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Biomedical subjects

D S Postma

Publications and source records attributed to D S Postma.

At least 199 records · Page 11Linked to original sources
PubMed1997

Comparison of guidelines and self-management plans in asthma.

Since the rise in asthma mortality and morbidity, many guidelines and self-management plans have been published. Many of these guidelines and self-management plans are not, however, based on results of previous studies but on the opinion of experts. We compared the five most frequently cited asthma guidelines concerning treatment steps and self-management plans with special regard to peak expiratory flow (PEF)-guided plans in asthma. We also compared results of published studies with asthma-management in the context of the guidelines. Classification of asthma severity differed considerably between the guidelines. This was also true for PEF-guided patient self-management plans. Although there was agreement on the type of drug to be used, guidelines varied with respect to when to use the drug, the "best" strategy to increase the dose, and the maximum dose. The studies available on self-management do not make it possible to determine which part of the programme is most important or cost-effective. The latter is an important issue.

Asthma↗
PubMed1997

Peak flow variation in childhood asthma: relationship to symptoms, atopy, airways obstruction and hyperresponsiveness. Dutch CNSLD Study Group.

Although home recording of peak expiratory flow (PEF) is considered useful in managing asthma, little is known about the relationship of PEF variation to other indicators of disease activity. We examined the relationship of PEF variation, expressed in various ways, to symptoms, atopy, level of lung function, and airways hyperresponsiveness in schoolchildren with asthma. One hundred and two asthmatic children (aged 7-14 yrs) recorded symptoms and PEF (twice daily) in a diary for 2 weeks after withdrawal of all anti-inflammatory maintenance medication. PEF variation was expressed as amplitude % mean, as standard deviation and coefficient of variation of all recordings, and as low % best (lowest PEF as percentage of the highest of all values). Atopy and level of forced expiratory volume in one second (FEV1) % predicted were not significantly related to PEF variation. The provocative dose of histamine causing a 20% fall in FEV1 (PD20) and symptom scores were significantly, but weakly, related to PEF variation. The index, low % best, proved easy to calculate and effective in identifying a short-term episode of reduced PEF. We conclude that peak expiratory flow variation in children with stable, moderately severe asthma is significantly, but weakly, related to symptoms and airways hyperresponsiveness. These three phenomena, therefore, all provide different information on the actual disease state. Expressing peak expiratory flow variation as low % best is easy to perform and appears to be clinically relevant.

Adolescent↗
PubMed1997

Water vapour and carbon dioxide decrease nitric oxide readings.

Measurement of nitric oxide levels in exhaled air is commonly performed using a chemiluminescence detector. However, water vapour and carbon dioxide affect the chemiluminescence process. The influence of these gases at the concentrations present in exhaled air, has not yet been studied. For this in vitro study, mixtures of 50, 100 and 200 parts per billion (ppb) NO in air were prepared and fed into the NO analyser either directly or bubbled through water. Mixtures with CO2 were prepared by adding 0-10% CO2 to the diluent air. We found a significant decrease in NO readings in the water-saturated samples compared to the dry gas (p < 0.001), strongly dependent on the partial pressure of water. NO levels in exhaled air (mean 10 +/- 2 ppb) showed a decrease of 17 +/- 3% when water vapour was not absorbed. From the experiments with CO2 we found a decrease in NO reading of 1.04 +/- 0.07% per volume CO2 (%). Presence of water vapour, thus, leads to a systematic underestimation of NO levels. Insertion of a water absorber might, therefore, be advantageous. The influence of CO2 concentrations in the normal respiratory range is negligible. With high expiratory CO2 levels as applied in permissive hypercapnia, the effects may be substantial.

Carbon Dioxide↗
PubMed1997

Lack of correlation between bronchoconstrictor response and bronchodilator response in a population-based study.

