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Biomedical subjects

Dirkje S Postma

Publications and source records attributed to Dirkje S Postma.

At least 55 records · Page 3Linked to original sources
PubMed2005

The influence of intravenous hydrocortisone on cytokine levels in children with asthma.

Nocturnal airway obstruction occurs frequently in childhood asthma and results from increased airway inflammation. Lymphocytes are believed to be key effector cells of airway wall inflammation, releasing pro-inflammatory mediators and cytokines. A previous study showed that hydrocortisone infusion, an effective anti-inflammatory treatment, improves nocturnal and daytime FEV(1) values. This study in 16 children with moderate asthma was designed to assess whether there exists day and night differences in IL-4, IL-5, IL-8, and IFN-gamma production of concanavaline A stimulated peripheral blood mononuclear cells. Furthermore, we investigated whether substitution of low serum cortisol levels with intravenous hydrocortisone would affect those parameters. Saline (as a placebo) or hydrocortisone (30 microg/m(2) body surface area/24 h) was intravenously administered in a randomized, double blind, cross-over design. Measurements under saline or hydrocortisone infusions were separated by 1 wk. At 04:00 and 16:00 hours 10 ml blood was taken for determination of peripheral blood mononuclear cell isolation and stimulation, and an eosinophil count. Hydrocortisone infusion significantly reduced the nocturnal fall in FEV(1). Median values of IFNgamma, IL-4, IL-5, and IL-8 produced by peripheral blood mononuclear cells did not significantly differ at 04:00 and 16:00 hours, both with saline and hydrocortisone infusion. Our results suggest that FEV(1) improvement is not due to suppression of circulating peripheral blood mononuclear cell activation. We hypothesize that it is rather due to its effect on local lung tissue epithelial and/or fibroblasts thereby reducing airway inflammation and vascular leakage.

Adolescent↗
PubMed2005

Detrimental effects of beta-blockers in COPD: a concern for nonselective beta-blockers.

INTRODUCTION: beta-Blockers are known to worsen FEV(1) and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment. OBJECTIVE: To determine the effects of beta-blockers on AHR (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]), FEV(1), and response to formoterol in patients with COPD. DESIGN: A double-blind, placebo-controlled, randomized, cross-over study. SETTING: An ambulatory, hospital outpatient clinic of pulmonary diseases. PATIENTS: Patients with mild-to-moderate irreversible COPD and AHR. INTERVENTION: Fifteen patients received propranolol (80 mg), metoprolol (100 mg), celiprolol (200 mg), or placebo for 4 days, followed by a washout period >/= 3 days. On day 4 of treatment, FEV(1) and PC(20) were assessed. Immediately hereafter, formoterol (12 microg) was administered and FEV(1) was measured for up to 30 min. RESULTS: PC(20) was significantly lower (p < 0.01) with propranolol and metoprolol treatment (geometric means, 2.06 mg/mL and 2.02 mg/mL, respectively) than with placebo (3.16 mg/mL) or celiprolol (3.41 mg/mL). FEV(1) deteriorated only after propranolol treatment (2.08 +/- 0.31 L) [mean +/- SD] compared with placebo (2.24 +/- 0.37 L). The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV(1) at 3 min, 6.7 +/- 8.9%) but was unaffected by the other beta-blockers (16.9 +/- 9.8%, 22 +/- 11.6%, and 16.9 +/- 9.0% for placebo, metoprolol, and celiprolol, respectively). CONCLUSIONS: Pulmonary effects did not occur by celiprolol. Only propranolol reduced FEV(1) and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of beta-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a beta-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV(1), AHR, and response to additional beta(2)-agonists.

Adrenergic beta-Agonists↗
PubMed2004

Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21.

Asthma affects nearly 14 million people worldwide and has been steadily increasing in frequency for the past 50 years. Although environmental factors clearly influence the onset, progression, and severity of this disease, family and twin studies indicate that genetic variation also influences susceptibility. Linkage of asthma and related phenotypes to chromosome 6p21 has been reported in seven genome screens, making it the most replicated region of the genome. However, because many genes with individually small effects are likely to contribute to risk, identification of asthma susceptibility loci has been challenging. In this study, we present evidence from four independent samples in support of HLA-G as a novel asthma and bronchial hyperresponsiveness susceptibility gene in the human leukocyte antigen region on chromosome 6p21, and we speculate that this gene might contribute to risk for other inflammatory diseases that show linkage to this region.

