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D S Postma

Publications and source records attributed to D S Postma.

At least 289 records · Page 16Linked to original sources

There is no activation of O2- production by alveolar macrophages and neutrophil polymorphonuclear leukocytes in rat lung transplants during the reimplantation response and acute rejection.

Activation of phagocytes (alveolar macrophages [AM] and neutrophil polymorphonuclear leukocytes [PMN]) can cause tissue damage in inflammatory lung diseases. In this study we investigated whether phagocytes contribute to the development of tissue damage in lung grafts histologically observed during two different processes: the reimplantation response and the acute rejection. Therefore, the number and profile of bronchoalveolar lavage (BAL) and blood phagocytes and their in vitro spontaneous and serum-treated-zymosan (STZ)-stimulated O2- production were assessed after allogeneic (BN to LEW) and syngeneic (LEW to LEW) transplantation of the left lung in rats. BAL PMN numbers increased during the reimplantation response, whereas during the late phase of the rejection process BAL AM and PMN numbers were increased. The O2- production by the BAL phagocytes and blood PMN were not increased at any stage. Strikingly, the STZ-stimulated O2- production by the BAL phagocytes was significantly impaired during acute rejection. Our data suggest that activation of the O2- production by bronchoalveolar phagocytes does not play an important role in the development of tissue damage in lung transplants during the reimplantation response and acute rejection. The impaired O2- production by alveolar phagocytes during acute lung rejection may contribute to the increased susceptibility for pulmonary infections after lung transplantation.

Animals↗

Perception of airway obstruction in a random population sample. Relationship to airway hyperresponsiveness in the absence of respiratory symptoms.

Subjects with asymptomatic airway hyperresponsiveness in epidemiologic studies may have variable airway obstruction that is not perceived as dyspnea. We tested the hypothesis that such subjects are less likely to report an increase in dyspnea during histamine-induced bronchoconstriction than symptomatic hyperresponders. A random population sample of 412 middle-aged subjects was studied. Before and after a standardized histamine challenge test, subjects recorded Borg scores for dyspnea: any increase in Borg score was considered significant. More than 80% of hyperresponsive subjects (PC10 histamine < or = 16 mg/ml) had no symptoms. The presence of prechallenge dyspnea was related to increased airways responsiveness and current smoking. An increase in Borg score was associated with younger age, more severe airway responsiveness, atopy, and female sex. The level of and increase in the Borg score were not significantly related to level and change in airway caliber (FEV1). In hyperresponsive subjects (PC10 < or = 16 mg/ml), subjects who reported dyspnea, wheeze, or asthma were more likely to show an increase in Borg score during histamine provocation than asymptomatic subjects (adjusted odds ratio 4.01, 95% confidence interval 1.01 to 16.00, p = 0.049), after adjustment for age, sex, smoking habits, FEV1, and atopy. This suggests that asymptomatic hyperresponders may have variable airway obstruction that is not recognized as breathlessness.

Adult↗

Comparison of three normal breathing techniques to assess reversibility of airway obstruction.

Measurement of forced expiratory volume in one second (FEV1) is generally used to assess airway obstruction. Function tests during normal breathing are used as complementary tests as well as alternatives. Studies have been done comparing the esophageal pressure method with body plethysmography, and respiratory acoustical impedance with body plethysmography. We have not found any other studies comparing all three methods in the same subject. It is not clear whether those tests contribute to the assessment of reversibility of airways obstruction. We addressed the following questions: (1) How does the response of FEV1 to an inhaled beta agonist (400 micrograms fenoterol) relate to the response of lung function tests during normal breathing? (2) Are values obtained with three normal breathing techniques comparable in assessing severity of obstruction? We collected these data in 17 patients. A significant correlation was found between airway resistance measured with any of the three methods. The scatter was large, both before and after bronchodilation. The reversibility by the three methods expressed as absolute values (before and after inhalation) were comparable. In order of preference it appears that acoustical impedance is to be preferred to esophageal pressure because of less discomfort to the patient, and to body plethysmography because of the lower cost of the apparatus. Acoustical impedance can be used to assess acute changes in bronchomotor tone.

Adult↗

European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): hypothesis and design.