Bronchodilator and bronchoconstrictor responsiveness have been considered physiological opposites in patients with obstructive airways disease. Provocation challenges have been replaced by bronchodilator tests in the assessment of cases of severe airways obstruction. The aim of this study was to examine the relationship between bronchoconstrictor and bronchodilator responsiveness, and their supposed interchangeability, in a general population. From the Vlagtwedde-Vlaardingen follow-up study, 101 adults were recruited (mean (SD) age 55 (11) yrs, 67 males and 34 females, and 31 were smokers). All completed a questionnaire on airways symptoms. Bronchoconstrictor and bronchodilator responsiveness were assessed with cumulative dose-response curves, using histamine and terbutaline, respectively. Thus, it was possible to relate histamine sensitivity of the airways (the concentration of histamine, at which forced expiratory volume in one second (FEV1) falls by 10% (PC10)) to the maximal bronchodilator response (delta FEV1) and the sensitivity to the bronchodilator (cumulative dose of inhaled terbutaline at which FEV1 increases by 10% (RD10)). Subjects with a bronchoconstrictor response (PC10 < or = 16 mg x mL(-1); n=38) had more respiratory symptoms than those without (n=63) (40 versus 21%) and also lower baseline FEV1 values (90 versus 96% predicted), but had comparable bronchodilator responsiveness. Subjects with a bronchodilator response (delta FEV1 > or = 9% of the predicted value; n=13) did not differ from those without (n=88) for all parameters, including symptoms, allergy and pulmonary function. In those with a bronchoconstrictor response, there was a weak but significant correlation between the PC10 and RD10 (rho=-0.32), but not between PC10 and delta FEV1. This study suggests that bronchoconstrictor and bronchodilator responsiveness are not highly correlated, even in subjects with airways obstruction. Symptoms were associated with the presence of a bronchoconstrictor, but not a bronchodilator, response. We conclude that bronchoconstrictor and bronchodilator responsiveness are two different phenotypic markers that are not interchangeable in epidemiological studies.

Administration, Inhalation↗
PubMed1997

Techniques in human airway inflammation: differences in plastic-embedded and snap-frozen sections for CD3, CD4, and CD8 immunostaining of bronchial biopsy specimens.

Today, the quantification of inflammatory cells in human airway biopsies might be facilitated by better morphologic resolution provided by special resin (plastic)-embedding techniques. The present study compares the numbers of CD3-, CD4-, and CD8-positive cells in glycolmethacrylate-embedded versus snap-frozen biopsy specimens of normal bronchial mucosa in 10 patients with various pulmonary diseases. In general, larger numbers of CD3-, CD4-, and CD8-positive cells were counted in snap-frozen specimens than in plastic-embedded ones. Loss of antigenic properties during storage of plastic-embedded tissue (blocks) might have contributed to the weak correlation between both methods. An additional study showed that the number of CD3-, CD4-, and CD8-positive cells decreased significantly within a few months after embedding in glycolmethacrylate. Therefore, we recommend processing glycolmethacrylate-embedded specimens as soon as possible. For standard evaluation of established inflammatory cell parameters such as CD3, CD4, CD8, and EG2, frozen tissue is preferable because of the ease of the method and its reliable cell counting. Because glycolmethacrylate-embedded tissue shows superior morphologic resolution, under strict rules, this method seems attractive for the study, in particular, of cell-cell and cell-matrix relationships.

Biopsy↗
PubMed1996

IL-7 differentially modulates the expression of IFN-gamma and IL-4 in activated human T lymphocytes by transcriptional and post-transcriptional mechanisms.

We investigated the role of IL-7 on the expression of IFN-gamma and IL-4 in human T lymphocytes. IL-7 alone did not induce IFN-gamma or IL-4 mRNA. However, IL-7 dose-dependently up-regulates the anti-CD3- or anti-CD3/anti-CD28-induced IFN-gamma and IL-4 mRNA expression. Used at an optimal concentration, IL-7 (5 ng/ml) increased the accumulation of IFN-gamma (eightfold) and IL-4 (2.5-fold) mRNAs, which could not be blocked by anti-IL-12 treatment. The enhanced IFN-gamma mRNA accumulation was observed within 3 to 6 h, without altering the pattern of the kinetics. However, longer exposure (> 12 h) did not result in different IFN-gamma expression for anti-CD3/anti-CD28 vs anti-CD3/anti-CD28 plus IL-7-stimulated T lymphocytes. mRNA stability studies revealed that IL-7 stabilizes both IFN-gamma and IL-4 mRNA transcripts: 40 and 60 min in anti-CD3/anti-CD28-stimulated T cells vs 120 and 90 min in T cells costimulated with anti-CD3/anti-CD28 plus IL-7. Nuclear run-on assays revealed that the transcription rate of the IFN-gamma gene increased approximately twofold in the presence of IL-7, without affecting the transcription rate of the IL-4 gene. The IL-7-mediated IFN-gamma up-regulation could not be inhibited by cycloheximide treatment, in contrast to IL-4 gene expression. However, the promotive effect of IL-7 on IFN-gamma and IL-4 gene expression could be blocked by genistein and cyclosporin A. Finally, it was demonstrated that the effect of IL-7 on IFN-gamma mRNA accumulation was also reflected at the protein level. In summary, these data demonstrate that IL-7 preferentially up-regulates IFN-gamma expression in activated T lymphocytes, which is accomplished at transcriptional and post-transcriptional levels.