Adult↗
PubMed2004

Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is defined by progressive, irreversible airflow limitation and an inflammatory response of the lungs, usually to cigarette smoke. However, COPD is a heterogeneous disease in terms of clinical, physiologic, and pathologic presentation. We aimed to evaluate whether airflow limitation, airway responsiveness, and airway inflammation are separate entities underlying the pathophysiology of COPD by using factor analysis. A total of 114 patients (99 males/15 females, age 62 +/- 8 years, 42 pack-years smoking, no inhaled or oral steroids > 6 months) with irreversible airflow limitation (postbronchodilator FEV(1) 63 +/- 9% predicted, FEV(1)/inspiratory vital capacity [IVC] 48 +/- 9%) and symptoms of chronic bronchitis or dyspnea were studied in a cross-sectional design. Postbronchodilator FEV(1) and FEV(1)/IVC, reversibility to inhaled beta(2)-agonists, diffusing capacity, provocative concentration of methacholine required to produce a 20% drop in FEV(1), total serum IgE, exhaled nitric oxide, and induced sputum cell counts (% eosinophils, % neutrophils) were collected. Factor analysis yielded 4 separate factors that accounted for 63.6% of the total variance. Factor 1 was comprised of FEV(1), FEV(1)/IVC, and residual volume/total lung capacity. Factor 2 included reversibility, IgE, provocative concentration of methacholine required to produce a 20% drop in FEV(1,) and diffusing capacity. Factor 3 contained exhaled nitric oxide and factor 4 included sputum % neutrophils and % eosinophils. We conclude that airflow limitation, airway inflammation, and features commonly associated with asthma are separate and largely independent factors in the pathophysiology of COPD.

Aged↗
PubMed2004

Short-term smoke exposure attenuates ovalbumin-induced airway inflammation in allergic mice.

Little is known about effects of smoking on airway inflammation in asthma. We tested the hypothesis that smoking enhances established airway inflammation in a mouse model of allergic asthma. C57Bl/6j mice were sensitized to ovalbumin (OVA) and challenged with OVA (OVA-mice) or sham-sensitized to phosphate-buffered saline (PBS) and challenged with PBS aerosols (PBS-mice) for 7 wk. At 4 wk, mice were additionally exposed to air (nonsmoking controls) or mainstream smoke for 3 wk. Using whole body plethysmography, we found OVA-induced bronchoconstriction to be significantly inhibited in smoking OVA-mice as compared with nonsmoking OVA-mice (1 +/- 2% increase versus 22 +/- 6% increase in enhanced pause, respectively). Smoking did not change airway hyperresponsiveness (AHR) to methacholine in PBS-mice, yet significantly attenuated AHR in OVA-mice 24 h after OVA challenge as compared with nonsmoking mice. This was accompanied by reduced eosinophil numbers in lung lavage fluid and tissue of smoking OVA-mice compared with nonsmoking OVA-mice. In contrast to our hypothesis, short-term smoking reduced responsiveness to OVA and methacholine in OVA-mice and decreased airway inflammation when compared with nonsmoking mice. This effect of smoking may be different for long-term smoking, in which remodeling effects of smoking can be expected to interrelate with remodeling changes caused by asthmatic disease.

Administration, Inhalation↗
PubMed2004

Sex and gender differences in lung development and their clinical significance.

Factors that affect airway growth-as early in development as in utero-seem to cause physiologic effects that can be persistent. Reduced airway function early in life does not necessarily result in persistent symptoms, but it does increase the risk of reduced lung function and the development of persistent airflow limitation in adult life, both in men and women. Normal lung growth varies with age and sex and is affected by a number of risk factors, which we have described. The importance of the various risk factors may differ depending at what point during lung growth they come into play and whether they occur in men or in women.

Adult↗
PubMed2004

Bronchoalveolar lavage fluid characteristics in acute and chronic lung transplant rejection.