Chronic obstructive pulmonary disease (COPD) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality. Cigarette smoking is the most important aetiological factor. The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers. In cigarette smokers with poorly reversible airflow obstruction, the effect over 3 yrs of an inhaled glucocorticosteroid, budesonide 400 micrograms b.i.d., on the decline of lung function, measured as postbronchodilator forced expiratory volume in one second (FEV1), will be compared with that of placebo. The trial has been designed to detect a difference in yearly decline of at least 30 ml.year-1. The study is a parallel group, randomised, double-blind, multicentre study. Patients will be recruited from 47 centres in 12 countries in Europe. It will start with a run-in consisting of two 3 month periods. During the first 3 months, the patients will be offered a smoking cessation programme. All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested. After these two periods, patients will be randomised to receive either inhaled budesonide, 400 micrograms b.i.d., or placebo for a period of 3 yrs.

Administration, Inhalation↗

Long-term multicentre trial in chronic nonspecific lung disease: methodology and baseline assessment in adult patients. Dutch CNSLD Study Group.

Airways obstruction and airways hyperresponsiveness are two dominant features in patients with chronic nonspecific lung disease (asthma and chronic obstructive pulmonary disease (COPD)). We set up a study to determine whether long-term (3 yrs) therapeutic intervention directed at airways obstruction and hyperresponsiveness is superior to one directed at airways obstruction alone. Patients were selected on functional criteria (age, baseline forced expiratory volume in one second (FEV1), and airways hyperresponsiveness) and, furthermore, extensively characterized by history, smoking habits, allergy, reversibility of airways obstruction and quality of life. The methodology and practical problems of setting up this large multicentre study are outlined, together with an analysis of baseline data. Standardization of methods and techniques and recruitment of patients required much effort, recruitment taking about twice as long as expected. A 3 month feasibility study allowed us to eliminate minor problems in the protocol. Over a 16 month period, 274 adult patients (18-60 yrs) from the out-patient clinics of six university centres entered the study; 99 met the diagnostic criteria for asthma, 51 for COPD, 88 for asthmatic bronchitis, and 36 could not be classified. Their mean (SD) FEV1% pred was 65.1 (15.2)%. Their geometric mean provoking concentration of histamine producing a 20% fall in FEV1 (PC20 histamine) was 0.28 mg.ml-1. In a multiple regression analysis, more severe airways hyperresponsiveness was associated with lower prechallenge FEV1% pred (p less than 0.0001), higher pack-years of smoking (p = 0.0099), blood eosinophil count (p = 0.0004), skin test reactivity (p = 0.0047) and with female sex (p = 0.0302). We conclude that setting up long-term multicentre trials in chronic nonspecific lung disease (CNSLD) is feasible and that these may offer valuable information on treatment and outcome of the disease.

Adult↗

Effect of positive expiratory pressure breathing in patients with cystic fibrosis.

The effect of positive expiratory pressure breathing, alone and in combination with coughing, was investigated in eight patients with cystic fibrosis. Functional residual capacity and total lung capacity was measured with a body plethysmograph before, during, and immediately after breathing with expiratory pressure of 5 and 15 cm H2O, and after a coughing period. The positive expiratory pressure breathing was carried out five times for two minutes with a two minute interval between each period. Mucus transport was measured in a peripheral lung region and over the whole lung by a radioactive aerosol tracer technique. Clearance measurements were carried out continuously during positive expiratory pressure breathing and during a control period. Two minutes' breathing with an expiratory pressure of 5 and 15 cm H2O caused an increase in mean (SEM) functional residual capacity from 2.6 (0.1) to 3.6 (0.3) and 4.4 (0.5) 1 and an increase in total lung capacity from 5.1 (0.2) to 5.9 (0.3) and 6.9 (0.4) 1. Lung volumes were higher during breathing with an expiratory pressure of 15 cm H2O than with 5 cm H2O; both returned to baseline values immediately after positive expiratory pressure breathing. Spontaneous mucus clearance and mucus clearance by coughing were not influenced by positive expiratory pressure breathing at either expiratory pressure. Thus in patients with cystic fibrosis positive expiratory pressure breathing increases lung volumes in relation to the expiratory pressure imposed; these changes in lung volume did not, however, lead to an improvement of mucus transport.