Cells, Cultured↗
PubMed1996

Interleukin-4 gene expression in activated human T lymphocytes is regulated by the cyclic adenosine monophosphate-dependent signaling pathway.

In the present study, we have investigated the involvement of the cyclic adenosine monophosphate (cAMP)-dependent signaling pathway on interleukin-4 (IL-4) gene expression in freshly isolated human T lymphocytes. 2'-0-dibutyryl cAMP (db-cAMP) and prostaglandin E2 (PGE2) were used to directly and indirectly activate the protein kinase A pathway. Northern analysis showed that concanavalin A (Con A)-, anti-CD3 (alpha CD3)-, or anti-CD3 plus anti-CD28 (alpha CD3/alpha CD28)-induced accumulation of IL-4 mRNA was inhibited by db-cAMP (10(-3) mol/L). Db-cAMP showed a steep dose-dependent inhibition; concentrations < or = 10(-4) mol/L did not affect IL-4 mRNA accumulation. In contrast, GM-CSF mRNA expression showed a wider dose-dependent range; 10(-5) mol/L db-cAMP still affected GM-CSF accumulation. PGE2 inhibited the Con A- and alpha CD3/alpha CD28-induced accumulation of IL-4 mRNA in a dose-dependent fashion. Con A-induced IL-4 mRNA was inhibited by 10(-4) to 10(-7) mol/L PGE2; alpha CD3/alpha CD28-induced IL-4 mRNA was inhibited by 10(-5) to 10(-8) mol/L PGE2. Nuclear run-on experiments showed that the inhibitory effects of db-cAMP and PGE2 were accomplished at transcriptional level in Con A-activated T cells, whereas changes at transcriptional and posttranscriptional level were involved in alpha CD3/alpha CD28-activated T lymphocytes. In contrast to Con A and alpha CD3/alpha CD28 activation, phorbol myristate acetate plus A23187-induced IL-4 mRNA expression was insensitive to the inhibitory effect of db-cAMP and PGE2. Moreover, it appeared that the sensitivity for cAMP-mediated downregulation could not be blocked by stimulation T lymphocytes with alpha CD3/alpha CD28 in the presence of IL-2, IL-7, IL-10, IL-12, or a combination of these cytokines. Finally, it was shown that, in accordance with the mRNA studies, db-cAMP and PGE2 suppressed the IL-4 secretion in Con A- and alpha CD3/alpha CD28-activated T cells. In conclusion, these data show that IL-4 expression is negatively regulated by the protein kinase A-dependent signaling pathway by transcriptional and posttranscriptional mechanisms that depend on costimulatory signals.

Antibodies, Monoclonal↗
PubMed1996

Home assessment of peak inspiratory flow through the Turbohaler in asthmatic patients.

BACKGROUND: The efficacy of dry powder inhalers depends on the patient's inspiratory flow. Drug delivery from the Turbohaler (Turbuhaler in some countries), a multidose powder inhaler, is optimal at flows of > 40 l/min. The aim of this study was to investigate the peak inspiratory flow that can be generated by asthmatic patients through the budesonide Turbohaler (PIFTBH) during maintenance treatment at home. METHODS: Thirty asthmatic patients, consecutively recruited from the outpatient clinic, inhaled their maintenance dose of 800 (n = 16) or 1600 micrograms/day (n = 14) for two months or one month, respectively. The Turbohaler was connected to a modified Vitalograph Compact installed at home to obtain printed PIFTBH values for all inhalations. Peak expiratory flow (PEF) was measured twice daily. RESULTS: Flows were remarkably constant with individual mean PIFTBH values ranging from 55 l/min to 95 l/min. Only 13 of the 5248 PIFTBH recordings taken at home (three patients) were < 40 l/min and all were > 30 l/min. Weekly mean morning PEF values ranged from 114 l/min to 733 l/min. PIFTBH values could not be accurately predicted from lung function parameters in individual patients. CONCLUSIONS: In a group of stable asthmatic patients inspiratory flow rates rarely fell below the 40 l/min needed to operate a Turbohaler.

Adolescent↗
PubMed1996

Effects of cessation of terbutaline treatment on airway obstruction and responsiveness in patients with chronic obstructive pulmonary disease.

