Biomedical subjects

B Rutgers

Publications and source records attributed to B Rutgers.

13 recordsLinked to original sources

PubMed2005

Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers.

Smoking cessation is the only treatment in patients with chronic obstructive pulmonary disease (COPD) effective in slowing down disease progression. Its effect on airway inflammation in COPD is unknown, although cross-sectional studies suggest ongoing inflammation in ex-smokers. In order to elucidate the effect of smoking cessation on airway inflammation, 28 smokers with COPD (mean age: 55 yrs; forced expiratory volume in one second: 71% predicted) and 25 asymptomatic smokers with normal lung function (aged 50 yrs) were included in a 1-yr smoking cessation programme. Effects of smoking cessation on airway inflammation were investigated in bronchial biopsies (baseline, 12 months) and sputum samples (baseline, 2, 6 and 12 months). In the 12 candidates with COPD who successfully ceased smoking, airway inflammation persisted in bronchial biopsies, while the number of sputum neutrophils, lymphocytes, interleukin (IL)-8 and eosinophilic-cationic-protein levels significantly increased at 12 months. In the 16 asymptomatic smokers who successfully quitted, inflammation significantly reduced (i.e. number of sputum macrophages, percentage of eosinophils and IL-8 levels) or did not change. The current authors suggest that the observed persistent airway inflammation in patients with chronic obstructive pulmonary disease is related to repair of tissue damage in the airways. It remains to be elucidated whether this reflects a beneficial or detrimental effect.

Cytokines↗

PubMed2004

Smoking cessation improves both direct and indirect airway hyperresponsiveness in COPD.

Smoking induces chronic obstructive pulmonary disease (COPD) and is associated with airway inflammation and airway hyperresponsiveness (AHR). It has not been studied in COPD whether direct (methacholine) and indirect (adenosine-5'-monophosphate (AMP)) stimuli are associated with airway inflammation and neither whether smoking cessation improves these features. The current authors cross-sectionally investigated the relationship of AHR to methacholine and AMP with lung function and inflammatory cells in the sputum of 33 smokers with COPD. In addition, changes in these parameters were prospectively assessed in 14 smokers who successfully quit smoking for 1 yr. The presence of AHR to both methacholine and AMP was associated with lower lung function, but not with sputum inflammation. AHR to methacholine and AMP improved significantly after a 1-yr smoking cessation, yet this was unrelated to changes in sputum cell counts. The numbers of neutrophils and epithelial cells significantly increased with smoking cessation. Both direct and indirect airway hyperresponsiveness are associated with lower lung function, but not with sputum inflammation in chronic obstructive pulmonary disease. Interestingly, 1-yr smoking cessation improved both direct and indirect airway hyperresponsiveness, yet without a significant association with changes in lung function or sputum inflammation. Thus, other factors are likely to induce these improvements, e.g. a reduction in stimulation of irritant receptors, airway wall changes or mucus hypersecretion.

Adenosine Monophosphate↗

PubMed1998

Vascular adhesion molecules in nocturnal asthma: a possible role for VCAM-1 in ongoing airway wall inflammation.

BACKGROUND: Increased airway inflammation at night is thought to be one of the underlying mechanisms in nocturnal asthma. Vascular adhesion molecules may be important for the recruitment of inflammatory cells in the process of asthmatic airway inflammation. OBJECTIVE: To determine the possible role of vascular adhesion molecules in increased airway inflammation at night in subjects with nocturnal asthma. METHODS: Bronchial biopsies were obtained at 16.00 h and 04.00 h from 13 healthy controls, 15 asthmatic patients with PEF variation < or = 15% and 10 asthmatic patients with PEF variation > 15%. Biopsies were snap-frozen and double-immunostained for CD31 in combination with P-selectin, E-selectin, ICAM-1 or VCAM-1. RESULTS: No significant day-night differences in expression of adhesion molecules were found in any of the three groups. The percentage of VCAM-1 positive vessels in biopsies of asthmatic patients was higher than in biopsies of healthy controls: 5.8 vs 2.5% (P < 0.05) at 16.00h and 11 vs 0% (P<0.05) at 04.00 h. In asthma, VCAM-1 expression was correlated with the number of EG2 positive cells: at 16.00 h (rho = 0.57, P < 0.01) as well as at 04.00 h (rho = 0.64, P< 0.01). Moreover, VCAM-1 expression was correlated with the number of CD25 positive cells at 16.00 h (rho = 0.43, P < 0.05) and at 04.00 h (rho = 0.41, P < 0.05). CONCLUSION: Increased nocturnal airway obstruction in asthma is not associated with an increased nocturnal expression of vascular E-selectin, P-selectin, ICAM-1 or VCAM-1. The relationship between vascular VCAM-1 expression and sub-mucosal EG2 and CD25 positive cells, both at 16.00 h and 04.00 h, suggests a role for VCAM-1 in the ongoing airway wall inflammation of asthma.

Adult↗

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↗

PubMed1997

Interleukin-4, interferon-gamma and interleukin-5 in peripheral blood of children with moderate atopic asthma.