Adolescent↗

Nocturnal airflow obstruction, histamine, and the autonomic central nervous system in children with allergic asthma.

A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma, nine with (group 1) and nine without (group 2) nocturnal airflow obstruction, and an age matched control group. All drugs were withheld for three days before and during the study. On day 4 each child was admitted to hospital and a series of measurements was made every four hours for 24 hours. These included measurements of the forced expiratory volume in one second (FEV1), heart rate and sinus arrhythmia gap from an electrocardiogram (an indirect measure of parasympathetic activity) and urine sampling for determination of catecholamine and N'-methylhistamine concentrations (measures of sympathetic activity and histamine release respectively). Urinary N'-methylhistamine excretion was significantly higher over the 24 hours in children in group 1 than in children in group 2, and overnight values were also significantly higher in children in group 1 than those in group 2. Mean (SEM) values (mumol/mol creatinine) were 154.6 (11.2) in group 1 and 110 (11.2) in group 2 for 2400-0400 hours samples and 139.2 (13.1) and 101.2 (10.6) 0400-0800 hours samples. There was no evidence of decreased sympathetic or increased parasympathetic activity in association with the nocturnal airflow obstruction; noradrenaline concentrations were increased in group 1. These observations indicate that nocturnal airflow obstruction is associated with increased release of histamine overnight.

Adolescent↗

Effects of inhaled budesonide on spirometric values, reversibility, airway responsiveness, and cough threshold in smokers with chronic obstructive lung disease.

Inhaled corticosteroids are known to reduce respiratory symptoms and airway responsiveness in allergic patients with asthma. The aim of the present randomised, double blind study was to assess the effect of eight weeks' treatment with inhaled budesonide in non-allergic smokers with chronic obstructive lung disease. Twenty four subjects (23 male) entered the study. Their ages ranged from 40 to 70 (mean 57) years, with a mean of 35 (range 9-80) pack years of smoking; the mean FEV1 was 53% (range 32-74%) predicted and geometric mean PC20 (histamine concentration causing a 20% fall in FEV1) 0.96 (range 0.07-7.82) mg/ml. After a two week washout, single blind, placebo period, 12 patients were allocated to treatment with budesonide 1600 microgram/day and 12 to placebo for eight weeks. The only additional drug to be taken was ipratropium bromide "if needed." Twenty one patients completed the study, 10 in the budesonide group and 11 in the placebo group. The standard deviation of the difference between duplicate measurements of PC20 histamine and citric acid cough threshold made two weeks apart was below one doubling dose step. There was a significant reduction in dyspnoea in the budesonide group, but otherwise no change in symptom scores or use of ipratropium bromide over the eight weeks of treatment within or between the two groups. No significant differences in spirometric values, peak expiratory flow, PC20 histamine, or citric acid cough threshold were found between the groups. Although differences were not significant, some of the changes showed a trend in favour of budesonide. Whether a longer observation period would show a significant influence of inhaled corticosteroids in patients with chronic obstructive lung disease remains to be determined.

Administration, Inhalation↗

Citric acid cough threshold and airway responsiveness in asthmatic patients and smokers with chronic airflow obstruction.

The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction.

Adult↗

Relationship of airway hyperresponsiveness to respiratory symptoms and diurnal peak flow variation in patients with obstructive lung disease. The Dutch CNSLD Study Group.