BACKGROUND: Cessation of regular therapy with inhaled beta 2 agonists in patients with asthma may lead to a temporary deterioration of lung function and airway responsiveness. Few such studies have been reported in patients with chronic obstructive pulmonary disease (COPD), so an investigation was carried out to determine whether rebound airway responsiveness and rebound bronchoconstriction also occurs in COPD and if there is any relationship with the dose of beta 2 agonist being used. METHODS: Lung function (forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF)), airway responsiveness (PC20 methacholine (PC20)) and symptoms were assessed in a double blind, placebo controlled crossover study during and after cessation of two weeks regular treatment with placebo, and low dose (250 micrograms) and high dose (1000 micrograms) inhaled terbutaline via a dry powder inhaler (Turbohaler) all given three times a day. Sixteen non-allergic patients with COPD of mean (SD) age 58.7 (6.5) years, FEV1 57.1 (12.8)% of predicted, and reversibility on 1000 micrograms terbutaline of 4.5 (3.5)% predicted were studied. PC20 and FEV1 were measured 10, 14, 34 and 82 hours after the last inhalation of terbutaline or placebo. Measurements performed at 10, 14, and 34 hours were expressed relative to 82 hour values in each period, transformed into an area under the curve (AUC) value and analysed by ANOVA. RESULTS: Mean morning and evening PEF increased during terbutaline treatment. PC20 and FEV1 did not change after cessation of terbutaline treatment. CONCLUSIONS: Cessation of regular treatment with both low and high dose inhaled terbutaline does not result in a rebound bronchoconstriction and rebound airway responsiveness in patients with COPD.

Aged↗
PubMed1996

Eicosanoids and lipocortin-1 in BAL fluid in asthma: effects of smoking and inhaled glucocorticoids.

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Exogenous stimuli and circadian peak expiratory flow variation in allergic asthmatic children.

The influence of exogenous factors in the home on the circadian variation of airway obstruction has not been fully assessed in children with asthma. The aim of the present study was to investigate the contribution of exogenous stimuli to the degree of peak expiratory flow (PEF) variability during 24 h. Fifty-five children (33 boys and 22 girls; mean age, 9.3 +/- 1.7 yr) with symptoms of asthma, increased bronchial responsiveness, and a solitary allergy to house dust mite (HDM) participated. Their asthma symptoms were well-controlled for at least 4 mo with daily inhaled corticosteroids (ICS) and beta 2-adrenergic drugs if needed. Symptoms, peripheral blood eosinophils, total IgE, and specific IgE to HDM were assessed. Spirometry and PC20 histamine were performed. PEF amplitudes during 24 h (highest minus lowest as a percentage of the day's mean value) were obtained at home during and 6 d after withdrawal of ICS. Dust samples were collected from the total area of the living rooms, bedrooms, mattresses (n = 25), and classrooms to obtain the HDM allergen (HDMA) exposure to Der p I and Der p II. Family smoking habits, presence of pets, and types of floor-covering were recorded on a checklist. Mean PEF amplitude did not increase after withdrawal of ICS, but absolute PEF values were significantly lower (p = 0.05) at midnight and 4:00 A.M. Twenty-six children (47%) were exposed to environmental tobacco smoke (ETS), and 23 (42%) kept pets. Mattresses contained significantly higher amounts of HDMA compared with other locations. PEF amplitude after withdrawal of ICS was significantly higher in children exposed to ETS, a pet, or a high HDMA level in their mattress than in children who were not exposed (ETS: 29.7% [3.9 to 56.6] versus 19.4% [0.0 to 56.6], p < 0.05; pets: 31.4% [9.7 to 52.5] versus 21.9% [0.0 to 56.6], p < 0.05; high HDMA level in the mattress: 35.5% [10.2 to 56.6] versus 21.4% [3.9 to 56.6], p < 0.05). These factors combined with age and PC20 histamine and its interaction with ETS, especially in mild to moderate asthma, explained 48.4% of the variance of the PEF amplitude after withdrawal of ICS. Exogenous stimuli such as exposure to ETS, pets, and high HDMA levels in mattresses contribute to an increased circadian PEF amplitude after withdrawal of ICS and therefore to nocturnal worsening of asthma in HDM-allergic asthmatic children. Moreover, ETS exposure seems to especially worsen PEF variability in children with mild to moderately severe bronchial responsiveness.

Age Factors↗
PubMed1996

Rebound airway obstruction and responsiveness after cessation of terbutaline: effects of budesonide.