BACKGROUND: The detection of graft rejection by bronchoalveolar lavage remains controversial. METHODS: To assess the value of bronchoalveolar lavage fluid in acute and chronic rejection after lung transplantation we analyzed bronchoalveolar lavage fluid cellular differential characteristics, lymphocyte sub-types and interleukin-6 (IL-6) and interleukin-8 (IL-8) cytokine levels in patients with exclusively either acute rejection (n = 37) or bronchiolitis obliterans (BO; n = 48). Both groups were compared with a control group of lung transplantation patients without rejection or infection, matched for the time the lavage was performed after lung transplantation. RESULTS: The bronchiolitis obliterans group showed marked neutrophilia, high IL-8 and higher CD4(+)CD25(+) and CD8(+)CD45(+) bronchoalveolar lavage fluid levels when compared with their stable controls. When using a cut-off point of >3% neutrophils in the lavage, the sensitivity for BO is 87.0%, the specificity 77.6%. The sensitivity of IL-8 for BO when using a cut-off point of >71.4 pg/ml is 74.5%, the specificity 83.3%. Bronchoalveolar lavage fluid in acute rejection was characterized by marked lymphocytosis, but showed no difference when compared with stable controls in any of the lymphocyte sub-types studied. When using a cut-off point of <==1% lymphocytes in the lavage, the sensitivity for acute rejection (AR) is 40.4%, the specificity 95.6%. The marked neutrophilia, high IL-8 cytokine level and more activated lymphocyte population in bronchiolitis obliterans may indicate ongoing local allograft rejection. CONCLUSIONS: In the present study we were not able to show any difference in lymphocyte sub-types when comparing acute rejection and control subjects. Cellular and soluble parameters in bronchoalveolar lavage fluid appear useful for diagnosing bronchiolitis obliterans.

Acute Disease↗
PubMed2004

Perinatal risk factors for bronchial hyperresponsiveness and atopy after a follow-up of 20 years.

BACKGROUND: Perinatal risk factors are associated with lung function and respiratory symptoms in adult life. Whether the same holds for distinctive asthma features, such as bronchial hyperresponsiveness (BHR) and atopy, has scarcely been studied. OBJECTIVE: We sought to identify the perinatal risk factors for the development of BHR and atopy. METHODS: BHR and atopy were measured after 20 years' follow-up in 597 of 3162 babies born from 1975 through 1978. Factors directly related to delivery of these children were studied in association with the presence of BHR and atopy. RESULTS: Twenty-five percent had BHR, and 47% had atopy. Delivery duration of longer than 12 hours was associated with the development of atopy (odds ratio [OR], 2.24; 95% CI, 1.30-3.86), and severe respiratory infection in the first year of life was associated with the development of BHR (OR, 2.69; 95% CI, 1.41-5.16). Nonatopic subjects born after induced labor and current smokers were more likely to have BHR (ORs of 2.41 [95% CI, 1.07-5.41] and 2.50 [95% CI, 1.12-5.59], respectively). Prenatal smoke exposure and childhood pet keeping decreased the risk for atopy, especially in BHR-positive subjects (ORs of 0.51 [95% CI, 0.27-0.99] and 0.46 [95% CI, 0.24-0.88], respectively). CONCLUSIONS: It has been shown that events before or during birth still have an effect on respiratory health 20 years later. We put forward that an extreme hormonal status during delivery primes the fetal immune system toward atopy development. Furthermore, a severe respiratory infection in the first year of life appears associated with BHR development, and prenatal smoke exposure might be protective for the development of atopy, yet explanatory mechanisms are lacking thus far.

Adult↗
PubMed2004

The role of endogenous and exogenous AMP in asthma and chronic obstructive pulmonary disease.

Bronchial hyperresponsiveness is present in virtually all patients with asthma and in more than two thirds of patients with chronic obstructive pulmonary disease. Thus far, methacholine and histamine are usually used to measure bronchial hyperresponsiveness. Both are direct stimuli, because they act directly on airway smooth muscle. Another possible stimulus to measure bronchial hyperresponsiveness is AMP. AMP is an indirect stimulus, because it acts via the release of histamine and other mediators from immunologically primed mast cells. There is increasing interest in the role of AMP as a bronchoconstrictor stimulus because it has been suggested that the concentration of AMP causing the FEV 1 to decrease by 20% (PC 20 AMP) may be used as a noninvasive marker of airway inflammation. The aim of this article was to review the literature assessing AMP's value in asthma and chronic obstructive pulmonary disease.

Adenosine Monophosphate↗
PubMed2004

Cognitive performance in patients with COPD.