This study reports on the relationship of airway hyperresponsiveness (AH) with respiratory symptoms and diurnal peak flow expiratory (PEF) variation in 221 hyperresponsive patients with moderately severe airways obstruction. The disease was in a stable phase in all patients. Closely adhering to the American Thoracic Society criteria, patients were divided into three syndrome diagnoses based on a standardized history: asthma (n = 81), asthmatic bronchitis (AB, n = 69), and chronic obstructive pulmonary disease [( COPD] n = 44); 27 subjects could not be placed in any group. Mean (+/- SEM) log2 PC20 histamine values were significantly lower in the asthmatic group (-2.77 +/- 0.20 mg/ml) than in the COPD (-0.89 +/- 0.29 mg/ml) and AB groups (-1.37 +/- 0.25 mg/ml; one-way ANOVA, p less than 0.001). However, considerable overlap of individual responses existed. Differences between the groups could not be attributed to differences in prechallenge FEV1 levels. For every level of FEV1, asthmatic subjects were more hyperresponsive than patients with COPD. The dependence of PC20 on prechallenge FEV1 was comparable in all groups. There was a significant correlation between the degree of AH and diurnal PEF variation (rho = -0.401, p less than 0.001), which was stronger in asthma (rho = -0.409) than in COPD (rho = -0.325). Despite this obvious association, a wide range of diurnal PEF variation values existed for every level of PC20, indicating that PEF variability and AH are not interchangeable. The relationships between symptoms and both AH levels and PEF variation were weak. No significant differences were found between syndrome diagnosis groups with respect to diurnal PEF variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hyperresponsiveness as a determinant of the outcome in chronic obstructive pulmonary disease.

A better outcome of patients with chronic obstructive pulmonary disease (COPD) appears to be determined by higher FEV1, smoking cessation, lower airway hyperresponsiveness, and, at least in the presence of therapy, with a higher reversibility of airflow obstruction. In our opinion, these findings provide a firm ground for smoking cessation and most likely for institution of early treatment directed at both the reversible part of airflow obstruction and airway hyperresponsiveness in patients with COPD. But there are large gaps in our understanding of the effects of bronchodilator and antiinflammatory drugs on airway hyperresponsiveness. After acute administration, sympathomimetics cause a larger reduction of airway hyperresponsiveness than do anticholinergics, both in asthma and in COPD. What happens after longer periods of treatment is not yet clear in COPD, whereas in asthma there may occur a deterioration of airway responsiveness. Corticosteroids appear to have a beneficial effect on lung function and the severity of airway hyperresponsiveness in asthma. In COPD, however, no definite conclusion can be drawn as to the beneficial effect of corticosteroids, but short-term effects are not promising. The available data from the literature strongly suggest the need for long-term studies with large groups of patients in order to assess a potential treatment effect. In this way, also, a subgroup of patients with COPD who improve with corticosteroids and/or bronchodilators may be found. It seems advisable to include both subjective (i.e., quality of life, complaints, symptoms) and objective (i.e., hospitalization, survival, FEV1, PEFR, PC20, and reversibility) data as investigational tools for outcome analysis.

Asthma↗

Dissimilarity in methacholine and adenosine 5'-monophosphate responsiveness 3 and 24 h after allergen challenge.

Bronchial hyperresponsiveness (BHR) to methacholine and adenosine 5'-monophosphate (AMP) was studied in 15 allergic asthmatic patients before and 3 and 24 h after allergen challenge with house dust mite (HDM). Subjects attended the clinic on 3 consecutive days. On the first day a control solution was inhaled, and methacholine or AMP challenge was performed 3 h later. The next day HDM was inhaled, and 3 and 24 h later methacholine or AMP challenge was performed again. There were no significant difference in FEV1 baseline value between any of the study days. PD20 HDM, percentage decrease in FEV1, and AUC for both the EAR and LAR were not significantly different in the methacholine and AMP studies. After HDM challenge, PC20 methacholine decreased significantly from a geometric mean (+/- SEM) starting value of 1.39 +/- 0.63 mg/ml to 0.30 +/- 0.78 mg/ml (p less than 0.001) at 3 h and to 0.22 +/- 0.75 mg/ml (p less than 0.001) at 24 h. The magnitude of the decrease in PC20 methacholine at 3 h correlated with the severity of the late asthmatic reaction (LAR) as measured by the percentage fall in FEV1 and area under the curve (AUC) (r = -0.60 and r = 0.55; p less than 0.05). A significant decrease was observed in the PC20 AMP at 3 h, from a geometric mean value of 12.2 +/- 0.96 mg/ml after challenge with the control solution to 4.47 +/- 0.99 mg/ml (p less than 0.05) after HDM challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗

Characterization of cough associated with angiotensin-converting enzyme inhibitors.