BACKGROUND: In asthmatic inflammation, TH2 cells play an important role. TH2 cells specifically secrete cytokines like IL-4 and IL-5. IL-4 stimulates IgE production and IL-5 is involved in hemopoiesis, chemotaxis, priming and activation of eosinophils. IFNgamma, produced by TH1 cells, has an inhibitory action on IgE production. OBJECTIVES: To investigate the TH1/TH2-cell pattern in the cytokine production of peripheral blood of asthmatic children. We determined IL-4, IFNgamma and IL-5 in serum and in supernatants of unstimulated and stimulated (24 h with Concanavaline A) cultures of peripheral blood mononuclear cells (PBMCs) in 22 children with moderate asthma (mean age 9.3 years) and in 17 healthy controls (mean age 10.3 years). All children visited the out-patient department (OPD) where history taking, physical examination and blood sampling took place. Children younger than 8 years of age performed symptom and peak flow registration during 1 week after the visit to the OPD. RESULTS: The number of eosinophils were significantly higher in children with asthma, compared with healthy controls. The concentration of IFNgamma in supernatants of cultures of stimulated PBMCs was significantly lower and the ratio of IL-4/IFNgamma was significantly higher in children with asthma compared with healthy controls. The FEV1 was directly and IgE was inversely related to the concentration of IFNgamma in supernatants of cultures of stimulated PBMCs. CONCLUSION: IFNgamma may play an important role in the pathophysiology of childhood atopic asthma.

Adolescent↗

PubMed1995

Inflammatory cell number and mediators in bronchoalveolar lavage fluid and peripheral blood in subjects with asthma with increased nocturnal airways narrowing.

BACKGROUND: Increased nocturnal airways narrowing (NAN) in asthma is thought to occur as the result of intensification of inflammatory processes in the airways. In this study we investigated the presence of inflammatory cells and mediators in bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) and assessed their relationship with the occurrence of increased NAN. METHODS: BAL fluid and PB samples were assessed at 16:00 and 04:00 hours, separated by 7 days or more, in eight nonatopic healthy subjects (group 1) and 17 atopic subjects with asthma who were using inhaled bronchodilators only. The latter subjects were prospectively assigned to groups with and without NAN, as defined by a mean circadian peak expiratory flow variation of less than 15% (group 2) and 15% or more (group 3), respectively. RESULTS: Significantly higher eosinophil numbers and inflammatory activation products (eosinophil cationic protein, eosinophil-derived neurotoxin, histamine) were found in BAL fluid and PB from subjects with asthma in comparison with control subjects. However, increased NAN was not generally associated with a circadian fluctuation in cell number and inflammatory mediators in BAL fluid and PB. No differences in inflammatory cell numbers existed that distinguished between groups 2 and 3. However, in group 3 significantly higher BAL prostaglandin D2 levels (70 vs 24 pg/ml; range, 28 to 102 vs 11 to 90 pg/ml; p = 0.04) and serum eosinophil cationic protein levels (17.6 vs 16.1 ng/ml; range, 6.3 to 17.5 vs 6.3 to 60.3 ng/ml; p = 0.03) at 16:00 hours were detected compared with group 2. CONCLUSIONS: Our findings suggest that increased NAN is more likely to occur in subjects with asthma with ongoing increased cellular activation during the day.

Adolescent↗

PubMed1995

Lymphocyte and macrophage activation in bronchoalveolar lavage fluid in nocturnal asthma.

Increased nocturnal airway narrowing is thought to occur as a consequence of an intensification of inflammatory processes at night. Lymphocyte and alveolar macrophage (AM) activation are thought to be associated with the clinical expression of asthma, and may be important in the occurrence of nocturnal asthma as well. The expression of CD25 and HLA-DR receptors on lymphocytes from bronchoalveolar lavage (BAL) and peripheral blood (PB) CD4+, as well as of CD14, IgG Fc, and CD11/CD18 leukocyte adhesion receptors on AM in BAL fluid and monocytes in PB, were determined at 16.00 and 04.00 h by flow cytometry. Their relationship with the occurrence of nocturnal asthma was investigated in eight nonatopic controls (Group 1) and 17 atopic asthmatic subjects, prospectively assigned to groups with a mean circadian peak expiratory flow (PEF) variation < 15% (Group 2) and > or = 15% (Group 3). The occurrence of an increased circadian variation in PEF in asthmatic subjects was on the whole not associated with a day-night fluctuation in lymphocyte numbers and subsets in PB or BAL fluid, nor with day-night changes in receptor expression on AM from BAL or monocytes from PB. The only exception was the presence of a greater day-night change in the proportion of HLA-DR-expressing CD4+ lymphocytes in the BAL fluid along with an increasing circadian PEF rhythm in asthmatic subjects (r = 0.68, p = 0.03). A further finding was that a lower number of BAL CD4+ lymphocytes at daytime was significantly related to a higher circadian PEF variation in asthmatic subjects (r = -0.66, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990