BACKGROUND: Hypoxemic patients with Chronic Obstructive Pulmonary Disease (COPD) have impaired cognitive performance. These neuropsychological impairments are related to the degree of hypoxemia. So far, cognitive performance has not been tested in non-hypoxemic patients with COPD. METHODS: We recruited patients with stable COPD and PaO2 > 8.0 kPa (60 mmHg), as well as healthy subjects, who were matched for age, intelligence quotient (IQ), and level of education. Cognitive performance was studied by Stroop Colour Word Test, Trailmaking, digit-symbol of the Wechsler Adult Intelligence Scale, addition subtest of the Groningen Intelligence Test, and Story Recall. RESULTS: Thirty patients with COPD (FEV1 49.8% pred, mean age 64.8 yr) and 20 healthy volunteers (65.6 yr) were enrolled. COPD patients performed significantly worse on trailmaking B, the digit-symbol test, and on the addition subtest. There was no significant correlation between the tests of cognitive performance and disease specific health status (Chronic Respiratory Questionnaire). CONCLUSIONS: We conclude that even non-hypoxemic patients with COPD show significant impairments in cognitive performance. These impairments are not associated with deteriorations in health related quality of life. Prospective evaluation of the impact of treatment on cognitive performance in non-hypoxemic patients with COPD would be a logical subsequent study.

Aged↗
PubMed2004

Relief of dyspnoea by beta2-agonists after methacholine-induced bronchoconstriction.

Virtually all asthma patients use brorichodilators. Formoterol and salbutamol have a rapid onset of bronchodilating effect, whereas salmeterol acts slower. We studied the onset of improvement of dyspnoea sensation after inhalation with these bronchodilators and placebo to reverse a methacholine-induced bronchoconstriction as a model for an acute asthma attack. Seventeen patients with asthma completed this randomised, double-blind, crossover, double-dummy study. On 4 test days, forced expiratory volume in 1 s (FEV1) and Borg score were recorded and patients were challenged with methacholine until FEV1 fell with > or = 30% of baseline value. Thereafter, formoterol 12 microg via Turbuhaler, salbutamol 50 microg via Turbuhaler, salmeterol 50 microg via Diskhaler, or placebo was inhaled. FEV1 and Borg scores were assessed during the following 60 min. The first sensed improvement of Borg score was significantly (P<0.05) faster achieved with formoterol (geometric mean (Gmean) (range) 1.5 (1-40) min) and salbutamol 1.8 (1-10) min than with salmeterol 4.5 (1-30) min and placebo 3.4 (1-40) min. The Borg score returned significantly faster to the baseline value with formoterol, salbutamol, and salmeterol (Gmean time 13.8 (1-75), 13.4 (1-60), and 18.0 (1-75) min, respectively) than with placebo (33.6 (1-75 min). Formoterol and salbutamol act significantly faster than salmeterol in relieving dyspnoea induced by methacholine-induced bronchoconstriction, in patients with asthma.

Adolescent↗
PubMed2004

Gender differences in the management and experience of Chronic Obstructive Pulmonary Disease.

Whether women receive the same medical care for COPD as men and if they are at risk of different outcomes as a result, is not known. The Confronting COPD International Survey was performed in the USA, Canada, France, Italy, Germany, The Netherlands, Spain and the UK in 2000 with 3265 COPD participants. Forty-one per cent were women; mean age in women and men was 61.2 (SD 10.5) and 64.4 (11.0) years, mean pack-years of smoking 36 (29) and 46 (35) years, respectively. After adjusting for age, pack-years, country and severe dyspnea (MRC scores 5 and 4), women were less likely to have had spirometry (OR 0.84, 95% C.I. 0.72-0.98) but more likely to get smoking cessation advice (OR 1.57, 1.33-1.86). Despite significantly lower pack-years of smoking, women were more likely to report severe dyspnea than men (OR 1.30, 1.10-1.54), with similar cough (OR 1.08, 0.92-1.27) and less sputum (OR 0.84, 0.72-0.98). There were no differences in the risk of hospitalisation or emergency room visit. This study indicates that gender differences in COPD care and outcomes exist.

Aged↗
PubMed2004

Identification of polymorphisms in the human glucocorticoid receptor gene (NR3C1) in a multi-racial asthma case and control screening panel.