Chronic cough is a side effect of the angiotensin-converting enzyme (ACE) inhibitor class of antihypertensives. The cough is thought to be a result of inhibition of the enzymes that break down some of the mediators of inflammation, such as the bradykinins and tachykinins. We report 20 patients with chronic cough caused by ACE inhibitors and some of the characteristics of the cough. The cough is typically dry, nonproductive, and worse at night. Interference with sleep is common and was severe in three patients. Women outnumbered men in this series: urinary stress incontinence developed in five, rectal and vaginal prolapse developed in one. Three patients felt they were incapacitated by the cough. Most had been on multiple medications; only oxycodone was reported to be effective in controlling the cough, and four patients thought they were addicted to that. All coughs resolved with withdrawal of the ACE inhibitor. Chronic cough is common among individuals taking ACE inhibitors. It may be severe and associated with complications. The incidence and potential severity is understated in drug information sources, and patients and physicians often fail to recognize cough as a drug side effect.

Adult↗

In vitro release of neutrophil elastase, myeloperoxidase and beta-glucuronidase in patients with emphysema and healthy subjects.

Evidence is accumulating that cigarette smoking plays an important role in the protease-antiprotease imbalance in alpha 1-antitrypsin-sufficient emphysema. Since most smokers, however, do not develop emphysema, it has to be presumed that other factors in addition to smoking contribute to the origin of the imbalance. The major source of proteases is the polymorphonuclear leucocyte (PMN). We tested the hypothesis that an abnormality in the releasability of PMN might predispose for the development of emphysema. Therefore, the release of elastase, myeloperoxidase, and beta-glucuronidase from PMN was investigated in patients with emphysema and healthy controls, matched for sex, age, and smoking habits. PMN were isolated from peripheral blood and stimulated with calcium-ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), and serum-treated zymosan (STZ). Total enzyme content of PMN was measured after cell lysis with Triton X-100. Total elastase, myeloperoxidase, and beta-glucuronidase content of PMN were not significantly different in healthy subjects and patients with emphysema. In vitro release of elastase and myeloperoxidase from both stimulated and unstimulated PMN was not significantly different in healthy subjects and emphysematous patients. Moreover, no differences were found between smoking and ex-smoking individuals. Beta-glucuronidase release tended to be lower in patients with emphysema than in healthy controls. We conclude that an abnormality in the releasability of peripheral PMN is unlikely to be a pathogenetic factor in emphysema.

Glucuronidase↗

The Dutch hypothesis (chronic non-specific lung disease) revisited.

In 1961 the hypothesis (later referred to as the Dutch Hypothesis (DH)) was put forward that asthma, chronic bronchitis and emphysema should be considered as different expressions of one disease entity, in which both endogenous (host) and exogenous (environmental) factors play a role in the pathogenesis. A hereditary predisposition to develop allergy and bronchial hyperreactivity were considered to be important denominators of disease susceptibility. Complications and complicating diseases would also contribute to the ultimate phenotype of the patient. In the present paper we discuss the relevance of this hypothesis in 1990. Until now it has not been refuted; circumstantial evidence in its favour has accumulated, but formal proof is still lacking. Further research should pay more attention to the genetic aspects of the disease. Arguments are presented against the use of the terms asthma, chronic bronchitis, and emphysema as indicators of disease entities, and in favour of the use of an umbrella-term, e.g. chronic non-specific lung disease (CNSLD), provided that, in addition, every patient is characterized using so-called defining criteria.

Asthma↗

Nocturnal asthma, histamine and vagal activity.

In a study of two groups of nine allergic asthmatic children, consisting of one group with (group I) and one group without (group II) increased nocturnal airflow obstruction, we determined whether an increase in vagal activity, or inflammatory mediators like histamine are responsible for the nocturnal increase in airflow obstruction. The results of investigations in the two groups of asthmatics were compared to the results of an age matched control group. Forced expiratory volume in one second (FEV1) and electrocardiogram recordings of one minute were obtained every 4 hours during 24 hours. Heart rate and sinus arrhythmia gap were used to express vagal activity indirectly. N tau-methylhistamine was determined in urine samples collected in periods of 4 hours between the measurements. In group I, overall N tau-methylhistamine excretion was on a higher level than in both other groups, and was significantly higher overnight. Parasympathetic stimulation did not seem of importance to the increase of airflow obstruction at night.

Adolescent↗