Regular monotherapy with inhaled beta 2-agonists may lead to a temporary increase of airway obstruction and increase of airway responsiveness after cessation of treatment. We investigated whether anti-inflammatory therapy may affect these rebound phenomena. In a double-blind, placebo-controlled study, we assessed lung function (FEV1) and airway responsiveness (PC20 methacholine [PC20]) during and after cessation of 2 wk of regular treatment with placebo and low-dose (250 micrograms) and high-dose (1,000 micrograms) inhaled terbutaline three times daily. Patients with mild allergic asthma (means [+/- SD] age of 28.2 +/- 6.6 yr, mean FEV1% of 91.9 +/- 14.6%, and geometric mean PC20 of 0.25 mg/ml) were studied. One group (n = 16) was randomized to budesonide treatment, 400 micrograms three times daily; the other group (n = 14) to placebo. PC20 and FEV1 were measured 10, 14, 34, and 82 h after the last terbutaline or placebo inhalation. A different method of statistical analysis was used, in that measurements performed at 10, 14, and 34 h were expressed relative to 82 h values in each period as an area-under-the-curve (AUC) value. FEV1 did not significantly change during placebo and budesonide treatment. Mean PC20 and morning and evening peak expiratory flow were significantly higher during budesonide treatment (p < 0.01). PC20 did not significantly change after cessation of terbutaline treatment in both placebo and budesonide treatment groups. AUC-FEV1 values after cessation of treatment with both doses of terbutaline were significantly different from the 82 h values (p < 0.05). The decrease in FEV1 was significantly greater after the last terbutaline and placebo inhalation in the placebo group compared with the budesonide treatment group (p = 0.02). We conclude that cessation of regular treatment after 2 wk with both low-dose and high-dose inhaled terbutaline does not result in a significant rebound airway responsiveness in patients with mild asthma. However, the results suggest a small rebound bronchoconstriction that does not occur when asthmatic patients are also treated with budesonide.

Administration, Inhalation↗
PubMed1996

Long-term effects of home rehabilitation on physical performance in chronic obstructive pulmonary disease.

A pilot study was set up to assess the long-term effects of once weekly versus once monthly follow-up of pulmonary rehabilitation after a comprehensive home rehabilitation program on physical performance in patients with chronic obstructive pulmonary disease (COPD) during an 18-mo period. Thirty-six patients with a mean FEV1 of 1.3 +/- 0.4 L (43% pred) were included in the study. Groups A and B (n = 23) visited the physical therapist twice weekly for 3 mo. Thereafter, 11 patients (Group A) had a follow-up of pulmonary rehabilitation once a week, and 12 patients (Group B) had a follow-up once a month. Thirteen patients received no rehabilitation at all (Group C). Long-term home rehabilitation does not appear to improve exercise tolerance; however, on the other hand, there is a deterioration in vital capacity (p < 0.01), walking distance (p < 0.01), and maximal work load (p < 0.05), as shown in the control group. A small improvement in exertional dyspnea (p < 0.01) after 18 mo and inspiratory muscle function (p < 0.05) after 12 mo was shown only in Group A. Because of the insufficient number of patients enrolled in this pilot study, no clear benefit on physical performance of long-term home rehabilitation with either weekly or monthly supervision could be demonstrated.

Exercise Test↗
PubMed1996

PEF variability, bronchial responsiveness and their relation to allergy markers in a random population (20-70 yr).

We investigated the coherence of bronchial hyperresponsiveness (BHR) and peak expiratory flow (PEF) variability in their relation to allergy markers and respiratory symptoms in 399 subjects (20-70 yr). Bronchial hyperresponsiveness to methacholine was defined by both the provocative dose causing a fall in FEV1 of 20%, and the dose-response slope. PEF variability was determined as diurnal PEF variation (amplitude percent mean) and between-day PEF variation. Skin tests positivity, serum total IgE, and specific IgE (RAST) for house-dust mite (HDM), cat, timothy grass, and birch ("pollen") were determined, as well as the number of peripheral blood eosinophils. Wheeze and nocturnal dyspnea were defined as asthma-like symptoms; dyspnea > or = grade 3, cough and phlegm as chronic obstructive pulmonary disease (COPD)-like symptoms. The reciprocal of the dose-response slope and PEF variability were significantly correlated (r = -0.39). Subjects with a positive skin test for HDM (odds ratio [OR] = 3.9), cat (OR = 8.3), or pollen (OR = 3.6), or specific IgE for HDM (OR = 2.3), cat (OR = 3.4), or pollen (OR = 1.9) had increased risk of BHR compared with the reference group (all p values < 0.05). Higher levels of serum total IgE were significantly associated with higher odds for BHR (OR = 2.5 per log unit). There was no significant association between skin test positivity, serum total IgE, or presence of specific IgE and PEF variability. Neither BHR nor PEF variability were associated with higher numbers of peripheral blood eosinophils. There are different associations of BHR and PEF variability with allergy markers. Although BHR and PEF variability are significantly correlated, they cannot be used interchangeably in epidemiologic settings.

Adult↗