ages 22 to 32 yr occurs in asthmatics who quit smoking and who continue to use inhaled corticosteroids. Our data stress the importance of studying intervention strategies for asthma in young childhood and early adulthood in order to prevent or postpone further lung function deficits.

Adolescent↗
PubMed1999

Physiotherapy and bronchial mucus transport.

Cough and expectoration of mucus are the best-known symptoms in patients with pulmonary disease. The most applied intervention for these symptoms is the use of chest physiotherapy to increase bronchial mucus transport and reduce retention of mucus in the airways. Chest physiotherapy interventions can be evaluated using different outcome variables, such as bronchial mucus transport measurement, measurement of the amount of expectorated mucus, pulmonary function, medication use, frequency of exacerbation and quality of life. Measurement of the transport rate of mucus in the airways using a radioactive tracer appears to be an appropriate outcome variable for short-term studies. Evaluation of chest physiotherapy only with pulmonary function tests appears to be inadequate in short-term studies. The popularity of using pulmonary function tests is probably based more on the availability of the instruments than on a theoretical basis related to the question of chest physiotherapy improving mucus transport. Quality of life and progression of the disease are not often used as outcome variables, but it may be worthwhile to use these in the future.

Bronchi↗
PubMed1999

Factors to consider when designing phase III clinical trials involving economic evaluations.

Given the recognized need to examine cost-effectiveness data in addition to clinical data when making decisions relating to choice of clinical interventions, there is a growing interest and experience in undertaking economic evaluations alongside clinical trials. It has been argued, when an economic evaluation is necessary for assessing the cost-effectiveness of a medical intervention, the integration of both the medical and clinical issues need to be included at the start of designing a clinical trial. A proposal has been made for how clinical researchers and health economists may cooperate successfully at the successive phases in designing a clinical trial. Therefore, discussion points for clinical researchers and health economists are given, and the possible methodological consequences of adding an economic evaluation to a trial are addressed.

Clinical Trials, Phase III as Topic↗
PubMed1998

Relationship between subjective fatigue and physiological variables in patients with chronic obstructive pulmonary disease.

Patients with chronic illnesses, such as chronic obstructive pulmonary disease (COPD), report an increase in the perception of fatigue in the clinical setting. Subjective fatigue associated with physiological factors has not been reported. The purpose of this study was to determine the relationship between subjective fatigue and pulmonary function, respiratory and peripheral muscle force and exercise capacity in patients with COPD. Nineteen patients with COPD participated in the study [mean (SD) FEV1 38% (17%) predicted]. Fatigue was measured with the Multidimensional Fatigue Inventory 20 (MFI-20) that includes the following subscale dimensions: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. The following physical variables were measured: forced expiratory volume in 1 s (FEV1), vital capacity (VC), maximal inspiratory peak pressure (PImax), symptom-limited bicycle exercise capacity (maximum workload) and maximal voluntary isometric muscle force of both left and right quadriceps (Qu), hamstrings (Ha), biceps (Bi) and triceps (Tr). The MFI-20 fatigue dimensions, reduced activity and reduced Motivation, are significantly correlated with FEV1 (% predicted) (r = -0.62, r = -0.55 respectively). No significant correlation was found between the dimensions of fatigue and maximum workload. In contrast the fatigue dimension, physical fatigue, shows significant correlations with seven of eight muscle forces measured (Qu left r = -0.49, right r = -0.54; Ha left r = -0.49, right r-0.38; Tr left r = -0.61, right r = -0.45; Bi left r = -0.46, right r = -0.48). Data from this study show that activity and physical dimensions of subjective fatigue are related to pulmonary function and skeletal muscle force in COPD patients. Interventions to improve skeletal muscle force might improve subjective fatigue in patients with COPD.

Exercise Tolerance↗
PubMed1998

The importance of serum IgE for level and longitudinal change in airways hyperresponsiveness in COPD.

BACKGROUND: Airways hyperresponsiveness (AHR) is an important feature of patients with chronic obstructive pulmonary disease (COPD). Little is known about factors that modulate AHR in COPD. OBJECTIVE: To study these factors, we performed a long-term, double-blind, parallel intervention study in 58 male, non-allergic patients with COPD. METHODS: During a period of 2 years, patients were treated with inhaled budesonide (1600 microg/day), inhaled budesonide (1600 microg/day) plus oral prednisolone (5 mg/day), or placebo. PC20 histamine was measured at 4-monthly intervals. The influence of treatment, smoking, age, level of lung function, initial serum IgE level and peripheral blood eosinophils on level and longitudinal change of PC20 histamine was analysed. RESULTS: During follow-up, PC20 decreased in our group, and this decrease was not influenced by treatment. PC20 tended to decrease faster in current smokers than in ex-smokers. PC20 was significantly associated with pre-challenge FEV1 at each time point. Level nor decline of PC20 were significantly related to age. A higher initial serum IgE level was independently associated with a lower PC20. Moreover, a higher initial serum IgE level was associated with a slower annual decline of PC20, regardless of treatment, pre-challenge FEV1, and other modulating factors. No significant associations were found between initial blood eosinophils and level or decline of PC20. CONCLUSION: We conclude that AHR increases over time in non-allergic patients with COPD. Treatment with an inhaled corticosteroid alone or in combination with oral prednisolone does not change this increase. Our study suggests an important role for IgE in the course of the disease, since a higher initial serum IgE level predicts a more favourable course with regard to annual decline of PC20 histamine.

Aged↗
PubMed1998

Eosinophil and mast cell parameters in children with stable moderate asthma.

UNLABELLED: Mast cells and eosinophils are important cells that contribute to the process of inflammation in asthma either by activating other cells or by secreting products which are potentially toxic to the respiratory epithelium. The influx of these cells in the airways and the secretion of toxic products by these cells is abrogated by inhaled corticosteroids. METHODS: In a double blind randomised, placebo controlled, study in children with stable moderate asthma (N = 34, 15 children received fluticasone propionate (FP), an inhaled corticosteroid, and 19 children used a placebo), we investigated the influence of treatment with FP 100 microg b.d. on various parameters of inflammation: number of eosinophils, secretory products of eosinophils i.e. ECP and EDN (in serum and urine) and a secretory product of mast cells, histamine, which is determined as the compound to which histamine is converted and excreted by the human body: NT-methyl-histamine. RESULTS: Previously we reported that lung function increased and bronchial hyperresponsiveness decreased in the 30 children that completed the study during treatment with FP. In these children we found that none of the laboratory parameters of inflammation changed significantly during treatment with either FP or placebo. However, the decrease in urinary EDN almost reached significance (P = 0.07). CONCLUSIONS: Our results indicate that the number of eosinophils, serum ECP and EDN and urinary EDN as well as urinary NT-methyl-histamine do not reflect asthma disease activity in children with stable moderate asthma. Our data on urinary EDN warrant further study of the use of this parameter to monitor asthma in children.

Administration, Inhalation↗