The glucocorticoid receptor (GR) gene (NR3C1) maps to 5q31, a region genetically linked to asthma. In this study, NR3C1 exons 1A, 1B, and exons 1C to 9 (alpha and beta) were sequenced in a screening panel of asthmatics and unaffected controls from US Caucasian, African American, US Hispanic, and Dutch Caucasian populations to identify polymorphisms for genetic association studies. Eight polymorphisms were identified in exon 1A, but none were located in putative transcription regulatory sites. Thirty-four polymorphisms were identified in exons 1B to 9 (alpha and beta), 17 of which were novel. Eight coding polymorphisms were identified (4 non-synonymous). One novel mutation (Ala229Thr) was identified in a Hispanic individual. Linkage disequilibrium (LD) was strongest between polymorphisms spanning intron 2 to exon 9beta. This data shows the variability of NR3C1 polymorphism frequencies between racial groups and confirms that NR3C1 non-synonymous coding polymorphisms are generally rare in mild/moderate asthmatics and unaffected controls.

Black or African American↗
PubMed2004

Feasibility of sputum induction in lung transplant recipients.

Sputum induction (SI) is nowadays being applied as a non-invasive and safe method to investigate airway inflammation in pulmonary diseases. We investigated the feasibility of SI after lung transplantation (LTX), and compared sputum and bronchoalveolar lavage (BAL) cellular characteristics and interleukin-8 (IL-8) levels. Results were also compared with 11 healthy subjects. SI as performed between 26 and 1947 d after LTX in 19 recipients, was successful in 16 of 22 attempts (73%). Six patients failed to produce sputum after induction, mostly just post-LTX and with having a lower forced expiratory volume in 1 s (FEV1). The success rate in clinically stable patients after the first month post-LTX was 93%. Side-effects were absent. Sputum recovery, viability and squamous cell contamination were comparable between LTX patients and healthy subjects. In the LTX group, total cell counts, neutrophil percentages and IL-8 levels were much higher in SI than BAL (1.6 x 10(6)/mL, 65.5% and 54.2 ng/mL vs. 0.1 x 10(6)/mL, 3.0% and 0.01 ng/mL; p < 0.001). Although LTX-neutrophil percentages in SI and BAL correlated properly (rho=0.72, p=0.04), both techniques are not interchangeable. We conclude that sputum induction is feasible, well tolerated, and without major side-effects in stable patients after the first month post-LTX. Induced sputum may be a useful tool to study inflammatory changes of the airways after LTX, and because of the large quantity of neutrophils sampled, especially for further studies on the pathogenesis of bronchiolitis obliterans.

Adult↗
PubMed2004

Localization and enhanced mRNA expression of the orphan chemokine receptor L-CCR in the lung in a murine model of ovalbumin-induced airway inflammation.

Various CC chemokine receptors are expressed on effector cells in allergic inflammation and their distinct expression pattern may dictate, to a large extent, the migration of inflammatory cells to sites of airway inflammation. The lipopolysaccharide (LPS)-inducible CC chemokine receptor (L-CCR) is an orphan chemokine receptor that has previously been identified in the murine macrophage cell line RAW 264.7 and in murine brain glial cells. In this study we investigated the induction and localization of L-CCR mRNA expression in mouse lung after ovalbumin (OVA)-induced airway inflammation. Both RT-PCR experiments and in situ hybridization (ISH) experiments in whole lung sections revealed a rapid upregulation of L-CCR mRNA expression as early as 1 hr and 3 hr after OVA challenge. Expression was found predominantly in MAC3(+) macrophages and in bronchial epithelium, as shown by ISH and immunohistochemistry (IHC). We demonstrated that L-CCR mRNA expression is strongly upregulated in mouse lung after OVA challenge and is localized in macrophages and bronchial epithelium. Regarding the likely role of L-CCR as a chemokine receptor with the putative ligand monocyte chemotactic protein-1 (MCP-1, CCL2), this receptor may have an important function in the early phase of airway inflammation.

Animals↗
PubMed2004

Rationale for the Dutch hypothesis. Allergy and airway hyperresponsiveness as genetic factors and their interaction with environment in the development of asthma and COPD.

The Dutch hypothesis, formulated in the 1960s, holds that the various forms of airway obstruction are different expressions of a single disease entity. It suggests that genetic factors (eg, airway hyperresponsiveness [AHR] and atopy), endogenous factors (eg, sex and age), and exogenous factors (eg, allergens, infections, and smoking) all play a role in the pathogenesis of chronic nonspecific lung disease. This review finds evidence that AHR and smoking are common risk factors for asthma and COPD. To prove the Dutch hypothesis definitively, however, genetic studies, preferably longitudinal, must be performed. Such studies must include subjects who have airway obstruction that does not necessarily meet the current strict definitions of asthma or COPD (ie, the extremes of these conditions) that are used in clinical studies.

Air Pollutants↗